Mucosal Disease Research Articles

Genomic attributes of airway commensal bacteria and mucosa

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Oral_voting_transfer: classification of oral microorganisms' function proteins with voting transfer model.

The oral microbial group typically represents the human body's highly complex microbial group ecosystem. Oral microorganisms take part in human diseases, including Oral cavity inflammation, mucosal disease, periodontal disease, tooth decay, and oral cancer. On the other hand, oral microbes can also cause endocrine disorders, digestive function, and nerve function disorders, such as diabetes, digestive system diseases, and Alzheimer's disease. It was noted that the proteins of oral microbes play significant roles in these serious diseases. Having a good knowledge of oral microbes can be helpful in analyzing the procession of related diseases. Moreover, the high-dimensional features and imbalanced data lead to the complexity of oral microbial issues, which can hardly be solved with traditional experimental methods. To deal with these challenges, we proposed a novel method, which is oral_voting_transfer, to deal with such classification issues in the field of oral microorganisms. Such a method employed three features to classify the five oral microorganisms, including Streptococcus mutans, Staphylococcus aureus, abiotrophy adjacent, bifidobacterial, and Capnocytophaga. Firstly, we utilized the highly effective model, which successfully classifies the organelle's proteins and transfers to deal with the oral microorganisms. And then, some classification methods can be treated as the local classifiers in this work. Finally, the results are voting from the transfer classifiers and the voting ones. The proposed method achieved the well performances in the five oral microorganisms. The oral_voting_transfer is a standalone tool, and all its source codes are publicly available at https://github.com/baowz12345/voting_transfer.

PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial–mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

B12 deficiency-related glossitis is highly associated with high gastrin-17 and low pepsinogen I.

The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

Clinical and molecular epidemiological features of critically ill patients with invasive group A Streptococcus infections: a Belgian multicenter case-series

BackgroundRecent alerts have highlighted an increase in group A streptococcal (GAS) infections since 2022 in Europe and the United States. Streptococcus pyogenes can cause limited skin or mucosal disease, but can also present as severe invasive disease necessitating critical care. We performed a multicenter retrospective study of patients with GAS infections recently admitted to Belgian intensive care units (ICUs) since January 2022. We describe patient characteristics and investigate the molecular epidemiology of the S. pyogenes strains involved.ResultsBetween January 2022 and May 2023, a total of 86 cases (56 adults, 30 children) with GAS disease were admitted to critical care in the university hospitals of Leuven, Antwerp and Liège. We noted a strikingly high incidence of severe community-acquired pneumonia (sCAP) (45% of adults, 77% of children) complicated with empyema in 45% and 83% of adult and pediatric cases, respectively. Two-thirds of patients with S. pyogenes pneumonia had viral co-infection, with influenza (13 adults, 5 children) predominating. Other disease presentations included necrotizing fasciitis (23% of adults), other severe skin/soft tissue infections (16% of adults, 13% of children) and ear/nose/throat infections (13% of adults, 13% of children). Cardiogenic shock was frequent (36% of adults, 20% of children). Fifty-six patients (65%) had toxic shock syndrome. Organ support requirements were high and included invasive mechanical ventilation (77% of adults, 50% of children), renal replacement therapy (29% of adults, 3% of children) and extracorporeal membrane oxygenation (20% of adults, 7% of children). Mortality was 21% in adults and 3% in children. Genomic analysis of S. pyogenes strains from 55 out of 86 patients showed a predominance of emm1 strains (73%), with a replacement of the M1global lineage by the toxigenic M1UK lineage (83% of emm1 strains were M1UK).ConclusionsThe recent rise of severe GAS infections (2022–23) is associated with introduction of the M1UK lineage in Belgium, but other factors may be at play—including intense circulation of respiratory viruses and potentially an immune debt after the COVID pandemic. Importantly, critical care physicians should include S. pyogenes as causative pathogen in the differential diagnosis of sCAP.

Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

P019 Development of hydrogel systems for targeted rectal delivery of intestinal cells to injured mucosa in inflammatory bowel disease

Abstract Background Crohn’s Disease (CD) and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases (IBD) affecting over 6.8 million people worldwide. CD and UC are chronic and progressive diseases, characterised by destructive inflammation of the intestinal tract. IBD management consists of drugs such as steroids, aminosalicylates, immunosuppressants, and biologics that aim to induce disease maintenance and remission. However, frequent, and systemic drug administration leads to limited local effects, severe side effects, and low patient compliance. Ultimately, about 20% of UC and up to 80% of CD patients require surgical colon removal. Thus, new approaches to locally restore the inflamed mucosa and initiate colonic wound repair are required. Human intestinal organoids (HIOs) are 3D cell aggregates derived from primary tissue or stem cells grown in vitro. They demonstrate a similar composition architecture to the primary intestinal tissue. Studies showed that HIOs can engraft into injured colonic mucosa resulting in wound repair. Thus, delivery of HIOs to damaged intestinal epithelium represents a promising therapeutic option in IBD treatment. The project aims to develop hydrogel systems with embedded HIOs and obtain human-relevant information on their efficacy in the restitution of injured colonic mucosa using an improved and human-relevant organ-on-a-chip technology. Methods A series of thermoresponsive hydrogels were fabricated (based on methylcellulose/hyaluronic acid polymers) and characterised. Following the embedment of HIOs into hydrogels, the morphology and viability of HIOs were determined using microscopy and MTT assays. Inflammation was induced through the administration of LPS to the basolateral side of the gut chip. Hydrogel/HIO systems were applied to the apical chip compartment via flow for 24 hours. Subsequently, hydrogel/HIO systems were removed from the chip, and HIO engraftment into injured mucosa was determined utilising permeability (4 kDa dextran) and cytokine release assays (ELISA IL-8). Results Our findings show that the gels were liquid at 25 °C and solidified at 37 °C and demonstrated low cytotoxicity. Additionally, our results suggest that the hydrogel systems had a restorative and possibly protective effect on the villi structures in the gut chip. Microscopy results clearly demonstrated the presence of fully differentiated villi structures in the chips that were treated with the hydrogel/cell systems (Figure 1B). These villi structures were absent in the not-treated chips (Figure 1A). Conclusion This study suggests that development of organoid-based hydrogels that can serve as a safe, effective, and inexpensive therapy (compared to surgery) and significantly improve the treatment of IBD.

Screening as a stage in the prevention of oral mucosal diseases in patients undergoing chemotherapy for malignant growths

Relevance. The incidence of malignant growths in the maxillofacial area has consistently increased over the years. Chemotherapy stands out as one of the most effective treatments for cancerous tumors. Chemotherapeutic drugs possess the capability to either inhibit the proliferation of malignant cells or cause damage to them. However, while acting on abnormal cells, cytostatic drugs also impact actively dividing cells in normal tissues, including the mucous membranes in the oral cavity. As a result, various complications are observed in every patient undergoing treatment for malignant neoplasms (MN), particularly chemotherapy (CT). The nature and severity of side effects undergo changes based on the specific drugs and cytostatic treatment regimen employed. Adverse reactions and side effects inherent to each drug category manifest at different points throughout a chemotherapy course and its aftermath. Oral mucosal (OM) complications, such as oral mucositis, may ensue as a consequence of CT side effects.Materials and methods. In order to assess the effectiveness of screening for OM disorders arising as side effects of chemotherapy, a study involving 37 patients undergoing chemotherapy for an underlying condition was conducted. The screening study comprised two stages: Stage I involved a quality-of-life assessment utilizing questionnaires developed by the authors, while Stage II entailed a clinical examination of the oral mucosa. The obtained data were subjected to statistical analysis methods. Variation statistics were employed to assess the likelihood of data errors.Results. Comprehensive OM diagnostics in patients undergoing chemotherapy for an underlying oncology condition enable the early identification of oral mucosal diseases and the prevention of complications. It is recommended to conduct a thorough clinical examination and employ toluidine blue staining during each follow-up visit. Any observed clinical or stained tissue changes, the emergence of new erythematous lesions, erosions, or ulcers may serve as indicators of malignant transformation.Conclusion. It is advisable to incorporate screening diagnostics into each patient's dental visit to proactively prevent the onset of various pathological conditions.

Orofacial complications from immune checkpoint inhibitors: A retrospective analysis from two academic medical centers.

Immune checkpoint inhibitors (ICIs) are FDA-approved for various cancers, yet their orofacial immune-related adverse events (irAEs) remain poorly understood. Our two-center retrospective study aims to better understand the prevalence and nature of these orofacial irAEs. We retrospectively collected demographics, ICI details, and onset of orofacial irAEs in ICI-treated patients at University of California San Francisco and City of Hope (2013-2021). Orofacial irAEs were identified by ICD-10 codes and data categorized as dry mouth/xerostomia, oral mucosal lesions, and orofacial neuropathies. Patients with pre-existing orofacial conditions resembling the reported irAEs were excluded. Among 3768 ICI-treated patients, 408 (10.8%) developed 467 orofacial irAEs: oral mucosal diseases (41.4%), dry mouth/xerostomia (41.0%), and orofacial neuropathies (17.6%). Notably, head and neck cancers had the highest incidence of orofacial irAEs. Orofacial irAEs are relatively common in patients receiving ICIs, necessitating careful monitoring and management of these complications during and after the treatment.

Cytological Features of Oral Cytobrush Smears in Type II Diabetes Mellitus Patients

Oral cytology is a renewed field that aids in diagnosis and observation of possible epithelial changes associated with oral mucosal diseases. Aim; to study the main cytomorphological alteration in gingival and buccal smears from type II diabetics in relation to their hyperglycemic status. The study includes 40 type II diabetic patients (20 new-diagnosed and 20 treated diabetics patients) and 20 healthy persons of both sex. Papanicolaou stained smear were prepared from their cheek and gingiva. The morphological features of 100 unfolded epithelial cells were evaluated under light microscope. Results of this study show that diabetics’ oral mucosa cells characterized by large nuclei with frequent evidence of binucleation, granular chromatin, prominent nucleoli. However, there was frequent small blue cytoplasm and buccal smears showed altered keratinization. As conclusion oral cytology from type II diabetics is associated with detectable cytomorphological changes that is site specific and indicate epithelial cell regeneration and degeneration with altered keratinization especially in buccal mucosa.

A bibliometric study on research trends and hotspots of recurrent aphthous stomatitis

Background/purposeRecurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach. Materials and methodsThe Elsevier's Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country. ResultsA list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries. ConclusionThis report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

Thalidomide for management of refractory oral mucosal diseases

Thalidomide has anti-inflammatory properties and has been used off-label for multiple mucocutaneous disorders, but its application in managing refractory oral mucosal diseases is unclear. This study aimed to review the efficacy and safety of thalidomide in treating various oral mucosal disorders refractory to conventional therapies. The medical records of patients who were prescribed thalidomide from 2002 through 2021 for oral mucosal disorders were reviewed. Data collected included demographic characteristics, oral mucosal disease diagnosis, treatment courses, and thalidomide dose, duration, response, and side effects. Thalidomide was prescribed for 28 patients with diagnoses of recurrent aphthous stomatitis (n = 14), inflammatory oral lichenoid lesions (n = 6), traumatic ulcerative granuloma with stroma eosinophilia (n = 5), chronic radiation-induced mucositis (n = 2), and orofacial granulomatosis (n = 1). Patients were treated for a median duration of 84 days (range 2-1,582). Clinical improvement was observed in 19 of 22 patients who completed at least 1 cycle of thalidomide (86.4%), with complete resolution in 12 patients (54.5%). Adverse events occurred in 75% of patients (n = 21), with 8 requiring thalidomide discontinuation. The most common adverse events included peripheral neuropathy (42.9%), drowsiness (28.6%), and constipation (21.4%). Thalidomide may be considered for the management of refractory oral mucosal disorders. Drug side effects are common and need monitoring closely during use.

Clinical value of random esophageal biopsies in patients with dysphagia and normal endoscopy who are treated with a proton pump inhibitor.

Rome IV recommended esophageal biopsies in patients with dysphagia and normal endoscopy to exclude mucosal disease. Thus far, studies evaluating the utility of this recommendation remain scarce. The aims of this study were to determine the value of random esophageal biopsies in heartburn patients with dysphagia and normal endoscopy and compare the yield of random esophageal biopsies between younger versus older patients. Data were collected from consecutive patients presenting with dysphagia, 18years and older, who were on proton pump inhibitors and had normal upper endoscopy. Biopsy results of patients with and without heartburn were recorded. Logistic regression analysis was used to compare normal versus abnormal biopsy results in younger and older patients accounting for confounding variables. The number of abnormal biopsies was significantly higher than normal biopsies (68% and 32%, respectively, P = 0.0001). Among abnormal biopsy results, microscopic gastroesophageal reflux disease was significantly more common than all other findings (39%, P = 0.0495). There was no significant difference in biopsy results in patients with and without heartburn as well as younger versus older patients (P = 0.3384, P = 0.1010, and P = 0.8468, respectively). Our study demonstrated that most patients with dysphagia and normal upper endoscopy who are on proton pump inhibitor have some type of histologic mucosal abnormality, which can direct future management. Among abnormal biopsies, microscopic reflux was by far the most common finding in patients with or without a history of heartburn. While this supports the management strategy proposed by Rome IV, age did not drive esophageal biopsy results.

Optical coherence tomography: Promising imaging technique for the diagnosis of oral mucosal diseases.

This review aims to summarize the latest application of optical coherence tomography (OCT) in oral mucosal diseases, promoting an accurate and earlier diagnosis of such disorders, which are difficult to be differentiated. References on the application of OCT in oral mucosal diseases were mainly obtained from PubMed, Embase, Web of Science and Scopus databases, using the keywords: "optical coherence tomography and 'oral mucosa/oral cancers/oral potentially malignant diseases/oral lichen planus/oral leukoplakia/oral erythroplakia/discoid lupus erythematosus/oral autoimmune bullous diseases/oral ulcers/erythema multiforme/oral mucositis'". It is found that OCT is showing a promising application potential in the early detection, diagnosis, differential diagnosis, monitoring of oral cancer and oral dysplastic lesions, as well as the delineation of tumor margins. OCT is also playing an increasingly important role in the diagnosis of oral potentially malignant disorders, oral mucosal bullous diseases, oral ulcerative diseases, erythema multiforme, and the early detection of oral mucositis. Optical coherence tomography, as a novel optical technique featured by real-time, noninvasive, dynamic and high-resolution imaging, is of great use to serve as an adjunct tool for the diagnosis, differential diagnosis, monitoring and therapy evaluation of oral mucosal diseases.

Notch2 with retinoic acid license IL-23 expression by intestinal EpCAM+ DCIR2+ cDC2s in mice.

Despite the importance of IL-23 in mucosal host defense and disease pathogenesis, the mechanisms regulating the development of IL-23-producing mononuclear phagocytes remain poorly understood. Here, we employed an Il23aVenus reporter strain to investigate the developmental identity and functional regulation of IL-23-producing cells. We showed that flagellin stimulation or Citrobacter rodentium infection led to robust induction of IL-23-producing EpCAM+ DCIR2+ CD103- cDC2s, termed cDCIL23, which was confined to gut-associated lymphoid tissues, including the mesenteric lymph nodes, cryptopatches, and isolated lymphoid follicles. Furthermore, we demonstrated that Notch2 signaling was crucial for the development of EpCAM+ DCIR2+ cDC2s, and the combination of Notch2 signaling with retinoic acid signaling controlled their terminal differentiation into cDCIL23, supporting a two-step model for the development of gut cDCIL23. Our findings provide fundamental insights into the developmental pathways and cellular dynamics of IL-23-producing cDC2s at steady state and during pathogen infection.

Salivary microbiota and metabolic phenotype of patients with recurrent aphthous ulcers.

Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. 16S rRNA sequencing (16S rRNA-seq) and non-targeted liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). Findings from 16S rRNA -seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC-MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA-seq and LC-MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU.

Triggered Pemphigus with Koebner Phenomenon: A Coincidence?

Abstract Pemphigus includes a group of autoimmune bullous diseases of skin and/or mucous membranes characterized by intraepidermal acantholytic blisters. The onset and course of pemphigus vulgaris (PV) depend on a variable interaction between predisposing and inducing/triggering factors. Genetic predisposition has an important role and is alone not sufficient to initiate the autoimmune mechanism. The interference of inducing or triggering environmental factors seems to be crucial to set out the disease. Triggering of PV by physical agents, contact allergens, dietary factors, and emotional stress are rare, but well-documented events. The Koebner phenomenon (KP), which is described as the appearance of typical skin lesions of a certain dermatosis in uninvolved skin as a result of different kinds of trauma, is rarely documented in pemphigus. We would like to report this case due to the unusual coexistence of thermal burns triggering pemphigus and KP occurring in the same patient.

Inflammatory cloacogenic polyp: differential diagnose with endoscopic malignant lesions.

Inflammatory cloacogenic polyp is an unusual anorectal lesion associated with benign polyp with malignant appearance. This pathology is associated with mucosal prolapse syndrome and inflammatory intestinal disease. The surgery is the gold standard treatment if malignancy cannot be excluded or the patient is symptomatic.

Synthetic mucus barrier arrays as a nanoparticle formulation screening platform.

A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris(2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to N-acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.

Helicobacter pylori infection and inflammasomes

AbstractHelicobacter pylori (H. pylori) causes the most prevalent bacterial infection worldwide, and more than half of the world's population is infected with H. pylori. Classified as a group 1 carcinogen of gastric cancer, H. pylori infection causes the most common chronic gastritis, which is able to progress to chronic atrophic gastritis, dysplasia, and even gastric cancer. The inflammasomes are important cytosolic multiprotein complexes to coordinate the host defense against foreign microorganisms and control the inflammatory response. It is also well‐known that inflammasome plays an important role in the occurrence of H. pylori‐induced gastric inflammation. During infection and inflammation, the activation process of inflammasome is tightly regulated by host immune system. However, excessive activation of inflammasome is closely related to the production of excessive cytokines that cause the body injury and resulting in various inflammatory diseases. In this review, we elaborate the activation and assembly mechanisms of inflammasome, the structure of different inflammasome complexes, host factors in vivo and drugs in vitro that regulate inflammasome signaling during H. pylori infection, aiming to provide novel insights and strategies for identifying new therapeutic targets for the treatment of H. pylori‐associated gastric mucosal diseases.