Updated epithelial barrier dysfunction in chronic rhinosinusitis: Targeting pathophysiology and treatment response of tight junctions.

Tight junction (TJ) proteins establish a physical barrier between epithelial cells, playing a crucial role in maintaining tissue homeostasis by safeguarding host tissues against pathogens, allergens, antigens, irritants, etc. Recently, an increasing number of studies have demonstrated that abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases, including chronic obstructive pulmonary disease, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS) with or without nasal polyps. Among them, CRS with nasal polyps is a prevalent chronic inflammatory disease that affects the nasal cavity and paranasal sinuses, leading to a poor prognosis and significantly impacting patients' quality of life. Its pathogenesis primarily involves dysfunction of the nasal epithelial barrier, impaired mucociliary clearance, disordered immune response, and excessive tissue remodeling. Numerous studies have elucidated the pivotal role of TJs in both the pathogenesis and response to traditional therapies in CRS. We therefore to review and discuss potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process.

An unusually high prevalence of allergic rhinitis at high altitudes in 6-7 year old children - An epidemiological study.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.

Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy.

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.

Mometasone furoate intranasal spray is effective in reducing symptoms and adenoid size in children and adolescents with adenoid hypertrophy / El aerosol nasal de mometasona furoato es efectivo para reducir los síntomas y el tamaño de las adenoides en niños y adolescentes con hipertrofia adenoidea

INTRODUCTION: The use of mometasone furoate (MF) intranasal spray in treating adenoid hypertrophy (AH) has a variable outcome due the different methods of adenoid size evaluation. The aim of our study was to evaluate the effect of MF intranasal spray in children and adolescents with AH using a reliable and consistent endoscopic evaluation. MATERIAL AND METHOD: A prospective interventional study was conducted. Evaluation took place during the first visit (week 0) and second visit (week 12). Symptoms of nasal obstruction, rhinorrhoea, cough and snoring were assessed, and an overall total symptoms score was obtained. A rigid nasoendoscopic examination using a four-grading system of adenoid size from 1 to 4 was performed. Patients were treated with MF intranasal spray for 12 weeks. Patients' aged 7-11-years old used 1 spray in each nostril once daily, while patients aged 12-17 used two sprays in each nostril once daily. Reassessment was carried out during the second visit (week 12). RESULTS: A total of 74 patients was recruited. There were significant improvements from week 0 to week 12 in the symptoms' score for nose obstruction, rhinorrhoea, cough, snoring including the total nasal symptoms' score (p < 0.001). AH significantly reduced in size from week 0 (2.89±.87) to week 12 (1.88±.83) (p < 0.001). CONCLUSION: MF intranasal spray is effective in improving the symptoms attributed to AH as well as reducing the adenoid size. MF intranasal spray is advocated as a treatment option before adenoidectomy is considered

INTRODUCCIÓN: El papel del aerosol nasal de mometasona furoato (MF) para tratar la hipertrofia adenoidea (HA) tiene un resultado variable, debido a los diferentes métodos de evaluación del tamaño de las adenoides. El objetivo de nuestro estudio fue evaluar el efecto del aerosol nasal de MF en niños y adolescentes con HA, utilizando una evaluación endoscópica fiable y consistente. MATERIAL Y MÉTODO: Se llevó a cabo un estudio prospectivo intervencionista. La evaluación se realizó durante la primera visita (semana 0) y la segunda visita (semana 12). Se valoraron los síntomas de obstrucción nasal, rinorrea, tos y ronquidos, obteniéndose una puntuación de síntomas totales globales. Se realizó un examen nasoendoscópico rígido utilizando un sistema de clasificación del tamaño adenoideo, con valores de 1 a 4. Los pacientes fueron tratados con aerosol intranasal de MF durante 12 semanas. Los pacientes con edades comprendidas entre 7 y 11 años utilizaron 1 pulverización en cada fosa nasal una vez al día, mientras que los pacientes de 12 a 17 años utilizaron 2 pulverizaciones en cada fosa nasal una vez al día. La re-evaluación se realizó durante la segunda visita (semana12). RESULTADOS: Reunimos a un total de 74 pacientes. Se produjeron mejoras significativas de la semana 0 a la 12 en cuanto a puntuación de los síntomas de obstrucción nasal, rinorrea, tos y ronquidos, incluyendo la puntuación total de síntomas nasales (p < 0,001). Se redujo significativamente el tamaño de HA de la semana 0 (2,89 ±0,87) a la semana 12 (1,88 ±0,83) (p < 0,001). CONCLUSIÓN: El aerosol intranasal de MF es efectivo para mejorar los síntomas atribuidos a HA, así como reducir el tamaño de las adenoides. Se propone el uso de dicho aerosol intranasal como opción de tratamiento, antes de considerarse la adenoidectomía