Human Nasal Mucosa Research Articles

Three-dimensional morphologic and molecular atlases of nasal vasculature

Understanding the function of the nasal vasculature in homeostasis and pathogenesis of common nasal diseases is important. Here we describe an extensive network of venous sinusoids (VSs) in mouse and human nasal mucosa. The endothelium of the VSs expressed Prox1 (considered to be a constitutive marker of lymphatic endothelium) and high levels of VCAM-1 and exhibited unusual cell-to-cell junctions. VSs are supported by circular smooth muscle cells (SMCs) and surrounded by immune cells. The nasal mucosa also showed a rich supply of lymphatic vessels with distinctive features, such as the absence of the lymphatic marker LYVE1 and sharp-ended capillaries. In mouse models of allergic rhinitis or acute Coronavirus Disease 2019 (COVID-19) infection, Prox1+ VSs were regressed or compromised. However, in aged mice, the VSs lost the SMC support and were expanded and enlarged. Our findings demonstrate three-dimensional morphological and molecular heterogeneities of the nasal vasculature and offer insights into their associations with nasal inflammation, infection and aging.

A Novel Preparation Technique for Human Nasal Respiratory Mucosa to Disclose Its Glycosylation Pattern for Bioadhesive Drug Delivery

To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.

IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

The nasal polyps (NPs) microenvironment comprises multiple cell types, including mesenchymal stromal cells (MSCs). Insulin-like growth factor binding protein 2(IGFBP2) plays crucial roles in cell proliferation, differentiation and more. However, the role of NPs-derived MSCs (PO-MSCs) and IGFBP2 in NPs pathogenesis remains poorly defined. Herein, primary human nasal epithelial cells (pHNECs) and MSCs were extracted and cultured. Extracellular vesicles (EVs) and soluble proteins were isolated to investigate the role of PO-MSCs on epithelial-mesenchymal transition (EMT) and epithelial barrier function in NPs. Our data showed that IGFBP2, but not EVs from PO-MSCs (PO-MSCs-EVs), exhibited a crucial role in EMT and barrier destruction. Moreover, focal adhesion kinase (FAK) signaling pathway is necessary for IGFBP2 to exert its functions in human and mice nasal epithelial mucosa. Altogether, these findings may improve the current understanding of the role of PO-MSCs in NPs microenvironment and ultimately contribute to the prevention and treatment of NPs.

Silencing SOX11 Alleviates Allergic Rhinitis by Inhibiting Epithelial-Derived Cytokines

Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa affecting the quality of life of patients. SRY-box transcription factor 11 (SOX11) was reported to play important roles in inflammatory responses, but its role in AR is poorly understood. To explore the role of SOX11 in the development of allergic rhinitis. Cell culture and animal study. An in vivo murine allergic rhinitis model was established using ovalbumin treatment in female mice. Interleukin-13-stimulated human nasal mucosa epithelial cells were used for in vitro studies. Expression levels of SOX11, epithelial-derived cytokines, and mucin were determined in both modesls. SOX11 was highly expressed in allergic rhinitis mice. Allergy symptoms, serum ovalbumin-specific IgE, histamine, eosinophils, goblet cells, and type 2 cytokine secretion were increased in ovalbumin-treated mice. Furthermore, allergic rhinitis mice exhibited overproduction of epithelial-derived cytokines (thymic stromal lymphopoietin, interleukin-25, interleukin-33), C-C motif chemokine ligand 26 (CCL26), and mucin 5 AC (MUC5AC). Silencing SOX11 alleviated the behavioral symptoms and upregulation of epithelial-derived cytokines, CCL26, and MUC5AC. In human nasal mucosa epithelial cells, interleukin-13 enhanced SOX11 expression in a time-dependent manner, and signal transducer and activator of transcription 6 (STAT6) was involved in the interleukin-13-mediated expression of SOX11 by regulating transcription. Knockdown of SOX11 reduced epithelial-derived cytokine expression and MUC5AC levels in interleukin-13-treated human nasal mucosa epithelial cells. SOX11 plays a critical role in allergic rhinitis development by regulating epithelial-derived cytokines and might be a new therapeutic target for allergic rhinitis.

Soluplus® promotes efficient transport of meloxicam to the central nervous system via nasal administration

In our present series of experiments, we investigated the nasal applicability of the previously developed Soluplus® - meloxicam polymeric micelle formulation. Utilizing the nasal drug investigations, moderately high mucoadhesion was experienced in nasal conditions which alongside the appropriate physicochemical properties in liquid state, contributed to rapid drug absorption through human RPMI 2650 cell line. Ex vivo studies also confirmed that higher nasal mucosal permeation could be expected with the polymeric micelle nanoformulation compared to a regular MEL suspension. Also, the nanoformulation met the requirements to provide rapid drug permeation in less 1 h of our measurement. The non-toxic, non-cell barrier damaging formulation also proved to provide a successful passive transport across excides human nasal mucosa. Based on our in vivo investigations, it can be concluded that the polymeric micelle formulation provides higher meloxicam transport to the central nervous system followed by a slow and long-lasting elimination process compared to prior results where physical particle size reduction methods were applied. With these results, a promising solution and nanocarrier is proposed for the successful transport of non-steroidal anti-inflammatory drugs with acidic character to the brain.

Human Olfactory Ecto-mesenchymal Stem Cells Displaying Schwann-cell-like Phenotypes and Promoting Neurite Outgrowth in Vitro.

Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage. OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries.

Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection.

There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.

Angiotensin converting enzyme 2 activation improves allergic rhinitis and suppresses Th2 cytokine release.

Allergic rhinitis (AR) is primarily regulated by type I hypersensitivity, with Th2 and immunoglobulin E (IgE) playing essential roles. This study aimed to determine whether angiotensin converting enzyme (ACE)2 could participate in the regulation of AR. Nasal mucosal tissues of AR patients were collected to determine ACE2 levels. Following AR mouse models were established, ACE2 levels in nasal mucosa were determined. Then the influences of diminazene aceturate (ACE2 agonist) on AR symptoms, pathology, specific antibodies, histamine, and interleukins (ILs) release in vivo were evaluated. Afterward, human nasal mucosa epithelial cells were exposed to IL-13, and the impacts of ACE2 overexpression on the secretion of pro-inflammatory factors in vitro were assessed. ACE2 levels significantly declined in nasal mucosa both in patients and mouse models (p < .001). Diminazene aceturate treatment elevated the ACE2 level in mice (p < .01), accompanied by reduced frequency of nasal spray and nasal friction, decreased eosinophils and goblet cells (p < .001) according to histopathological staining. Furthermore, lgE, lgG1, histamine, and IL levels in mice were also decreased (p < .05). In vitro experiments revealed that ACE2 overexpression suppressed the secretion of pro-inflammatory factors (p < .001). Together, ACE2 activation can alleviate the symptoms of AR in mice and inhibit the release of Th2 cytokines. Activating ACE2 is a promising therapeutic approach for AR.

TRPA1/M8 agonists upregulate ciliary beating through the pannexin-1 channel in the human nasal mucosa

BackgroundNasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by thermoreceptors for cool temperatures. We herein investigated the effect of the activation of thermosensitive transient receptor potentials (TRPs) for cool/cold temperatures on ciliary beating to search for a compensatory mechanism.MethodsInferior turbinates were collected from patients with chronic hypertrophic rhinitis. Ex vivo ciliary beat frequency (CBF) and ATP release were measured using a high-speed digital video camera and by luciferin-luciferase assay, respectively. Intracellular Ca2+ ([Ca2+]i) imaging of isolated ciliated cells was performed using Fluo-8. The nasal mucosae were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8.ResultsCBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist). This increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Cinnamaldehyde and l-menthol also increased the ATP release from the nasal mucosa and [Ca2+]i of isolated ciliated cells. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface including the cilia and in the submucosal nasal glands. Existence of these receptors were confirmed at the transcriptional level by real-time RT-PCR.ConclusionsThese results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense against the fall of temperature under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1.

In vitro interactions of aerosol formulations with human nasal epithelium using real-time monitoring of drug transport in a nasal mucosa-on-a-chip

The current organ-on-chip platforms used for studying respiratory drug delivery are limited to the administration of drug solutions and suspensions, lacking the in vivo aerosol drug administration and aerosol interaction with the respiratory tract barrier. Moreover, they mostly rely on conventional assays that require sample collection and ‘off the chip’ analyses, which can be labor-intensive and costly. In this study, a human nasal epithelial mucosa (NEM)-on-a-chip is developed that enables the deposition of aerosolized nasal formulations while emulating realistic shear stresses (0.23 and 0.78 Pa), exerted to the inferior and middle turbinate of the human nasal cavity. Under these different dynamic conditions in the donor channel of the NEM-on-a-chip, the deposited dose of aerosols and particle size distributions varied. In addition, the increase in the shear stress to 0.78 Pa adversely affected the cells' viability, reflected by a 36.9 ± 5.4% reduction in the transepithelial electrical resistance. The epithelial transport profiles of aerosolized ibuprofen formulations under 0.23 Pa shear stress were successfully monitored in real-time by an electrochemical sensor embedded in the acceptor channel, where the NEM-on-a-chip was able to monitor the effect of permeation enhancer in the test formulation on the rate of drug transport. The novel NEM-on-a-chip can potentially be a promising physiologically relevant tool for reliable nasal aerosol testing in vitro.

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study

BackgroundMalaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.MethodsThe permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry.ResultsThe experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.ConclusionArtesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells.

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). 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. 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. showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

Cover story: Eur. J. Immunol. 8'22

European Journal of ImmunologyVolume 52, Issue 8 Cover PictureFree Access Cover story: Eur. J. Immunol. 8'22 First published: 04 August 2022 https://doi.org/10.1002/eji.202270080AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Our cover depicts a comparison between uninfected (blue) and infected (red) human nasal mucosa. The SARS-CoV-2 has caused severe structural damage to the nasal mucosa. The image related to the article by Zhili Zhang et al., in which the authors report highly efficient SARS-CoV-2 viral infection and production in human nasal mucosa. Further examinations suggested that human NECRS nasal mucosa is particularly susceptible to SARS-CoV-2 infection, presumably due to an increase in ACE2-expressing cells and a deficiency in antiviral immune response. Therefore, patients with NECRS may be at a particularly high risk of viral infection and transmission and close monitoring should be considered. Volume52, Issue8August 2022 RelatedInformation

MicroRNA-21-5p promotes mucosal type 2 inflammation via regulating GLP1R/IL-33 signaling in chronic rhinosinusitis with nasal polyps

It has been known that chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammation-dominated disease; however, the reasons causing such type of mucosal inflammation in CRSwNP are not well elucidated. We sought to investigate the role of microRNA-21-5p (miR-21-5p) in regulating mucosal type 2 inflammation in CRSwNP. miR-21-5p expression was detected in nasal mucosa of patients with CRSwNP. Correlations between miR-21-5p and indicators of type 2 inflammation were further analyzed. miR-21 knockout mice were used to explore the role of miR-21-5p in a murine model of eosinophilic (E) CRSwNP. Target gene of miR-21-5p related to type 2 inflammation in CRSwNP was identified. The upregulated miR-21-5p in the nasal mucosa of patients with CRSwNP, compared with control subjects, was expressed higher in patients with ECRSwNP than in patients with nonECRSwNP. miR-21-5p expression was positively correlated with mucosal eosinophil infiltrations and the expression of type 2 inflammatory cytokines. In the CRSwNP mice, miR-21 knockout significantly attenuated type 2 inflammation, as indicated by eosinophil infiltrations and expression of cytokines/chemokines in nasal mucosa and lavage fluid; moreover, genes associated with type 2 inflammation were extensively downregulated at the transcriptome level in miR-21 knockout mice. Glucagon-like peptide-1 receptor, which was negatively correlated with miR-21-5p expression in human nasal mucosa, was identified as the target of miR-21-5p. Overexpression of miR-21-5p induced IL-33 expression, whereas glucagon-like peptide-1 receptor agonist decreased IL-33 production in airway epithelial cells. miR-21-5p aggravates type 2 inflammation in the nasal mucosa of patients with CRSwNP via targeting glucagon-like peptide-1 receptor/IL-33 signaling, which may be a potential therapeutic target for CRSwNP.

Feasibility and reliability of measures of bioactive lipids in human plasma and nasal mucosa

Analysis of bioactive lipids is increasingly useful in clinical studies, and there is a need for non-invasive and easy-to-use sampling methods that meet the demands of reliability. Samples that can be taken by a non-professional and that can be taken repeatedly so as to provide more detailed information about the inflammatory process are often desired. In this study, the feasibility of non-invasive sampling of nasal mucosa and saliva for the analysis of bioactive lipid mediators (e.g. oxylipins and endocannabinoids) was evaluated in a pilot study (n = 10). In a second study, the reliability (relative and absolute) of sampling of these lipid mediators derived from nasal mucosa and from plasma was assessed by calculation of the intraclass correlation coefficient and Bland–Altman’s limit of agreement. Samples were taken at the same time of day on two occasions from a cohort of individuals with and without building-related intolerance (n = 37). Nasal mucosa proved to be a suitable matrix for the analysis of bioactive lipids and was therefore included in the study on reliability together with the plasma samples. Relative reliability varied among the identified oxylipins and endocannabinoids. Arachidonic acid derivatives showed generally better reliability. Absolute reliability measures also varied indicating that only a subset of the oxylipins and endocannabinoids were suitable as biomarkers in either nasal mucosa or plasma and should therefore be used with caution for that purpose.

Establishment of a culture system for human nasal mucosa organoids with controllable differentiation

To establish a culture system for human nasal mucosal organoids with controllable differentiation to reproduce the structure and function of the source tissue through staged expansion-differentiation culture. Fresh samples of surgically resected middle turbinate and nasal polyp tissues were collected, from which the nasal mucosa epithelial cells were isolated by enzymatic digestion and filtration for continuous culture at the air-liquid interface for expansion (EO group) or staged culture for expansion and differentiation (DO group). Immunohistochemical staining was used to characterize the structure, cellular composition and ciliary function of nasal mucosal organoids in the two groups. The secretion function of the differentiated nasal mucosal organoids in DO group was evaluated using PAS staining. Both of the two organoid culture systems yielded vacuolar or solid spherical 3D organoids, and their diameters increased progressively with time. On day 16 of culture, more vacuolar organoids occurred in DO group, while more solid spherical organoids were seen in EO group, and the proportion of vacuoles was significantly greater in DO group than in EO group [(54.67±13.26)% vs (21.67±8.57)%, P < 0.05]. Short tandem repeat (STR) test of the nasal mucosal organoids and the source tissue showed a 100% match between them. On day 21 of culture, scanning and transmission electron microscopy of the nasal mucosal organoids identified ultrastructure of cilia in DO group and short villi structure in most of the organoids in EO group. Immunohistochemical staining showed positivity for P63 (basal cells), β-tubulin (ciliated columnar cells), and MUC5AC (goblet cells) in the organoids. Compared with those in EO group, the organoids in DO group showed significantly greater percentages of ciliated cells [(7.95±1.81)% vs (27.04±5.91)%, P < 0.05] and goblet cells [(14.46±0.93)% vs (39.85±5.43)%, P < 0.05) with a similar percentage of basal cells [(56.91±14.12)% vs (53.42±15.77)%, P > 0.05]. The differentiated nasal mucosal organoids in DO group were positively stained for glycogen. The staged expansion-differentiation culture method allows more stable and prolonged growth of the cultured cells in vitro to produce organoids with controllable differentiation closely resembling the morphological structure and functions (ciliary function and secretory function) of the source tissue.

Solid Anorganic Particles and Chronic Rhinosinusitis: A Histopathology Study.

Although extensive research has shown the pathological effect of fine and ultrafine airborne particles, clear evidence of association of environmental exposure to them and inflammatory changes in human nasal mucosa is missing. Meanwhile, pathogenesis of chronic rhinosinusitis, despite being a disease with high prevalence in the population, is still unclear. The increasing evidence of the pro-inflammatory properties of these particles raises the question of their possible role in chronic rhinosinusitis. The presented study focused on detection of microsized anorganic particles and clusters of nanosized anorganic particles in the nasal mucosa of patients with chronic rhinosinusitis by Raman microspectroscopy and comparison of their composition to histologic findings. The results were compared to the findings in mucosa obtained from cadavers with no history of chronic rhinosinusitis. Solid particles were found in 90% of tissue samples in the group with chronic rhinosinusitis, showing histologic signs of inflammation in 95%, while in the control group, the particles were found in 20% of samples, with normal histologic findings in all of them. The main detected compounds were graphite, TiO2, amorphous carbon, calcite, ankerite and iron compounds. The results are in accordance with the premise that exogenous airborne particles interact with the nasal mucosa and possibly deposit in it in cases where the epithelial barrier is compromised in chronic rhinosinusitis.

The Genotoxic Effect of Nasal Steroids on Human Nasal Septal Mucosa and Cartilage Cells In Vitro.

To determine whether budesonide (Bud) and triamcinolone acetate (TA) cause DNA fractures in the nasal mucosa and septal cartilage cells through examinations using the comet assay technique. Prospective, controlled experimental study. University hospital. Septal mucosal epithelial and cartilage tissue samples were taken from 9 patients. Cell cultures were prepared from these samples. Then, budesonide and triamcinolone acetate active ingredients at 2 different doses of 0.2 and 10 µM were separately applied to the cell cultures formed from both tissues of each patient, except the control cell culture, for 7 days in one group and 14 days in one group. After the applications, genotoxic damage was scored with the comet assay technique and the groups were compared. In both the budesonide and triamcinolone acetate groups, the comet scores at low and high doses, on the 7th and 14th days were found to be significantly higher in both cartilage and epithelial tissue than in the control group. The study results showed that budesonide and triamcinolone acetate lead to a significantly high rate of genotoxic damage in both epithelial tissue and cartilage tissue.

Differential susceptibility to SARS‐CoV‐2 in the normal nasal mucosa and in chronic sinusitis

Human nasal mucosa is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and serves as a reservoir for viral replication before spreading to other organs (e.g. the lung and brain) and transmission to other individuals. Chronic rhinosinusitis (CRS) is a common respiratory tract disease and there is evidence suggesting that susceptibility to SARS‐CoV‐2 infection differs between the two known subtypes, eosinophilic CRS and non‐ECRS (NECRS). However, the mechanism of SARS‐CoV‐2 infection in the human nasal mucosa and its association with CRS has not been experimentally validated. In this study, we investigated whether the human nasal mucosa is susceptible to SARS‐CoV‐2 infection and how different endotypes of CRS impact on viral infection and progression. Primary human nasal mucosa tissue culture revealed highly efficient SARS‐CoV‐2 viral infection and production, with particularly high susceptibility in the NECRS group. The gene expression differences suggested that human nasal mucosa is highly susceptible to SARS‐CoV‐2 infection, presumably due to an increase in ACE2‐expressing cells and a deficiency in antiviral immune response, especially for NECRS. Importantly, patients with NECRS may be at a particularly high risk of viral infection and transmission, and therefore, close monitoring should be considered.

Expression and Distribution Pattern of Retinoic Acid Receptors in the Nasal Mucosa

Background and Objectives: Retinoids are naturally occurring vitamin A derivatives that regulate cellular processes and metabolism. In particular, retinoids play a key role in cellular proliferation by binding to retinoic acid receptors (RAR)-alpha, beta, and gamma. Considering the functional role of nasal mucosa where active cell regeneration occurs, RAR may play a role in tissue remodeling of the human nasal mucosa.Methods: In this study, we investigated the expression and distribution pattern of RAR using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and Western blot in normal ethmoid mucosa (NE), chronic rhinosinusitis (IE) and polyp (P).Results: IE and P samples showed higher expression levels of RAR in RT-PCR and Western blot than NE samples. RAR reactivity was also observed in the NE group, which indicates that cell regeneration also occurs in normal condition. Through IHC, we found the localization of RAR. RAR-α was distributed in the epithelial cells, submucosal glands, and endothelial cells. RAR-β was located in the basal epithelium, while RAR-γ was present in goblet cells and submucosal glands. The staining intensity of RAR-α, β and γ was higher than that in the NE group. Especially in the P group, RARs were abundantly distributed in the stalks of polyps.Conclusion: The stalk region contains a lot of collagen and fibroblasts to support polyp formation, and the greater amount of RAR in the stalk suggested that RARs may be associated with angiogenesis and cell proliferation. Accordingly, elevated RAR levels in chronic rhinosinusitis could indicate that RARs play a critical role in cell regeneration, angiogenesis and immunomodulation under inflammatory conditions in the human nasal mucosa.