Nasal Tissue Research Articles

TNF-α Regulates the Glucocorticoid Receptor Alpha Expression in Human Nasal Epithelial Cells Via p65-NF-κb and p38-MAPK Signaling Pathways.

Tumor necrosis factor (TNF)-α induces changes in the glucocorticoid receptor (GR) isoforms' expression in human nasal epithelial cells (HNECs) in chronic rhinosinusitis (CRS). However, the underlying mechanism of TNF-α induced GR isoforms' expression in HNECs remains unclear. Here, we explored changes in inflammatory cytokines and glucocorticoid receptor alpha isoform (GRα) expression in HNECs. To explore the expression of TNF-α in nasal polyps and nasal mucosa of CRS, fluorescence immunohistochemical analysis was employed. To investigate changes in inflammatory cytokines and GRα expression in HNECs, RT-PCR and western blotting were performed following the cells' incubation with TNF-α. Cells were pretreated with the nuclear factor-κB gene binding (NF-κB) inhibitor QNZ, the p38 inhibitor SB203580, and dexamethasone for one hour, then a TNF-α. Western blotting, RT-PCR, and immunofluorescence had been utilized for the cells' analysis and the ANOVA for the data analysis. The TNF-α fluorescence intensity was mainly distributed in nasal epithelial cells of nasal tissues. TNF-α prominently inhibited the expression of GRα mRNA from 6 to 24 h in HNECs. GRα protein was decreased from 12 to 24 h. Treatment with QNZ, SB203580, or dexamethasone inhibited the TNF-α and interleukin (IL)-6 mRNA expression and increased the GRα levels. TNF-α induced changes in the GR isoforms' expression in HNECs, and it was mediated through p65-NF-κB and p38-MAPK signal transduction pathways, which could be considered a promising neutrophilic CRS treatment.

Circulating levels of Bcl-2 and its expression in the nasal mucosa of patients with chronic rhinosinusitis

<b>Aim: </b>To evaluate expression of anti-apoptotic Bcl-2 protein in the nasal tissue and its levels in blood serum of patients with chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP).<br /> <b>Material and methods:</b> Expression of Bcl-2 in the sinonasal tissue and its levels in blood serum of patients with CRSsNP and CRSwNP were evaluated immunohistochemically and using ELISA, respectively.<br /> <b>Results:</b> In patients with CRSsNP, Bcl-2 was overexpressed in nasal epithelial cells mainly in the atrophic regions. However, its upregulation was also observed in regions with epithelial cell proliferation. Immunostaining for Bcl-2 was stronger both in the stroma and epithelial lining compared with control subjects. The level of Bcl-2 in blood serum was elevated in both forms of chronic rhinosinusitis with a more pronounced increase in CRSwNP.<br /> <b>Conclusion:</b> CRSsNP and especially CRSwNP are associated with overexpression of anti-apoptotic Bcl-2 in nasal epithelial and cells in the lamina propria against the background of elevated circulating concentrations of Bcl-2.

Molecular epidemiology of clinical filamentous fungi in Qatar beyond Aspergillus and Fusarium with notes on the rare species

Due to an increasing number of patients at risk (i.e., those with a highly compromised immune system and/or receiving aggressive chemotherapy treatment), invasive fungal infections (IFI) are increasingly being reported and associated with high mortality rates. Aspergillus spp., particularly A. fumigatus, is the major cause of IFI caused by filamentous fungi around the world followed by Fusarium spp., however, other fungi are emerging as human pathogens. The aim of this study was to explore the epidemiology and prevalence of the non-Aspergillus and non-Fusarium filamentous fungi in human clinical samples over an 11-year period in Qatar using molecular techniques. We recovered 53 filamentous fungal isolates from patients with various clinical conditions. Most patients were males (75.5%), 9.4% were immunocompromised, 20.7% had IFI, and 11.3% died within 30 days of diagnosis. The fungal isolates were recovered from a variety of clinical samples, including the nasal cavity, wounds, respiratory samples, body fluids, eye, ear, tissue, abscess, and blood specimens. Among the fungi isolated, 49% were dematiaceous fungi, followed by Mucorales (30%), with the latter group Mucorales being the major cause of IFI (5/11, 45.5%). The current study highlights the epidemiology and spectrum of filamentous fungal genera, other than Aspergillus and Fusarium, recovered from human clinical samples in Qatar, excluding superficial infections, which can aid in the surveillance of uncommon and emerging mycoses.

Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study.

To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6months in patients who underwent Reboot surgery. Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-β, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4days pre-surgery, and 1, 3 and 6months after Reboot surgery. Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1month (P < 0.05) after surgery and remained stable for 6months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward. Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients.

Local Allergen-Specific IgE Production in Turbinate Tissue of Pediatric Patients.

The objective of this study is to compare serum allergen-specific IgE to IgE levels in nasal tissue taken from the inferior turbinates of pediatric patients undergoing turbinate reduction. Twenty-six pediatric patients were recruited at the time of turbinate reduction surgery. At the time of recruitment, parents of patients completed the validated 22 item Sinonasal Outcome Test (SNOT-22) to describe symptoms prior to surgery. A sample of turbinate tissue was taken during turbinate reduction and blood was collected. Tissue and serum IgE were measured and differences in the group characteristics were evaluated using Chi-square tests for binary variables and Wilcoxon-Mann-Whitney tests for continuous variables. Student's t test was used to assess differences in means of total SNOT-22 scoring between the groups, and Wilcoxon-Mann-Whitney tests were used again for the rest of the SNOT-22 analysis. Levels of IgE in the serum were compared to levels in the turbinate tissue from all patients for each individual allergen. Every allergen except Alternaria displayed significant correlation between the serum and turbinate IgE levels. Additionally, each allergen except Alternaria and oak tree resulted in a strong correlation (r > .7) based on the correlation coefficients. Levels of Alternaria were found to be poorly correlative between serum and turbinate tissue, and significance was not achieved (r = -.346, P = .11). Certain allergen-specific IgE antibodies in the nasal mucosa seem to be highly associated with those in the serum, based upon the significant correlations we found between the two.

Expression Levels of Glutathione S-Transferase and Cytochrome P450 Isoenzymes in Nasal Polyp Tissue.

Nasal polyps are benign sinonasal masses composed of eosinophils and extracellular edema. Pathogenesis of the polyp formation is unclear but several studies strongly suggest a correlation with infection, inflammation and allergy conditions. Our aim is to investigate the potential link between allergy and nasal polyp in tissue level. Nasal polyp group included 60 patients whose diagnosis was confirmed with biopsy and the control group included 38 healthy patients. Tissue sample of the control group was taken from inferior turbinate mucosa under local anesthesia and nasal polyp tissue was collected from functional endoscopic sinus surgery. The glutathione S-transferase (GST) and cytochrome P450 (CYP) isoenzyme expressions of the tissue samples were investigated under light microscopy and graded by a senior pathologist. GSTP1 protein expression was significantly higher in tissue samples from nasal polyp group compared to that of control group (p < 0.05). However, CYP1A1, GSTM1 and GSTA1 isoenzymes were not different between the two groups (p > 0.05). We have found that GSTP1 isoenzyme was elevated in nasal polyp tissue compared to the control. The increase in protein expression of GSTP1 might have occured as a tissue response to the increased oxidative stress thus suggesting a role of GSTP1 in polyp formation.

Protective effects of inhalation of essential oils from Mentha piperita leaf on tight junctions and inflammation in allergic rhinitis.

Allergic rhinitis is one of the most common diseases, which is caused by IgE-mediated reactions to inhaled allergens. Essential oils from the Mentha piperita leaf (EOM) are known to be effective for various diseases, such as respiratory diseases. However, the effect of inhalation of EOM on tight junctions and inflammation related to allergic rhinitis is not yet known. The purpose of this research was to explain the effects of the inhalation of EOM on tight junctions and inflammation of allergic rhinitis through network pharmacology and an experimental study. For that purpose, a pharmacology network analysis was conducted comprising major components of EOM. Based on the network pharmacology prediction results, we evaluated the effect of EOM on histological changes in mice with ovalbumin and PM10-induced allergic rhinitis. Allergic symptoms, infiltration of inflammatory cells, and regulation of ZO-1 were investigated in mice with allergic rhinitis. Other allergic parameters were also analyzed by reverse transcription polymerase chain reaction and western blot in nasal epithelial cells. In the network analysis, the effects of EOM were closely related to tight junctions and inflammation in allergic rhinitis. Consistent with the results from the network analysis, EOM significantly decreased epithelial thickness, mast cell degranulation, goblet cell secretion, and the infiltration of inflammatory cells in nasal tissue. EOM also regulated the MAPK-NF-κB signaling pathway, which was related to tight junctions in nasal epithelial cells. This research confirmed that inhalation of EOM effectively restores tight junctions and suppresses inflammation in the allergic rhinitis model. These results reveal that EOM has a therapeutic mechanism to treat allergic rhinitis.

The activation of FPR3/PKA/Rap1/ERK1/2 and FPR3/p-IκB/NF-κB axis in fibroblasts promote capsular contracture after rhinoplasty

BackgroundCapsular contracture may occur after rhinoplasty due to rejection of silicone implants by the immune system. Our previous high-throughput sequencing of RNA in nasal capsular contracture tissue revealed that FPR3 was significantly increased in grade IV capsular contracture tissue, compared with grade II. ObjectiveThis study aimed to elucidate the effect and specific mechanism of FPR3 on capsular formation and contracture following rhinoplasty. MethodsUsing the GeneMANIA Database, the genes involved with FPR3 expression were searched, and the Gene Ontology analysis was performed to annotate the biological functions of the aforementioned genes. The mRNA and protein expressions of related genes in fibroblasts and capsular contracture tissues were analyzed using quantitative real-time PCR, western blot, and immunohistochemical staining. CCK-8 was used to determine the viability of cells. The migration capacity of fibroblasts was assessed using a wound healing assay. ELISA was used to detect levels of IL-1β, TNF-α, and IL-6. ResultsAfter rhinoplasty, the expression of FPR3 in the capsular tissue increased in proportion to the degree of contracture. By activating the PKA/Rap1/ERK1/2 axis, overexpression of FPR3 can significantly increase the cell viability of fibroblasts and promote their transformation into myofibroblasts. Moreover, FPR3 phosphorylates IκB to decrease NF-κB inhibition, thereby promoting the synthesis and release of the inflammatory cytokines IL-1β, TNF-α, and IL-6. ConclusionFPR3 is a crucial molecule that causes capsular development and contracture following rhinoplasty. In the future, local suppression of FPR3 may be an effective treatment for relieving capsular contracture.

Artemisia gmelinii Extract Alleviates Allergic Airway Inflammation via Balancing TH1/TH2 Homeostasis and Inhibiting Mast Cell Degranulation.

A new terminology "combined allergic rhinitis and asthma syndrome (CARAS)" was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation.

Expression and predictive value of type Ⅱ inflammatory cytokines in nasal secretion in eosinophilic chronic rhinosinusitis with nasal polyps

Objective:To analyze the expression of type Ⅱ inflammatory-related cytokines in nasal secretions of patients with eosinophilic chronic rhinosinusitis with nasal polyps（ECRSwNP）, and to preliminarily explore the role of type Ⅱ inflammatory cytokines in nasal secretions in predicting ECRSwNP. Methods:A prospective analysis was made of 91 patients with CRSwNP who underwent endoscopic sinus surgery in Peking University Third Hospital from November 2020 to June 2021. All the selected patients had their SNOT-22 score, Lund-Mackay score and blood eosinophilia collected before surgery. Percentage and absolute value; the nasal secretions of patients were collected before operation, and enzyme-linked immunosorbent assay was used to detect the typeⅡinflammatory cytokines（IL-4, IL-5, IL-13, IL-25, IL-33, Eotaxin-3, periostin）, intraoperative nasal polyp tissue was collected for eosinophil count. According to the proportion of eosinophils in the tissue≥10%, they were divided into ECRSwNP group and nECRSwNP group. The clinical baseline data and type Ⅱ inflammatory cytokines were compared between the two groups, and the related factors of ECRSwNP were evaluated by univariate logistic regression analysis. The receiver operating characteristic（ROC） curve was used to evaluate the predictive potential of each clinical index. Results:The SNOT-22 score, Lund-Mackay score, blood eosinophil percentage and absolute value in the ECRSwNP group were higher than those in the nECRSwNP group（P<0.05）. In the nECRSwNP group（P<0.01）. Logistic regression analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage were risk factors for ECRSwNP（P<0.05）. ROC analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage had predictive diagnostic value（P<0.01）, among which blood eosinophil percentage had the greatest predictive value（AUC=0.756）. The prediction model composed of Eotaxin-3, SNOT-22 score, sinus CT Lund-Mackay score, blood eosinophil percentage and blood eosinophil absolute value had better prediction effect on ECRSwNP（AUC=0.873）. Conclusion:Type Ⅱ inflammatory cytokines IL-5 and Eotaxin-3 in nasal secretions may be involved as biomarkers for early diagnosis of ECRSwNP.

Nasal mucociliary clearance after extremely low frequency by scintigraphic and histopathologic evaluation.

To investigate the effect of exposure to extremely low-frequency magnetic fields (ELF-MFs) on nasal mucociliary clearance (MCC) by rhinosintigrapic and histopathological evaluation. The rats were separated into three groups according to ELF-MFs intensity and control group. The exposure groups were standardized for the ELF-MFs of 1, 1.5, and 2 mT emitted by 3 Helmholtz coils for 4 h/day for 30 days. Rhinoscintigraphy was performed to measure nasal MCC. The nasal tissues were examined for edema, inflammation, hyperemia, necrosis, ciliary loss, goblet cell density, and fibroblast proliferation. The data were evaluated statistically (p < 0.05). Nasal mucociliary clearance rates (NMCR) were calculated as 33.13 ± 5.91% in control, 27.78 ± 4.7% in 1 mT, 22.67 ± 5.43% in 1.5 mT, and 18.11 ± 6.33% in 2 mT. NMCR were decreased with increasing ELF-MFs, in 1.5 and 2 mT groups (p < 0.05) compared to control. Nasal mucociliary transport rate (NMTR) values were found to be 2.17 ± 0.33 mm/min in control, 1.82 ± 0.32 mm/min in 1 mT, 1.46 ± 0.34 mm/min in 1.5 mT and 1.24 ± 0.29 mm/min in 2 mT. NMTR was decreased in the groups exposed to 1.5 and 2 mT (p < 0.05) compared to control. The edema, hyperemia, inflammation, ciliary loss, and goblet cell density were statistically significant differences between control and groups exposed to 1.5 and 2 mT (p < 0.05). Our rat model has shown nasal mucosa damage and decreased NMCR and NMTR by rhinoscintigraphy as ELF-MFs intensity increases. It may be detrimental to nasal mucosa mucociliary function depending on the ELF-MFs intensity. N/A Laryngoscope, 133:2081-2089, 2023.

Research advances in roles of microRNAs in nasal polyp.

MicroRNAs (miRNAs), a subset of endogenous RNAs highly conservative with short chains, play key regulatory role in the biological relevant events of the cells. Exosomes are extracellular vesicles like the plasma membrane components being able to deliver information molecules such as miRNA between cells and to regulate the fate of the target cells. The progression of chronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with significant alterations of miRNA levels in both cells and exosomes. RNA-binding proteins (RBPs) have been acknowledged to play important roles in intracellular miRNA transport to exosomes, and specific membrane proteins such as caveolin-1 critically involved in HNRNPA1 -mediated transport of miRNA to exosomes. Aberrant alteration in endogenous miRNA levels significantly contributes to the process of airway remodeling in the nasal tissue and to the occurrence and progression of inflammatory responses in CRSwNP. Exogenous miRNAs delivered via exosomes has also been shown to play an important role in activating macrophages or in regulating vascular permeability in the CRSwNP.This paper highlights the mechanism of RBP-mediated delivery of miRNAs to exosomes and the important contribution of endogenous miRNAs to the development of CRSwNP in response to inflammation and airway remodeling. Finally, we discuss the future research directions for regulation of the miRNAs to CRSwNP.Delivery of exogenous miRNAs by exosomes alters the endogenous miRNAs content in nasal mucosal epithelial cells or in associated inflammatory cells in the CRSwNP, and altered endogenous miRNAs affects the inflammatory response and airway remodeling, which then regulates the occurrence and progression of CRSwNP.RBPs and associated membrane proteins such as caveolin-1 may play a crucial role in the entry of exogenous miRNA into exosomes.

Uptake of Cationic PAMAM-PLGA Nanoparticles by the Nasal Mucosa

Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa.

Effects of Surgically Assisted Rapid Palatal Expansion on Facial Soft Tissues: A Systematic Review

Surgically assisted rapid palatal expansion (SARPE) is a successful method for treating transverse discrepancies in adult patients. The relocation of maxillary segments may induce changes at the surrounding soft tissues as well. The aim of this systematic review was to examine the possible effects that SARPE may have in the soft tissues of the face. Our search strategy included electronic databases (Pubmed, Scopus, ProQuest, Google Scholar, Cochrane Library) and a hand search of the reference list of found reviews. A priori definition of inclusion and exclusion criteria was made. Finally, 15 articles were included in qualitative synthesis. Risk of bias was generally high among the included studies. Study outcomes included nasal, labial, nasolabial and other facial soft tissue measurements. The evaluation of the changes was two-dimensional in six studies, and three-dimensional in nine studies. Meta-analysis was unfeasible due to lack of standardization, important methodological limitations, and shortcomings of the studies. A post-surgical increase in the dimensions of the alar width and the alar base width was commonly reported among the included studies. However, the above should be considered with caution due to the high risk of bias and the inability for quantitative synthesis.

Over-expression of CRTH2 indicates eosinophilic inflammation and poor prognosis in recurrent nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by recurrent nasal polyp (NP) growth following surgical removal, but the mechanisms are still not clear. This study aimed to investigate the expression of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor on NP and the role it plays in eosinophil inflammation and polyp recurrence. Forty-one CRSwNPs patients and seventeen controls were enrolled in this study. mRNA was extracted from nasal tissues and evaluated for expression of CRTH2. Immunofluorescence staining was performed to confirm the distribution and expression of CRTH2 protein. CRTH2 expression on peripheral blood eosinophils was quantified by flow cytometry. The eosinophil count and clinical implications were also evaluated and their correlations with CRTH2 expression were analyzed. Nasal polyps displayed increased expression of CRTH2 in mRNA level compared with control samples, with the highest expression observed in recurrent NP. Immunofluorescence confirmed over-expression of CRTH2 in recurrent NP and this was independent of the concurrent presence of asthma. CRTH2 expression was positively correlated with tissue eosinophil number (Spearman's ρ=0.69, P<0.001) and the postoperative sino-nasal outcome test-22 (SNOT-22) score (Spearman's ρ=0.67, P<0.001). Receiver operating characteristic (ROC) curves revealed CRTH2 was more predictive for NP recurrence compared to either eosinophil number and concomitant asthma, with an area under the ROC curve of 0.9107. The over-expression of CRTH2 in recurrent nasal polyps correlates with greater eosinophilic inflammation and poor prognosis which is independent of concomitant asthma.

Expression and clinical significance of TYRP1, ABCB5, and MMP17 in sinonasal mucosal melanoma.

Sinonasal mucosal melanoma (SNMM) is a lethal malignancy with poor prognosis. Treatment outcomes of SNMM are poor. Novel prognostic or progression markers are needed to help adjust therapy. RNA-seq was used to analyze the mRNA expression of tumor tissues and normal nasal mucosa from primary SNMM patients (n= 3). Real-time fluorescent quantitative PCR (qRT-PCR) was used to validate the results of RNA-seq (n= 3), while protein expression was analyzed by immunohistochemistry (IHC, n= 31) and western blotting (n= 3). Retrospective studies were designed to determine the clinical parameters and the total survival rate, and correlation between the protein expression levels of the most significant key genes and prognosis was analyzed. In total, 668 genes were upregulated and 869 genes were downregulated in SNMM (fold change ⩾ 2, adjusted p value < 0.01). Both mRNA and protein expression levels of the key genes in SNMM tumor tissues were higher than those in the normal control nasal mucosal tissues. The expression rates of TYRP1, ABCB5, and MMP17 in 31 primary SNMM cases were 90.32%, 80.65%, and 64.52%, respectively. In addition, age, typical symptoms, and AJCC stage were related to overall survival rate of patients with SNMM (p< 0.05). Furthermore, the expression of ABCB5 was age-related (p= 0.002). Compared with individuals with negative ABCB5 expression, those with positive expression exhibited significantly poor overall survival (p= 0.02). The expression levels of TYRP1, ABCB5, and MMP17 were significantly upregulated in SNMM tissues, and the expression of ABCB5 was related to poor prognosis in SNMM. Thus, ABCB5 may serve as a progression marker and can predict unfavorable prognosis in patients with SNMM.

Caesalpinia sappan Linn. Ameliorates Allergic Nasal Inflammation by Upregulating the Keap1/Nrf2/HO-1 Pathway in an Allergic Rhinitis Mouse Model and Nasal Epithelial Cells.

Allergic rhinitis (AR) is a common upper-airway inflammatory disease of the nasal mucosa caused by immunoglobulin (IgE)-mediated inflammation. AR causes various painful clinical symptoms of the nasal mucosa that worsen the quality of daily life, necessitating the urgent development of therapeutic agents. Herein, we investigated the effects of Caesalpinia sappan Linn. heartwood water extract (CSLW), which has anti-inflammatory and antioxidant properties, on AR-related inflammatory responses. We examined the anti-inflammatory and anti-allergic effects of CSLW in ovalbumin (OVA)-induced AR mice and in primary human nasal epithelial cells (HNEpCs). Administration of CSLW mitigated allergic nasal symptoms in AR mice, decreased total immune cell and eosinophil counts in nasal lavage fluid, and significantly reduced serum levels of OVA-specific IgE, histamine, and Th2 inflammation-related cytokines. CSLW also inhibited the infiltration of several inflammatory and goblet cells, thereby ameliorating OVA-induced thickening of the nasal mucosa tissue. We found that CSLW treatment significantly reduced infiltration of eosinophils and production of periostin, MUC5AC, and intracellular reactive oxygen species through the Keap1/Nrf2/HO-1 pathway in HNEpCs. Thus, our findings strongly indicate that CSLW is a potent therapeutic agent for AR and can improve the daily life of patients by controlling the allergic inflammatory reaction of the nasal epithelium.

Outlook of magnesium alloy for rhinoplasty material

Rhinoplasty is one of the famous cosmetic surgeries all over the world, as it not only benefits congenital nasal bone dysplasia patients, but also satisfy a part of people who want to look more beautiful and perfect. The materials commonly used in current rhinoplasty are prone to failure of rhinoplasty because of autologous absorption, loosening and slipping of nasal scaffold due to poor tissue compatibility, and difficulties in secondary repair[1-2]. Biodegradable magnesium alloy material is one of the most ideal biomedical materials with great application value. Mechanically, the biodegradable magnesium alloy material has good mechanical properties, similar to the mechanical properties of human bone; the density is similar to that of human bone. Biologically, degradable magnesium alloy material has the characteristics of excellent biocompatibility, biological activity, degradation products can be easily absorbed or excreted by human tissues; degradable magnesium alloy can induce cell differentiation growth and blood vessel growth[3]. This article analyzes the possibility of using degradable magnesium alloy material as a scaffold material for rhinoplasty and suggests that this porous nasal scaffold can be prepared by 3D printing method. By using this method, a restorative nasal plastic effect can be obtained by guiding the regrowth of autologous nasal bone tissue. From a long-term perspective, the surgical results achieved by using magnesium alloy as a scaffold material for rhinoplasty are what the medical aesthetic community has been seeking. The use of biodegradable magnesium alloy as a rhinoplasty material is a new approach that is feasible and has potential for future economic and social benefits, but this approach needs further research and experiments to be validated in the future.

Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential. In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of β-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-κB (NF-κB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4+ IFN-γ+ ) / Th2 (CD4+ IL-4+ ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry. Apigenin significantly inhibited compound 48/80-induced secretion of β-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-κB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as β-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice. Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-κB signaling pathway.

Mucormycosis threats: A systemic review.

During the catastrophic wave of Coronavirusdisease 2019, health agencies started to report an infrequent but lethal mucormycosis or black fungal infection. Primarily, it causes sinusitis by affecting nasal, oral, lung, brain, ocular, and other body tissues. It becomes more fatal, especially in diabetic, cancer, and immune-compromised patients. Before 2020, the prevalence of mucormycosis was very rare but it has rapidly emerged globally from late 2020 to mid-2021. Recently, the mucormycosis got worse and epidemic with more than 30,000 cases reported across India. The etiology of infection can be diagnosed by molecular, serological, microscopic, and clinical methods. However, early diagnosis of this ailment is still a challenging task due to no standalone diagnostic tool available along with clinical manifestations of the ailment resembling other fungal diseases. The treatment of mucormycosis is also challenging and frequently requires long-term treatment. Amphotericin B was found to be an effective antifungal for preventing mucormycosis but it failed if infection disseminated to necrotizing tissues or adjacent organs. Removal of infected tissue/organ by surgery is an alternative treatment to control mucormycosis. In addition, reversal of underlying predisposing conditions based on therapy is also in practice for its prevention. This review highlights different aspects of mucormycosis such as pathogenesis, diagnosis, treatment, and their challenges and so on. We also emphasized the epidemiological shift during the recent outbreak and its influence on the different regions of India.