Human Nasal Inferior Turbinate-Derived Neural Stem Cells Improve the Niche of Substantia Nigra Par Compacta in a Parkinson's Disease Model by Modulating Hippo Signaling.

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer's disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells. METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs. RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms. CONCLUSION: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.

Prognostic Value of Polypoid Changes of the Middle Turbinate in Relapsed Nasal Polypi after FESS: A Prospective Cohort Study.

Introduction Despite the high level of patient satisfaction with functional endoscopic sinus surgery (FESS) and the clinical improvement, polyp recurrence is observed in 23% to 87% of patients and requires reoperation. Objective To assess the prognostic value of polypoid changes of the middle turbinate (PCMT) in relapse of paranasal sinus polyps in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) after FESS and the effect of partial middle turbinectomy (PMT) on the outcome of surgery. Methods We conducted a prospective clinical study on 60 patients with CRSwNP with and without PCMT. The patients were allocated into three groups: group I included twenty patients without PCMT; group II, twenty patients with PCMT; and group III included twenty patients with PCMT submitted to PMT. The patients were evaluated endoscopically according to the Lund-Kennedy endoscopic scoring system, radiologically according to the Lund-Mackay scoring system, and symptomatically through the 22-item Sinonasal Outcome Test (SNOT-22). Results The total postoperative Lund-Kennedy score differed significantly among the 3 groups ( p < 0.001), with a group II presenting a significantly higher total score compared to groups I and III. The Preoperative SNOT-22 score differed significantly among the three groups ( p = 0.013), with group II presenting a significantly higher score compared to group I. There was a significant association involving the 3 groups and relapse at 12 months ( p = 0.029); relapse was higher in group II (50.0%) than in groups I (20%) and III (15.0%). Conclusion There was a significant association between PCMT and the relapse of nasal polyps. Also, nasal polyposis recurred at a lower rate in the group submitted to middle turbinate resection compared to the group in whom it was preserved.

Mulberry Posterior Inferior Nasal Turbinate Is Associated with a Lower Pharyngeal pH Environment.

OBJECTIVES: Mulberry-like changes of the posterior inferior nasal turbinate (MPINT) can lead to nasal obstruction. Extraesophageal reflux (EER) characterized by lower pH causes mucosal inflammation and therefore can contribute to sinonasal pathologies. No prior studies have objectively examined the possible association between acidic pH and MPINT formation. Therefore, this study is aimed to investigate the 24-h pharyngeal pH value in patients with MPINT. STUDY DESIGN: Prospective case-control multi-center study. METHODS: Fifty-five patients with chronic EER symptoms were included in the study. They filled in questionnaires aimed at reflux and sinonasal symptoms (RSI®, SNOT-22) and underwent video endoscopy evaluating the laryngeal findings (RFS®) and the presence or absence of the MPINT. And, 24-h oropharyngeal pH monitoring was used to detect the acidic pH environment in the pharynx. RESULTS: Out of the 55 analyzed patients, 38 had the MPINT (group 1), and in 17 patients, the MPINT was absent (group 2). Based on the pathological RYAN Score, in 29 (52.7%) patients, severe acidic pH drops were detected. In group 1, the acidic pH drops were diagnosed significantly more often (68.4%) compared with those in group 2 (p = 0.001). Moreover, in group 1, a significantly higher median total percentage of time spent below pH 5.5 (p = 0.005), as well as a higher median number of events lasting more than 5 min (p = 0.006), and higher median total number of events with pH drops (p = 0.017) were observed. CONCLUSION: In this study, the MPINT was significantly more often present in patients with acidic pH events detected by 24-h oropharyngeal pH monitoring. Acidic pH in the pharynx might lead to MPINT formation. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:62-68, 2024.

Prognostic Value of Polypoid Changes of the Middle Turbinate in Relapsed Nasal Polypi after FESS: A Prospective Cohort Study

Abstract Introduction Despite the high level of patient satisfaction with functional endoscopic sinus surgery (FESS) and the clinical improvement, polyp recurrence is observed in 23% to 87% of patients and requires reoperation. Objective To assess the prognostic value of polypoid changes of the middle turbinate (PCMT) in relapse of paranasal sinus polyps in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) after FESS and the effect of partial middle turbinectomy (PMT) on the outcome of surgery. Methods We conducted a prospective clinical study on 60 patients with CRSwNP with and without PCMT. The patients were allocated into three groups: group I included twenty patients without PCMT; group II, twenty patients with PCMT; and group III included twenty patients with PCMT submitted to PMT. The patients were evaluated endoscopically according to the Lund-Kennedy endoscopic scoring system, radiologically according to the Lund-Mackay scoring system, and symptomatically through the 22-item Sinonasal Outcome Test (SNOT-22). Results The total postoperative Lund-Kennedy score differed significantly among the 3 groups (p < 0.001), with a group II presenting a significantly higher total score compared to groups I and III. The Preoperative SNOT-22 score differed significantly among the three groups (p = 0.013), with group II presenting a significantly higher score compared to group I. There was a significant association involving the 3 groups and relapse at 12 months (p = 0.029); relapse was higher in group II (50.0%) than in groups I (20%) and III (15.0%). Conclusion There was a significant association between PCMT and the relapse of nasal polyps. Also, nasal polyposis recurred at a lower rate in the group submitted to middle turbinate resection compared to the group in whom it was preserved.

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.

Nasal turbinate mucosal graft for management of contracted anophthalmic socket.

A 67-year-old Caucasian male presented with severe contraction of socket lining 8 years after enucleation, dermis fat graft and successful ocular prosthesis fitting. Following two failed attempts at using amniotic membrane grafts to reform the socket lining, a total socket reconstruction was attempted using a novel nasal turbinate mucosal graft technique. This was performed in a staged fashion with lower fornix reconstruction followed by upper fornix reconstruction 3 months later. The patient was stable at 12 months review, with a satisfactory cosmetic outcome. Nasal turbinate mucosa was used as it was surgically accessible, provided natural socket lubrication due to its mucosal surface, and avoided oral mucosa and its associated morbidity. This case report suggests that nasal turbinate mucosa is a suitable autologous grafting material for total socket reconstruction in contracted anophthalmic sockets.

Surgical Treatment for Empty Nose Syndrome Using Autologous Dermal Fat: Evaluation of Symptomatic Improvement.

Background: Empty nose syndrome (ENS) is caused by nasal turbinate surgery. The standard treatment for ENS is an inferior meatus augmentation procedure (IMAP) in which autologous tissue such as auricular cartilage, rib cartilage, or artificial material is transplanted into the nasal cavity. However, some challenges like a very small auricular cartilage are associated with these autologous tissue types. Moreover, since using rib cartilage is a highly invasive technique, the scar on the chest from where the harvesting is done is easily visible, and the artificial material is susceptible to infection. We used autologous dermal fat (ADF) in IMAPs in our study for the following reasons: the quantity of ADF could be increased or reduced as needed, ADF is considered a safer option than rib cartilage because it is harvested from superficial tissue, it is superior in terms of cosmetic appearance to harvested rib cartilage, and it has a lower risk of infection than any artificial material.Objective: The purpose of our study was to investigate the efficacy and safety of IMAPs using ADF.Methods: We included nine patients with ENS who underwent an IMAP using ADF. The patients' backgrounds and responses to the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) were recorded. Changes in each item of the ENS6Q before and after surgery (up to 3 months) were analyzed.Results: The postoperative ENS6Q total score and parameters were significantly better than their preoperative counterparts. Nasal dryness improved slightly less than other symptoms. There were no complications.Conclusions: The IMAP using ADF was effective in improving ENS symptoms; however, some physiological functions were difficult to improve, and dryness persisted. Autologous dermal fat is larger than auricular cartilage, less invasive than rib cartilage, and has a lower risk of infection than artificial material.

Nasal and Parotid Blood Pool Activity Is Significantly Correlated with Metabolic Syndrome Components and Sleep Apnea.

Background: Patients with metabolic syndrome components were frequently noted to have increased nasal and parotid activity on clinically referred scintigraphic whole-body blood pool scans. This increase in activity was not observed in patients without metabolic syndrome. Increased nasal blood pool activity in patients with elevated body mass indices (BMIs) has implications for (1) sleep apnea, (2) risk of nasal infection, and (3) possible impaired nasal lymphatic drainage of brain waste proteins. Methods: To follow-up this clinical observation, a retrospective study was performed on 200 patients having whole-body blood pool scans referred over a 3-year period. The whole-body blood pool scans were evaluated for an association between nose and parotid region of interest (ROI) to heart ROI maximum (max) pixel ratios as correlated with clinical conditions, including obesity, diabetes, hypertension, and sleep apnea. Continuous variables of BMI, hemoglobin A1c (HbA1c), blood glucose, and blood lipids were also correlated with these ratios. Results: A direct association of nose to heart max ratio (NHMR) with diabetes, sleep apnea, and hypertension was found with an increase in the ratio of +0.10 (P = 0.002), +0.13 (P = 0.0002), +0.08 (P = 0.0123), respectively. Correlation of NHMR with continuous variables had moderate correlation with BMI (r = 0.36, P < 0.0001), glucose (r = 0.27, P = 0.0001), HbA1c (r = 0.25, P = 0.0008) and less association with the number of diabetes medications (r = 0.22, P = 0.0021). Similar associations were found for parotid to heart max ratios but were weaker than the NHMR. Conclusions: Patients with metabolic syndrome components have significantly increased nasal and parotid activity on blood pool scans. These associations have implications for the treatment of sleep apnea, for nasal infections involving such agents as Covid-19, and for the risk of dementias related to decreased clearance of brain waste proteins through nasal turbinate lymphatics in patients with metabolic syndrome. If further studies support these findings, the nasal turbinates and the increased parasympathetic activity controlling their dilation could become a new therapeutic target.

Pediatric turbinate radiofrequency ablation improves quality of life and rhinomanometric values. A prospective study.

OBJECTIVE: turbinate surgery in pediatric patients is gradually increasing in popularity amongst pediatric otolaryngologists. However, despite this, there is scarce information regarding this surgical procedure in children. The present research is designed with the aim of assessing changes in nasal resistance, nasal airflow and quality of life in pediatric patients undergoing turbinate radiofrequency ablation. METHODS: A prospective uncontrolled intervention clinical trial design was followed. Children between 4 and 15 years old undergoing turbinate radiodiofrequency ablation (TRA) were consecutively selected. Children were examined preoperatively and 1, 3, 6 and 12 months after turbinate surgery. Anterior active rhinomanometry with and without nasal decongestant and examination of the turbinates and adenoid size were carried out in each follow-up visit. The SN5 quality of live survey was answered by parents. RESULTS: 81 children were included, 28 with associated adenoidectomy. A significant improvement in quality of life was demonstrated since the first month after TRA. Regarding nasal resistance, there was an improvement 1 month after surgery, but it only reached statistical significance for the whole sample (p < 0.001)) and for the cohort of isolated turbinate surgery (p < 0.001) at 3 months, while the values for the cohort of children who underwent adenoidectomy reached significance at 6 months after surgery (p = 0.04). The difference in nasal resistance before and after decongestant was compared to the change in nasal resistance after surgery. It demonstrated a strong correlation with the change in nasal resistance at 1 month (R = 0.985; p < 0.001), 3 months (R = 0.995; p < 0.001), 6 months (R = 0.98; p < 0.001) and 12 months (R = 0.98; p < 0.001) after surgery. CONCLUSIONS: turbinate surgery in pediatric patients seems to be a safe procedure which objectively and subjectively improves the symptoms of children suffering from nasal obstruction.

The Long-term Effect of Inferior Turbinate Surgery Techniques on Nasal Obstruction and Quality of Life.

OBJECTIVE: The aim of the study was to compare the long-term effects of radiofrequency ablation (RFA), microdebrider-assisted inferior turbinoplasty (MAIT), and diode laser techniques on the severity of nasal obstruction and quality of life (QOL) in a 3-year follow-up. METHODS: The patients filled a Visual Analog Scale (VAS) regarding the severity of nasal obstruction and the Glasgow Health Status Inventory (GHSI) questionnaire preoperatively and during the control visits at 3 months and 3 years. Acoustic rhinometry was also performed. A total of 78 patients attended both control visits. RESULTS: All 3 techniques improved the VAS score for the severity of nasal obstruction and the GHSI total score significantly compared to the preoperative values at both 3 months and 3 years. Compared to the preoperative values, all 3 techniques increased the V2 to 5 cm values significantly at 3 months. After 3 years, compared to the preoperative values, the MAIT (P = .005) and diode laser (P < .001) still had a statistically significant volume increase in V2 to 5 cm, whereas the RFA (P = .06) did not achieve a statistically significant effect. CONCLUSION: The RFA, MAIT, and diode laser all improved both the patients' subjective sensation of the severity of nasal obstruction and QOL significantly. The response was sustained during the 3-year follow-up period with all 3 techniques. A weakening in the objective treatment response to RFA was found in the longer follow-up, but that did not cause a weakening of the patients' subjective treatment response.

Isolation and development of bovine primary respiratory cells as model to study influenza D virus infection.

Influenza D virus (IDV) is a novel type of influenza virus that infects and causes respiratory illness in bovines. Lack of host-specific in vitro model that can recapitulate morphology and physiology of in vivo airway epithelial cells has impeded the study of IDV infection. Here, we established and characterized bovine primary respiratory epithelial cells from nasal turbinate, soft palate, and trachea of the same calf. All three cell types showed characteristics peculiar of epithelial cells, polarized into apical-basolateral membrane, and formed tight junctions. Furthermore, these cells expressed both α-2,3- and α-2,6-linked sialic acids with α-2,3 linkage being more abundant. IDV strains replicated to high titers in these cells, while influenza A and B viruses exhibited moderate to low titers, with influenza C virus replication not detected. These findings suggest that bovine primary airway epithelial cells can be utilized to model infection biology and pathophysiology of IDV and other respiratory pathogens.

Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 µg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.

Glomangiopericytoma of the inferior nasal turbinate: A case report.

INTRODUCTION: Glomangiopericytoma is defined as a sinonasal tumor with perivascular myoid phenotype, which was first described in 1942 by Stout and Murray as a soft tissue tumor with characteristic proliferation including branching vessels and small vessel perivascular hyalinization. The tumor accounts for less than 0.5 % of all sinonasal neoplasms. The World Health Organization (WHO) classified this tumor as glomangiopericytoma in 2005. CASE REPORT: A 47-year-women presented with two years history of permanent left nasal obstruction and frequent epistaxis. Rhinoscopy revealed a friable grayish pink polypoidal mass, fully occupying the left anterior naris. Computed tomography showed a lesion involving the left nasal cavity, with a soft tissue density (70 UH) measuring 50 × 16 mm, widely infiltrative. Endoscopic surgery was performed to remove the mass, considering the size, limited expansion and the accessible location of the tumor. The immunohistochemistry examination showed positive staining b-catenin tumor cells which confirmed the diagnostic of glomangiopericytoma. After a 2 years follow-up, the patient showed no signs of recurrence. CONCLUSION: Glomangiopericytomas generally arises in the nasal cavity and may extend into the paranasal sinuses. It is categorized as a borderline low malignancy tumor by the WHO classification. Complete transnasal endoscopic excision is the optimal treatment.

Sniffin' Sticks to Measure Olfactory Function and Recovery Following Bilateral Superior Turbinate Resection as Part of Endoscopic Transsphenoidal Approach.

BACKGROUND: Extended endoscopic transsphenoidal (EET) approaches can include complete resection of both superior turbinate (ST) for wider exposure. Moreover, ST resection has been associated with postoperative olfactory impairment. OBJECTIVE: We sought to determine the impact of bilateral ST resection on olfaction during a transsphenoidal approach. METHOD: A prospective observational study was conducted on 29 patients undergoing endoscopic skull base surgery sparing the olfactory tracts at a tertiary academic center. Olfactory function was measured with Sniffin' Sticks at the preoperative visit, 2-weeks and 6 to 8 weeks postoperatively. All components: odor threshold (OT), odor discrimination (OD), odor identification (OI) and composite scores (TDI = OT+OD+OI) were evaluated. RESULT: Study was completed in 15 patients with 14 excluded due to a variety of reasons. At 2 weeks, a significant decrease was noted in composite scores (32.3 ± 5.4 vs. 23.8 ± 5.8, P < .05) and OT (7.7 vs. 3.2, P < .05). There was a significant increase in olfactory scores between post-op weeks 2 and 6 to 8 weeks in TDI (23.8 vs. 31.4, P < .05) as well as in OT (3.2 vs. 7.6, P < .05), OD (9.4 vs. 11.1, P < .05), and OI (11.1 vs. 12.7, P < .05). No significant difference was found between TDI (32.3 ± 5.4 vs. 31.4 ± 5.1), OT (7.7 vs. 7.6), OD (11.4 vs. 11.1) and OI (13.2 vs. 12.7) from preoperative and 6-8 weeks postoperative visits. CONCLUSION: Patients undergoing bilateral ST resection during EET procedures experience transient hyposmia postoperatively. However, the olfactory function normalizes to preoperative levels at 6 to 8 weeks. The resection of the bilateral superior turbinate does not appear to decrease olfactory function.

Rare Anatomic Variation: Pneumatized Secondary Middle Turbinate.

The nasal turbinates adhere to the lateral nasal wall and are subjected to various morphological variations. A common variation is concha bullosa, the pneumatization of a nasal turbinate. Another possible variation is the secondary middle turbinate (SMT) which originates from the lateral wall of the middle nasal meatus. Pneumatized SMTs were previously found only twice in Computed Tomography (CT) studies. It is hereby reported the third such evidence, gathered in a 44 y.o. male patient which was scanned in Cone Beam CT (CBCT) for routine dental medical procedures. In the present case the superior turbinates were pneumatized and were found bilateral SMTs. The left SMT was unpneumatized and projected medially and the right SMT was pneumatized and projected infero-medially. The right pneumatized SMT was communicating through a narrow isthmus with the ethmoidal bulla; beneath these two, a large ethmoidal infundibulum opened medially through a narrow semilunar hiatus. Such extremely rare anatomic variations could impede on the normal drainage of the ostiomeatal unit and could lead to inadvertent surgical corridors if they are not documented in CT or CBCT.

Relationship Between the Bilateral Removal of the Middle Nasal Turbinate and the Olfactory Function in Endoscopic Skull Base Surgery.

OBJECTIVE: To determine the impact of endonasal endoscopic access to the skull base on the olfaction sense, involving the harvest of a nasoseptal flap, with the removal of the middle nasal turbinate. METHODS: A study was performed on a prospective cohort of 50 patients who underwent transnasal endoscopic surgery of the anterior skull base, with the harvest of a nasoseptal and reverse flap. The patients were divided into 2 groups: partial unilateral removal of the middle nasal turbinate and bilateral removal. Connecticut Chemosensory Clinical Research Center tests were administered before surgery and in months 1, 3, and 6 after surgery. RESULTS: There was no difference in the olfactory sense, when comparing the partial removal of the middle nasal turbinate and the bilateral removal, as well as when comparing the side without the middle nasal turbinate and the side with this structure preserved. There was a worsening in olfaction (P < 0.001) in months 1 and 3 after surgery, returning to baseline in month 6 (P > 0.05). CONCLUSIONS: Bilateral removal of the middle nasal turbinate, compared with unilateral resection, showed no impact on the olfactory function 6 months after surgery. In both groups, there was a transitory decrease in the first month, but this normalized by the sixth postoperative month.

Supreme Nasal Turbinate as an Additional Surgical Landmark in Endoscopic Sinus and Skull Base Surgeries.

During endoscopic sinus and skull base surgeries, surgical landmarks are routinely used to guide surgeons navigating in the narrow corridor of the sinonasal region. Risk of complications is higher in difficult cases when there is excessive bleeding or alteration of the normal anatomical landmarks by tumour. An additional landmark is advantageous to prevent complications and serves as a guide. We present a case of supreme turbinate found incidentally during an endoscopic transsphenoidal surgery. Not much is known about the role of supreme turbinate. When it is present, the sphenoid ostium is located medial to its posteroinferior attachment, and behind its vertical part. Hence, the identification of this structure serves as an additional landmark besides superior turbinate during surgery.

Nasal cavities and the nasal septum: Anatomical variants and assessment of features with computed tomography.

The nasal cavities are complex anatomical structures with high inter-individual variability that relates to different functions. Different anatomic variants may manifest at this site, mainly belonging to the nasal septum and turbinates. Precise knowledge of the anatomy and variants is fundamental for both radiologists and ENT surgeons. This article provides an overview of the main anatomic variants and their frequency, according to the existing literature, as well as ongoing research on nasal cavity segmentation in order to obtain personal 3D models and to predict post-surgical results.

Specific bacteriophage of Bordetella bronchiseptica regulates B. bronchiseptica-induced microRNA expression profiles to decrease inflammation in swine nasal turbinate cells.

BACKGROUND: Respiratory diseases in pigs are the main health concerns for swine producers. Similar to the diseases in human and other animals, respiratory diseases are primary related to morbidity and are the result of infection with bacteria, viruses, or both. B. bronchiseptica causes serious respiratory diseases in the swine airway track. However, the B. bronchiseptica-specific bacteriophage has diverse advantages such as decreasing antibiotic overuse and possible therapeutic potential against bacteria. OBJECTIVE: The objects of this study were to investigate the therapeutic effect of specific B. bronchiseptica bacteriophages and to identify genes related to bacteriophage signaling utilizing RNA microarrays in swine nasal turbinate cells. METHODS: Bor-BRP-1 phages were applied 24 h prior to B.bronchiseptica infection (1 × 107 cfu/ml) at several concentrations of bacterial infection. Cells were incubated to detect cytokines and 24 h to detect mucin production. And real-time quantitative PCR was performed to examine related genes expression. To determine the change of total gene expression based on B.bronchiseptica and Bor-BRP-1 treatment, we performed RNA sequencing experiments. RESULTS: The results showed that B. bronchiseptica induced increased expression of several inflammatory genes such as IL-1ß, IL-6, and Muc1 in a dose-dependent manner. However, Bor-BRP-1 induced reduction of gene expression compared to the B. bronchiseptica induction group. In addition, microarrays detected Bor-BRP-1-altered inflammatory gene expression against B. bronchiseptica, reducing B. bronchiseptica-induced airway inflammation in swine epithelial cells. CONCLUSION: These results suggest that the specific bacteriophage has a therapeutic potential to defend against B. bronchiseptica infection by altering inflammatory gene expression profiles.

Pasteurella multocida specific bacteriophage suppresses P. multocida-induced inflammation: identification of genes related to bacteriophage signaling by Pasteurella multocida-infected swine nasal turbinate cells.

BACKGROUND: Although Pasteurella multocida is highly prevalent pathogen in animals and plays an important role in swine respiratory diseases, only a few studies on the use of bacteriophages specific to Pasteurella multocida disease have been reported. OBJECTIVE: The object of this study was to investigate the therapeutic effect of specific P. multocida bacteriophages and to identify genes related to bacteriophage signaling utilizing RNA microarrays in swine nasal turbinate cells. METHODS: Pas-MUP-1 phages were applied 24 h prior to P. multocida infection (1 × 107 cfu/ml) at several concentrations of bacterial infection. Cells were incubated to detect cytokines and 24 h to detect mucin production. And real-time quantitative PCR was performed to examine related genes expression. To determine the change of total gene expression based on P. multocida and Pas-MUP-1 treatment, we performed RNA sequencing experiments. RESULTS: We found that P. multocida-infected PT-K75 cells show increased gene expression of IL-1ß, IL-6, and Muc1 in a dose-dependent manner. Interestingly, these genes resulted in decreased expression in P. multocida pretreated with the P. multocida-specific Pas-MUP-1 bacteriophage. RNA sequencing analysis revealed that bacteriophage administration regulated genes associated with immune and inflammatory responses, and the regulated genes were dramatically concentrated in the cytokine/chemokine-based signaling pathways. Pas-MUP-1 treatment was shown to regulate P. multocida induced gene expression in the bacteria. CONCLUSION: These results suggest the specific bacteriophage has therapeutic potential as an alternative to antibiotic treatment to defend against P. multocida infection by altering inflammatory gene expression profiles.