Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

Enhancing Craniofacial Bone Reconstruction with Clinically Applicable 3D Bioprinted Constructs.

Medical imaging and 3D bioprinting can be used to create patient-specific bone scaffolds with complex shapes and controlled inner architectures. This study investigated the effectiveness of a biomimetic approach to scaffold design by employing geometric control. The biomimetic scaffold with a dense external layer showed improved bone regeneration compared to the control scaffold. New bone filled the defected region in the biomimetic scaffolds, while the control scaffolds only presented new bone at the boundary. Histological examination also shows effective bone regeneration in the biomimetic scaffolds, while fibrotic tissue ingrowth is observed in the control scaffolds. These findings suggest that the biomimetic bone scaffold, designed to minimize competition for fibrotic tissue formation in the bony defect, can enhance bone regeneration. This study underscores the notion that patient-specific anatomy can be accurately translated into a 3D bioprinting strategy through medical imaging, leading to the fabrication of constructs with significant clinical relevance.

Value of Quantitative Salivary Gland SPECT/CT for the Detection of Saliva Leakage.

ABSTRACT: A 47-year-old woman presented to our emergency department with a 10-day history of pain, halitosis, and swelling below the left jaw. The patient was diagnosed with left sialadenitis and left submandibular abscess by tissue biopsy. An otolaryngologist performed transcervical incision and drainage of the abscess 1 day after admission. Postoperatively, the patient complained of a sensation of fluid leakage from the mouth, and a continuous purulent discharge was observed. One month postoperatively, a salivary gland scan and SPECT/CT were performed to investigate the sialorrhea and the cause of the discharge. Salivary gland SPECT/CT images localized the saliva leakage site.

Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. STATEMENT OF SIGNIFICANCE: In this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment.

Matrix Metalloproteinase 1 as a Marker of Tonsil-Derived Mesenchymal Stem Cells to Assess Bone Marrow Cell Migration.

BACKGROUND: To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient's bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration. METHODS: To examine the donor-to-donor variation of TMSCs in potentiating BMC migration, we isolated TMSCs from 25 independent donors. Transcriptome of TMSCs and proteome of conditioned medium derived from TMSC were analyzed. RESULTS: Enhanced BMC migration by conditioned medium derived from TMSCs was variable depending on TMSC donor. The TMSCs derived from 25 donors showed distinct expression profiles compared with other cells, including fibroblasts, adipose-derived MSCs and bone marrow-derived MSCs. TMSCs were distributed in two categories: high- and low-efficacy groups for potentiating BMC migration. Transcriptome analysis of TMSCs and proteome profiles of conditioned medium derived from TMSCs revealed higher expression and secretion of matrix metalloproteinase (MMP) 1 in the high-efficacy group. MMP1 knockdown in TMSCs abrogated the supportive efficacy of conditioned medium derived from TMSC cultures in BMC migration. CONCLUSION: These data suggest that secreted MMP1 can be used as a marker to evaluate the efficacy of TMSCs in enhancing BMC migration. Furthermore, the strategy of analyzing transcriptomes and proteomes of the MSCs may be useful to set the standard for donor variation.

CD49f and CD146: A Possible Crosstalk Modulates Adipogenic Differentiation Potential of Mesenchymal Stem Cells.

BACKGROUND: The lack of appropriate mesenchymal stem cells (MSCs) selection methods has given the challenges for standardized harvesting, processing, and phenotyping procedures of MSCs. Genetic engineering coupled with high-throughput proteomic studies of MSC surface markers arises as a promising strategy to identify stem cell-specific markers. However, the technical limitations are the key factors making it less suitable to provide an appropriate starting material for the screening platform. A more accurate, easily accessible approach is required to solve the issues. METHODS: This study established a high-throughput screening strategy with forward versus side scatter gating to identify the adipogenesis-associated markers of bone marrow-derived MSCs (BMSCs) and tonsil-derived MSCs (TMSCs). We classified the MSC-derived adipogenic differentiated cells into two clusters: lipid-rich cells as side scatter (SSC)-high population and lipid-poor cells as SSC-low population. By screening the expression of 242 cell surface proteins, we identified the surface markers which exclusively found in lipid-rich subpopulation as the specific markers for BMSCs and TMSCs. RESULTS: High-throughput screening of the expression of 242 cell surface proteins indicated that CD49f and CD146 were specific for BMSCs and TMSCs. Subsequent immunostaining confirmed the consistent specific expression of CD49f and CD146 and in BMSCs and TMSCs. Enrichment of MSCs by CD49f and CD146 surface markers demonstrated that the simultaneous expression of CD49f and CD146 is required for adipogenesis and osteogenesis of mesenchymal stem cells. Furthermore, the fate decision of MSCs from different sources is regulated by distinct responses of cells to differentiation stimulations despite sharing a common CD49f+CD146+ immunophenotype. CONCLUSIONS: We established an accurate, robust, transgene-free method for screening adipogenesis associated cell surface proteins. This provided a valuable tool to investigate MSC-specific markers. Additionally, we showed a possible crosstalk between CD49f and CD146 modulates the adipogenesis of MSCs.

Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads.

Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (w/v) alginate solution containing TMSCs into a 5% CaCl2 solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.

Procollagen C-Endopeptidase Enhancer 2 Secreted by Tonsil-Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL-60 Cells.

Reactive oxygen species (ROS) generated by neutrophils provide a frontline defence against invading pathogens. We investigated the supportive effect of tonsil-derived mesenchymal stem cells (TMSCs) on ROS generation from neutrophils using promyelocytic HL-60 cells. Methods: Differentiated HL-60 (dHL-60) cells were cocultured with TMSCs isolated from 25 independent donors, and ROS generation in dHL-60 cells was measured using luminescence. RNA sequencing and real-time PCR were performed to identify the candidate genes of TMSCs involved in augmenting the oxidative burst of dHL-60 cells. Transcriptome analysis of TMSCs derived from 25 independent donors revealed high levels of procollagen C-endopeptidase enhancer 2 (PCOLCE2) in TMSCs, which were highly effective in potentiating ROS generation in dHL-60 cells. In addition, PCOLCE2 knockdown in TMSCs abrogated TMSC-induced enhancement of ROS production in dHL-60 cells, indicating that TMSCs increased the oxidative burst in dHL-60 cells via PCOLCE2. Furthermore, the direct addition of recombinant PCOLCE2 protein increased ROS production in dHL-60 cells. These results suggest that PCOLCE2 secreted by TMSCs may be used as a therapeutic candidate to enhance host defences by increasing neutrophil oxidative bursts. PCOLCE2 levels in TMSCs could be used as a marker to select TMSCs exhibiting high efficacy for enhancing neutrophil oxidative bursts.

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

Progressive Multifocal Leukoencephalopathy With Hyper-IgM Syndrome in a 6-Year-Old Boy.

Hyper-immunoglobulin (Ig) M syndrome is a congenital immunodeficiency disorder characterized by increased serum IgM with low serum IgG, IgA, and IgE. We report the case of a 6-year-old boy with hyper-IgM syndrome as an underlying disease who showed progressive multifocal leukoencephalopathy findings on brain magnetic resonance imaging after visiting the hospital due to left upper extremity muscle weakness, gait disturbance, and speech impairment. At the time of hospitalization, he was treated with steroids and intravenous immunoglobulin, and his condition improved somewhat, but 6 months later, he visited the hospital with rapid deterioration.

Transient receptor potential vanilloid 2 mediates the inhibitory effect of far-infrared irradiation on adipogenic differentiation of tonsil-derived mesenchymal stem cells.

AIMS: Far-infrared (FIR) irradiation inhibits adipogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs) by activating Ca2+-dependent protein phosphatase 2B (PP2B), but it stimulates osteogenic differentiation in a PP2B-independent pathway. We investigated the potential involvement of transient receptor potential vanilloid (TRPV) channels, a well-known Ca2+-permeable channel, in the effects of FIR irradiation on adipogenic or osteogenic differentiation of TMSCs. METHODS: TMSCs, in the absence or presence of activators or inhibitors, were exposed to FIR irradiation followed by adipogenic or osteogenic differentiation, which was assessed using Oil red O or Alizarin red S staining, respectively. RT-PCR, qRT-PCR, and Western blotting were used to determine gene and protein expression of calcium channels and adipocyte-specific markers. RESULTS: Treatment with the calcium ionophore ionomycin simulated the inhibitory effect of FIR irradiation on adipogenic differentiation but had no effect on osteogenic differentiation, indicating the involvement of intracellular Ca2+ in adipogenic differentiation. Inhibition of pan-TRP channels using ruthenium red reversed the FIR irradiation-induced inhibition of adipogenic differentiation. Among the TRP channels tested, inhibition of the TRPV2 channel by tranilast or siRNA against TRPV2 attenuated the inhibitory effect of FIR irradiation on adipogenic differentiation, accompanied by a decrease in intracellular Ca2+ levels. By contrast, activation of the TRPV2 channel by probenecid simulated FIR irradiation-induced inhibition of adipogenic differentiation. Expectedly, the stimulatory effect of FIR irradiation on osteogenic differentiation was independent of the TRPV2 channel. CONCLUSION: Our data demonstrate that the TRPV2 channel is a sensor/receptor for the inhibited adipogenic differentiation of TMSCs associated with FIR irradiation.

Porcine Tracheal Mucosa-Derived Decellularized Patch to Prevent Septal Perforation in a Rabbit Model.

BACKGROUND: Nasal septal perforation is caused by bilateral septal mucosal injuries resulting from nasal trauma and septal surgeries. Previous studies have reported that biocompatible materials may be effective for repairing nasal septal perforations. However, they were primarily used for treatment; no study has investigated their use for prevention of nasal septal perforation. OBJECTIVE: To determine whether porcine tracheal mucosa-derived decellularized patch can prevent the progression of nasal mucosa injuries to septal perforations. METHODS: Bilateral nasal septal mucosal defects were surgically induced in 36 rabbits. Silastic sheets were applied bilaterally in all rabbits, and decellularized mucosal patch was applied unilaterally (n = 12) or bilaterally (n = 12) at the defect site in the respective experimental groups. Between 1 and 8 weeks postoperatively, the animals were sacrificed, and their nasal septa were completely removed. The excised septa were examined macroscopically and microscopically (histopathological examinations). Moreover, glycosaminoglycan (GAG) estimations of the septa were performed to evaluate mucosal regeneration and mechanical properties. RESULTS: Septal perforations occurred in 5 animals in the control group (5/12; 42%), 1 in the unilateral group (1/12; 9%), and in none in the bilateral group. Compared with the control group, the experimental groups showed significantly different mucosal and cartilage regeneration. CONCLUSION: Decellularized porcine tracheal mucosa can prevent mucosal defects from progressing to septal perforation, promote the repair of mucosal defects, and protect the nasal cartilage.

Dietary factors associated with inflammatory laryngeal disease in South Korea.

Laryngeal inflammation causes not only benign diseases of the larynx, such as laryngitis and granuloma, but also malignancy. Dietary factors are known to control or modulate the inflammatory reaction in the body. To date, the association between laryngeal inflammation and dietary factors has not been reported using nationwide population-based data. The aim of this study was to analyze the association between several dietary factors and inflammatory laryngeal disease in the Korean population. This study analyzed the data from Korean National Health and Nutrition Examination Surveys which is cross-sectional nationwide-population-based study. Association between the dietary nutrient intake and the prevalence of inflammatory laryngeal diseases was analyzed in 21,116 participants who underwent a laryngoscopy and filled in the dietary intake questionnaires. Of the 21,116 participants included in the analysis, 758 (3.59%) were diagnosed with inflammatory laryngeal disease. Prevalence of inflammatory laryngeal disease was higher in men (4.58%) than in women (2.84%). The mean age of patients was 53.77 years. When analyzing the risk using propensity score matching, ILD group tend to consume more coffee and to intake less fiber and iron than normal group. On Logistic regression analysis, an increased intake of carbohydrate, fiber, and iron was associated with lowered risk of having ILD in female. The association between inflammatory laryngeal disease and dietary factors was prominent in the group aged ≥50 years and female. Increased intake of fiber, iron, and vitamin A were associated with lower risk in the group aged ≥50 years. In female, increased intake of fiber, iron were associated with lower risk of having ILD. In the group aged ≤50 years, only an increased consumption of makgeolli, Korean traditional rice wine, was associated with a higher risk of ILD.

Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

Safety of drainless excision of the submandibular gland / Segurança na excisão da glândula submandibular sem o uso de drenos

Abstract Introduction: Percutaneous drains can be associated with several complications, including infection, fistula formation, discomfort and prolonged hospitalization. Objective: The aim of this study was to evaluate the safety of submandibular gland excision without the use of surgical drains. Methods: We analyzed the surgery time, postoperative complications such as bleeding, facial palsy, seroma, and repeat exploration of wounds and duration of the hospital stay. Excision of the submandibular gland via a transcervical approach was undertaken by two surgeons. Prior to wound closure, the skin flap and wound bed were approximated using hemostatic fibrin glue (Greenplast-Q PFS KIT®, GC Greencross, Youngin, Korea). Neither saline irrigation nor insertion of a percutaneous drain were included. Results: A total of 23 patients underwent submandibular gland excision. The study group consisted of 14 men (60.8%) and 9 women (39.2%) (mean age, 47.6 years; range, 24-70 years). There were two patients who had minor complications. One patient showed minor bleeding on the skin incision line immediately postoperatively, and one developed a seroma at 7 days postoperatively. There were no major surgical complications. Total duration of the surgery from skin incision to closure averaged 44.86 minutes. Mean duration of the hospital stay was 3.17 days. Patients were discharged on average at 1.17 days after surgery. Conclusion: The submandibular gland can be safely excised without the use of a surgical drain, therefore allowing early patient discharge.

Resumo Introdução: Os drenos percutâneos apresentam várias complicações associadas, inclusive infecção, formação de fístulas, desconforto e permanência hospitalar prolongada. Objetivo: Avaliar a segurança da excisão da glândula submandibular sem o uso de drenos cirúrgicos. Método: Analisamos o tempo de cirurgia, as complicações pós-operatórias tais como sangramento, paralisia facial, seroma e necessidade de reexploração de ferida operatória, e a duração da internação hospitalar. A excisão da glândula submandibular por via transcervical foi realizada por dois cirurgiões. Antes do fechamento da incisão, o retalho cutâneo e o leito da ferida operatória foram aproximados utilizando cola hemostática de fibrina (Greenplast-Q PFS KIT®, GC Greencross, Youngin, República da Coréia). Não houve irrigação salina nem uso de dreno percutâneo. Resultados: Foram submetidos 23 pacientes à excisão da glândula submandibular. O grupo de estudo consistiu em 14 homens (60,8%) e 9 mulheres (39,2%) (média de 47,6 anos; variação de 24 a 70). Dois pacientes apresentaram complicações menores. Um paciente apresentou pequeno sangramento na incisão da pele no pós-operatório imediato e um deles teve seroma aos 7 dias de pós-operatório. Não houve complicações cirúrgicas importantes. A duração total da cirurgia, desde a incisão na pele até o fechamento, foi de 44,86 minutos. A duração média da internação hospitalar foi de 3,17 dias. Os pacientes receberam alta em média 1,17 dia após a cirurgia. Conclusão: A glândula submandibular pode ser excisada com segurança sem o uso de dreno cirúrgico, permitindo que o paciente tenha alta hospitalar mais precocemente.

Guidelines for the Management of Unilateral Vocal Fold Paralysis From the Korean Society of Laryngology, Phoniatrics and Logopedics.

The Korean Society of Laryngology, Phoniatrics and Logopedics appointed a task force to establish clinical practice guidelines for the management of unilateral vocal fold paralysis (UVFP). These guidelines cover a comprehensive range of management-related factors, including the diagnosis and treatment of UVFP, and provide in-depth information based on current, up-to-date knowledge. Detailed evidence profiles are provided for each recommendation. The CORE databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers, using a predefined search strategy. When insufficient evidence existed, expert opinions and Delphi questionnaires were used to fill the evidence gap. The committee developed 16 evidence-based recommendations in six categories: initial evaluation (R1-4), spontaneous recovery (R5), medical treatment (R6), surgical treatment (R7-14), voice therapy (R15), and aspiration prevention (R16). The goal of these guidelines is to assist general otolaryngologists and speech-language pathologists who are primarily responsible for treating patients with UVFP. These guidelines are also intended to facilitate understanding of the condition among other health-care providers, including primary care physicians, nurses, and policy-makers.

Development of Acellular Respiratory Mucosal Matrix Using Porcine Tracheal Mucosa.

BACKGROUND: Respiratory mucosa defects result in airway obstruction and infection, requiring subsequent functional recovery of the respiratory epithelium. Because site-specific extracellular matrix (ECM) facilitates restoration of organ function by promoting cellular migration and engraftment, previous studies considered decellularized trachea an ideal ECM; however, incomplete cell removal from cartilage and mucosal-architecture destruction are frequently reported. Here, we developed a decellularization protocol and applied it to the respiratory mucosa of separated porcine tracheas. METHODS: The trachea was divided into groups according to decellularization protocol: native mucosa, freezing-thawing (FT), FT followed by the use of Perasafe-based chemical agents before mucosal separation (wFTP), after mucosal separation (mFTP), and followed by DNase decellularization (mFTD). Decellularization efficacy was evaluated by DNA quantification and hematoxylin and eosin staining, and ECM content of the scaffold was evaluated by histologic analysis and glycosaminoglycan and collagen assays. Biocompatibility was assessed by cell-viability assay and in vivo transplantation. RESULTS: The mFTP mucosa showed low antigenicity and maintained the ECM to form a proper microstructure. Additionally, tonsil-derived stem cells remained viable when cultured with or seeded onto mFTP mucosa, and the in vivo host response showed a constructive pattern following implantation of the mFTP scaffolds. CONCLUSION: These results demonstrated that xenogenic acellular respiratory mucosa matrix displayed suitable biocompatibility as a scaffold material for respiratory mucosa engineering.

Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model.

BACKGROUND: We first determined the efficacy of lesional injection of tonsil-derived MSCs (mesenchymal stem cells) for the treatment of 5-fluorouracil induced oral mucositis. METHODS: Oral mucositis was induced in hamsters by administration of 5-fluorouracil (day 0, 2, 4) followed by mechanical trauma (day 1, 2, 4). The experimental groups included MT (mechanical trauma only), 5-FU + MT (mechanical trauma with 5-fluorouracil administration), TMSC (mechanical trauma with 5-fluorouracil administration, tonsil-derived mesenchymal stem cells injection), DEXA (mechanical trauma with 5-fluorouracil administration, dexamethasone injection), and saline (mechanical trauma with 5-fluorouracil administration, saline injection). RESULTS: On day 10, gross and histologic analyses showed that nearly complete healing and epithelialization of the cheek mucosa of the TMSC group, whereas the other groups showed definite ulcerative lesions. Compared with the MT and DEXA groups, CD31 expression was greater in the TMSC group on days 10 and 14. Tendency towards a decrease in MMP2 expression with the time in the TMSC group was observed. In addition, the TMSC group showed higher expression of TGF-ß, and NOX4 on day 10 compared with the other groups. Scratch assay demonstrated that the conditioned media harvested from tonsil-derived MSCs significantly increased migratory efficacy of NIH3T3 cells. Transwell assay showed that the preferential migration of tonsil-derived MSCs to the wound area. CONCLUSION: Intralesional administration of tonsil-derived MSCs may accelerate wound healing of 5-fluorouracil induced oral mucositis by upregulating neovascularization and effective wound contraction. In addition, tonsil-derived MSCs might contribute to oral ulcer regeneration via the stimulation of fibroblast proliferation and migration.

Trends in the Incidence and Treatment of Benign Vocal Fold Lesions in Korea, 2006-2015: A Nationwide Population-based Study.

OBJECTIVE: The aim of this study was to determine the prevalence and demographics of benign vocal fold lesions (BVFL) and trends in its treatment in Korea based on data collected from the National Health Insurance Service database. MATERIAL AND METHODS: Data for patients diagnosed with BVFL (ICM-10 codes J381, J382, J384) from 2006 to 2015 were selected for analysis. Patient characteristics, including sex, age, income, area of residence, and comorbidity, were analyzed. Treatment was divided into surgical management and conservative management using operation codes. RESULTS: The prevalence and incidence of BVFL increased from 7.07% and 5.29%, respectively, in 2006 to 12.47% and 7.98% in 2015. Compared with the non-BVFL population, patients with BVFL were more likely to be female, reside in an urban area, and have gastroesophageal reflux disease. There was no significant change in the incidence of surgical treatment during the study period (around 6000 per year); however, the surgical treatment rate decreased from 19.29% to 8.38%. The probability of undergoing surgical treatment for BVFL was higher in men, those aged 50-59 years, and those in the lowest quartile for income, except for the medical aid group. CONCLUSION: In Korea, there was an increase in the number of patients diagnosed with BVFL and a decrease in the operation rate for this condition between 2006 and 2015. Diagnosis of BVFL varied significantly based on income and sex; however, the only variable affecting the operation rate was patient age.