Differential dependence on microbiota of IL-23/IL-22-dependent gene expression between the small- and large-intestinal epithelia.

In the intestine, interleukin (IL)-23 and IL-22 from immune cells in the lamina propria contribute to maintenance of the gut epithelial barrier through the induction of antimicrobial production and the promotion of epithelial cell proliferation. Several previous studies suggested that some of the functions of the IL-23/IL-22 axis on intestinal epithelial cells are shared between the small and large intestines. However, the similarities and differences of the IL-23/IL-22 axis on epithelial cells between these two anatomical sites remain unclear. Here, we comprehensively analyzed the gene expression of intestinal epithelial cells in the ileum and colon of germ-free, Il23-/- , and Il22-/- mice by RNA-sequencing. We found that while the IL-23/IL-22 axis is largely dependent on gut microbiota in the small intestine, it is much less dependent on it in the large intestine. In addition, the negative regulation of lipid metabolism in the epithelial cells by IL-23 and IL-22 in the small intestine was revealed, whereas the positive regulation of epithelial cell proliferation by IL-23 and IL-22 in the large intestine was highlighted. These findings shed light on the intestinal site-specific role of the IL-23/IL-22 axis in maintaining the physiological functions of intestinal epithelial cells.

High-frequency low-intensity semiconductor laser irradiation enhances osteogenic differentiation of human cementoblast lineage cells.

PURPOSE: Laser irradiation activates a range of cellular processes in the periodontal components and promotes tissue repair. However, its effect on osteogenic differentiation of human cementoblast lineage cells remains unclear. This study aimed to examine the effects of high-frequency semiconductor laser irradiation on the osteogenic differentiation of human cementoblast lineage (HCEM) cells. METHODS: HCEM cells were cultured to reach 80% confluence and irradiated with a gallium-aluminum-arsenide (Ga-Al-As) semiconductor laser with a pulse width of 200 ns and wavelength of 910 at a dose of 0-2.0 J/cm2. The outcomes were assessed by analyzing the mRNA levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and type I collagen (COLL1) using real-time polymerase chain reaction (PCR) analysis 24 h after laser irradiation. Cell mineralization was evaluated using ALP activity, calcium deposition, and Alizarin Red staining. RESULTS: The laser-irradiated HCEM cells showed significantly enhanced gene expression levels of ALP, RUNX2, and COLL1 as well as ALP activity and calcium concentration in the culture medium compared with the non-irradiated cells. In addition, enhanced calcification deposits were confirmed in the laser-irradiated group compared with the non-irradiated group at 21 and 28 days after the induction of osteogenic differentiation. CONCLUSION: High-frequency semiconductor laser irradiation enhances the osteogenic differentiation potential of cultured HCEM cells, underscoring its potential utility for periodontal tissue regeneration.

Longitudinal effects of estrogen on mandibular growth and changes in cartilage during the growth period in rats.

Estrogen is a steroid hormone that induces skeletal growth and affects endochondral ossification of the long tubular bone growth plate during the growth period. However, the effects of estrogen on endochondral ossification of the mandibular condylar cartilage are unclear. In this study, ovariectomized Wistar/ST rats were used to investigate the longitudinal effects of estrogen on mandibular growth. The rats were administered different doses of estrogen. Longitudinal micro-computed tomographic scanning, histological staining and ELISA on plasma growth hormone were performed to examine the effects of estrogen on mandibular growth. The results showed that mandibular growth was suppressed throughout the growth period by estrogen in a dose-dependent manner. In addition, long-term administration of a high dose of estrogen to the rats resulted in significant increase in growth hormone throughout the growth period, significant circularization of cell nuclei in the proliferative layer, intensely staining cartilage matrix in the subchondral bone, and significant suppression of estrogen receptor (ER) alpha and beta expression in the mandibular cartilage. However, regardless of estrogen concentration, in the posterior part of the mandibular cartilage, ER expression extended to both the hypertrophic and proliferative layers. These results indicate that estrogen suppresses mandibular growth throughout the growth period. Additionally, it influences endochondral ossification via its effect on ERs.

High-frequency near-infrared semiconductor laser irradiation suppressed experimental tooth movement-induced inflammatory pain markers in the periodontal ligament tissues of rats.

High-frequency near-infrared (NIR) semiconductor laser-irradiation has an unclear effect on nociception in the compressed lateral periodontal ligament region, a peripheral nerve region. This study aimed to investigate the effects of NIR semiconductor laser irradiation, with a power of 120 J, on inflammatory pain markers and neuropeptides induced in the compressed lateral periodontal ligament area during ETM. A NIR semiconductor laser [910 nm wavelength, 45 W maximum output power, 300 mW average output power, 30 kHz frequency, and 200 ns pulse width (Lumix 2; Fisioline, Verduno, Italy)] was used. A nickel-titanium closed coil that generated a 50-g force was applied to the maxillary left-side first molars and incisors in 7-week-old Sprague-Dawley (280-300 g) rats to induce experimental tooth movement (ETM) for 24 h. Ten rats were divided into two groups (ETM + laser, n = 5; ETM, n = 5). The right side of the ETM group (i.e., the side without induced ETM) was evaluated as the untreated group. We performed immunofluorescent histochemistry analysis to quantify the interleukin (IL)-1ß, cyclooxygenase-2 (COX2), prostaglandin E2 (PGE2), and neuropeptide [calcitonin gene-related peptide (CGRP)] expression in the compressed region of the periodontal tissue. Post-hoc Tukey-Kramer tests were used to compare the groups. Compared with the ETM group, the ETM + laser group showed significant suppression in IL-1ß (176.2 ± 12.3 vs. 310.8 ± 29.5; P < 0.01), PGE2 (104.4 ± 14.34 vs. 329.6 ± 36.52; P < 0.01), and CGRP (36.8 ± 4.88 vs. 78.0 ± 7.13; P < 0.01) expression. High-frequency NIR semiconductor laser irradiation exerts significant effects on ETM-induced inflammation. High-frequency NIR semiconductor laser irradiation can reduce periodontal inflammation during orthodontic tooth movement.

S100A8 enhances IL-1ß production from nasal epithelial cells in eosinophilic chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. METHODS: We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. RESULTS: S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1ß secretion in human nasal epithelial cells. CONCLUSIONS: Our data demonstrate that S100A8 results in production of interleukin-1ß in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

High-frequency near-infrared diode laser irradiation suppresses IL-1ß-induced inflammatory cytokine expression and NF-κB signaling pathways in human primary chondrocytes.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are common inflammation-associated cartilage degenerative diseases. Recent studies have shown that low-level diode laser treatment can reduce inflammatory cytokine expressions in cartilage. We recently reported that high-frequency low-level diode laser irradiation attenuates matrix metalloproteinases (MMPs) expression in human primary chondrocytes. However, the molecular mechanism underlying the effect of high-frequency low-level diode laser on chondrocytes remains unclear. Therefore, we aimed to elucidate the effect of high-frequency low-level diode laser irradiation on inflammatory cytokine expression in human primary chondrocytes. Normal human articular chondrocytes were treated with recombinant interleukin-1 beta (IL-1ß) for 30 min or 24 h and irradiated with a high-frequency NIR diode laser at 8 J/cm2. The expression of IL-1ß, interleukin-6, and tumor necrosis factor-alpha was assessed using western blot analysis. To evaluate the nuclear factor-kappa B (NF-κB) signaling pathway, the phosphorylation, translocation, and DNA-binding activity of NF-κB were detected using western blot analysis, immunofluorescence analysis, electrophoretic mobility shift assay, and enzyme-linked immunosorbent assay analysis. High-frequency low-level diode laser irradiation decreased inflammatory cytokine expression in IL-1ß-treated chondrocytes. Moreover, high-frequency low-level diode laser irradiation decreased the phosphorylation, nuclear translocation, and DNA-binding activity of NF-κB in the IL-1ß-treated state. However, irradiation alone did not affect NF-κB activity. Thus, high-frequency low-level diode laser irradiation at 8 J/cm2 can reduce inflammatory cytokine expressions in normal human articular chondrocytes through NF-κB regulation. These findings indicate that high-frequency low-level diode laser irradiation may reduce the expression of inflammatory cytokines in OA and RA.

Effects of high-frequency near infrared laser irradiation on experimental tooth movement-induced pain in rats.

Discomfort and dull pain are known side effects of orthodontic treatment. Pain is expected to be reduced by near-infrared (NIR) lasers; however, the mechanism underlying effects of short-pulse NIR lasers in the oral and maxillofacial area remains unclear. This study aimed to examine the effects of high-frequency NIR diode laser irradiation on pain during experimental tooth movement (ETM) on 120 J. NIR laser with 910 nm wavelength, 45 W maximum output power, 300 mW average output power, and 200 ns pulse width (Lumix 2; (Lumix 2; Fisioline, Verduno CN, Italy) was used for the experiment. A nickel-titanium-closed coil was used to apply a 50-gf force between the maxillary left-side first molar and incisor in 7-week-old Sprague-Dawley rats (280-300 g) to induce ETM. We measured facial-grooming frequency and vacuous chewing movement (VCM) period between laser-irradiation and ETM groups. We performed immunofluorescent histochemistry analysis to quantify levels of Iba-1, astrocytes, and c-fos protein-like immunoreactivity (Fos-IR) in the trigeminal spinal nucleus caudalis (Vc). Compared with the ETM group, the laser irradiation group had significantly decreased facial-grooming frequency (P = 0.0036), VCM period (P = 0.043), Fos-IR (P = 0.0028), Iba-1 levels (P = 0.0069), and glial fibrillary acidic protein (GFAP) levels (P = 0.0071). High-frequency NIR diode laser irradiation appears to have significant analgesic effects on ETM-induced pain, which involve inhibiting neuronal activity, microglia, and astrocytes, and it inhibits c-fos, Iba-1, and GFAP expression, reducing ETM-induced pain in rats. High-frequency NIR diode laser application could be applied to reduce pain during orthodontic tooth movement.

Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis. Clinical markers for ECRS disease activity and treatment strategies have not been sufficiently established. Although semaphorins are originally identified as neuronal guidance factors, it is becoming clear that they play key roles in immune regulation and inflammatory diseases. OBJECTIVE: We sought to investigate the pathological functions and therapeutic potential of semaphorin 4D (SEMA4D) in ECRS. METHODS: Serum soluble SEMA4D levels in patients with paranasal sinus diseases were measured by ELISA. The expression of SEMA4D in blood cells and nasal polyp tissues was assessed by flow cytometry and immunohistochemistry, respectively. Generation of soluble SEMA4D was evaluated in matrix metalloproteinase-treated eosinophils. Endothelial cells were stimulated with recombinant SEMA4D, followed by eosinophil transendothelial migration assays. Allergic chronic rhinosinusitis was induced in mice using Aspergillus protease with ovalbumin. The efficacy of treatment with anti-SEMA4D antibody was evaluated histologically and by nasal lavage fluid analysis. RESULTS: Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Tissue-infiltrated eosinophils in nasal polyps from patients with ECRS stained strongly with anti-SEMA4D antibody. Cell surface expression of SEMA4D on eosinophils from patients with ECRS was reduced, which was due to matrix metalloproteinase-9-mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model. CONCLUSIONS: Eosinophil-derived SEMA4D aggravates ECRS. Levels of serum SEMA4D reflect disease severity, and anti-SEMA4D antibody has therapeutic potential as a treatment for ECRS.

Examination of the effect of combined use of Er:YAG laser irradiation and mechanical force loading on bone metabolism using primary human gingival fibroblasts.

Prolonged treatment and painful tooth movement are major problems for patients undergoing orthodontic treatment. Accelerating the movement of teeth leads to shortening of the treatment period, so various studies on the movement of teeth have been conducted in the field of orthodontics. In previous studies, we performed a fiber incision-like fiberotomy using an Er:YAG laser in rats and confirmed acceleration of tooth movement. Therefore, in this study, the effect of Er:YAG laser irradiation on human gingival fibroblasts was investigated in vitro. Human gingival fibroblasts (2.0 × 105 cells) were seeded in a 6-well plate and reached 80% confluence 24 h later. A control group not undergoing any irradiation and 3 groups undergoing laser irradiation at 0.6 W, 1.0 W, and 1.2 W were investigated. Laser irradiation was performed 24 h after cell seeding. The cells were then recovered 24 h later, and the cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), bone morphogenetic protein-2 (BMP-2), and BMP-4 genes were confirmed by PCR. In addition, a control group not undergoing any procedures, a group undergoing only Er:YAG laser irradiation, a group undergoing only centrifugal loading, and a group undergoing both Er:YAG laser irradiation and centrifugal force loading were investigated. After 24 h, cells were collected and PCR was performed. Twenty-four hours after laser irradiation, gene expressions were examined by quantitative RT-PCR, which showed that the gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 increased depending on the amount of irradiation energy, with the largest value at 1.2 W. Gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 were significantly higher in the laser with centrifugal load group than in the load group. These results suggest that genes related to bone metabolism are activated in human gingival fibroblasts when mechanical stimulation and laser irradiation are combined. This helps to elucidate the effects of Er:YAG laser irradiation during tooth movement.

Effects of Nd:YAG low-level laser irradiation on cultured human osteoblasts migration and ATP production: in vitro study.

Low-level laser therapy has become one of the fastest growing fields of medicine in recent years. Many in vivo and in vitro studies have shown that laser irradiation activates a range of cellular processes in a variety of cell types and can promote tissue repair. However, few in vitro experiments have evaluated the effects of laser irradiation on cells in real time. The purpose of this study was to examine the effects of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser irradiation on the migration of cultured human osteoblasts. A dedicated 96-well plate was used, and confluent cultures of the human osteoblast-like cell line, Saos-2, were injured with a wound maker. The wounded cells were then exposed to the Nd:YAG laser (wavelength of 1064 nm) for 60 s at 0.3 W (10 pps, 30 mJ). The total energy density was about 10.34 J/cm2. Images of the wounds were automatically acquired inside the CO2 incubator by the IncuCyte ZOOM™ software. In addition, after laser irradiation, the production of adenosine triphosphate (ATP) was measured using the CellTiter-Glo™ Luminescent Cell Viability Assay. Migration of cells from the border of the original scratch zone was accelerated by laser irradiation. In addition, compared with the control group, significant enhancement of ATP production was observed in the irradiated group. The present study showed that Nd:YAG laser irradiation (wavelength of 1064 nm, 0.3 W, 10 pps, 30 mJ, 10.34 J/cm2, irradiation time 60 s) may contribute to the regeneration of bone tissues owing to enhanced osteoblast cell migration.

Orthodontic Treatment of a Patient With Non-Syndromic Oligodontia and a Skeletal Class â ¢ Relationship: A Case Report and Six Years' Follow-Up.

Partial edentulism, characterized by the congenital absence of six or more permanent teeth (oligodontia), excluding the third molars, manifests with variable maxillofacial skeletal morphologies and occlusions, depending on the site and number of missing teeth, complicating treatment planning for occlusion and gain of function. Herein, we describe the case of a patient with seven non-syndromic congenitally missing permanent teeth (four in the maxillary and three in the mandibular dentition, excluding the third molars), who underwent orthodontic treatment, restorative procedures, and long-term follow-up for six years. The patient was an 18-year-old man presenting with a chief complaint of congenital absence of some permanent teeth and dental malalignment on the first visit. The mandibular right central incisor, bilateral mandibular second premolars, bilateral maxillary lateral incisors, and bilateral maxillary canines were congenitally absent, while the deciduous maxillary lateral incisors, maxillary canines, and mandibular second molars were over-retained bilaterally. Since the persisting deciduous teeth were remarkably well preserved, the patient was willing to retain them as far as possible; thus, we chose orthodontic and restorative treatment to preserve the deciduous teeth. Occlusion was established after the initiation of dynamic orthodontic treatment; restorative treatment with resin-based materials was performed for the bilateral maxillary deciduous incisors, bilateral maxillary deciduous canines, and bilateral mandibular second primary molars after bracket removal, and the retention phase of orthodontic treatment was initiated. At present, six years after establishing retention, the patient exhibits a good occlusal relationship. It is difficult to achieve complete space closure using orthodontic treatment alone in cases with six or more congenitally missing permanent teeth. In addition to considerations for age, esthetic issues due to missing permanent teeth, and maxillofacial skeletal morphology, it is necessary to preserve the deciduous teeth as much as possible and ensure multidisciplinary medical cooperation, including the transition to prosthodontic treatment during long-term follow-up.

Stem cells derived from human exfoliated deciduous teeth-based media in a rat root resorption model.

OBJECTIVE: Root resorption may occur during orthodontic treatment. Herein, we investigated the effect of a culture supernatant of stem cells derived from human exfoliated deciduous teeth on root resorption. DESIGN: Twelve 8-week-old male Sprague-Dawley rats were used, and their maxillary first molars were pulled with excessive orthodontic force to induce root resorption. On days 1 and 7 after traction initiation, stem cells derived from human exfoliated deciduous teeth and alpha minimum essential medium (control group) were administered. After 14 days, the maxillary bone was evaluated for tooth movement. The expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 was evaluated on the compression side and tension side. RESULTS: No significant difference in tooth movement was observed between the two groups. Root resorption decreased in the group administered the culture supernatant compared with in the control. Immunohistochemical staining revealed increased osteoprotegerin expression and decreased receptor activators for nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 on the compression side and tension side. CONCLUSIONS: Administration of stem cells derived from human exfoliated deciduous teeth affected the expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6 and interleukin 17; hence, these stem cells may inhibit root resorption by regulating their expression.

Effects of Peripheral Nerve Injury on the Induction of c-Fos and Phosphorylated ERK in the Brainstem Trigeminal Sensory Nuclear Complex.

Background: Sequential changes in brainstem and spinal cord neurons after traumatic injury to peripheral nerves are related to neuropathic pain symptoms. Purpose: This study was conducted to elucidate the influence of nerve insult on stimulus-induced c-Fos expression and ERK phosphorylation by brainstem neurons. Methods: The brainstem trigeminal sensory nuclear complex (BTSNC) was examined for neuronal profiles immunolabeled with c-Fos and phosphorylated ERK (p-ERK) antibodies elicited by stimulation of the tongue with capsaicin after lingual or inferior alveolar nerve (IAN) injury. Results: Abundant neuronal profiles immunolabeled for c-Fos and p-ERK elicited by capsaicin were distributed in the spinal trigeminal nucleus caudalis (Vc) without nerve injury. The spinal trigeminal nucleus oralis (Vo) contained limited numbers of these neuronal profiles after stimulation of the tongue. A significant reduction of these neuronal profiles in the ipsilateral Vc was detected after lingual nerve injury. After IAN injury, an increased number of neuronal profiles immunolabeled for c-Fos elicited by capsaicin was noted, while that of p-ERK was left unchanged in the ipsilateral Vc. On the both sides of the Vo, an increased number of capsaicin-induced neuronal profiles immunolabeled for c-Fos and p-ERK was detected after lingual or IAN injury. Conclusion: Differential effects of lingual or IAN injury on stimulus-induced c-Fos expression and ERK phosphorylation by Vo and Vc neurons may be involved in the complex nature of symptoms of trigeminal neuralgia.

Effect of Er: YAG Laser Irradiation on Bone Metabolism-Related Factors Using Cultured Human Osteoblasts.

Introduction: A variety of laser treatments have been applied in numerous medical fields. In dentistry, laser treatments are used for caries, root canals, and periodontal disease, as well as surgical resection. Numerous reports have recently been published on the use of lasers for bone regeneration. If laser irradiation is found to promote the activation of bone metabolism, it might also be effective for periodontal treatment, peri-implantitis, and bone regeneration. Therefore, the present in vitro study aimed to elucidate the mechanisms underlying the effects of erbium-doped yttrium aluminum garnet (Er: YAG) laser irradiation on the bone using osteoblast-like cells. Methods: Osteoblast-like Saos 2 cells (5.0×104 cells) were seeded in 24-well plates. 24 hours after being seeded, the cells were subjected to 0.3 W, 0.6 W, and 2.0 W Er: YAG laser irradiation and then allowed to recover for 48 hours. The expression levels of bone metabolism-related factors alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteoprotegerin (OPG) were then evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Results: Saos 2 cells subjected to Er: YAG laser irradiation at 0.3 W, 0.6 W, and 2.0 W showed normal growth. When the Er: YAG laser irradiation and control groups were compared after 48 hours, increases were observed in ALP, BSP, and OPG gene and protein expression in the 2.0 W group. Similar results were obtained in the western blot analysis. Conclusion: These findings suggest that the Er: YAG laser irradiation of osteoblast-like cells is effective for activating bone metabolism factors.

Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon.

In the intestine, mucin 2 (Muc2) forms a network structure and prevents bacterial invasion. Glycans are indispensable for Muc2 barrier function. Among various glycosylation patterns of Muc2, sialylation inhibits bacteria-dependent Muc2 degradation. However, the mechanisms by which Muc2 creates the network structure and sialylation prevents mucin degradation remain unknown. Here, by focusing on two glycosyltransferases, St6 N-acetylgalactosaminide α-2,6-sialyltransferase 6 (St6galnac6) and ß-1,3-galactosyltransferase 5 (B3galt5), mediating the generation of desialylated glycans, we show that sialylation forms the network structure of Muc2 by providing negative charge and hydrophilicity. The colonic mucus of mice lacking St6galnac6 and B3galt5 was less sialylated, thinner, and more permeable to microbiota, resulting in high susceptibility to intestinal inflammation. Mice with a B3galt5 mutation associated with inflammatory bowel disease (IBD) also showed the loss of desialylated glycans of mucus and the high susceptibility to intestinal inflammation, suggesting that the reduced sialylation of Muc2 is associated with the pathogenesis of IBD. In mucins of mice with reduced sialylation, negative charge was reduced, the network structure was disturbed, and many bacteria invaded. Thus, sialylation mediates the negative charging of Muc2 and facilitates the formation of the mucin network structure, thereby inhibiting bacterial invasion in the colon to maintain gut homeostasis.

Organized Hematoma after Intra-Arterial Chemoradiotherapy for Maxillary Sinus Cancer: A Case Report.

An organized hematoma (OH) is a relatively rare benign lesion of the paranasal sinuses. Traditionally, it has been reported to occur following trauma, surgery, and sinus hemorrhagic lesions and in various bleeding predispositions. OHs are sometimes difficult to differentiate from malignancy because of the similar clinical symptoms and bone destruction. It is especially difficult when OHs occur in the same location as the primary tumor after treatment of a malignant tumor. In this paper, we report two cases of OH that occurred after intra-arterial chemoradiotherapy (IACRT) for maxillary sinus cancer. In one case, FDG accumulation was found in PET/CT and suspected to be a cancer recurrence. However, the postoperative pathology showed no malignant findings. This suggests that OH may show accumulation on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). In both cases, bleeding from the maxillary sinus continued after surgery. In one case, recurrence was observed, and in the other, nasal irrigation prevented the pooling of blood in the maxillary sinus, and no recurrence was observed. These cases suggest that OH after IACRT may easily recur because the bleeding continues even after surgery. In such cases, nasal irrigation or preoperative embolization may be helpful to avoid recurrence.

Effects of Human Deciduous Dental Pulp-Derived Mesenchymal Stem Cell-Derived Conditioned Medium on the Metabolism of HUVECs, Osteoblasts, and BMSCs.

In this study, we assessed the effects of human deciduous dental pulp-derived mesenchymal stem cell-derived conditioned medium (SHED-CM) on the properties of various cell types. The effects of vascular endothelial growth factor (VEGF) in SHED-CM on the luminal architecture, proliferative ability, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) were determined. We also investigated the effects of SHED-CM on the proliferation of human-bone-marrow mesenchymal stem cells (hBMSCs) and mouse calvarial osteoblastic cells (MC3T3-E1) as well as the expression of ALP, OCN, and RUNX2. The protein levels of ALP were examined using Western blot analysis. VEGF blockade in SHED-CM suppressed the proliferative ability and angiogenic potential of HUVECs, indicating that VEGF in SHED-CM contributes to angiogenesis. The culturing of hBMSCs and MC3T3-E1 cells with SHED-CM accelerated cell growth and enhanced mRNA expression of bone differentiation markers. The addition of SHED-CM enhanced ALP protein expression in hBMSCs and MT3T3-E1 cells compared with that of the 0% FBS group. Furthermore, SHED-CM promoted the metabolism of HUVECs, MC3T3-E1 cells, and hBMSCs. These findings indicate the potential benefits of SHED-CM in bone tissue regeneration.

Co-Treatment with Steroid and Dupilumab for Eosinophilic Chronic Rhinosinusitis after Eosinophilic Pneumonitis Caused by Dupilumab.

Eosinophilic chronic rhinosinusitis (ECRS) is a Type 2 inflammatory disease that manifests as chronic inflammation of the paranasal sinus. IL-4/IL-13 receptor monoclonal antibodies (dupilumab) to suppress Type 2 inflammation have become a good treatment option for patients who are refractory to surgery. Most patients respond normally, although significant side effects such as eosinophilic pneumonia may occur, requiring discontinuation of dupilumab. Here, we present a case in which dupilumab administration caused a side-effect of eosinophilic pneumonia. A 65-year-old woman presented with nasal obstruction and olfactory dysfunction due to a nasal polyp. Her symptoms temporarily improved with dupilumab; however, dupilumab was discontinued due to eosinophilic pneumonia. Discontinuation of dupilumab resulted in the rapid resolution of eosinophilic pneumonia and reappearance of nasal polyps. We, therefore, resumed dupilumab treatment in combination with low-dose steroids; eosinophilic pneumonia did not flare up, and the nasal polyps shrank steadily. There is no established treatment strategy in cases where a side effect of eosinophilic pneumonia arises while treating ECRS with dupilumab. Based on the described case, we recommend that a combination of a low-dose steroids and dupilumab be considered as a treatment option to counter the side-effect of eosinophilic pneumonia induced by dupilumab alone.

A Case of Endonasal Endoscopic Surgery for Intraorbital Metastasis of Gastric Ring Cell Carcinoma.

Gastric signet ring cell carcinoma has well-known metastatic features, including peritoneal dissemination and carcinomatous lymphangitis of the lung, but no intraorbital metastases were reported previously. A woman in her 60s developed left eye pain, sudden vision loss, and headache 12 years after gastric cancer treatment. Symptoms did not improve despite steroid pulses. Craniotomy showed no malignant findings. The patient was referred to our department for symptomatic relief and biopsy due to the lack of a definitive diagnosis and no improvement in her ocular pain. Endonasal endoscopic surgery was performed for diagnostic purposes and to relieve symptoms through orbital decompression. Preoperative computed tomography examination revealed a tumor at the left medial orbit, extending to the orbital apex. Orbital decompression through the open left medial orbital wall was performed with biopsy of the intraorbital tumor. Pathological findings were consistent with metastatic signet ring cell carcinoma. Pain and subjective improvement of visual acuity were noted the day after surgery. Twelve months postoperatively, diplopia remains, but there has been no worsening of symptoms.

Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan.

OBJECTIVE: This study aimed to assess the health-related QoL (HR-QoL) of patients with hereditary hemorrhagic telangiectasia (HHT), with emphasis on the role/social aspects, and validate the Japanese version of the epistaxis severity score (ESS) in these patients. METHODS: The Japanese version of the ESS was created through forward and reverse translation, and consultation with the original author. A validation analysis was performed by comparing ESS severity with the invasiveness of previous treatments for epistaxis and assessing the correlation between the ESS and HR-QoL. Medical history forms, ESS questionnaires, and the Medical Outcomes Study Short Form 36 (SF-36) were distributed to participants with HHT in August 2020. The relation between the ESS and summary scores of SF-36 was assessed by performing analysis of variance and Spearman's correlation. RESULTS: In total, 73 participants were included in this study. The average ESS was 5.02; there were mild (32.9%), moderate (45.2%), and severe (21.9%) epistaxis groups. Patients with higher ESS received a significantly more invasive treatment (Fisher's exact test, p < 0.05). The ESS was also negatively correlated with the physical component score (PCS) (r = -0.489, p < 0.001). Comorbid liver and gastrointestinal arteriovenous malformations significantly reduced the PCS (p < 0.05). Multiple regression analysis revealed that the ESS was a significant variable (p < 0.01). The role/social component score was significantly lower in the severe ESS group than in the mild or moderate group. CONCLUSION: The Japanese version of the ESS was considered valid and may be useful as an outcome measure of future HHT-associated epistaxis trials in Japan.