CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively.

INTRODUCTION: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear. METHODS: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed. RESULTS: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively. CONCLUSIONS: Our results suggested that CD69+ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

Metastasis of Primary Cutaneous Adenoid Cystic Carcinoma to the Nasal Septum after 17 years: A Case Report.

Primary cutaneous adenoid cystic carcinoma (PCACC) is extremely rare, and although distant metastasis has been reported, to date, there are no reports regarding metastasis to the nasal septum. We report a rare case of PCACC that metastasized to the nasal septum 17 years after the first surgery in a 59-year-old woman. She initially presented with a mass under the skin of her left mammary papilla. After a biopsy revealed the presence of an adenoid cystic carcinoma, the tumor was excised and definitively diagnosed as a PCACC. Five years after surgery, the patient presented with left lung metastasis and underwent a partial resection of the left lung. However, 8 years after this procedure, the patient had to undergo a partial resection of the right lung because of right lung metastasis. Four years thereafter, the patient presented with nasal septal metastasis. The tumor was excised successfully using a combined technique integrating intranasal and extranasal approaches. The patient is currently undergoing regular follow-up tests. Thus, in such cases, lifelong follow-up is necessary while checking for both distant metastasis and instances of local recurrence.

Two cases of glottic closure for refractory aspiration pneumonia after vertical partial laryngectomy.

Vertical partial laryngectomy is a well-established surgical procedure for early glottic cancers with acceptable functional and oncological outcomes. However, on a long-term basis, aspiration might be a serious problem with aging. Here we presented two cases of refractory aspiration pneumonia after vertical laryngectomy. Case 1: A 76-year old gentleman with a past history of malignant lymphoma treated by chemotherapy and radiotherapy had glottic cancer, which was treated by repeated vertical partial laryngectomies. Although glottic caner had been well controlled, he started to suffer from refractory aspiration pneumonia. Since his cervical skin was very thin and hard and his general condition was poor, we employed modified Kano's method for glottic closure. Case 2: A 87-year old Japanese male had a past history of glottic cancer treated by radiotherapy and vertical partial laryngectomy. He was repeatedly hospitalized for severe aspiration pneumonia. At the age of 87, he had second primary oropharyngeal cancer. Kano's method was simultaneously performed at the time of resection of oropharyngeal cancer. Postoperative courses were uneventful without sign of leakage in both cases. The patients started oral intake 2 weeks after the surgery. They have been alive without aspiration pneumonia and takes normal diet.

Synthesis and activity characteristics of visible light responsive polymer photocatalyst system with a styrene block copolymer containing TiO2 gel.

A polymer photocatalyst system was synthesized using a poly(styrene-block-acrylic acid) (PS-b-PAA) containing TiO2 gel without calcination, and its activity characteristics were assessed with methylene blue (MB) photodegradation test in water under visible light irradiation. The initial photodegradation activity was controllable by the polymer chain length and PAA/PS molar ratio. The longer polymer chain length provoked the activity decrease by macromolecular crowding effect. The lower molar ratio did an increase in the photocatalytic surface area by generation of a large number of anatase TiO2 crystal nuclei, leading to the activity increase. The copper phthalocyanine (CuPc) loading remarkably improved the activity. A higher active site was formed on the interface and showed good recycling performance.

Rebamipide reduces amyloid-ß 1-42 (Aß42) production and ameliorates Aß43-lowered cell viability in cultured SH-SY5Y human neuroblastoma cells.

Amyloid-beta (Aß) peptides, Aß 1-42 (Aß42) and Aß43, in particular, have been implicated in the pathophysiology of neurodegenerative disease such as Alzheimer's disease (AD). Rebamipide (REB), a gastrointestinal protective drug, can cross the blood-brain barrier after oral administration; however, the effects of REB on neuronal cells have not yet been reported. In this study, we investigated the effects of REB on Aß43-induced cytotoxicity (monomers, 10µM) in cultured SH-SY5Y human neuroblastoma cells. Addition of REB (10-1000nM) into the media partially ameliorated the reduced cell viability observed after Aß43 treatment, which was determined by the MTT assay. REB reduced the levels of intracellular Aß oligomers (100-150kDa) that were formed from the exogenous addition of Aß43 monomers. In addition, REB (30nM) reduced endogenous Aß42 secretion, which was analyzed by the enzyme-linked immunosorbent assay. Furthermore, REB enhanced the expression of tumor necrosis factor-α-converting enzyme/a disintegrin and metalloproteinase-17, neprilysin, matrix-metalloproteinase-14 (MMP-14)/membrane type-1 MMP, cyclooxygenase-2, and sirtuin 1, even in cells challenged with Aß43. These results suggest that REB improves the cell viability by inducing genes that regulate Aß levels and also genes that are cytoprotective. The secondary use of REB may have potential in the prevention of Aß-mediated diseases, particularly AD.