SOX4 reversibly induces phenotypic changes by suppressing the epithelial marker genes in human keratinocytes.

BACKGROUND: SOX4 is a transcription factor belonging to the SOX (Sry-related High Mobility Group [HMG] box) family and plays a pivotal role in various biological processes at various stages of life. SOX4 is also expressed in the skin in adults and has been reported to be involved in wound healing, tumor formation, and metastasis. METHODS AND RESULTS: In this study, we investigated the role of SOX4 in keratinocyte phenotypic changes. We generated a SOX4-overexpressing keratinocyte cell line that expresses SOX4 in a doxycycline (DOX)-inducible manner. DOX treatment induced a change from a paving stone-like morphology to a spindle-like morphology under microscopic observation. Comprehensive gene analysis by RNA sequencing revealed increased expression of genes related to anatomical morphogenesis and cell differentiation as well as decreased expression of genes related to epithelial formation and keratinization, suggesting that SOX4 induced EMT-like phenotype in keratinocytes. Differentially expressed genes (DEGs) obtained by RNA-seq were confirmed using qRT-PCR. DOX-treated TY-1 SOX4 showed a decrease in the epithelial markers (KRT15, KRT13, KRT5, and CLDN1) and an increase in the mesenchymal marker FN1. Protein expression changes by Western blotting also showed a decrease in the epithelial marker proteins keratin 15, keratin 13, and claudin 1, and an increase in the mesenchymal marker fibronectin. Removal of DOX from DOX-treated cells also restored the epithelial and mesenchymal markers altered by SOX4. CONCLUSION: Our results indicate that SOX4 reversibly induces an EMT-like phenotype in human keratinocytes via suppression of epithelial marker genes.

[Total Arch Replacement using the Frozen Elephant Trunk for Kommerell Diverticulum with Right Aortic Arch:Report of a Case].

A 42-year-old woman with dysphagia was referred to our hospital. Computed tomography (CT) revealed Kommerell diverticulum( KD) associated with right aortic arch( RAA) and aberrant left subclavian artery (ALSCA). We performed total arch replacement (TAR) using a frozen elephant trunk (FET) technique. We ligated ALSCA at the distal portion of the KD after perfusing from a 8 mm tubular graft from left axillar artery. We inserted a FET from the ascending aorta to avoid locating the nonstented portion at the steep-angled site of RAA. Postoperatively dysphagia disappeared and CT scan showed complete exclusion of KD without leakage of the stent graft and successful reconstruction of the arch. The TAR and FET technique is an effective procedure for KD with RAA and ALSCA.

Changes in denture retention with denture adhesives and oral moisturizers for the oral cavity: an in vitro study.

BACKGROUND: It is difficult to maintain complete dentures during meals in place. This in vitro study aimed to assess changes in denture retention between rest and function using denture adhesives and oral moisturizers in an oral cavity model. METHODS: The following test samples were applied between the palatal plate and the edentulous jaw ridge model: denture adhesive, denture adhesive for dry mouth, oral moisturizer, and denture moisturizer. The retentive force was measured under two conditions: at rest while immersed in water and during function with a 2.5-kg load applied. The plate was pulled perpendicular to the occlusal plane and the retentive force was measured using a digital force gauge. RESULTS: Under dry conditions, denture adhesive for dry mouth and oral moisturizer had a significantly higher retentive force than denture adhesive and denture moisturizer. After 30 min of immersion in water, the retentive force of the denture adhesive increased while that of the oral moisturizer decreased. After 30 min of function, the retentive force of the denture adhesive and denture adhesive for dry mouth remained high, while that of the oral moisturizer and denture moisturizer significantly decreased. Between rest and function, the retentive force of the denture adhesive and denture adhesive for dry mouth was high, and that of the oral moisturizer was low. CONCLUSIONS: Immediately after use, denture adhesive for dry mouth exhibited high retentive force, but retention gradually decreased due to its water content.

Eruptive xanthomas in a patient with soft-drink diabetic ketosis and apolipoprotein E4/2.

Soft-drink diabetic ketosis, characterized by acute onset ketosis induced by excessive ingestion of sugar-containing drinks, is often seen in obese, young patients, even with undiagnosed type 2 diabetes. We herein report a 15-year-old obese patient with the apolipoprotein E4/2 phenotype, in whom eruptive xanthomas lead to a diagnosis of soft-drink diabetic ketosis. He developed multiple asymptomatic yellowish papules on the auricles, back, buttocks and the extensor surfaces of the elbows and knees. He initially visited a dermatology clinic and his blood triglyceride and HbA1c levels were found to be 6,490 mg/dL and 16.5%, respectively. He was referred to our hospital for treatment of hyperglycemia and hypertyriglyceridemia. On admission, he had ketonuria and increased blood levels of 3-hydroxybutylate and acetoacetate. He habitually drank 1-3 litters of sweet beverages daily to quench his thirst. Therefore, "soft-drink diabetic ketosis" was diagnosed. Severe hypertriglyceridemia was considered to have been a consequence of impaired insulin action and his apolipoprotein E4/2 phenotype. We treated the diabetic ketosis and hypertriglyceridemia with intensive insulin therapy and a fat-restricted diet. At discharge, he no longer required insulin therapy and his blood glucose levels were controlled with metformin and voglibose. Along with amelioration of the hyperglycemia, triglyceride levels decreased to 247 mg/dL without administration of anti-hyperlipidemia agents. The eruptive xanthoma lesions gradually diminished in size and number and eventually disappeared by 12 months. This case provides an instructive example of eruptive xanthomas serving as a sign of severe dysregulation, not only of lipid, but also glucose, metabolism.

Repeated coil embolization of traumatic basilar artery pseudoaneurysm accompanied by bilateral traumatic internal carotid artery stenosis following severe head injury in a pediatric patient: A case report and literature review.

Background: Few cases of pediatric traumatic intracranial aneurysms (pTICAs) in the posterior circulation involving the basilar artery (BA) following severe head trauma have been reported. Here, we describe a pediatric case of traumatic BA pseudoaneurysm accompanied by bilateral traumatic internal carotid artery (ICA) stenosis following blunt head trauma. Case Description: A 16-year-old boy presented to our emergency department after being hit by a car. The patient was initially diagnosed with multiple skull base fractures underlying traumatic subarachnoid hemorrhage and left acute epidural hematoma. Seven days following emergency craniectomy, magnetic resonance imaging revealed bilateral ICA stenosis, BA stenosis, and BA pseudoaneurysm. We decided to perform coil embolization, resulting in body filling and a volume embolization ratio of 15.7%. Twenty-eight days after coil embolization, digital subtraction angiography revealed aneurysmal rupture. We performed repeated coil embolization, resulting in body filling and a volume embolization ratio of 20.9%. Conclusion: We reported a pediatric case of traumatic BA pseudoaneurysm accompanied by bilateral traumatic ICA stenosis following a severe head injury treated with repeated coil embolization. Considering the risk of further brain injury due to high incidence of rupture, early vascular survey and appropriate treatment may be the most important prognostic factors in pTICAs.

Ustekinumab treatment for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a follicular occlusive inflammatory skin disease that occurs in the axilla, groin, buttocks and vulval region. Control of the intractable inflammation is a primary goal of HS treatments. Benefit of anti-tumor necrosis factor (TNF) antibodies against HS have been reported, and adalimumab has been approved for HS in Europe, the USA and Japan. However, the alternative therapies for anti-TNF antibodies have not been established yet. We experienced a case of HS which developed during the infliximab treatment for Crohn's disease (CD) and was well managed by ustekinumab (UST). We reviewed the articles relating to ustekinumab treatments for HS. Twenty-four HS patients, 16 women and eight men, have been treated with ustekinumab. The average age was 35.7 ± 10.8 years (mean ± SD). All were of Hurley stage II or III. Ten (10/24, 41.6%) had received anti-TNF drugs including infliximab, adalimumab and etanercept prior to UST treatment for HS. Although the initial doses varied from 45 mg s.c. to 390 mg i.v., all cases were treated with 45 or 90 mg s.c. every 8 or 12 weeks at the regular dose, by following the regimen for psoriasis or CD. HS in most of the cases started to improve after 3-5 months of UST initiation, and some achieved complete remission. To our knowledge, our case is the first Asian HS patient improved by UST. Overall, UST is useful for HS and could be an alternative treatment if HS patients do not respond to other medications including anti-TNF drugs.

Pembrolizumab resolves adult ashy dermatosis developing in patients with squamous cell carcinoma of the lung.

Ashy dermatosis is a rare cutaneous disorder of unknown etiology. We describe a case of adult ashy dermatosis developing in a patient with squamous cell carcinoma of the lung, which was resolved by the administration of pembrolizumab in parallel with multiple vitiligo. Interestingly, immunohistochemical staining revealed that lesional skin of the ashy dermatosis contained cytotoxic T cells and programmed death ligand 1 expressing cells. To our knowledge, this is the first case of adult ashy dermatosis resolved by pembrolizumab.

PD-L1-Expressing Radiation-Associated Angiosarcoma after Primary Breast Cancer.

Radiation-associated angiosarcoma (RAAS) is a type of radiation-associated sarcoma (RAS) that develops at the previous field of radiation in breast cancer patients. Although several reports have suggested a poor prognosis for RAAS, the 5-year overall survival of RAAS is better than that of cutaneous angiosarcoma (CAS), suggesting that the prognostic factors of RAAS and CAS might be different, at least in part. In this report, we describe a case of RAAS, and employed immunohistochemical (IHC) staining of PD-L1 and MMP9 as well as periostin, IL-4, and CD163. Interestingly, IHC staining revealed that the RAAS in our case was positive for PD-L1 and negative for MMP9. Moreover, the predominant stromal factor of our case was periostin, suggesting that TAMs in the present case was not immunosuppressive, but an inflammatory subtype. These results might explain, at least in part, the better prognosis of RAAS compared to CAS.