Search

Background and aims Oxidative stress contributes to development of diabetic nephropathy. We implicated SH3YL1 in oxidative stress-induced inflammation and examined whether SH3YL1 could be used as a new biomarker of diabetic nephropathy. Methods and results In this study, we investigated the relationship between plasma level of SH3YL1 and diabetic nephropathy in patients with type 2 diabetes. In addition, we examined the physiological role of SH3YL1 in db/db mice and cultured podocytes. Plasma SH3YL1 concentration was significantly higher in patients with diabetes than in controls, even in normoalbuminuric patients, and was markedly increased in the macroalbuminuria group. Plasma SH3YL1 level was positively correlated with systolic blood pressure, HOMA-IR, postprandial blood glucose, plasma level of retinol binding protein 4 (RBP 4), and urinary albumin excretion (UAE) and was inversely correlated with BMI. Regression analysis showed that plasma level of RBP 4, UAE, and BMI were the only independent determinants of plasma SH3YL1 concentration. In db/db mice, plasma and renal SH3YL1 levels were significantly increased in mice with diabetes compared with control mice. In cultured podocytes, high glucose and angiotensin II stimuli markedly increased SH3YL1 synthesis. Conclusion These findings suggest that plasma level of SH3YL1 offers a promising new biomarker for diabetic nephropathy.

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H2O2), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

Central odontogenic fibroma (COF) is defined as a fibroblastic odontogenic tumor characterized by varying density of the tooth epithelium. It is an extremely rare benign neoplasm that occurs in the maxilla and the mandible; only a few reports of COF are available in the literature. Diagnosis of the lesion based only on the radiological features of COF is difficult due to variation in the findings regarding this condition. This report describes 2 clinical cases of middle-aged women with COF. Clinical examination revealed palatal mucosal depression; additionally, oral examination, as well as panoramic radiographs, intraoral radiographs, and computed tomography scans, revealed severe root resorption. This report highlights the clinical and radiological imaging features of COF, with the goal of enabling straightforward differential diagnosis of the lesion by the clinician and thereby appropriate treatment of the patient.

Acantholytic squamous cell carcinoma (ASCC) is an uncommon, histopathologically distinct variant of squamous cell carcinoma. ASCC commonly occurs in areas of skin exposed to sunlight and has only rarely been seen on mucosal surfaces such as the oral cavity. Although the World Health Organization has defined ASCC as an original entity, the imaging findings of ASCC have not been adequately described. We herein report a case of ASCC occurring in the oral mucosa with emphasis on the findings of several imaging studies: panoramic radiography, intraoral radiography, contrast-enhanced computed tomography, magnetic resonance imaging, and fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography.

The aim of this study was to present an optimal diagnostic protocol by comparing and analyzing a conventional examination and the quantitative light-induced fluorescence (QLF) technique. Selected were 297 teeth of 153 patients to take QLF images and bitewing radiographs. Occlusal dental caries, proximal dental caries and cracks were evaluated and scored using QLF, X-ray and/or visual criteria. The sensitivity, specificity, and area under the curve (AUC) of a receiver operating characteristic analysis were calculated. Two fluorescence parameters (|ΔFmax| and ΔRmax) were utilized to evaluate the fluorescence pattern according to the severity of lesions based on QLF or X-ray criteria. QLF showed higher scores for detecting occlusal dental caries and cracks than the conventional method. ΔRmax increased more clearly than ΔFmax did with occlusal dental caries. The |ΔFmax| values of occlusal dental caries, proximal dental caries and cracks showed good AUC levels (0.84, 0.81 and 0.83, respectively). The ΔRmax of occlusal dental caries showed the highest AUC (0.91) and the ΔRmax of proximal dental caries showed a fail level (0.59) compared to bitewing radiographs. The QLF image could visualize and estimate the degree of occlusal dental caries or cracks. Consequently, the QLF technique may be an adjunct tool to conventional methods for the detection of occlusal caries and peripheral cracks.

Summary: Cytosolic proteins are required for regulation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) isozymes. Here we show that Src homology 3 (SH3) domain-containing YSC84-like 1 (SH3YL1), as a Nox4 cytosolic regulator, mediates lipopolysaccharide (LPS)-induced H2O2 generation, leading to acute kidney injury. The SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins (SYLF) region and SH3 domain of SH3YL1 contribute to formation of a complex with Nox4-p22phox. Interaction of p22phox with SH3YL1 is triggered by LPS, and the complex induces H2O2 generation and pro-inflammatory cytokine expression in mouse tubular epithelial cells. After LPS injection, SH3YL1 knockout mice show lower levels of acute kidney injury biomarkers, decreased secretion of pro-inflammatory cytokines, decreased infiltration of macrophages, and reduced tubular damage compared with wild-type (WT) mice. The results strongly suggest that SH3YL1 is involved in renal failure in LPS-induced acute kidney injury (AKI) mice. We demonstrate that formation of a ternary complex of p22phox-SH3YL1-Nox4, leading to H2O2 generation, induces severe renal failure in the LPS-induced AKI model.

Oculofaciocardiodental (OFCD) syndrome is a rare genetic disease, first reported by Hayward in 1980. This syndrome presents with various ocular, facial, cardiac, and dental symptoms, including congenital cataract, dysmorphic facial features, congenital heart disease, and enlarged roots, respectively. The most important criteria for the diagnosis of OFCD syndrome are dental abnormalities, especially extreme elongation of canine roots. Here, we report detailed analysis of the dentofacial region, as well as ocular, facial, cardiac, and dental findings in a female with OFCD syndrome. To the best of our knowledge, the patient in this case is the first such patient reported in South Korea.

목적: 본 연구는 천연성분 Ectoin의 피부 보습, 모공, 피부색, pH 등에 미치는 전반적인 효과를 규명하고자 하였다. 방법: Ectoin 분말 추출 시료는 클렌징폼, 토너, 크림, 로션으로 제조하여 실험군과 대조군에게 매일 아침, 저녁으로 2회씩 4주간 안면에 사용하 도록 하였다. 수집된 자료는 통계 프로그램 SPSS 24.0o fr Windows를 이용하여 분석하였다. 결과: 유분의 경우, 대조군은 T존과 U 존 모두에서 유분 증가가 나타난 반면, 실험군은 T존에서는 유분이 감소하였고, U존에서는 유분이 증가하였다. 수분의 경우, 대조 군과 실험군 모두 수분이 증가했지만, 모든 항목에서 대조군보다 실험군의 수분 함유량 증가가 크게 나타났으며, 실험군은 턱을 제 외한 모든 항목에서 수분이 유의하게 증가하였다. Transepidermal water loss (TEWL)의 경우, 대조군은 턱을 제외한 모든 항목에 서 TEWL이 증가했고, 실험군은 모든 항목에서 TEWL의 감소를 나타냈다. 모공의 경우, 대조군에서는 모공의 증가와 감소가 교차 하는 경향을 나타냈지만, 실험군에서는 모든 항목에서 모공의 감소를 나타냈다. pH는 사전, 사후 모두 평균 4.5-6.5에 해당하는 피 부의 정상 pH 범주를 보였으며, 유의한 변화는 나타나지 않았다. 피부색의 경우, 대조군의 멜라닌은 증가와 감소가 교차하는 반면, 실험군의 멜라닌은 좌우 모두에서 유의한 감소를 나타냈고, 홍반은 대조군과 실험군 모두 감소를 나타냈으나, 실험군의 홍반이 대 조군에 비해 크게 감소하였다. 결론: 본 실험결과를 통해 천연성분인 Ectoin이 함유된 크림이 피부 보습 및 수분에 미치는 긍정적인 영향을 객관화, 수치화하였고, 이를 통해 화장품에 들어가는 천연 보습 원료로서의 가능성을 확인하였다

Purpose This study was conducted to evaluate the accuracy of linear measurements of 3-dimensional (3D) images generated by cone-beam computed tomography (CBCT) and facial scanning systems, and to assess the effect of scanning parameters, such as CBCT exposure settings, on image quality. Materials and Methods CBCT and facial scanning images of an anthropomorphic phantom showing 13 soft-tissue anatomical landmarks were used in the study. The distances between the anatomical landmarks on the phantom were measured to obtain a reference for evaluating the accuracy of the 3D facial soft-tissue images. The distances between the 3D image landmarks were measured using a 3D distance measurement tool. The effect of scanning parameters on CBCT image quality was evaluated by visually comparing images acquired under different exposure conditions, but at a constant threshold. Results Comparison of the repeated direct phantom and image-based measurements revealed good reproducibility. There were no significant differences between the direct phantom and image-based measurements of the CBCT surface volume-rendered images. Five of the 15 measurements of the 3D facial scans were found to be significantly different from their corresponding direct phantom measurements (P

Osseointegrated implants are now commonplace in contemporary dentistry. However, a number of complications can occur around dental implants, including peri-implantitis, maxillary sinusitis, osteomyelitis, and neoplasms. There have been several reports of a malignant neoplasm occurring adjacent to a dental implant. In this report, we describe 2 such cases. One case was that of a 75-year-old man with no previous history of malignant disease who developed a solitary plasmacytoma around a dental implant in the left posterior mandible, and the other was that of a 43-year-old man who was diagnosed with squamous cell carcinoma adjacent to a dental implant in the right posterior mandible. Our experiences with these 2 cases suggest the possibility of a relationship between implant treatment and an inflammatory cofactor that might increase the risk of development of a malignant neoplasm.

BackgroundPredicting how long a patient with far advanced cancer has to live is a significant part of hospice and palliative care. Various prognostic models have been developed, but have not been fully compared in South Korea.ObjectivesWe aimed to compare the accuracy of the Prognosis in Palliative Care Study (PiPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) and Objective Prognostic Score (OPS) for patients with far advanced cancer in a palliative care unit in South Korea.MethodsThis prospective study included patients with far advanced cancer who were admitted to a single palliative care unit at the National University Hospital. Variables for calculating the prognostic models were recorded by a palliative care physician. The survival rate was estimated using the Kaplan-Meier method. The sensitivity, specificity, positive predictive value and negative predictive value of each model were calculated.ResultsA total of 160 patients participated. There was a significant difference in survival rates across all groups, each categorised through the five prognostic models. The overall accuracy (OA) of the prognostic models ranged between 54.5% and 77.6%. The OA of clinicians’ predictions of survival ranged between 61.9% and 81.3%.ConclusionThe PiPS, PPI, PaP and OPS were successfully validated in a palliative care unit of South Korea. There was no difference in accuracy between the prognostic models, and OA tended to be lower than in previous studies.

PurposeTo evaluate knowledge of secondhand smoke (SHS) risks, sources of information, and associated factors and behaviors among hospital staff.MethodsWe conducted a cross-sectional survey using a 40-item self-administered questionnaire among 328 employees at a university hospital. The questions on representative diseases related to SHS were used to measure the degree of knowledge of SHS. Multiple regression analysis was used to determine the correlation between SHS knowledge scores and variables.ResultsFemales had better SHS knowledge scores than males, regardless of smoking status (pConclusionSHS knowledge is high among females, when hospital staff are educated about SHS risks, and when they have experienced any SHS exposure-related symptoms or felt uncomfortable when exposed to SHS. SHS risk education is an effective tool to increase SHS knowledge in hospital staff.

All‑trans retinoic acid (ATRA) can protect fibroblasts against ultraviolet (UV)‑induced oxidative damage, however, its underlying molecular mechanism is still unclear. The present study aimed to investigate the role of 3‑hydroxy‑3‑methylglutaryl reductase degradation (Hrd1) in the protective effect of ATRA on human skin fibroblasts exposed to UV. The expression of Hrd1 in human or mice skin was assessed by immunohistochemistry (IHC) staining and western blot analysis. Hrd1 siRNA (si‑Hrd1) and Hrd1 recombinant adenoviruses (Ad‑Hrd1) were used to downregulate and upregulate Hrd1 expression in fibroblasts, respectively. The interaction between Hrd1 and NF‑E2‑related factor 2 (Nrf2) was assessed by co‑immunoprecipitation (co‑IP) and immunofluorescence analysis. The results revealed that Hrd1 expression was increased but Nrf2 expression was decreased in UV‑exposed human skin fibroblasts. In addition, ATRA could reverse the increase of Hrd1 expression induced by UV radiation in vivo and in vitro. ATRA or knockdown of Hrd1 could increase Nrf2 expression in fibroblasts exposed to UV radiation, and Hrd1 could directly interact with Nrf2 in skin fibroblasts. Notably, overexpression of Hrd1 abolished the protective effect of ATRA on the UV‑induced decrease of Nrf2 expression, the production of reactive oxygen species (ROS) and the decrease of cell viability. In conclusion, the present data demonstrated that ATRA protected skin fibroblasts against UV‑induced oxidative damage through inhibition of E3 ligase Hrd1.

Ultrasound (US)-guided salivary gland irrigation is a popular conservative treatment method that improves the success rate and reduces complications of the sialo-irrigation procedure. US is routinely used for evaluation of various salivary gland diseases because of its easy accessibility and absence of ionizing radiation. US also allows dynamic studies with real-time imaging during diagnostic or surgical procedures. However, conventional US images have limitations in salivary duct visualization. Although US images acquired with saline irrigation have improved visualization because of ductal system dilation by the pulling effect, the resultant image quality remains insufficient for diagnosis. Therefore, contrast agents are required during US-guided sialo-irrigation procedures to produce diagnostic image quality. Air bubbles in saline solution have high echogenicity and enhance image quality by acting as a US contrast agent. The aim of this study was to assess the clinical significance of US-guided sialo-irrigation with a saline-air contrast medium, to estimate its diagnostic and treatment efficacy, and to examine the procedure in two patients. In the study, two patients underwent US-guided salivary gland irrigation with air-bubble mixed saline solution. During the procedure, we were able to visualize the salivary gland duct and subsequently irrigate and clean the inside of the duct. As a result, the patients' symptoms were relieved and saline solution mixed with air bubbles was confirmed to be an effective contrast agent.

Purpose This study was performed to investigate the influence of object shape and distance from the center of the image on the volumetric accuracy of cone-beam computed tomography (CBCT) scans, according to different parameters of tube voltage and current. Materials and methods Four geometric objects (cylinder, cube, pyramid, and hexagon) with predefined dimensions were fabricated. The objects consisted of Teflon-perfluoroalkoxy embedded in a hydrocolloid matrix (Dupli-Coe-Loid TM; GC America Inc., Alsip, IL, USA), encased in an acrylic resin cylinder assembly. An Alphard Vega Dental CT system (Asahi Roentgen Ind. Co., Ltd, Kyoto, Japan) was used to acquire CBCT images. OnDemand 3D (CyberMed Inc., Seoul, Korea) software was used for object segmentation and image analysis. The accuracy was expressed by the volume error (VE). The VE was calculated under 3 different exposure settings. The measured volumes of the objects were compared to the true volumes for statistical analysis. Results The mean VE ranged from -4.47% to 2.35%. There was no significant relationship between an object's shape and the VE. A significant correlation was found between the distance of the object to the center of the image and the VE. Tube voltage affected the volume measurements and the VE, but tube current did not. Conclusion The evaluated CBCT device provided satisfactory volume measurements. To assess volume measurements, it might be sufficient to use serial scans with a high resolution, but a low dose. This information may provide useful guidance for assessing volume measurements.

// Guideock Kwon 1, * , Md Jamal Uddin 1, * , Gayoung Lee 1 , Songling Jiang 1 , Ahreum Cho 1 , Jung Hwa Lee 1 , Sae Rom Lee 2 , Yun Soo Bae 2 , Sung Hwan Moon 3 , Soo Jin Lee 3 , Dae Ryong Cha 4 and Hunjoo Ha 1 1 Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea 2 Department of Life Science, Ewha Womans University, Seoul, Korea 3 Aptabio Therapeutics Inc, Yongin-si, Korea 4 Department of Internal Medicine, Division of Nephrology, Korea University, Seoul, Korea * These authors contributed equally to this work Correspondence to: Hunjoo Ha, email: hha@ewha.ac.kr Keywords: APX-115, diabetic kidney disease, mitochondria and peroxisome, oxidative stress, pan-Nox inhibitor Received: March 24, 2017 Accepted: June 05, 2017 Published: June 16, 2017 ABSTRACT NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5-hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury. Diabetes was induced by intraperitoneal injection of STZ at 50 mg/kg/day for 5 days in C57BL/6J mice. APX-115 (60 mg/kg/day) or losartan (1.5 mg/kg/day) was administered orally to diabetic mice for 12 weeks. APX-115 effectively prevented kidney injury such as albuminuria, glomerular hypertrophy, tubular injury, podocyte injury, fibrosis, and inflammation as well as oxidative stress in diabetic mice, similar to losartan. In addition, both APX-115 and losartan treatment effectively inhibited mitochondrial and peroxisomal dysfunction associated with lipid accumulation. Our data suggest that APX-115, a pan-Nox inhibitor, may become a novel therapeutic agent against diabetic kidney disease by maintaining peroxisomal and mitochondrial fitness.

Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol. APX-115 significantly improved insulin resistance in diabetic mice, similar to GKT137831. Oxidative stress as measured by plasma 8-isoprostane level was decreased in the APX-115 group compared with diabetic controls. All lipid profiles, both in plasma and tissues improved with Nox inhibition. APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. APX-115 decreased urinary albumin excretion and preserved creatinine level. In diabetic kidneys, APX-115 significantly improved mesangial expansion, but GKT137831 did not. In addition, F4/80 infiltration in the adipose tissue and kidney decreased with APX-115 treatment. We also found that TGF-β stimulated ROS generation in primary mouse mesangial cells (pMMCs) from wild-type, Nox1 KO, and Duox1 KO mice, but did not induce Nox activity in pMMCs from Nox2 knockout (KO), Nox4 KO, or Duox2 KO mice. These results indicate that activating Nox2, Nox4, or Duox2 in pMMCs is essential for TGF-β-mediated ROS generation. Our findings suggest that APX-115 may be as effective or may provide better protection than the dual Nox1/Nox4 inhibitor, and pan-Nox inhibition with APX-115 might be a promising therapy for diabetic nephropathy.