Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

Refractory pseudocyst of auricle treated with surgical deroofing and tie-over dressing

( Won Ku Lee ),( Jeong Min Kim ),( Gun Wook Kim ),( Je Ho Mun ),( Margaret Song ),( Hyun Chang Ko ),( Byung Soo Kim ),( Moon Bum Kim ),( Hoon Soo Kim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Pseudocyst of the auricle (PCA) is characterized by asymptomatic dome shaped cystic swelling on the anterior surface of the auricle and caused by an intracartilaginous accumulation of viscous fluid. Despite various therapeutic approaches, it relapses frequently. A 66-year-old man presented with a 2-month history of an asymptomatic nodule on the right ear. Physical examination revealed a skin colored, fluctuant swelling on the scaphoid. Needle aspiration of the swelling yielded approximately 1ml of yellowish viscous fluid. With the diagnosis of PCA, sclerotherapy with sodium tetradecyl sulfate and minocycline had been performed, but the swelling appeared within few days after each attempt. Then, we tried multiple holing with 1mm punch biopsies and pressure dressing, however, the fluctuant swelling recurred. And so, we finally did surgical deroofing and tie-over dressing. The procedure was composed of resection of the anterior cartilaginous leaflet of the cyst and repositioning of the overlying skin flap followed by tie-over dressing. The lesion disappeared with complete adhesion between the skin and the cartilage after 1 week. The lesion has not recurred during 10 months of follow-up. We suggest that surgical deroofing followed by tie-over dressing is excellent surgical option of PCA as it is known with very less rate of recurrence, gives a cosmetically acceptable result, and can be easily done by dermatologists.

Genipin inhibits allergic responses in ovalbumin-induced asthmatic mice

Ko, Je-Won,Shin, Na-Rae,Park, Sung-Hyeuk,Cho, Young-Kwon,Kim, Jong-Choon,Seo, Chang-Seob,Shin, In-Sik ELSEVIER 2017 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.53 No.-

<P><B>Abstract</B></P> <P>Genipin is a natural compound isolated from the fruit of <I>Gardenia jasminoides</I> with various pharmacological effects. In this study, we investigated whether genipin effectively alleviates allergic responses in a murine model of ovalbumin (OVA)-induced asthma. The mice were administered an intraperitoneal injection of OVA on day 0 and 14 to boost the immune response; genipin was then administered from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was determined on day 24 by plethysmography. Genipin significantly reduced the inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic mice. In histology, genipin significantly decreased airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA-induced increases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic mice. Overall, genipin effectively alleviated the asthmatic inflammatory response in an OVA-induced asthmatic model. Therefore, our results suggest that genipin has therapeutic potential for treating asthma.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Effects of genipin on ovalbumin (OVA)-induced asthmatic mice </LI> <LI> Genipin decreased airway hyperresponsiveness and eosinophilia in asthmatic mice </LI> <LI> Genipin reduced IL-5, IL-13 and OVA-specific IgE in asthmatic mice </LI> <LI> Genipin suppressed airway inflammation and mucus production in asthmatic mice </LI> <LI> Genipin inhibited iNOS, COX-2 and MMP-9 in lung tissue from asthmatic mice </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

P050 : Dermoscopic patterns of m alignant melanomas on the trunk and extremities in Koreans

( Je Ho Mun ),( Woo Il Kim ),( Gun Wook Kim ),( Hyun Ho Cho ),( Won Jeong Kim ),( Margaret Song ),( Hoon Soo Kim ),( Hyun Chang Ko ),( Byung Soo Kim ),( Moon Bum Kim ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Dermoscopy has been proven to increase diagnostic accuracy of malignant melanomas. However, dermoscopic features of melanomas in Asians have been scarcely reported. Objectives: To investigate dermoscopic patterns and evaluate diagnostic algorithmic approach in Korean patients with melanomas in trunk and extremities. Methods: Dermoscopic evaluation of histopathologically confirmed melanomas at 2 university hospitals from 2007 to 2014 was performed. Dermoscopic scores were evaluated using various dermoscopic algorithmic methods. Results: Sixteen patients with 16 primary melanomas and 5 patients with 15 metastatic melanomas were included. In primary melanomas, several dermoscopic melanoma-associated features were found: blue-white veil (76%), blotches (62%), atypical dots/globules (52%), ulcer (48%), atypical pigment network (43%), irregular peripheral streaks (43%), atypical vessels (38%), shiny white lines (29%), and regression (10%). Mean scores of 7-point checklist, revised 7-point checklist, 3-point checklist, ABCD rule, and CASH algorithm were 6.3, 4.1, 2.6, 7.6, and 10.9. In metastatic melanomas, the algorithmic approaches were not accurate as the mean scores were 1.7, 0.9, 0.8, 2.0, 4.1. Conclusion: Dermoscopy can be useful in diagnosingmalignant melanomas in trunk and extremities in Koreans. Dermoscopic algorithmic approaches were useful in detecting primary melanomas; however, they were not precise in identifying metastatic melanomas.

Inhibitory effects of Pycnogenol®, a pine bark extract, in a rat model of testosterone propionate-induced benign prostatic hyperplasia

Ko, Je-Won,Park, So-Won,Shin, Na-Rae,Kim, Woong-Il,Kim, Jong-Choon,Shin, In-Sik,Shin, Dong-Ho Korean Association for Laboratory Animal Science 2018 Laboratory Animal Research Vol.34 No.3

<P>Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.</P>

Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho

Ko, Je-Won,Shin, Na-Rae,Jung, Tae-Yang,Shin, In-Sik,Moon, Changjong,Kim, Sung-Ho,Lee, In-Chul,Kim, Sung-Hwan,Yun, Won-Kee,Kim, Hyoung-Chin,Kim, Jong-Choon Elsevier 2019 Food and chemical toxicology Vol.129 No.-

<P><B>Abstract</B></P> <P>This study investigated the protective effects of melatonin (MT) against cisplatin (CP)-induced acute kidney injury in rats as well as its possible mechanism of action associated with anti-aging protein Klotho. The following four experimental groups were evaluated: vehicle control, CP (7 mg/kg), CP&MT20 (20 mg/kg/day), and CP&MT40 (40 mg/kg/day). The concomitant administration of MT significantly ameliorated CP-induced acute kidney injury in rats, as evidenced by increased kidney weight, increased serum levels of blood urea nitrogen and creatinine, and increased incidence of histopathological alterations with renal tubular cell apoptosis. In addition, MT treatment protected kidney tissue against oxidative damages and significantly upregulated the expression level of Klotho decreased by CP treatment, resulting in reduced phosphorylation of protein kinase B (AKT) and forkhead box O (FOXO) as well as reduced expression levels of B-cell lymphoma 2-associated X protein (Bax) and caspase-3. MT not only partially regulated oxidative stress via AKT/FOXO signaling, but also reduced apoptosis caused by CP by inhibiting the Bax/caspase-3 pathway. Our results indicated that MT could prevent acute kidney injury induced by CP in rats, presumably through upregulating the expression of Klotho, resulting in elevated anti-oxidant and anti-apoptotic properties.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Melatonin (MT) attenuated acute kidney injury induced by cisplatin (CP). </LI> <LI> MT upregulated the expression level of Klotho decreased by CP treatment. </LI> <LI> Upregulated Klotho attenuated oxidative stress and apoptosis induced by CP. </LI> </UL> </P>

P212 : The impact of Vitamin D seems to be overestimated in some dermatoses

( Won Jeong Kim ),( Min Young Park ),( Gun Wook Kim ),( Hyun Ho Jo ),( Je Ho Mun ),( Margaret Song ),( Hoon Soo Kim ),( Hyun Chang Ko ),( Byung Soo Kim ),( Moon Bum Kim ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Deficiency of vitamin D is reported as an important associated factor of various dermatoses such as atopic dermatitis, psoriasis, urticaria, and skin cancers in these days. However, the association between them is disputable and has not been clarified. Objectives: To evaluate the status of serum 25-hydroxyvitamin D in patients with psoriasis and chronic urticaria, and the relationship between vitamin D levels and disease activity compared with sex and age matched healthy control. Methods: A cross-sectional study of 34 patients with psoriasis, 73 patients with chronic idiopathic urticaria and sex and age matched healthy controls was conducted. An objective severity scoring of psoriasis (PASI) and urticaria (UAS) and a serum 25-hydroxyvitamin D level was measured for each subject. Results: Serum 25-hydroxyvitamin D levels in patients with psoriasis were not significantly lower than healthy control (P>0.05). The patients with chronic idiopathic urticaria also showed no significant differences compared with control subjects. Furthermore, no significant inverse correlation was found between disease severity and serum 25-hydroxyvitamin D level in both psoriasis and chronic idiopathic urticaria patients (P>0.05). Conclusion: Deficiency of vitamin D in patients with psoriasis and chronic idiopathic urticaria was not common than healthy control. The impact of vitamin D in these dermatoses seems to be overestimated and needs more study to prove its real association.

Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling

Ko, Je-Won,Shin, Na-Rae,Park, Sung-Hyeuk,Kim, Joong-Sun,Cho, Young-Kwon,Kim, Jong-Choon,Shin, In-Sik,Shin, Dong-Ho Korean Association for Laboratory Animal Science 2017 Laboratory Animal Research Vol.33 No.2

<P>Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.</P>

Acetaminophen-induced nephrotoxicity via oxidative stress and inflammation: protective role of diallyl disulfide by inhibiting CYP2E1-medaited bioactivation and NF-κB pathway

Je-Won Ko,In-Chul Lee,Suk-Kyu Koh,Changjong Moon,Sung-Ho Kim,Jong-Choon Kim 한국실험동물학회 2014 한국실험동물학회 학술발표대회 논문집 Vol.2014 No.8

Silica dioxide nanoparticles aggravate airway inflammation in asthmatic mice model via NLRP3 inflammsome activation

Je-Won Ko,Na-Rae Shin,In-Sik Shin,Jong-Choon Kim 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.1