Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Hepatocellular Carcinoma in the Elderly: Clinical Characteristics, Outcomes and Treatment Efficacy, Safety in Older than 75 Years

( Ji Ho Seo ),( Sunmin Kim ),( Eunae Cho ),( Chung Hwan Jun ),( Sun Young Park ),( Sung Bum Cho ),( Chang Hwan Park ),( Hyun Soo Kim ),( Sung Kyu Choi ),( Jong Sun Rew ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) has been increasing because the increase in the longevity of the general population. But there is no proper management based on age stratification in elderly patients. We compared clinical characteristics, outcomes and treatment efficacy, safety between oldest-old (aged more than 85 years), middle-old (aged between 80 and 85 years) and young-old (aged between 75 and 80 years) patients with HCC. Methods: We conducted a retrospective cohort study, from January 2010 to December 2016, at Chonnam National University Hospital. A total of 550 elderly patients whose data included demographics, co-morbidity, etiology of liver disease, presence of cirrhosis, staging of HCC, treatment modality and treatment related adverse event were evaluated retrospectively. Also overall survival was assessed in enrolled patient. Results: Fifty one patients (oldest-old; median 87 years old), 153 patients (middle-old; median 82 years old) and 346 patients (young-old; median 77 years old) were diagnosed with HCC. Both oldest- and middle-old patients, compared to young-old patients had significantly lower rate of alcohol-related disease (13.7% vs 20.9% vs 34.1%, P = 0.001). There were no significant difference in underlying sex, body mass index, presence of co-morbidity, hepatitis C-related disease and stage of HCC. The Child-Pugh class (CPT class A 88.9% vs 84.1% vs 83.6%, CPT class B 11.1% vs 15.9% vs 15.0% and CPT class C 0.0% vs 0.0% vs 1.3%, respectively, P = 0.912) and Model for End Stage Liver Disease score (mean MELD score 7.22±3.34 vs 5.88±3.01 vs 5.77±3.14, P = 0.166) were no significant difference between the patients with active treatment. The modified UICC staging (stage I 5.6% vs 17.1% vs 18.6%, stage II 55.6% vs 46.3% vs 47.3%, Stage III 22.2% vs 24.4% vs 24.8%, Stage IV-A 11.1% vs 6.1% vs 4.9% and Stage IV-B 5.6% vs 6.1% vs 4.4%, respectively, P = 0.826) and Barcelona Clinic Liver Cancer staging (stage 0 5.6% vs 9.8% vs 9.3%, stage A 16.7% vs 17.1% vs 22.1%, stage B 27.8% vs 29.3% vs 24.8%, stage C 50.0% vs 43.9% vs 41.2% and stage D 0.0% vs 0.0% vs 2.7%, respectively, P = 0.878) were no significant difference between the patients with active treatment. Furthermore, there were no difference between the age groups in treatment modality (Surgical resection 0.0% vs 3.3% vs 5.2%, P = 0.166; Radiofrequency ablation 2.0% vs 8.5% vs 11.0%, P=0.113; Transcatheter arterial chemoembolization 21.6% vs 34.6% vs 41.6%, P=0.014; Best supportive care 62.7% vs 40.5% vs 29.2%, P < 0.001), adverse event related treatment (P = 0.731) and disease-free survival days (329 .3±309.1 days vs 271.7 ± 414.2 days vs 357.2 ± 511.6 days, P = 0.336). Multivariate analysis showed that age, performance status, CTP class, MELD score, modified UICC staging, presence of portal vein thrombosis and ruptured HCC are risk factors for mortality. Conclusions: Clinician should make an active treatment in elderly patients with HCC not a age but performance status, liver function and disease status of cancer.

불안 증상을 동반한 신체화 환자의 인지적 특성

나영석,정한용,권영준,이소영,박준호 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.6

Objectives : Assuming that somatization closely interacts with anxiety symptoms, one might speculate that anxiety symptoms will produce the significant differences in development, course and treatment of somatization and the cause of these differences will be elucidated in the cognitive aspect. This study was performed to examine the cognitive characteristics in terms of the somatosensory amplification and the symptom interaction in patients with somatization accompanied by anxiety symptoms. Methods : The following measures were administered to subjects who had a T-score of >60 on somatization subscale of Symptom Checklist-90-Revision (SCL-90-R) : 1) Minnessota Multiphasic Personality Inventory-Korean Version (MMPI-K), 2) Somato-sensory Amplification Scale (SSAS), 3) Symptom Interpretation Questionnaire (SIQ). There was a comparison of differences in the somatosensory amplification and the symptom interpretation between the anxiety group and the non-anxiety group divided by T-score of >60 on the psychasthenia subscale of MMSE-K. Multiple regression analysis was performed to determine the effect of the differences in the somatosensory amplification and the symptom interpretation on age, sex, marital status and level of education between those two groups. Results : There was a greater amplification of sensation in the anxiety group than the non-anxiety group. The former showed a higher level of physical, psychological and catastrophic interpretation than non-anxiety group except with regard to environ-mental interpretation. Somatization was affected by somatosensory amplification and physical interpretation in both groups, as well as psychological interpretation in the anxiety group. Conelusion : Regarding the cognitive aspect, the somatosensory amplification and symptom interpretation were more severely distorted in patients accompanied by anxiety symptoms. These results suggest that a therapeutic approach based on the cognitive charactehstics is essential for the effective management of somatizer.

만성 승모판폐쇄부전증 이환견의 치료 1례

김영실,박정희,신영지,박성준,이영원,최호정,송근호 忠南大學校 獸醫科大學 動物醫科學硏究所 2005 動物醫科學硏究誌 Vol.13 No.-

A 8 years old intact male Shih-tzu dog with respiratory distress was referred to the Veterinary Medical Teaching Hospital of Chungnam National University. The dog also had a history of several episodes of syncope prior to visit. Physical examination revealed tachypnea, panting, mucous membrane of pale and cyanosis. Holosystolic murmur at the left apex region by auscultation, left sided cardiac enlargement by thoracic radiography and mitral regurgitated flow by echocardiography were detected. Clinical signs were improved by treatment of diuretics, ACE inhibitor, bronchodilator and oxygen therapy.

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Lee, Young-Man,Auh, Q-Schick,Lee, Deok-Won,Kim, Jun-Yeol,Jung, Ha-Jin,Lee, Seung-Ho,Kim, Eun-Cheol Hindawi Publishing Corporation 2013 BioMed research international Vol.2013 No.-

<P>Although previous studies have shown that mollugin, a bioactive phytochemical isolated from <I>Rubia cordifolia</I> L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G<SUB>1</SUB> phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-<I><I>κ</I></I>B and NF-<I><I>κ</I></I>B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-<I><I>κ</I></I>B.</P>

민주지산의 수서곤충 군집에 관한 연구

남상호,조영호,박영준,이선영 대전대학교 기초과학연구소 2003 自然科學 Vol.14 No.1

충청북도, 경상북도와 전라북도의 3개 도가 경계를 이루고 있는 민주지산에서 발원한 물한계곡의 수서곤충 군집구조를 조사한 결과 총 5목 17과 29종이 조사되었다. 분류구별 출현양상은 하루살이류가 5과 17종으로 가장 많이 조사되었으며, 현존량 역시 하류살이류가 292개체(48.42%)로 가장 높게 나타났다. 전체 우점종은 두갈래하루살이와 깔따구류로 0.38의 우점도지수를 기록하였다. 종다양도는 제 2지점인 삼도봉 약수터부근에서 2.59로 가장 높게 나타났고, 제 5지점인 황룡사 부근에서 2.00으로 가장 낮게 조사되었다. 전 조사지점별 오수생물계열은 β-중부수성으로 비교적 양호하게 조사되었다. Aquatic insect communities were investigated in a mountain streams of Mt. Minjujisan from May 31 to June 1, 2002. As a result, 29 species of aquatic insects in 17 families and in 5 orders appeared during the study period, the order Ephemeroptera and Plecoptera of which were the most appeared. Ephemeroptera was consisted of 17 species of 5 families and 292 individuals(48.42%) of total individual number. Dominant species was Paraleptophlebia chocorata and the subdominant species was Chironmidae sp.. Dominant species index of Paraleptophlebia chocorata and Chironmidae sp. was 0.38. The highest species diversity index was observed of site 2 as 2.59 and the lowest species diversity index was observed of site 5 as 2.00. Dominance indices ranged between 0.30 and 0.57 while diversity indices between 2.00 and 2.59. In relation to species diversity indicesm, Mt. Minjisan streams were determined as β-saproblty area. In general, all sites of survey area were clean.

忠南 錦山郡 西臺山 一帶의 나비目 昆蟲相

남상호,조영호,장석원,박영준,이선영,나선희 대전대학교 기초과학연구소 2002 自然科學 Vol.13 No.2

충청남도 금산군 서대산 일대의 나비목 곤충상을 조사한 결과 22과 344종 1,936개체가 조사되었다. 이중 밤나방과가 102종 589개체, 자나방과가 67종 440개체로 이 2과가 전체의 50%이상을 차지하였다. 자나방과의 두줄가지나방은 1,936 개체중 85개체가 채집되어 4.4%의 가장 높은 우점도를 나타냈다. 월별 우점종은 4월 노랑무늬물결자나방, 5월 별박이세줄나비, 6월 목도리불나방, 7월 청백무늬밤나방, 8월 두줄가지나방, 9월은 털뿔가지나방이 조사되었다. 월별 종다양도는 4월 2.95, 5월 3.37, 6월 4.63, 7월 4.62, 8월 4.23, 9월은 2.97이었으며, 평균 종다양도는 3.80으로 서대산 일대의 나비목 곤충상은 비교적 양호한 편으로 조사되었다. This study was carried out to investigate Lepidopterous insect fauna from Mt. Seodae in Geumsan-gun, Chungnam. The samples were collected from April to September in 2001. Total 1,936 individuals belonging to 344 species, 22 families of Lepidoptera were collected. The sum of individuals belonging to Noctuidae and Geometridae exceed 50% of the collected samples in that Noctuidae was consisted of 102 species 589 individuals and Geometridae was 67 species 440 individuals. The dominant species in surveyed area was Rikiosatoa grisea of Geometridae, the dominant species by month were Idiotephria amelia in April, Neptis pryeri in May, Paraona staudinger in June, Ercheia niveostrigata in July, Rikiosatoa grisea in August and Alcis angulifera in September respectively. Species diversity indices by month were 2.93 in April, 3.37 in May, 4.63 in June, 4.62 in July, 4.23 in August and 2.97 in September respectively. Mean species diversity index was 3.80.

Synthesis and photophysical study of heteroleptic iridium(III) complex

Kim, Jun Ho,Kim, Young Sik Research Institute of Science and Technology HONGI 2005 Hongik Journal of Science and Technology Vol.9 No.-

The synthesis and photophysical study of efficient phosphorescent iridium(III) complexes having two different (CˆN) ligands are reported. In order to improve the luminescence efficiency by avoiding triplettriplet (T-T) annihilation, the iridium complex, Ir(ppy)_(2)(dpq), is designed and prepared where ppy and dpq represent 2-phenylpyridine and 2,4-diphenylquinoline, respectively. Two ppy ligands and a dpq ligand act as a source of energy supply. Since Ir(ppy)_(3) and Ir(dpq)_(3)can be placed in the metal-to-ligand charge transfer (MLCT) excited state, they absorb light effectively. When Ir(ppy)_(2)(dpq) is placed in excited state, the excitation energy is not quenched or deactivated but quickly intramolecular transferred from two ppy ligands to one luminescent dpq ligand. This is because the triplet energy level of ppy is higher than that of dpq and light is emitted from dpq ligand in the end. Thus, Ir(ppy)_(2)(dpq) shows strong photoluminescence from dpq ligand. To analyze luminescent mechanism, we calculated these complexes having two different ligand sets theoretically by using computational method.

Increased 11β-hydroxysteroid dehydrogenase type 1 contributes to barrier dysfunction in aged skin

( Beom Jun Kim ),( Noo Ri Lee ),( Chung Hyeok Lee ),( Young Bin Lee ),( Solam Lee ),( Hyun Jee Hwang ),( Eunjung Kim ),( Eung Ho Choi ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone into cortisol, an active form, and is expressed by several tissues including the skin. Excessive active glucocorticoid (GC) deteriorates skin barrier function. Objectives: To find out if 11β-HSD1 affects on the barrier function in aged skin. Methods: We have performed human and in vivo studies. We measured cortisol in stratum corneum (SC) and oral epithelium of the elderly and young. Hairless mice were used for 11β-HSD1 immunohistochemistry staining of skin and measuring skin barrier function and serum cytokines. 11β-HSD1 knock-out (KO) mice and its wild-type were used for measuring lipid synthesis related enzyme. Results: Cortisol levels were elevated in SC and oral epithelium of the elderly rather than young. The 11β -HSD1 expression was increased in immunohistochemistry stain of aged mice skin. Aged mice showed decreased transepidermal water loss (TEWL) and SC hydration, and increased SC integrity than young. Serum inflammatory cytokines including interleukin-1α, -4, -10, -31 and tumor necrosis factor-α were increased in aged mice than young. The expressions of lipid synthesis related enzymes in epidermis were elevated in KO mice and topical 11β -HSD1 inhibitor applied mice. Conclusion: 11β-HSD1 expression is elevated in aged skin. It increases active GC and then deteriorates skin barrier function.