Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells

김대경,Yongwei Piao,So Yoon Yun,Zhicheng Fu,Ji Min Jang,Moon Jung Back,Ha Hyung Kim 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.9

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs’ alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

Systematic Review of Heavy Metal Concentrations in Fish and Shellfish in Korea

Shinhee Ye,Jiyoung Shin,Jueun Lee,Eun Mi Jung,Jeongsook Lee,Eunsun Yun,Yeosook Kim,Younghee Oh,Eun-Hee Ha 이화여자대학교 의과학연구소 2018 EMJ (Ewha medical journal) Vol.41 No.1

Objectives: Heavy metals ingested through the consumption of aquatic products can accumulate in the human body over the long-term and cause various health problems. This study aims to present comprehensive data on the amount of heavy metals found in fish and shellfish in Korea using a systematic review of studies that report on that issue. Methods: The study used the following databases: PubMed, Korean Studies Information Service System, and Research Information Sharing Service. The search terms for PubMed included fish OR shellfish OR seafood AND mercury OR cadmium OR lead OR heavy metal AND Korea. The search terms for Korean Studies Information Service System and Research Information Sharing Service included eoryu sueun, eoryu kadeumyum, eoryu nab, eoryu jung-geumsog, paeryu sueun, paeryu kadeumyum, paeryu nab, paeryu jung-geumsog, eopaeryu sueun, eopaeryu kadeumyum, eopaeryu nab, and eopaeryu jung-geumsog. Results: A total of 32 articles were selected for review. The total mercury, lead, and cadmium concentrations in fish and shellfish reported in each of the articles are summarized, as are the species of fish and shellfish with relatively high concentrations of heavy metals. Total mercury concentrations tended to be higher in predatory fish species, such as sharks, billfishes, and tuna, while lead and cadmium concentrations tended to be higher in shellfish. Conclusion: This paper is the first to report a comprehensive summary of the concentrations of heavy metals in fish and shellfish. This data could be used as evidence to protect Koreans from exposure to heavy metals due to the consumption of highly polluted aquatic products.

육제품 중 아질산염 잔류량과 몇 가지 농산물의 질산염 함량

하정욱,이승철,윤이란 慶南大學校 附設 工業技術硏究所 1998 硏究論文集 Vol.16 No.-

식육 햄, 식육 소시지 및 어육 소시지 등의 시료를 각각 15개씩 취하여 아질산염 잔류량을 정량하고, 또한 구기자, 오미자, 결명자, 시금치, 오렌지, 피망, 고추, 마늘 및 레몬 등의 몇가지 농산물을 구입하여 질산염의 함량을 측정한 결과는 다음과 같았다. 즉, 육제품의 경우 아질산염 잔류량은 식육 햄 12.8∼32.85 ppm, 식육 소시지 1.12∼14.71 ppm 및 어육 소시지 0.02∼0.45 ppm으로 식육 제품은 큰 변동치를 보였으나 어육 제품은 상당히 낮은 수준의 잔유량을 나타내었다. 한편 어육 소시지 15개 시료 중 8개 시료에서는 아질산염이 검출되지 않았다. 농산물 시료 중의 질산염 함량은 구기자 10,347 ppm(건물기준), 피망 7,236 ppm, 결명자 5,820 ppm(건물기준), 오렌지 4,152 ppm으로 유럽의 기준치 (1500∼3500 ppm)보다 많았으며, 나머지는 오미자 2,910 ppm, 시금치 2,078 ppm, 마늘 1,061 ppm, 고추 575 ppm, 레몬 170 ppm 순이었다. The residues of nitrite in meat products such as meat ham, meat sausage and fish sausages were determined with 15 samples, respectively. And the nitrate content of various agricultural products such gugija (Lycium chinese Mill.), omija(Maximowiczia chinensis Repr.), gyeolmyeongja (Cassia tora L.), spinach, orange, sweet pepper, red pepper, garlic bulb and lemon. The residues of nitrite in meat ham, meat sausage and fish sausage were 12.85∼32.85 ppm, 1.12∼14.71 ppm and 0.02∼0.4 ppm, respectively. The average residual content of nitrite in fish sausage was 0.17±0.13 ppm and was not detected from 7 samples of fish sausage among 15. The respective nitrate content of gugija, gyeolmyeongja and sweet pepper were 10.347 ppm (dry basis ), 5,820 ppm and 7.236 ppm (dry basis) and other results showed 4,152 ppm for orange, 2,910 ppm for omija, 2.78 ppm for spinach, 1,061 ppm for garlic bulb, 575 ppm for red pepper and 170 for lemon.

구기자, 오미자 및 결명자의 아질산염 소거작용

하정욱,황용일,윤이란 慶南大學校 附設 工業技術硏究所 1999 硏究論文集 Vol.17 No.-

기호음료의 재료인 구기자, 오미자, 및 결명자 등으로부터 물 추출물과 메탄올 추출물을 조제한 다음, phenol 화합물의 함량, 전자공여작용 및 아질산염 소거작용 등을 관찰하고, 이들 요인 간의 상관관계를 검토하였다. 추출물 중 오미자와 결명자의 메탄올 추출물이 비교적 높은 전자공여작용을 나타내었고, 방향족 화합물의 함량은 결명자>구기자>오미자의 순이었다. 물추출물의 아질산염 소거작용은 pH 1.2에서 구기자가 85.61%로 가장 현저하였고, 소거율은 구기자>오미자>결명자의 순이었으며, pH의존적으로 감소하였다. 메탄올 추출물의 아질산염 소거작용은 pH 1.2에서 구기자 96.03%. 결명자 89.38%. 및 오미자 87.23%로 매우 높은 소거율을 보였으며, pH 증가시 급격하게 감소하는 경향을 나타내었다. 그리고. 아질산염 소거작용과의 상관관계면에서 전자공여작용은 비교적 낮은 상관계수를 나타내었고, 방향족 화합물은 낮은 pH에서는 비교적 높은 값을 보였으나, pH 6.0에서는 상관관계를 거의 볼 수 없었다. 그리고 전반적으로 메탄올 추출물이 물 추출물에 비해 높은 아질산염 소거율을 유지하였다. This study was conducted to investigate the content of phenolic compounds, electron donating ability(EDA) and nitrite scavenging ability of water extracts and methanol extracts from Lycium chinese Mill Shizanda chinensis Baillon, and Cassia tora L. Methanol extracts from Shizandra chinensis Baillon showed comparatively higher EDA, and the content of phenolic compounds was in the sequence of Cassia tora L.>Lycium chinense Mill>Schizandra chinensis Baillon. The nitrite scavenging ability of water extracts from Lycium chinense Mill showed higher ratio of 85.61% than Shizandra chinensis Baillon and Cassia tora L. at pH 1.2, and decreased remarkably in the higher range of pH. The nitrite scavenging ratios of methanol extracts were 96.03% of Lycium chinense Mill, 89.30% of Cassia tora L. and 87.23% of Shizandra chinensis Baillon and the decreasing tendency was clearly pH-dependent. Generally methanol extracts showed higher coefficients than water extracts and the content of phenolic compounds had higher coefficients at lower pH range against nitrite scavenging ability.

Thioamide와 Benzothiazole 유도체의 합성

정대일,신규하,김인식,김윤영,정두희,이용균 東亞大學校 1998 東亞論叢 Vol.35 No.-

The thioamides; {N-(6-methyl-2-pyridinecarbothionyl)-3-methoxyaminobenzene (27), N-(6-methyl-2-pyridinecarbothionyl)-4-methoxyaminobenzene (29), N-(6-methyl-2-pyridine-carbothionyl)-3-ethoxyaminobenzene (31), N-(6-methyl-2-pyridinecarbothionyl)-4-ethoxyamion-benzene (33), N-(6-methyl-2-pyridinecarbothionyl)-3-bromoaminobenzene (35), N-(6-methyl-2-pyridinecarbothionyl)4-bromoaminobenzene (37), N-(6-methyl-2-pyridinecarbothionyl)-3-chloroaminobenzene (39), N-(6-methyl-2-pyridinecarbothionyl)-4-chloroaminobenzene (41)} were synthesized by the treatment of 2,6-lutidine(22) with sulfur in aniline derivatives (23). The benzothiazole derivatives; {5-methoxy-2-(6-methylpyridy)benzothiazole (46) and 6-ethoxy-2-(6-methylpyridyl)benzothiazole (47)} were respecively synthesized by the treatment of synthesized thioamides; N-(6-methyl-2-pyridinecarbothionyl)-3-methoxy-aminobenzene (27) and N-(6-methyl-2-pyridinecarbothionyl)-4-ethoxyaminobenzene (33) with zirconium (Ⅳ) oxide catalyst in sodium carbonate solution.

地下層 規模 設定에 관한 硏究 : 서울특별시 강남구 사례를 중심으로 Focus on the Case of KangNamGu

정윤용,어인준,김영하 대한건축학회 2004 대한건축학회논문집 Vol.20 No.11

The purpose is to identify how big the area is and which regulations should be preceded. if the part of Basement floors is to be calculated as the size of a building, according to characteristic of basement floor. The details of examination and analysis focused on such purpose of this research are summarized as follows: In view of all these, the size of buildings cannot be precisely estimated by the current floor area ratio computation method. To accurately calculate the size of buildings for urban growth management system: the inclusion in the calculation of floor area ratio in the case where basement floors are built for individual needs and benefits, rather than built as auxiliary use of a building such as basement or store room, is worth considering.

시금치 및 마늘의 아질산염 소거작용 및 전자공여작용

하정욱,이승철,윤이란 경남대학교 공업기술연구소 2000 硏究論文集 Vol.18 No.-

주요 야채 및 향신료로 이용되고 있는 시금치와 마늘로부터 물 추출물과 메탄을 추출물을 조제한 다음, phenol 화합물의 함량, 전자공여작용 및 아질산염 소거작용 등을 측정하고 검토하였다. 시금치와 미늘의 methanol 추출물이 물 추출물보다는 다소 높은 전자공여 작용을 나타내었으며, 방향족 화합물의 함량은 시금치의 methanol 추출물과 마늘의 물 추출물이 다른 두 종류의 추출물 보다는 비교적 높은 전자공여작용을 보였다. 그리고 물 추출물과 methanol 추출물 중에서 pH1.2에서 마늘의 물 추출물이 98.62%로 가장 두드러진 아질산염 소거율을 나타내었으며, 이 외에는 아질산염 소거작용면에서 거의 전반적으로 methanol 추출물이 물 추출물보다는 훨씬 효과적이었다. This study was conducted to investigate the electron donating ability(EDA) and nitrite scavenging ability of water extracts and methanol extracts from spinach and garlic-bulb. Methanol extracts from two samples showed comparatively higher EDA, and the content of phenolic substances of methanol extract from spinach and water extract from garlic-bulb was more than another extracts. The nitrite scavenging ability of water extracts from garlic-bulb showed the highest ratio of 98.62% among those extracts at pH1.2 and the decreasing tendency was clearly pH-dependent. Generally methanol extracts from two samples showed higher effective nitrite scavenging abilities than water extracts.

만성신부전 환자에서 발생한 파종결핵

정가영,나선경,윤혜원,송하응,류정화,류동열 이화여자대학교 의과학연구소 2013 EMJ (Ewha medical journal) Vol.36 No.1

Patients with chronic renal failure (CRF) are known to be more susceptible to tuberculosis infection due to impairment of the host defense mechanism. Although extrapulmonary tuberculosis is more prevalent in those subjects and it may induce dismal outcome, its diagnosis has been challenging since there is no specific symptoms of the disease and the clinical course is usually atypical. Herein, We report a case of disseminated tuberculosis diagnosed by ultrasound-guided liver biopsy in a 31-year-old CRF patient presenting sustained fever despite broad-spectrum antimicrobial therapy and progressive cholestatic jaundice.

김치유래 젖산균의 균체지방산 분석을 이용한 분류학적 연구

이정숙,정민철,김우식,이근철,김홍중,박찬선,이헌주,주윤정,이근종,안종석,박완,박용하,민태익 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.2

표준균주를 포함한 230여개의 김치유래 젖산균에 대한 균체지방산(FAMEs)을 분석하였다. FAMEs profiles는 Euclidian Distance 17.5에 의해 7개의 Major Cluster와 1개의 Single Cluster로 나뉘어졌다. 이중 A, B, C 및 Cluster는 Leuconostoc속으로 분석되어졌고, F는 Lactobacillus속으로 분석되어졌다. 그리고 E와 G cluster는 두개의 Genus가 혼재되어 나타났으며 보충적인 연구가 필요하다. 앞으로 김치유래 젖산균의 균체지방산 분석결과를 기반으로 한 데이타베이스에 95가지 탄소원을 이용하는 수치분류학적 접근방법 및 Pyrolysis Mass Spectrometry 등의 화학적 분석 방법과 분자친화적 연구를 통한 종합적 분류정보 체계가 갖추어지면 젖산균의 신속, 정확한 동정 및 연구에 활발히 이용되어질 것이다. Two hundreds and thirty lactic acid bacteria, mostly isolated from Kimchi, including type strains were sued for analysis of cellular fatty acids. The 230 test strains were recoverd in 7 major and 1 single clusters defined a Euclidian distance of 17.5. These aggregate taxa were equivalent to the genus Leuconostoc (aggregate group A, B, C and D), and the genera Leuconostoc and Lactobacillus (aggregate group G). It is concluded as evident that FAMEs (Fatty Acid Methyl Esters) profile of cell can be used as a criterion in classification of lactic acid bacterial from kimchi. Additional comparative taxonomic studies need to be carried out on well chosen representative strains to determine the most appropriate methods of value.

강박장애 환자에서 Sertraline 치료반응의 예측인자에 관한 연구

유은정,우행원,김영철,연규월,김종원,임원정 대한신경정신의학회 2000 신경정신의학 Vol.39 No.2

연구목적: 1980년 중반부터 강박장애의 치료로 SSRIs가 널리 쓰이고 있으나 치료반응의 예측인자에 대한 연구는 미비한 실정이다. 본 연구에서는 sertraline 투여후 호전군과 비호전군의 인구학적 특성, 발병연령, 이환기간, 과거의 강방장애에 대한 투약경력, 정신과 질환의 가족력, 증상의 심각도, 임상양상 등의 변수들을 관찰하여 sertraline 치료반응과의 상관관계를 살펴보았으며 치료방응을 예측 할 수 있는 인자를 알아보았다. 방법: 연구 대상은 이대부속 동대문병원 정신과에 입원 또는 외래치료를 받은 환자들 중 정신과 진단 편람제 4판 진단 기준에 의거하여 강박장애로 진단 받은 31명(남자 10명, 여자 21명)이었다. 연구 방법은 sertraline을 하루 50mg씩 투약하면서 Y-BOCS, NIMHOCS, CGI로 강박증상의 변화를 평가하였고, HAM-A로 불안정도의 변화를 측정하여 투약 전 점수와 비교하였다. 결과: 1) Y-BOCS 점수 40%이상 감소와 함께 CGI 점수 2점 이상 감소를 보인 호전군은 대상환자 31명중 17명(54.8%)이었고, 비호전군은 14명이었다. 호전군이 비호전군에 비해 늦은 나이에 발병하는 경향을보였고(p<0.1), 이환기간이 짧았으며(p<0.05), 과거의 강박장애에 대한 투약경력은 적었다(p<0.05), 정신과 질환의 가족력은 두 집단간에 차이가 없었다. 2) 호전군에서 투약 전 Y-BOCS의 강박행동 점수가 유의하게 낮았으며(p<0.05), 기타 다른 평가척도에서는 두 집단간에 유의한 차이가 없었다. 3) 평균 Y-BOCS 점수는 투약 전에 비해 sertraline 투약 12주째 43.5%가 감소하였다. 투약 전과 비교하여 투약 2주째부터 불안을 평가하는 HAM-A 점수가 유의하게 감소하였고, 투약 4주째부터 Y-BOCS, NIMHOCS, CGI 점수가 유의하게 감소되기 시작하여 12주까지 지속되었다.(p<0.01). 4) 호전군에서 오염에 대한 강박사고와 씻음의 강박행동의 유의하게 많았으며(p<0.05), 셈의 강박행동은 없었다(p<0.05), 병적 의심은 비호전군에서 많은 경향을 보였다(p<0.1). 결론: 이상의 결과를 종합하면, 질병의 이환기간이 짧으며 과거의 강박장애에 대한 투약경력이 적고 투약 전강박행동이 심하지 않으며, 주된 임상양상이 오염에 대한 강박사고와 씻음의 강박행동인 경우 sertra-line에 좋은 치료반응을 보이지만, 셈의 강박행동이 있는 경우에는 치료반응이 좋지 않다고 예측할 수 있다. Objectives: The pharmacologic treatment of obsessive-compulsive disorder(OCD) with serotonergic antidepressant agents is well established in clinical psychiatry on the basis of serotonin hypothesis. Studies on predictive factors of treatment reponse to OCD are relatively scarce. The author compared the demographic factors, age of onset, length of illness, family history of mental illness, previous drug history for OCD, severity and type of symptoms between the drug reponders and non-responders to find out the predicitive factors that may be related to treatment response. Methods: The subjects were 31, both inpatients and outpatients who met the diagnostic criteria for OCD by DSM-IV and scored 20 or higher on the Yale-Brown Obsessive-Com-pulsive Scale(Y-BOCS) completed 12-week trial of sertraline. Y-BOCS, National Institute of Mental Health Obsessive-Compulsive Scale(NIMHOCS), Clinical Global Impression Scale(CGI) were scored to measure the changes of obsessive-compulsive symptoms, and Hamilto Anxiety Scale(HAM-A) was measured at each visit. Results: 1) The responders, defined as achieving at least a 40% decrease in the Y-BOCS total score and more than a 2 point decrease in CGI score, were 17(54.8%), and non-responders were 14(45.2%). Responders tended to show later onset(p<0.1), and shorter duration of illness(p<0.05), and less previous drug therapy for OCD(p<0.05) than non-responders. There were no significant differences in family history of mental illness between the two groups. 2) The basline Y-BOCS compulsive score was significantly lower in responders(p<0.05), although there was no significant difference in the basline severity of other measures. 3) The obsession of contamination and washing behaviors were more frequent, but compulsive counting was not shown, in responders(p<0.05). The pathological doubt tended to be more common in nonresponders(p<0.1). Conclusions: In summary, the patients with shorter duration of illness, less prior drug ther-apy for OCD, and less severe compulsive behaviors, and the obsession of contamination and washing behaviors are expected to be better outcome with sertraline, whereas compulsive counting are the predictor of poor response.