Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

식물의 대사에 미치는 요소질소의 영향 (2) 대맥근에 (大麥根) 흡수된 후의 질소대사

김준호 (Joon Ho Kim) 한국식물학회 1962 Journal of Plant Biology Vol.5 No.2

KIM. Joon Ho (Dept. of Biology, Kongju Teacher`s College): The effects of urea nitrogen on the metabolism of plants. Ⅱ. The response of some nitrogen components of barley to urea and other nitrogen in water culture. Kor. Jour. Bot. V(2), 6-12. 1962. For the comparison with the previous paper (4) the present report deals with the absorption and metabolism of urea and other nitrogen ions in barley seedling absorbed through root. 1. The amount of nitrate in barley treated with urea reach it pcak on the 8 th day, NO_3 on the 4 th, NH_4 on the 6 th or 8th. respectively. 2. The ammonia content in urea group reaches its peak on the 6 th day but other groups on the 4 th day. The present data in the urea group show to shorten 4 days compared with that of the previous paper (4). 3. The content of total amide from the present data are gradually increased on all of the groups during this experiment. These are agreement with the result of the previous paper (4). 4. The alcohol soluble nitrogen in the urea group shows the similar tendency to the NaNO_3 group but reaches its peak 2 days later than in the (NH4)_2SO_4 group. 5. The content of total nitroaen in the urea series has the lowest amount at the beginning while the richest from the 4th day after. These would be explained on that the absorption of urea is delayed and the PH in the urea solution does not change, so called physiological neutralily. The author should like to express his sincere thanks to Prof. M. J. Lee of Seoul National University for his valuable advices.

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

치과 기공사들에게서 나타나는 호흡기 증상과 이의 관련 요인

김웅철,오세윤,김지환,김진완,이준석,이가영,이세훈,유진호,김태석 高麗大學校 倂設 保健大學 保健科學硏究所 2001 保健科學論集 Vol.27 No.1

This study was carried out to investigate subjective respiratory symptoms and their attributable factors in Korean dental laboratory technicians. A questionnaire was mailed to randomly selected 1,900 dental laboratory technicians. Among them, 1,344 dental technicians completed the questionnaires and returmned them. Validity and reliability tests on the questionnaires were carried out before the main survey. To investigate risk factors on respiratory subjective symptoms, we performed analysis on distribution of characteristics, and then investigated univariate analysis and multiple logistic regression analysis. The prevalence rate of wheezing, cough and phlegm, and dyspnea was 4.8%, 33.9%, 54.9%, respectively. Statistically significant factors inducing subjective respiratory symptoms by multiple logistic regression analysis were sex, smoking, exercise, health examination, work hours a day, investment gas, investment dust, metal fume, resin vapor, and asbestos dust. Considering the results above, it seems that most subjective respiratory symptoms are related with health habits and occupational environmental-related factors. The result, consideration in mind, suggest that health promotion programs for smoking cessation, regular health examination, and physical exercise in health habit, and improvement on casting and resin work in dental technological environment be necessary.

고리원자력발전소 주변의 식생과 식물현존량 추정

김성종,이호준,김인택,김창호,정홍락 建國大學校基礎科學硏究所 1995 理學論集 Vol.20 No.-

고리원자력발전소 주변의 식생에 대한 식물사회학적 조사를 실시하였으며, 순1차생산력과 식물현존량을 추정하였다. 또한 상관에 의한 현존식생도 및 녹지자연도를 작성하였다. 종조성표에 의한 식물군락은 소나무군락, 곰솔군락, 서어나무-굴참나무군락, 아까시나무군락으로 구분되었다. 소나무군락은 아교목층(평균식피율 35%)이 빈약하였으며, 서어나무-굴참나무군락은 비교적 안정된 계층구조를 이루고 있었다. 전체적으로 교목층에서 소나무, 곰솔, 아교목층에서 사방오리, 졸참나무, 저목층에서 졸참나무, 사스레피나무, 초본층에서 산거울, 주름조개풀 등의 피복지수가 높았다. 삼림토양의 pH는 4.30~4.85, 유기물함량은 6.04~9.40%의 범위였다. 현존식생도에 의한 분포비율은 곰솔군락(31.4%)이 가장 높았으며, 평균녹지자연도는 5.4였다. Montreal model에 의한 순1차생산력은 1555.2g/㎡/yr, 식물현존량은 단위면적당16,982,21ton/k㎡으로 추정되었다. The forest vegetation and estimation of phytomass and net primary production in the vicinity of Kori Atomic Power Plant was analyzed on the basis of the phytosociological data. Depending on physiognomy, actual vegetation map and the degree of green naturality(DGN) was also drawn in the of 1:50,000. According to Z-M method, the forest vegetation was classified into four communities, which include Pinus densiflora, Pinus thunbergii, Carpinus laxiflora-Quercus variabilis, and Robinia pseudo-acacia communities. The Pinus densiflora community was most poorly covered in tree-2 layer. The Carpinus laxiflora-Quercus variabilis community was relatively stable in the stratum structure. It was generally shown that Pinus densiflora and Pinus thunbergii in tree-1 layer, Alnus firma and Quercus serrata in tree-2 layer, Quercus serrata and Eurya japonica in shrub layer, and Carex humilis and Oplismenus undulatifolius in herb layer had high coverage index. The pHs and contents of organic matter of the forest soil collected in each sites was in the range of 4.30 to 4.85 and 6.04% to 9.40% in average in the communities. The Pinus thunbergii community showed the highest distribution rate(31.4%) in the actual vegetation map. The average DGN was approximately 5.4. Net primary production and phytomass per unit area obtained by Montreal model were estimated to be 1555.2g/㎡/yr and 16,982.21ton/k㎡, respectively.

자가 말초혈액 조혈모세포 이식술의 임상적용

김혁,안명주,오석중,이영열,김인순,정태준,최일영,오미란,임호준,이항,김신규 한양대학교 의과대학 1999 한양의대 학술지 Vol.19 No.1

Responses to chemotherapy correlate with the increased dose of chemotherapeutic agents in some cancers, e.g. breast cancer, Ewing's sarcoma, Hodgkin's disease(HD) and non-Hodgkin's lymphoma(NHL), then for the improvement of the chemotherapy responsiveness, high-dose chemotherapy(HDCT) was proposed. But, it's application was limited due to complications, especially bone marrow suppression. HDCT and succeeding autologous peripheral blood stem cell transplantation(APBSCT) was introduced to overcome this problem. This study was designed to determine the clinical pictures including clinical parameters and the responsiveness of HDCT followed by APBSCT in Hanyang University Hospital. Ten patients were enrolled. They were 8 adults (3 breast cancers, 3 multiple myelomas, 1 HD, 1 NHL) and 2 children (1 acute myelogenous leukemia (AML), 1 neuroblastoma). Mobilization chemocherapy(MCT) followed by Granulocyte Colony Stimulating Factor(G-CSF) was administered to mobilize stem cells from bone marrow to peripheral blood. The stem cells were collected by using CS-3000 and cryopreserved at -196℃ with programmed controlled rate freezer as the mixture with 10% dimethyl sulfoxide(DMSO). HDCT was administered and cryopreserved peripheral stem cells were infused on day 0 as planned. Patients' mean age was 41 years old. After induction chemotherapy three patients achieved complete response and 5 partial response. The median time for bone marrow recovery after MCT was 11.5 days for neutrophil(〉500/㎣) and 4.8 days for platelet(〉20,000/㎣). There were three cases of neutropenic fever and one case of gingivitis. After HDCT with APBSCT, one patient was converted partial response to complete response, and one patient achieved complete response after HDCT without induction chemotherapy. The median time for bone marrow recovery was 12.7 days for neutrophil(〉500/㎣) and 14.7 days for platelet(〉20,000/㎣). Eight patients developed neutropenic fever and required systemic antibiotics. Transfusion was required 1.6 pints for packed red cell and 23.4 pints for platelet concentrates. Toxicity consisted mainly of vomiting, diarrhea, and mucositis which were mild. HDCT with APBSCT can be performed safely with minimal complications. For the evaluation of the exact role of HDCT with APBSCT in malignant diseases, further studies are required as a large scale of patients and lung-term follow up.