Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

건조 상추 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.3

상추는 가장 선호하는 녹색 채소 중 하나이다. 상추는 폴리페놀성 화합물을 비롯한 다양한 성분을 함유하고 있으며, 항균, 항산화, 항염증 등의 생리활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 건조상추의 에탄올 추출물(DLE)을 제조하고 이들의 항염증 활성을 연구하였다. DLE의 항염증 활성을 측정하기 위하여 LPS로 활성화된 마우스 대식세포 RAW 264.7 세포주에서 nitric oxide (NO) 생성을 측정하였다. DLE는 세포주의 생존에는 영향을 미치지 않으면서 NO 생산을 현저하게 저해하였다. DLE에 의해 염증 유전자인 iNOS와 COX-2의 유전자와 단백질의 발현이 모두 감소하였으며, 6개의 염증관련 cytokine 유전자(IL-1α, IL-1β, IL-1F6, TNF-α, CSF2, 그리고 CXCL10)의 발현이 모두 감소하였다. 또한, DLE의 처리는 MAPKs 경로의 인산화를 모두 저해하였으며, NF-κB p65의 핵으로의 이동을 저해하였다. 이러한 결과는 DLE의 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 시사한다. 또한, DLE는 농도의존적으로 reactive oxygen species (ROS)의 생산을 저해하였으며, hemeoxygenase-1 (HO-1) 단백질의 발현을 증가시켰으며, HO-1의 전사조절인자인 Nrf2의 핵으로의 이동을 증가시켰다. 결론적으로, 이러한 연구결과는 DLE가 염증관련 유전자의 발현을 감소시키며, MAPKs, NF-κB, 그리고 Nrf2/HO-1 등 다양한 경로를 조절함으로써 항염증 활성을 가지는 것을 제시한다. Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including IL-1α, IL-1β, IL-1F6, TNF-α, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and NF-κB pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

연잎, 연자육, 연자방 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.4

연은 아시아 국가에서 음식과 약재로 널리 사용되는 재료이다. 본 연구에서는 연의 잎(leaf, NL), 자육(seed, NS), 자방(seedpod, NSP)으로부터 에탄올 추출물을 제조하고 이들의 항염증 활성과 작용기전을 규명하였다. 이들의 항염증 활성을 연구하기 위하여 LPS로 자극된 RAW 264.7 세포에서 nitric oxide (NO) 생산을 측정하였다. NL, NS, NSP는 세포 생존율에 영향을 주지 않으면서, 농도의존적으로 NO의 생산을 현저하게 저해하였으며, iNOS 및 COX-2와 같은 pro-inflammatory 중재자들의 단백질 발현을 감소시켰다. 또한, NL, NS, NSP는 MAPKs 단백질의 인신화를 감소시키고 NF-κB p65의 핵으로의 이동을 저해함으로써, 세 추출물에 의한 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 제시한다. 게다가, ROS의 생성이 세 추출물에 의해서 모두 저해되었으며, HO-1의 발현과 HO-1의 전사조절인자인 Nrf2의 핵으로의 이동이 증가되었다. 결론적으로, 이러한 연구결과는 연의 다양한 부위의 추출물인 NL, NS 그리고 NSP는 항염증 활성을 가지고 있으며, MAPKs, NF-κB, Nrf2/HO-1 등 다양한 신호경로를 통해 조절할 수 있음을 제시한다. Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-inflammatory activities in mouse macrophage RAW 264.7 cells. To evaluate the anti-inflammatory activities of NL, NS, and NSP, nitric oxide (NO) production was measured in LPS-stimulated RAW 264.7 cells. NL, NS, and NSP significantly reduced NO production in a dose-dependent manner without affecting cell viabilities. NL, NS, and NSP dramatically decreased the protein expression of pro-inflammatory genes such as iNOS and COX-2. NL, NS, and NSP also suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating they have their anti-inflammatory activities via regulating mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways. In addition, we analyzed the production of reactive oxygen species (ROS) by the treatment of NL, NS, and NSP. All extracts reduced ROS production in a dose-dependent manner. And also, they increased heme oxygenase-1 (HO-1) protein expression and the nuclear translocation of nuclear respiratory factor 2 (Nrf2). In conclusion, our results suggest that Nelumbo nucifera has its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

On the Strengthening Effects Affecting Tensile and Low Cycle Fatigue Properties of Low-Alloyed Seismic/Fire-Resistant Structural Steels

Jung‑Ho Sim,Tae‑Yeong Kim,Jun‑Yeon Kim,Chi‑Won Kim,Jun‑Ho Chung,Joonoh Moon,Chang‑Hoon Lee,Hyun‑Uk Hong 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.2

In the present study, low carbon ferritic and bainitic steels with different contents of Mo, Ti, and Nb were designed for bothseismic and fire-resistant applications. The microstructure of steels containing 0.3 wt% Mo–0.02 wt% Nb (‘A’ hereinafter)was mainly composed of bainite. By contrast, the microstructure of steels with 0.2 wt% Mo–0.13 wt% Ti (‘B’ hereinafter)consisted of ferrite with a high density of nano-sized (Ti,Mo)-rich MX precipitates. The results showed that the bainiticmicrostructure (‘A’ steel) was quite favorable to high-temperature strength and thermal stability. The yield strength of ‘A’ steelat both room and 600 °C temperatures increased consistently with increasing thermal exposure time (600 °C/200–1000 h),since the precipitation of NbC particles occurred while maintaining bainitic ferrite platelets with a high density of dislocationsduring exposure. In the ‘B’ steel, the formation of nano-sized (Ti,Mo)-rich MX particles was effective to impededislocation movement, leading to excellent plasticity (lower yield ratio) at room temperature. However, their contributionto precipitation hardening was not so much at 600 °C, as compared to the bainitic strengthening. During low cycle fatiguetests at room temperature, the main different feature between the two steels is that the ‘A’ steel showed cyclic softeningwhile cyclic hardening was evident in the ‘B’ steel. The bainitic microstructure showed a better fatigue life due to increasedductility manifested by cyclic softening, by which dislocation cell was developed.

위암 환자의 복강내 투여를 위한 Activated Charcoal-Alginate Bead 제형으로부터 Mitomycin C의 용출 거동

이진호,최선웅,서중기,김동민,정경수,오정연,김진향,노승무,민병무,김용백,김창식,박근성,강대영,송규상,양준묵,조준식,정현용,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherapy seems a logical choice for cancer chemotherapy. In this study, Mitomycin C (MMC)-activated charcoal (CH)-alginate (ALG) beads were prepared by the mixtures of CH particles adsorbed with MMC as an anti-cancer drug and aqueous alginate solution. The alginate is recognized as biodegradable, nontoxic, and biocompatible. The release of MMC from the beads in 0.1 M Tris buffer was stable and continuous until about 1 week. The MMC-CH-ALG beads can be applied in the peritoneal cavity for intraperitoneal chemotherapy since they provide a good adhesiveness on the tissue and controlled release pattern of the drugs.

원위 대퇴골의 고립성 골연골종에서 발생한 속발성 연골 육종 1례 보고

정필현,황장수,강석,김용민,오형호,채동주,김종필 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

연골육종은 비교적 서서히 자라며 늦게 전이하는 악성 연골 종양으로 알려져 있다. 골 연골종에서 발생한 속발성 연골육종은 발생빈도는 드물며 타부위로의 전이가 적고 악성도가 낮은 경우가 많아 적합한 수술적 치료로서 좋은 예후를 보이는 것으로 보고되고 있다. 본 동국대학교 정형외과학 교실에서는 우측 대퇴골 원위부 골간단부에 생긴 고립성 골 연골종에서 이차적으로 발생한 연골육종을 치험한 바 문헌고찰과 함께 보고하는 바이다. A case of Secondary Chondrosarcoma Arising from Solitary Osteochondroma of the Distal Femur Department of Orthopaedic Surgery, College of Medicine, DongGuk University Phil Hyun Chung M.D., Jung Su Hwang M.D., Suk Kang M.D., Yang Mln Kim M.D., Hyung Ho Oh M.D., Dong Ju Chae M.D., Jong Pil Kim M.D. Chondrpsarcoma is a malignant cartilage-forming tumor that grows slowly and metastasis of this tumor occurs in late stage. Secondary chondrosarcomas arising from a solitary osteocartilaginous exostosis are rare and those have a better prognosis than other chondrosarcomas, and they rarely metastasize. We present our experience with a case of secondary chondrpsarcoma arising in solitary osteochondroma of distal metaphysis of right femur with clinical details.

중독한 추체로 증상을 보인 cyclosporine에 의한 뇌증 1예

강정현,곽승근,신현영,김성은,이정호,이정찬,곽상혁,윤환중,조덕연,김삼용,김제,송창준 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.1

The use of cyclosporine(CsA), a potent immunosuppressive agent, is associated with numerous side effects. Neurotoxicity was earlier less well known, but with growing experience central nervous system side effects are now reported up to 40% of patients. Among various CsA-induced neurotoxicities, tremor is most common and posterior leukoencephalopathy is well characterized. An encephalopathy presenting with pyramidal weakness, however, seems to be rare and poorly documented. We report here a case of encephalopathy presenting with multiple generalized seizures followed by fluctuating quadriparesis developed a few days after starting CsA and resolved spontaneously after withdrawal of the drug . A 48-year-old woman with aplastic anemia was placed upon immmunosuppressive treatment consisting of antithymocyte globulin(ATG), CsA, and methylprednisolone. Two days after starting the therapy, she developed a generalized seizure. The next day she developed 2 more episodes of seizure and the therapy was stopped. Computed tomogram of the brain was normal. Six days after starting therapy, she developed mild motor weakness and paresthesia of both lower extremities, which progressed to a definite quariparesis confining her to a bed in 3 days. Magnetic resonance imaging(MRI) of the brain revealed asymmetric, bilateral high-signal abnormalites in the subcortical white matter of fronto-temporal areas. After reaching to a maximum with some fluactuation(14 days after starting the therapy) the motor weakness started to be resolved. She was discharged with a almost complete resolution of the weakness 45 days after starting the therapy. Five months later she did well and brain MRI was negative.

Inducing apoptpsis by the inhibition of c-myb in oral squamous carcinoma cell line, KB cell

Lee,Jung-Chang 대한구강생물학회 2007 International Journal of Oral Biology Vol.32 No.4

Oral squamous cell carcinoma (OSCC) is the most commonmalignancy and is a major cause of worldwide cancer mortality.The proto-oncogene c-myb plays an important role in regulationof cell growth and differentiation, and it is expressed at highlevels in hematopoietic cells and many other types of cancers.However, the function of c-myb is not well known in OSCC.The present study aimed to reveal the function of c-myb and totest the alternation of cell growth and signaling by c-myb inOSCC. In this study, c-myb and dominant-negatibe myb(DN-myb) were expressed in an adenovirus-mediated gene deliverysystem to KB cells. The over-expressed c-myb broughtincreased cellular proliferation compared with control cells.However, DN-myb infected KB cells showed significantreduction of cell growth and enhanced induction of apoptosis toactivate PARP and caspase 9. c-myb induced increase of IGF-I,-II and IGF-IR expressions while DN-myb down-regulatedthese expression. Activation of ERK and Akt/PKB pathwaywas shown only in c-myb transduced cells. These findingssuggest that the role of c-myb in cell growth of oral cancer cellsis partially mediated through the modulation of IGFs, ERK andAkt/PKB. From this results, DN-myb is strongly recommendedas a curable gene for the treatment of c-myb dependentmalignancies such as OSCC.

White luminescence of Ho3+/Tm3+/Yb3+-codoped CaWO4 synthesized via citrate complex route assisted by microwave irradiation

CHO, Hyun,HWANG, Seok Min,LEE, Jae Bin,KA, Dong Hyun,KIM, Tae Wan,LEE, Bo Seul,LEE, Ji Young,LEE, Jung-Il,RYU, Jeong Ho Elsevier 2014 Transactions of Nonferrous Metals Society of China Vol.24 No.suppl1