Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

개의 전신성 피부사상균증의 진단과 치료증례

김건우,송근호,김덕환,박성준 충남대학교 수의과대학 동물의과학연구소 2004 動物醫科學硏究誌 Vol.12 No.-

A 5.2kg, 5month-old castrated male Cocker spaniel dog with 1 month history of generalized scaling, alopecic skin disease was referred to the Veterinary Medical Teaching Hospital of Chungnam National University. On physical examination, lesions were observed on entire cutaneous surface and were characterized by pustules, scales, and generalized alopecia. Skin scraping and tape strip tests of skin lesions revealed cocci and Malassezia infection was detected on external ear canal. Masses of dermatophyte spores surrounding the hair shafts were found by direct microscopic examination. Based on the result of examination and clinical signs above, generalized dermatophytosis with superficial pyoderma and Malassezia otitis externa were diagnosed. Treatment with administration of antibiotic and antifungals combined with topical antifungal cream and shampoo for more than 8weeks had a good result of controlling dermatophytosis.

Beck Depression Inventory를 이용한 내과 환자의 우울성향 조사 보고

반건호,염태호,한홍무 大韓神經精神醫學會 1987 신경정신의학 Vol.26 No.3

It has been known that many medically ill patients have psychological problems, such as depression or anxiety. Many have attempted to define these problems objectively and several self-rating devices for depression or anxiety have been developed. This study was designed to investigate the characteristics of depressive trends in medically ill patients. The author performed Beck's Depression Inventory (BDI) on 82 inpatients & 93 outpatients in Kyung-Hee University hospital and 200 normal subjects from August to September, 1986. The results were as follows; 1) In comparison of the three groups, the difference of total score of BDI was significant, especially between inpatients and normal subjects. 2) The total score of BDI of female was significantly higher than that of male in outpatients and normal subjects. 3) The BDI score of low educational group was significantly higher than that of high educational group in outpatients and normal subjects. 4) In normal subjects, BDI score was significantly increased by aging, but not in inpatients and outpatients. 5) Categorized as depression were 39.0% of inpatients, 30.1% of outpatients, and 27.0% of normal subjects, when the tentative cut off score was 21. 6) The significant items among three groups were items, No. 3, 15, 16, 17, 18, 19, 20 and 21, which were manifestations of somatization in the depression. 7) Depending upon above findings, BDI is thought to be a useful device for screening depressive trends in medically ill patients.

HLA-DR2 陽性 反應을 보인 嗜眠病 1례

반건호,이기철,장환일 大韓神經精神醫學會 1988 신경정신의학 Vol.27 No.5

The authors experienced a 28 year old male narcoleptic patient who revealed narcoleptic tetrad ; sleep attack, cataplexy, sleep paralysis, and hypnagogic hallucination lasted for about 3 years. The patient has a history of poliomyelitis in early childhood and has sustained head trauma just before the onset of narcolepsy. And also HLA-DR2, DQwl, and DR4 positive reaction was confirmed with the method of microcytotoxicity using Terasaki HLA-ABC and HLA-DR tissure typing trays. Sleep attack was somewhat controlled with methylphenidate and cataplexy with imipramine, and other symptoms were also improved followed by the improvement of sleep attack and cataplexy. With this case report, aspect of biologic etiologies of narcolepsy were reviewed.

호흡기계 감염에 대한 Broncho-vaxom^�의 임상적 효과

최호경,이건수,서종진,정용헌 충남대학교 의과대학 지역사회의학연구소 1990 충남의대잡지 Vol.17 No.1

Thirty children with respiratory tract infections, 17 with acute and chronic bronchitis, 5 with sinusitis, 4 with rhinitis, 3 with asthma, 1 with tonsillitis, were given Broncho-vaxom^?? one capsule per day on an empty stomach for 1 month to evaluate the efficancy of the drug on acute and chronic respnatory tract infections in children. After the medication, we observed the changes of clinical symptoms, and side effects. The results are as follows; 1. The symptomatic improvements after Broncho-vaxom^?? administration were as follows; expectoration(80%), fever(72%), rhinorrhea(67%), hoarseness(67%), and coughing(65%). 2. Combined treatment with antibiotics was necessary in 19 cases(63%). 3. The degree of response were observed as mild improvement in 3 cases(10%), moderate improvement in 13 cases(84%), and excellent improvement in 1 cases(47%). 4. The side effect of Boncho-vaxom was not observed during this study.

급성신부전증 이환견에 대한 복막투석 치료 1례

김건우,이병희,김유수,심재현,김지용,이영원,김덕환,송근호 충남대학교 수의과대학 동물의과학연구소 2004 動物醫科學硏究誌 Vol.12 No.-

A fourteen-month-old intact female Poodle was referred to the Veterinary Teaching Hospital, College of Veterinary Medicine, Chungnam National University. The patient was presented with history of vomiting, inappetence, ataxia, insomnia, tachypnea and convulsion for 5 days. Biochemical examination revealed BUN (254.2 mg/dl), creatinine (9.22 mg/dl) and phosphate (14 mg/dl). Epithelial cells of urinary tract, neutrophils, macrophages, a large number of gram negative and smaller number of gram positive bacteria were presented on urine test. Ultrasonographic findings show hyperechogenic kidney and indistinguishableness of renal cortex and medulla. Based on the results of examination described above, this case was diagnosed as acute renal failure with interstitial nephritis by urinary tract infection (UTI). Treatments with fluids therapy, diuretics, and peritoneal dialysis during hospitalization showed good results with no clinical signs.

賃金格差가 勞使雙方에 미치는 影響

申建浩 단국대학교 상경대학 1982 商學論叢 Vol.18 No.-

치성감염에 의해 발생된 후측인두부 및 종격동 농양

이승호,정종철,김건중,정주성,유선열,박문성,김창룡 大韓顎顔面成形再建外科學會 1996 Maxillofacial Plastic Reconstructive Surgery Vol.18 No.4

Odontogenic infections are usually locally confined, self-limiting processes. However, under certain circumstances, they may break through the bony, muscular, and mucosal barriers and spread into contiguous fascial spaces or planes far from the initial site of involvement, resulting in severn life-threatening complications, such as retropharyngeal spread, suppurative mediastinal extension, airway obstruction, pleuropulmonary suppuration, and hematogenous dissemination to distant organs. The mortality arte for mediastinitis from odontogenic infection ranges from 40% to 60%. Therefore rapid evalution and treatment is essential with a combination of life support, antibiotic therapy, and surgical intervention. Recently, we experienced three cases of retropharyngeal and mediastinal abscesses secondary to odonogenic infections. In all patients, early diagnosis was possible by CT scanning and physical examination. The prognosis was good in all patients by using urgent aggressive surgical and antibiotic therapy.

마우스 악하선의 DMBA유도 발암시의 병리조직학적 변화

이호건,김진수 慶北大學校 齒科大學 1990 慶北齒大論文集 Vol.7 No.1

The purpose of this study was to investigate carcinogenic effect of DMBA on the mouse submandibular glands. Seventy female mice were used in this study. They were divided into 14 experimental groups of 42 animals and 14 control groups of 28 animals. The submandibular glands of each experimental animals were incised and implanted with pure DMBA pellet(about 1.25mg). In contrast ot these, animals of control group were only incised on the submandibular glands without implantation of DMBA. 3 animals out experimental groups and 2 out of control one were sacrificed at 1, 3, 5th day and 1, 2, 3, 5, 8, 11, 12, 13, 14, 15, 16th weeks after application of carcinogen. The specimens were taken from their submandibular glands immediately after sacrifice and were routinely processed for light microscopic observations. The results obtained from this study were as follows. ; 1. According to gross observations, visible and palpable lesions developed nearly all mices of experimental groups 11 weeks after experiment in the right submaxillary gland area implanted with DMBA pellet. In control animals, no significant change was noticeable except inflammatory changes at early stage. 2. The histopathological alterations of the mouse submandibular glands induced by DMBA revealed changes according to time. a. The mouse submandibular glands showed necrosis, inflammatory infiltration, atrophy of acinic cell and ductal hyperplasia of granular convoluted tubule cells at 1 to 2 weeks after experiment. b. They showed severe ductal hyperplasia, ductal squamous metaplasia, epidermoid cyst and basal cell plemorphism at 5 to 8 weeks after experiment. c. They showed obvious squamous cell carcinoma after 8 weeks of experiment. d. From 11 to 16 weeks, persistent squamous cell carcinoma development, invasion into the adjacent connective tissue, and multiple tumor islands were observed. e. At 13 weeks, sarcomatous-like squamous cell carcinoma was also observed in one experimental animal. 3. The sequence of hstopathologic changes of experimental carcinogenesis in this study was initial inflammation, acinic cell atrophy accompanied by necrosis of connective tissues, proliferation of ductal epithelium squamous metaplasia and occurrence of squamous cell carcinoma. 4. The malignant tumors induced in this study were mainly squamous cell carcinomas. 5. Squamous cell carcinoma was thought to be originated from the lining epithelial cells of the large excretory duct. J. Kyungpook Univ. Sch. Dent. Vol. 7, No. 1, 33∼47, 1990