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Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway
Bae, Yun-Ui,Choi, Joon-Hyuk,Nagy, Andras,Sung, Hoon-Ki,Kim, Jae-Ryong Federation of American Societies for Experimental 2016 The FASEB Journal Vol. No.
<P>Cellular senescence, an irreversible state of growth arrest, underlies organismal aging and age-related diseases. Recent evidence suggests that aging intervention based on inhibition of cellular senescence might be a promising strategy for treatment of aging and age-related diseases. Embryonic stem cells (ESCs) and ESC conditioned medium (CM) have been suggested as a desirable source for regenerative medicine. However, effects of ESC-CM on cellular senescence remain to be determined. We found that treatment of senescent human dermal fibroblasts with CM from mouse ESCs (mESCs) decreases senescence phenotypes. We found that platelet-derived growth factor BB in mESC-CM plays a critical role in antisenescence effect of mESC-CM through up-regulation of fibroblast growth factor 2. We confirmed that mESC-CM treatment accelerates the wound-healing process by down-regulating senescence-associated p53 expression in in vivo models. Taken together, our results suggest that mESC-CM has the ability to suppress cellular senescence and maintain proliferative capacity. Therefore, this strategy might emerge as a novel therapeutic strategy for aging and age-related diseases.</P>
윤수인 ( Yun Su In ),김혜영 ( Kim Hye Yeong ),김민옥 ( Kim Min Og ),김학의 ( Kim Hag Ui ),문기원 ( Mun Gi Won ),한정호 ( Han Jeong Ho ),한지숙 ( Han Ji Sug ),채희복 ( Chae Hui Bog ),권순길 ( Kwon Sun Gil ),배일현 ( Bae Il Hyeon ) 대한신장학회 2004 Kidney Research and Clinical Practice Vol.23 No.1
Sclerosing peritonitis is a rare but fatal complication of peritoneal dialysis (PD). Management of sclerosing peritonitis includes cessation of PD, total parenteral nutrition, and surgery. Recently, a few reports have indicated immunosuppression might be beneficial in sclerosing peritonitis. In these reports, all of patients had the combination therapy of steroid and immunosuppressant. A 37-year old man develped sclerosing peritonitis 3 months after switching from PD to hemodialysis because of uncontrolled peritonitis. An abdominal computed tomography (CT) scan demonstrated massive ascites with multilocuated fluid collection and extensive enhancement of the peritoneum. A peritoneal biopsy showed proliferation of fibrous collagenous tissue with infiltration of lymphocytes. We started corticosteroid for one month. A follow-up CT scan showed complete resolution with absence of peritoneum thickness and fluid collection 16 months after corticosteroid therapy. The paient currently remains free of symptoms in an outpatient hemodialysis unit. To our knowledge, this is the first case of sclerosing peritonitis successully treated with corticosteroid therapy alone in Korea. (Korean J Nephrol 2004;23(1):169-173)
배상욱 ( Bae Sang Ug ),정병화 ( Jeong Byeong Hwa ),윤보성 ( Yun Bo Seong ),김의혁 ( Kim Ui Hyeog ),정봉철 ( Jeong Bong Cheol ),박주현 ( Park Ju Hyeon ),신종승 ( Sin Jong Seung ),김세광 ( Kim Se Gwang ),박기현 ( Park Gi Hyeon ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.5
목적 : 본 연구는 1) 골반장기 탈출증 환자의 내인성 스테로이드 호르몬 대사가 정상인의 것과 다른지 2) 내인성 스테로이드 호르몬 대사물과 골반장기 탈출증 (pelvic organ prolapse)의 등급과 서로 연관성이 있는지를 알아보고자 하였다. 연구 방법 : 골반장기 탈출증으로 진단받은 20명의 폐경후 환자와 골반장기 탈출증을 진단받지 않은 20명의 폐경후 환자를 대상으로 하였다. 두 군간의 내인성 스테로이드의 소변 검출물 (urinary profile)을 비교하였고, 내인성 스테로이드의 소변 검출물과 골반장기 탈출증 정도와의 연관성을 조사하였다. 내인성 스테로이드 호르몬의 소변 검출물은 기체 크로마토그래피-질량 분광기 (gas chromatography-mass spectrometry)로 분석하였다. 결과 : 환자군과 대조군의 나이는 각각 64.6±6.5세와 63.5±3.9세였다. 신체질량지수는 각각 23.96±3.14 및 24.11±2.73 kg/m^2 였다. 각 등급별 환자수는 등급 Ⅰ이 4명, Ⅱ가 4명, Ⅲ이 6명, 그리고 Ⅳ가 6명이었다. 골반장기 탈출증 환자군에서 정상 대조군에 비해 5-Androstene-3β, 16β, 17β-triol (5-AT), 11β-hydroxy An과 17β-estradiol이 유의하게 높게 나타났다 (0.76±0.67 vs 0.06±0.03 μmole/g creatinine; p=0.002, 1.16±0.83 vs 0.65±0.23 μmole/g creatinine; p=0.04, 15.08±9.81 vs 8.53±6.19 μmole/g creatinine; p=0.04). 하지만, Tetrahydrocortisone(THE)는 정상 대조군이 환자군보다 유의하게 높게 나타났다 (9.80±6.21 vs 5.22±4.89 μmole/g creatinine; p=0.04). 안드로젠 대사물인 5-AT, THE는 골반장기 탈출증의 등급과 의미있게 연관성이 있는 걸로 나타났다 (R=0.418l p=0.027, R=0.46l p=0.016). 에스트로젠 대사물 중에서 17β-estradiol은 골반장기 탈출증의 등급과 연관성이 있었으나 유의하게 의미있지는 않았고 (R=0.38; p=0.05), 17β-Estradiol/Estrone 비와 골반장기 탈출증의 등급은 낮은 상관계수를 보이며, 연관성이 적은 것으로 나타났다 (R=0.14; p=0.49). 결론 : 17β-Estradiol, 5-AT 및 11β-hydroxy An의 소변 농도는 정상 대조군보다 골반장기 탈출증 환자에서 증가하였고, 5-AT, THE 및 17β-estradiol은 한국 여성의 골반장기 탈출증의 진행과 관련이 있었다. 따라서, 내인성 스테로이드 호르몬 대사물은 골반장기 탈출증의 병인론에 중요한 인자라 할 수 있겠다. Objective : To identify 1) whether the endogenous steroid hormone metabolism in patients with pelvic organ prolapse was different from that of normal women, 2) the relationship between endogenous steroid hormone metabolites and the stage of the pelvic organ prolapse. Methods : Twenty postmenopausal women who were clinically diagnosed as having pelvic organ prolapse and 20 volunteer postmenopausal women not having pelvic organ prolapse were included in the study. We compared the urinary profiles of endogenous steroids between the two groups and investigated the relationship between urinary profiles of the endogenous steroids and the degree of pelvic organ prolapse. Urinary profiles of the endogenous steroids were assayed by gas chromatography-mass spectrometry. Results : The ages of the patients and control group were 64.6±6.5 and 63.5±3.9 years, and the Body Mass Index (BMI) was 23.96±3.14 and 24.11± kg/m^2 in patients and in normal subjects, respectively. The number of patients in each stage were 4 in stage Ⅰ, 4 in stage Ⅱ, 6 in stage Ⅲ and 6 in stage Ⅳ. 5-androstene-3β, 16β, 17β-triol (5-AT), 11β-hydroxy androstenedione (An) and 17β-estradiol were significantly increased in patients with pelvic organ prolapse over that of the control group (0.76±0.67 vs 0.06±0.03 μmole/g creatinine; p=0.002, 1.16±0.83 vs 0.65±0.23 μmole/g creatinine; p=0.04, 15.08±9.81 vs 8.53±6.19 μmole/g creatinine; p=0.04). However, tetrahydrocortisone (THE) was significantly increased in the control group over that in patients having pelvic organ prolapse (9.80±6.21 vs 5.22±4.89 μmole/g creatinine; p=0.04). The androgen metabolites, 5-AT and THE significantly correlated with the POP-Q stage (R=0.418; p=0.027, R=0.46; p=0.016). Among the estrogen metabolites, 17β-estradiol was correlated to the POP-Q stage but not mathematically significantly (R=0.38; p=0.05) and the 17β-estradiol/extrone ratio weakly correlated to pelvic organ prolapse stage (R=0.14l p=0.49,), by showing a low correlation coefficiency. Conclusion : The urinary concentrations of 17β-estradiol, 5-AT and 11β-hydroxy an increased in patients with pelvic organ prolapse over that of the control group and 5-AT, THE and 17β-estradiol showed a relationship to the progression of pelvic organ prolapse in Korean women. The metabolites of endogenous steroid hormones could be contributing factors in the pathogenesis of pelvic organ prolapse.
Lee, Su Ui,Kim, Mun-Ock,Kang, Myung-Ji,Oh, Eun Sol,Ro, Hyunju,Lee, Ro Woon,Song, Yu Na,Jung, Sunin,Lee, Jae-Won,Lee, Soo Yun,Bae, Taeyeol,Hong, Sung-Tae,Kim, Tae-Don Korean Society for Molecular and Cellular Biology 2021 Molecules and cells Vol.44 No.1
Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.
문가을 ( Ga Ui Mun ),전혜지 ( Hye Ji Jeon ),조은규 ( Eun Kyu Cho ),김윤숙 ( Yun Sook Kim ),배동한 ( Dong Han Bae ),이석열 ( Seok Yul Lee ),조현득 ( Hyun Deuk Cho ) 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.7
Endometriosis is a relatively common gynecologic disease. Thoracic endometriosis syndrome occupies half of various types of external endometriosis, however it is very rare condition, We experienced a case of 40-year-old woman who presented with recurrent episodes of spontaneous right-sided pneumothorax that occurred during her menstrual periods. After the localization of the disease site by means of chest radiography and high resolution computed tomography of the thorax, thoracoscopic assisted diaphragm endometriosis resection and suture were performed. After pathologic diagnosis, a hormonal treatment with gonadotropin-releasing hormone agonist was also conducted. We report this case with a brief review of the concerned literatures.