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Therapeutic Angiogenesis as a Potential Future Treatment Strategy for Erectile Dysfunction
Ryu, Ji-Kan,Suh, Jun-Kyu Korean Society for Sexual Medicine and Andrology 2012 The World Journal of Men's Health Vol.30 No.2
<P>The cavernous endothelium plays a crucial role in regulating the tone of the underlying smooth muscle and physiologic penile erection. Recently, the link between erectile dysfunction (ED) and cardiovascular disease was unveiled, and the main etiology of ED was found to be vasculogenic. Although oral phosphodiesterase-5 inhibitors are generally effective for men with ED, such therapies do not cure underlying vasculopathy in the corpus cavernosum tissue. This review addresses current preclinical protein, gene, and cell or stem cell therapies for enhancing cavernous endothelial regeneration and restoring erectile function.</P>
Ryu, Ji-Kan,Zhang, Lu Wei,Jin, Hai-Rong,Piao, Shuguang,Choi, Min Ji,Tuvshintur, Buyankhuu,Tumurbaatar, Munkhbayar,Shin, Sun Hwa,Han, Jee-Young,Kim, Woo Jean,Suh, Jun-Kyu Blackwell Pub 2009 The journal of sexual medicine Vol.6 No.7
<P>Endothelial cell-to-cell junctions are crucial for vascular formation, networking, and remodeling of blood vessels as well as for inducing and integrating intracellular signals.</P>
Ryu, Ji-Kan,Cho, Chung-Hyun,Shin, Hwa-Yean,Song, Sun U.,Oh, Seung-Min,Lee, Minhyung,Piao, Shuguang,Han, Jee-Young,Kim, In-Hoo,Koh, Gou Young,Suh, Jun-Kyu Elsevier 2006 MOLECULAR THERAPY Vol.13 No.4
<P><B>Abstract</B></P><P>Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.</P>
Ryu, Ji-Kan,Tumurbaatar, Munkhbayar,Jin, Hai-Rong,Kim, Woo Jean,Kwon, Mi-Hye,Piao, Shuguang,Choi, Min Ji,Yin, Guo Nan,Song, Kang-Moon,Kang, Yong-Jin,Koh, Young Jun,Koh, Gou Young,Suh, Jun-Kyu Blackwell Pub 2012 JOURNAL OF SEXUAL MEDICINE Vol.9 No.12
<P>Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors.</P>
Lipopolysaccharide/D-Galactosamine에 의해 유도된 급성 간 손상 생쥐모델에서 굴가수분해물의 간 보호 효과
류지현(Ji Hyeon Ryu),김은진(Eun-Jin Kim),Chengliang Xie,Marie Merci Nyiramana,Adrian S. Siregar,박시향(Si-Hyang Park),조수범(Soo Buem Cho),송대현(Dae Hyun Song),김남길(Nam-Gil Kim),최영준(Yeung Joon Choi),강상수(Sang Soo Kan 한국식품영양과학회 2017 한국식품영양과학회지 Vol.46 No.6
산화스트레스와 염증은 간 손상의 진행과정에 중요한 인자로 작용한다. 굴가수분해물의 항산화 및 항염증 활성은 지질대사, 혈압 및 혈당, 면역기능의 조절과 같은 다양한 기능에 관여한다. 그러나 급성 간 손상 모델에서 굴가수분해물의 효과를 확인한 연구 결과는 아직 확인된 바 없다. 본 연구는 LPS/D-GalN에 의해 유도된 급성 간 손상 생쥐 모델에서 굴가수분해물의 효과를 확인하기 위해 수행되었다. 실험군은 대조군(생리식염수), LPS/D-GalN 간 손상군, LPS/DGalN과 굴가수분해물(100 mg/kg, 200 mg/kg, 400 mg/kg)의 병합투여군 및 LPS/D-GalN과 silymarin(25 mg/kg) 병합투여군으로 나누었다. 급성 간 손상 모델은 1 μg/kg의 LPS와 400 mg/kg의 D-GalN으로 유도되었다. 먼저 시료의 항산화 및 항염증 활성을 분석한 결과 굴가수분해물은 농도 의존적으로 높은 DPPH 및 ABTS 라디칼 소거 활성을 보였으며, 인간 정상 간세포주(Chang)에서 과산화수소에 의한 세포 내 활성산소의 생성을 유의적으로 감소시켰다. 또한, 굴가수분해물은 농도 의존적으로 높은 COX-2 및 5-LOX 억제능을 보였으며, LPS에 의해 활성화된 생쥐 대식세포주 RAW264.7에서 발현되는 TNF-α, IL-6 및 IL-1α의 염증성 사이토카인의 mRNA 발현률을 감소시켰다. 굴가수분해물 투여는 LPS/D-GalN에 의한 혈청 ALT 및 AST증가를 유의적으로 감소시켰으며, 간 조직의 출혈 및 간세포의 자멸사를 감소시켰다. 또한, 간 균질의 TNF-α, IL-1β 및 IL-6 함량을 감소시켰으며, 감소한 catalase의 활성을 유의적으로 증가시켰다. 이상의 결과로부터 굴가수분해물은 간 보호 효과를 가지는 것으로 판단되며, 급성 간 손상의 예방 및 치료에 도움이 될 수 있는 시료로 활용될 수 있을 것으로 기대된다. Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS (1 μg/kg) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1α expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in TNF-α, IL-1β, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.
The mouse as a model for the study of penile erection: moving towards a smaller animal
Piao, Shuguang,Ryu, Ji-Kan,Shin, Hwa-Yean,Han, Jee-Young,Lee, Hong-Sik,Suh, Jun-Kyu Scriptor Publisher ApS 2007 International journal of andrology Vol.30 No.5
<P>Summary</P><P>We evaluated erectile haemodynamics in mice and characterized the corpus cavernosum morphologically. Four-month-old male BALB/c mice and Sprague–Dawley rats were used. The following stimulation parameters were tested to achieve maximal erectile responses: voltage, 1–6 V; frequency, 6–24 Hz; pulse width, 1 msec; duration, 1 min (<I>n</I> = 7 per group). In a separate group of mice and rats (<I>n</I> = 10 per group), we measured systemic arterial pressure by use of either a 24-gauge angiocatheter or smaller calibre PE-10 tubing. Cavernous tissues from mice, rats or patients with psychogenic erectile dysfunction were stained for factor VIII, <I>&agr;</I>-actin and Masson trichrome. Electrical stimulation of the cavernous nerve in mice produced voltage-dependent erectile responses of up to 5 V, with the highest response at a frequency of 12 Hz. The maximal intracavernous pressure recorded at this stimulation parameter was comparable with that in rats. A PE-10 catheter was more reliable for measuring systemic arterial pressure in mice than was a 24-gauge angiocatheter, and the values recorded were similar between mice and rats. The content of endothelial cells, smooth muscle cells and collagen was similar between mice and rats. However, the cavernous tissue of both animals contained lesser amounts of smooth muscle cells and greater amounts of collagen than that of humans (<I>p</I> < 0.01). These results suggest that the mouse is a useful and technically feasible model for the study of penile erection and has functional and structural properties similar to those of rats.</P>