Intranasal Delivery of RGD Motif-Containing Osteopontin Icosamer Confers Neuroprotection in the Postischemic Brain via αvβ3 Integrin Binding

Jin, Yin-Chuan,Lee, Hahnbie,Kim, Seung-Woo,Kim, Il-Doo,Lee, Hye-Kyung,Lee, Yunjin,Han, Pyung-Lim,Lee, Ja-Kyeong Springer-Verlag 2016 Molecular neurobiology Vol.53 No.8

<P>Osteopontin (OPN) is a phosphorylated glycoprotein possessing an arginine-glycine-aspartate (RGD)-motif, which binds to several cell surface integrins and mediates a wide range of cellular processes. Inductions of OPN have been reported in the postischemic brain, and the neuroprotective effects of OPN have been demonstrated in animal models of stroke. In the present study, we showed a robust neuroprotective effect of RGD-containing icosamer OPN peptide (OPNpt20) in a rat model of focal cerebral ischemia (middle cerebral artery occlusion, MCAO). Intranasally administered OPNpt20 reduced mean infarct volume by 79.7 % compared to the treatment-na < ve MCAO control animals and markedly ameliorated neurological deficits. In addition, OPNpt20 significantly suppressed the inductions of iNOS and of inflammatory markers in postischemic brains and in primary microglial cultures, demonstrating anti-inflammatory effects. Administration of a mutant peptide, in which RGD was replaced by arginine-alanine-alanine (RAA), failed to suppress infarct volumes in MCAO animals and co-administration of OPNpt20 with anti-alpha(v)beta(3) integrin antibody failed to suppress iNOS induction in primary microglia culture, indicating that the RGD motif in OPNpt20 and endogenous alpha(v)beta(3) integrin play critical roles. Furthermore, pull-down assay revealed a direct binding between OPNpt20 and alpha(v)beta(3) integrin in primary microglia culture. Together, these results indicate that RGD-containing OPN icosamer has therapeutic potential in the postischemic brain and alpha(v)beta(3) integrin-mediated anti-inflammatory effect might be an underlying mechanism.</P>

Stabilizing the catalyst layer for durable alkaline membrane fuel cells

Chuan Hu,Seung Won Jung,Xiaohua Zhang,Young Jun Lee,Young Jun Lee,Young Moo Lee 한국막학회 2022 한국막학회 총회 및 학술발표회 Vol.2022 No.11

Precursor mass prediction by clustering ionization products in LC-MS-based metabolomics

Lee, Terk Shuen,Ho, Ying Swan,Yeo, Hock Chuan,Lin, Joyce Pei Yu,Lee, Dong-Yup Springer-Verlag 2013 Metabolomics Vol.9 No.6

Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist

Lee, Soonchul,Shen, Jia,Pan, Hsin Chuan,Shrestha, Swati,Asatrian, Greg,Nguyen, Alan,Meyers, Carolyn,Nguyen, Vi,Lee, Min,Soo, Chia,Ting, Kang,James, Aaron W. Mary Ann Liebert 2016 Tissue engineering. Part A Vol.22 No.23

<P>Hedgehog (Hh) signaling positively regulates both endochondral and intramembranous ossification. Use of small molecules for tissue engineering applications poses several advantages. In this study, we examined whether use of an acellular scaffold treated with the small molecule Smoothened agonist (SAG) could aid in critical-size mouse calvarial defect repair. First, we verified the pro-osteogenic effect of SAG in vitro, using primary neonatal mouse calvarial cells (NMCCs). Next, a 4mm nonhealing defect was created in the mid-parietal bone of 10-week-old CD-1 mice. The scaffold consisted of a custom-fabricated poly(lactic-co-glycolic acid) disc with hydroxyapatite coating (measuring 4mm diameterx0.5mm thickness). Treatment groups included dimethylsulfoxide control (n=6), 0.5mM SAG (n=7) or 1.0mM SAG (n=7). Evaluation was performed at 4 and 8 weeks postoperative, by a combination of high-resolution microcomputed tomography, histology (H & E, Masson's Trichrome), histomorphometry, and immunohistochemistry (BSP, OCN, VEGF). In vivo results showed that SAG treatment induced a significant and dose-dependent increase in calvarial bone healing by all radiographic parameters. Histomorphometric analysis showed an increase in all parameters of bone formation with SAG treatment, but also an increase in blood vessel number and density. In summary, SAG is a pro-osteogenic, provasculogenic stimulus when applied locally in a bone defect environment.</P>

Impact of Adjuvant Chemotherapy in Elderly Breast Patients in Taiwan, A Hospital-Based Study

Lee, Hsiu Chuan,Chen, Wei Yu,Huang, Wen Tsung,Cheng, Kuo Chen,Tian, Yu Feng,Ho, Chung Han,Tsao, Chao Jung,Feng, Yin Hsun Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Purpose: Decisions as to whether to provide adjuvant treatment in older breast cancer patients remains challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty. To aid decision-making, we retrospectively analyzed 110 women with breast cancer treated with a curative intention from 2006 to 2012. Survival data with clinical and pathological parameters were evaluated to address the role of adjuvant chemotherapy in this study population. Method: A total of 110 elderly (>70 years) patients that received mastectomy at two hospitals in Taiwan were observed retrospectively for a medium of 51 months. After mastectomy, patients received conservative treatment or adjuvant chemotherapy, or hormone therapy following clinical guidelines or physician's preference. Data were collected from the cancer registry system. Results: Median age at diagnosis was 75.7 years. Thirty-five percent of patients received adjuvant chemotherapy, these having a significantly younger age ($mean=74.0{\pm}5.3$ vs $77.5{\pm}5.3$, p<0.001) and higher tumor staging (p=0.003) compared with their non-chemotherapy counterparts.Five-year overall survival was non-significantly higher in patients who received adjuvant chemotherapy (with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635), while five-year recurrence free survival was non-significantly lower (with chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In this analysis, adjuvant chemotherapy tended to be given to patients with a younger age and higher tumor staging at our institute. It was not associated with any statistically significant improvement in survival and recurrence rate. Until age specific recommendations are available, physicians must use their clinical judgment and assess the tumor biology with the patient's comorbidities to make the best choice. Clinical trials focusing on this critical issue are warranted.

Proangiogenic functions of an RGD-SLAY-containing osteopontin icosamer peptide in HUVECs and in the postischemic brain

Lee, Hahnbie,Jin, Yin-Chuan,Kim, Seung-Woo,Kim, Il-Doo,Lee, Hye-Kyung,Lee, Ja-Kyeong Nature Publishing Group 2018 Experimental and molecular medicine Vol.50 No.1

<P>Osteopontin (OPN) is a phosphorylated glycoprotein secreted into body fluids by various cell types. OPN contains arginine-glycine-aspartate (RGD) and serine-leucine-alanine-tyrosine (SLAY) motifs that bind to several integrins and mediate a wide range of cellular processes. In the present study, the proangiogenic effects of a 20-amino-acid OPN peptide (OPNpt20) containing RGD and SLAY motifs were examined in human umbilical vein endothelial cells (HUVECs) and in a rat focal cerebral ischemia model. OPNpt20 exerted robust proangiogenic effects in HUVECs by promoting proliferation, migration and tube formation. These effects were significantly reduced in OPNpt20-RAA (RGD->RAA)-treated cells, but only slightly reduced in OPNpt20-SLAA (SLAY->SLAA)-treated cells. Interestingly, a mutant peptide without both motifs failed to induce these proangiogenic processes, indicating that the RGD motif is crucial and that SLAY also has a role. In OPNpt20-treated HUVEC cultures, AKT and ERK signaling pathways were activated, but activation of these pathways and tube formation were suppressed by anti-α<SUB>v</SUB>β<SUB>3</SUB> antibody, indicating that OPNpt20 stimulates angiogenesis via the α<SUB>v</SUB>β<SUB>3</SUB>-integrin/AKT and ERK pathways. The proangiogenic function of OPNpt20 was further confirmed in a rat middle cerebral artery occlusion model. Total vessel length and vessel densities were markedly greater in OPNpt20-treated ischemic brains, accompanied by induction of proangiogenic markers. Together, these results demonstrate that the 20-amino-acid OPN peptide containing RGD and SLAY motifs exerts proangiogenic effects, wherein both motifs have important roles, and these effects appear to contribute to the neuroprotective effects of this peptide in the postischemic brain.</P>

Reinventing Racial Forms : Japanese American Internment in Days of Waiting

Hsiu‐chuan Lee 21세기영어영문학회 2013 21세기영어영문학회 학술대회 Vol.2013 No.09

Reinventing Racial Forms: Japanese America Internment and the Case of Estelle Ishigo in Days of Waiting

( Hsiu Chuan Lee ) 한국현대영미소설학회 2013 현대영미소설 Vol.20 No.3

While the mass internment of Japanese Americans in World War II has highlighted the Asian exclusionism and racial persecution in the United States, this paper aims not simply to reassert an Asian American politics against racism but to find in the process and aftermath of Japanese American internment an important sociopolitical arena for our critical meditation on and creative imagination of race relations in the U.S. Probing into Asian Americans` intermediary position in the conventional black-white racial dyad, the first section of this paper draws on Colleen Lye`s idea of “racial form.” Instead of conceiving race as determined by inherent biological features or indicating transhistorical entities, Lye proposes to read race as “form” (which is constituted by active social relations) and privileges the formal and stylistic creativity of literary and cultural texts to invent racial forms. The second and third sections of this paper move to Japanese American internment and study the case of Estelle Ishigo in Steven Okazaki`s documentary Days of Waiting (1990). Attending to Ishigo`s cross-racial life story, my reading not only explores the changeable contours of racial categorization in the context of the internment but also reveals the inadequacy of the “whites vs. Japanese Americans” critical model in excavating the cross-racial dialectics evoked by Days of Waiting.

Hedging Performance and Stock Market Liquidity: Evidence from the Taiwan Futures Market

Hsiu-Chuan Lee,Cheng-Yi Chien 한국증권학회 2010 Asia-Pacific Journal of Financial Studies Vol.39 No.3

This paper examines the impact of stock market liquidity on the hedging performance of stock index futures, and extends the conditional OLS model described by Miffre [Journal of Futures Markets 24 (2004) 945] by including stock market liquidity in the regression model. The empirical results indicate that information regarding stock market liquidity is useful in predicting the optimal hedge ratio under different market conditions. In a bear market, the conditional OLS model with stock market liquidity provides the best hedging performance for the out-of-sample period. Although the OLS model outperforms the generalized autoregressive conditional heteroskedasticity and conditional OLS models for the out-of-sample period in a bull market, the conditional OLS model with stock market liquidity outperforms the conditional OLS model without stock market liquidity in terms of downside risks (lower partial moment).

Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

Kuei-Chuan Lee,Pei-Shan Wu,Han-Chieh Lin 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.1

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis.