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1.  IGF-1 Counteracts TGF-β-Mediated Enhancement of Fibronectin for in Vitro Human Lens Epithelial Cells 
Yonsei Medical Journal  2007;48(6):949-954.
To determine whether insulin-like growth factor (IGF-1) affects transforming growth factor (TGF-β)-mediated fibronectin accumulation in human lens epithelial cell line (HLE B-3) cells.
Materials and Methods
HLE B-3 cells were incubated for 24 hours with TGF-β (10 ng/mL), IGF-1 (10 ng/mL), or both. Expression of the fibronectin gene was determined using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Fibronectin levels were examined using western blot analysis and immunofluorescence staining.
Expression of the fibronectin gene was not different between the TGF-β/IGF-1 treated group and the TGF-β treated group (p = 0.116). However, western blot analysis demonstrated decreased fibronectin levels in human lens epithelial cells treated with TGF-β and IGF-1 compared to those treated with TGF-β only (p < 0.01). Immunofluorescence staining disclosed inhibition of TGF-β-induced fibronectin in the presence of IGF-1.
This study suggests that IGF-1 counteracts TGF-β-mediated fibronectin accumulation in human lens epithelial cells.
PMCID: PMC2628178  PMID: 18159585
Fibronectin; IGF-1; lens epithelial cells; TGF-β
2.  Expression of microRNAs in fibroblast of pterygium 
To screen microRNAs (miRNAs) and set up target miRNAs in pterygium.
Primary fibroblasts were isolated from pterygium and Tenon's capsule and cultured. Immunocytochemical analysis and Western blotting were performed to confirm the culture of fibroblasts. In all, 1733 miRNAs were screened in the first step by using GeneChip® miRNA3.0 Array. Specific miRNAs involved in the pathogenesis of pterygium were subsequently determined using the following criteria: 1) high reproducibility in a repetitive test; 2) base log value of >7.0 for both control and pterygial fibroblasts; and 3) log ratio of >1.0 between pterygial fibroblasts and control fibroblasts.
Primary screening showed that 887/1733 miRNAs were up-regulated and 846/1733 miRNAs were down-regulated in pterygial fibroblasts compared with those in control fibroblasts. Of the 1733 miRNAs screened, 4 miRNAs, namely, miRNA-143a-3p, miRNA-181a-2-3p, miRNA-377-5p and miRNA-411a-5p, met the above-mentioned criteria. Primary screening showed that these 4 miRNAs were up-regulated in pterygial fibroblasts compared with control fibroblasts and that miRNA-143a-3p had the highest mean ratio compared with the miRNAs in control fibroblasts.
miRNA-143a-3p, miRNA-181a-2-3p, miRNA-377-5p and miRNA-411a-5p are up-regulated in pterygial fibroblasts compared with control fibroblasts, suggesting their involvement in the pathogenesis of pterygium.
PMCID: PMC4951674  PMID: 27500101
microRNA; pterygium; fibroblast
3.  Effect of Floor Space Allowance on Pig Productivity across Stages of Growth: A Field-scale Analysis 
A total of 152 pig farms were randomly selected from the five provinces in South Korea. During the experiment, the average temperature and relative humidity was 24.7°C and 74% in summer and 2.4°C and 53% in winter, respectively. The correlation between floor space allowance (FSA) and productivity index was analyzed, including non-productive sow days (NPD), number of weaners (NOW), survival rate (SR), appearance rate of A-grade pork (ARA), and days at a slaughter weight of 110 kg (d-SW) at different growth stages. The objectives of the present study were i) to determine the effect of FSA on the pig productivity index and ii) to suggest the minimum FSA for pigs based on scientific baseline data. For the pregnant sow, NPD could be decreased if pregnant sows were raised with a medium level (M) of FSA (3.10 to 3.67 m2/head) while also keeping the pig house clean which improves hygiene, and operating the ventilation system properly. For the farrowing sows, the NOW tended to decrease as the FSA increased. Similarly, a high level of FSA (H) is significantly negative with weaner SR of farrowing sows (p-value = 0.017), indicating this FSA tends to depress SR. Therefore, a FSA of 2.30 to 6.40 m2/head (very low) could be appropriate for weaners because a limited space can provide a sense of security and protection from external interruptions. The opposite trend was observed that an increase in floor space (>1.12 m2/head) leads to increase the SR of growing pigs. For the fattening pigs, H level of FSA was negatively correlated with SR, but M level of FSA was positively correlated with SR, indicating that SR tended to increase with the FSA of 1.10 to 1.27 m2/head. In contrast, ARA of male fattening pigs showed opposite results. H level of FSA (1.27 to 1.47 m2/head) was suggested to increase productivity because ARA was most affected by H level of space allowance with positive correlation (R2 = 0.523). The relationship between the FSA and d-SW of fattening pigs was hard to identify because of the low R2 value. However, the farms that provided a relatively large floor space (1.27 to 1.54 m2/head) during the winter period showed d-SW was significantly and negatively affected by FSA.
PMCID: PMC4852238  PMID: 26954180
Floor Space Allowance; Pig Productivity; Performance; Field-scale Analysis
4.  TGF-β-induced interleukin-6 participates in transdifferentiation of human Tenon’s fibroblasts to myofibroblasts 
Molecular Vision  2009;15:2123-2128.
To gain a better understanding of the roles of interleukins (ILs) in subconjunctival fibrosis, we investigated their expression in transforming growth factor-β1 (TGF-β1)-stimulated Tenon’s fibroblasts and examined their association with the transdifferentiation of fibroblasts to myofibroblasts.
After primary culture, fibroblasts derived from human Tenon’s capsule were exposed to TGF-β1. The expression of α-smooth muscle actin (α-SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA levels of various ILs were also evaluated by multiplex reverse transcription (RT)-PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-β1-induced induction of α-SMA were determined.
In human Tenon’s fibroblasts, TGF-β1 stimulated the expression of α-SMA protein determined by western blot analysis and also increased the mRNA levels of IL-6 and IL-11 determined by multiplex RT-PCR. On the western immunoblots and immunofluorescence, the increased expression of α-SMA was attenuated only by the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the activator protein-1 binding sites of the IL-6 promoter region were deleted, the stimulation effects of TGF-β1 decreased.
Our data show that autocrine IL-6 may participate in the TGF-β1-induced transdifferentiation of human Tenon’s fibroblasts to myofibroblasts, which is known to be an essential step for subconjunctival fibrosis.
PMCID: PMC2765236  PMID: 19862334
5.  Incidental Microscopic Bile Duct Tumor Thrombi in Hepatocellular Carcinoma after Curative Hepatectomy 
Medicine  2015;94(6):e450.
In patients with hepatocellular carcinoma (HCC), the presence of bile duct tumor thrombi (BDTT) in the major bile ducts indicates poor prognosis compared with that of HCC patients without BDTT. However, the prognostic significance of incidental microscopic BDTT in the peripheral bile ducts after curative liver resection is not known. We compared the outcomes of HCC patients with and without microscopic BDTT in the peripheral bile ducts who underwent hepatectomy.
The electronic medical records of 31 patients with microscopic BDTT (BDTT group) were retrospectively reviewed. To compare the surgical outcomes, 62 patients (No BDTT group) were randomly chosen from the remaining HCC patients without BDTT based on age, sex, etiology of HCC, tumor size, tumor number, and modified Union for International Cancer Control T staging.
The 1-year, 2-year, and 3-year disease-free survival rates and overall survival rates were 54.8%, 34.0%, 34.0% and 90.1%, 69.2%, 61.0% in the BDTT group and 66.8%, 59.2%, 42.3% and 86.4%, 84.4%, 84.4% in the No BDTT group (P = 0.089 and P = 0.014, respectively). The overall survival curve in the No BDTT group was higher than that in the BDTT group. Multivariate analysis revealed that predisposing factors for tumor recurrence after curative liver resection included increased levels of the protein induced by vitamin K antagonist-II (PIVKA-II), tumor grades 3 and 4, and the presence of BDTT.
This study demonstrates that HCC prognosis is worse in patients with incidental microscopic BDTT in the peripheral bile ducts than it is in those without BDTT. The presence of BDTT should therefore be considered when evaluating a patient's HCC prognosis after curative hepatectomy.
PMCID: PMC4602767  PMID: 25674733
6.  OxLDL Induces PiT-1 Expression in Human Aortic Valve Interstitial Cells 
The Journal of surgical research  2013;184(1):10.1016/j.jss.2013.05.001.
The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of calcific aortic stenosis. When appropriately stimulated, AVICs undergo a phenotypic change from that of a myofibroblast to that of a bone-forming-like cell. Elevated blood levels of LDL-cholesterol are a clinical risk factor for aortic stenosis, and oxidized LDL-cholesterol (ox-LDL) is consistently found in calcified aortic valve leaflets. But whether it plays a role in the pathogenesis of aortic stenosis is unknown. The process of aortic valve leaflet calcification is associated with deposition of calcium- phosphate, mediated in part by the phosphate inorganic transporter 1 (PiT-1), a sodium-phosphate ion co-transporter. Therefore, we hypothesized that ox-LDL induces an osteogenic change in human AVICs marked by the induction of PiT-1. Using isolated human AVICs, the purpose of this study was to examine the effect of ox-LDL on the expression of PiT-1 and the osteogenic factor bone morphogenetic protein 2 (BMP-2), which is a protein necessary for bone formation.
Human AVICs were isolated from non-stenotic aortic valves obtained from explanted hearts of patients undergoing cardiac transplantation (n=4) and grown in culture. The cells were treated with serum free media, serum free media with DMSO (vehicle control), 40 μg/ml of ox-LDL or 40 μg/ml of Ox-LDL + 2.5 mM phosphonoformic acid. Phosphonoformic acid (PFA) is a competitive inhibitor of PiT-1 by mimicking inorganic phosphate. Cell lysis was performed at 24 hours following treatment. Cell lysates were analyzed via immunoblot and densitometry for PiT-1 and BMP-2. Statistics were by ANOVA. P < 0.05 was significant.
ox-LDL stimulation of AVICs induced an increase in PiT-1 and BMP-2. Ox-LDL induced increased production of the phosphate transporter, PiT-1, and the osteogenic factor, BMP-2. Inhibition of PiT-1 with PFA prevented ox-LDL-induced BMP-2 expression.
These data offer mechanistic insight into the pathogenesis of calcific aortic stenosis.
PMCID: PMC3879113  PMID: 23849774
aortic stenosis; aortic valve interstitial cell; oxLDL; PiT-1
7.  Interleukin-1 Beta Induces an Inflammatory Phenotype in Human Aortic Valve Interstitial Cells Through Nuclear Factor Kappa Beta 
The Annals of thoracic surgery  2013;96(1):10.1016/j.athoracsur.2013.04.013.
Mechanisms of inflammation have been implicated in the pathogenesis of aortic stenosis. When stimulated, human aortic valve interstitial cells (AVICs) have been shown to become inflammatory cells. Increased levels of interleukin (IL)-1β have been found in the leaflets of stenotic aortic valves. The purpose of this study was to determine the effects of IL-1β on isolated human AVICs and to determine the intracellular signaling pathway by which the effects are mediated. The results of this study demonstrated that IL-1β induces an inflammatory phenotype in human AVICs.
Human AVICs were isolated from normal aortic valves from explanted hearts of patients undergoing cardiac transplantation (n = 4) and grown in culture. When grown to confluence, the cells were treated with IL-1β (10 ng/mL). Cell culture media was analyzed for IL-6, IL-8, and monocyte chemoattractant protein-1 (enzyme-linked immunosorbent assay). Cell lysates were analyzed for intercellular adhesion molecule-1 (immunoblot). Inhibition of nuclear factor-κβ was by Bay 11-7085 (5 μM). Inhibition of extracellular signal regulated kinase-1/2 was by PD098059 (20 nM). Statistics were by analysis of variance, with p less than 0.05 significant.
Interluekin-1β induced an inflammatory phenotype in human AVICs. The IL-1β stimulation resulted in significantly increased production of the inflammatory cytokines, IL-6 and IL-8, the chemokine monocyte chemoattractant protein-1, and intercellular adhesion molecule-1. Inhibition of nuclear factor-κβ prevented these changes, whereas inhibition of extracellular signal regulated kinase-1/2 had no effect.
Interleukin-1β induced an inflammatory phenotype in human AVICs, which was prevented by inhibition of nuclear factor-κβ. These data implicate IL-1β in the pathogenesis of aortic stenosis.
PMCID: PMC3833085  PMID: 23735716
8.  Nanostructured conformal hybrid solar cells: a promising architecture towards complete charge collection and light absorption 
Nanoscale Research Letters  2013;8(1):359.
We introduce hybrid solar cells with an architecture consisting of an electrodeposited ZnO nanorod array (NRA) coated with a conformal thin layer (<50 nm) of organic polymer-fullerene blend and a quasi-conformal Ag top contact (Thin/NR). We have compared the performance of Thin/NR cells to conventional hybrid cells in which the same NRAs are completely filled with organic blend (Thick/NR). The Thin/NR design absorbs at least as much light as Thick/NR cells, while charge extraction is significantly enhanced due to the proximity of the electrodes, resulting in a higher current density per unit volume of blend and improved power conversion efficiency. The NRAs need not be periodic or aligned and hence can be made very simply.
PMCID: PMC3765516  PMID: 23965048
Photovoltaic; Electrodeposition; P3HT-PCBM; Bulk heterojunction; Nanostructured; ZnO nanorod arrays; Hybrid solar cells; 81; 88
9.  Effect of fibrin glue as an adjuvant to hang-back surgery 
BMC Ophthalmology  2012;12:14.
The hang-back surgery is a useful technique in the field of strabismus surgery. The aim of this study is to determine the stabilizing effects of fibrin glue as an adjuvant to hang-back surgery.
Materials and methods
Four (4)-mm hang-back recessions of the superior rectus muscle was performed in 32 eyes of 16 rabbits. Only in the left eye of the 16 rabbits, fibrin glue was applied between the recessed muscle bed and the sclera at the end of hang-back surgery (fibrin glue group). After 6 weeks, we compared the stability of the recessed rectus muscle between the fibrin glue group and the control group by evaluating the displacement of the muscle.
The frequency of stable insertion of the recessed muscle at the intended site was greater in the fibrin glue group (9 eyes) compared to the control group (3 eyes) (p = 0.028). In the control group, 5 eyes showed anterior displacement and 8 eyes showed posterior displacement and in the fibrin glue group, 1 eye showed anterior displacement, and 6 eyes showed posterior displacement. Anterior displacement was more common in the control group (6.3% Vs 31.3%). The control group and the fibrin glue group showed similar histological findings on microscopic examination.
Fibrin glue is effective in stabilizing the new rectus muscle insertion and decreasing the displacement in the hang-back surgery.
PMCID: PMC3473302  PMID: 22677044
Fibrin glue; Hang-back surgery; Rabbit
10.  Gender-Specific Transfusion Affects Tumor-Associated Neutrophil: Macrophage Ratios in Murine Pancreatic Adenocarcinoma 
Perioperative blood transfusion has been linked to decreased survival for pancreas cancer. Noting clinical data associating female blood products with increased morbidity, our lab has demonstrated that transfusion of female blood augments metastatic events compared to male blood in an immunocompetent murine pancreatic cancer model. It has been suggested that tumor-associated macrophages correlate with tumor progression by promoting angiogenesis. More recently, tumor-associated neutrophils have been implicated in aggressive tumor behavior. We hypothesize that differences in gender-specific transfusion-mediated pancreatic cancer progression are due to microenvironmental changes within the tumor. To test this hypothesis, we examined tumor-associated neutrophils and macrophage ratios in male and female mice with pancreatic cancer receiving blood transfusion from male or female donors.
C57/BL6 mice, age 7–9 weeks, underwent splenic inoculation with 2.5×105 PanO2 murine pancreatic adenocarcinoma cells. Mice were transfused on post-op day 7 with 1 ml/kg supernatant from day 42 male or female packed red cells. Necropsy was performed at 5 weeks or earlier for clinical deterioration, and tumors harvested. Frozen sections (5 μm) were stained for neutrophils and macrophages by immunofluorescence. Data were analyzed using ANOVA; p≤0.05 was used to determine significance; N≥3 per group.
Clinically, male mice had greater morbidity and mortality than female mice when receiving female blood products, with roughened hair coat, development of ascites and death due to bowel obstruction. In evaluating the tumor microenvironment from mice receiving female blood products, male mice were noted to have a greater neutrophil to macrophage ratio than female mice, 0.176±0.028 vs. 0.073±0.012, p=0.03. When examining neutrophil to macrophage ratio in mice receiving male blood products, no difference was noted (p=0.48).
Male mice with pancreas cancer have greater morbidity than female mice when receiving female blood products. Furthermore, the difference in neutrophil to macrophage ratio suggests that gender-specific blood transfusion promotes aggressive tumor behavior in male mice via microenvironmental changes. These data warrant further study to delineate sex-related differences in pancreatic cancer progression.
PMCID: PMC3133655  PMID: 20835771
Transfusion; Pancreas cancer; Metastasis; Erythrocytes; Immunomodulation; Neutrophil to macrophage ratio

Results 1-10 (10)