• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• Journal of Microbiology and Biotechnology
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• v.28 no.3
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• pp.367-374
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• 2018

RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment. Additionally, the BR2-VEGF siRNA complex exhibited significant serum stability and high levels of gene-silencing effects in vitro. Moreover, the transfection efficiency of the complex into a cancer cell line was higher than that observed in non-cancer cell lines, resulting in downregulated intracellular VEGF levels in HeLa cells and comprehensively improved antitumor efficacy in the absence of significant toxicity. These results indicated that BR2 has significant potential for the safe, efficient, and specific delivery of siRNA for diverse applications.

• Clinics in Shoulder and Elbow
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• v.22 no.2
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• pp.79-86
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• 2019

Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy. Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically. Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). Conclusions: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.506-518
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• 2021

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.687-694
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• 2003

Purpose : Regeneration and repair after ischemic renal injury appears to be modulated by circulating or locally produced growth factors. This study examined the changes of serum insulin like growth factor(IGF-I) and renal expression of IGF-I and II, vascular endothelial growth factor(VEGF), transforming growth $factor-{\beta}$($TGF-{\beta}$), and connective tissue growth factor(CTGF) during the active regeneration period after acute ischemic injury. Methods : Sera and kidney tissue samples(whole kidney, cortex, outer medullae and inner medullae) were obtained before and after one, three, five and seven days of 40 minutes bilateral renal pedicle clamping. Acute renal failure was assessed by measuring the concentration of serum creatinine. Serum IGF-I level was measured by radioimmunoassay. The mRNA expression in kidney was measured by RT-PCR. The distribution of IGF-I and CTGF was detected by immunohistochemistry. Resuts : Serum IGF-I concentration after one day following acute ischemic renal injury was significantly decreased compared to preischemic value. The mRNA levels of IGF-I, IGF-II, $TGF-{\beta}1$ and VEGF in whole kidney were temporally decreased on day one of ischemic injury. IGF-I and IGF-II expressions in outer medullae were significantly decreased on day one after ischemic injury. $TGF-{\beta}1$, CTGF and VEGF expressions were markedly decreased in medullae after one day of ischemic injury compared to other kidney sections. IGF-I was markedly decreased in cortical tubules on day one of uremic rat. CTGF was markedly increased on tubule within three days of ischemic injury. Conclusion : These findings suggest that IGFs, $TGF-{\beta}1$ and CTGF may involve in the pathogenesis or the recovery from acute ischemic renal injury.

• Journal of The Korean Ophthalmological Society
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• v.59 no.12
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• pp.1142-1151
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• 2018

Purpose: We assessed the visual and anatomical outcomes, and the safety profile of long-term intravitreal anti-vascular endothelial growth factor (VEGF) injections (aflibercept, ranibizumab, and bevacizumab) given to treat neovascular age-related macular degeneration (NAMD). Methods: We analyzed medical records collected over 7 years of treatment-naive NAMD patients who received outpatient clinic-based intravitreal anti-VEGF injections. All were treated employing either "treat-and-extend" or "as needed" protocols at the discretion of the retinal specialist. The number of injections, adverse events associated with injection, and measures of visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP) were recorded. Results: Overall, we assessed 196 eyes of 196 patients (average age $68.6{\pm}9.6years$; 77 females). Patients received an average of $17.3{\pm}13.5$ injections over $78.0{\pm}16.5months$ of clinical follow-up. The initial mean VA (logMAR) was $0.75{\pm}0.58$ and the CFT was $349.7{\pm}152.6{\mu}m$. Both parameters exhibited maximal improvements at the 6-month visit (p < 0.05). However, the clinical outcomes worsened over the 7-year clinical course; the best-corrected visual acuity (BCVA) was $0.91{\pm}0.78$ and the CFT was $284.5{\pm}105.8{\mu}m$ at 7 years. The BCVA at 7 years was significantly correlated with the initial BCVA. IOP-related events increased 11-fold and anterior chamber reactions increased 3-fold over the years, but no significant complications such as endophthalmitis were recorded. Conclusions: The use of intravitreal anti-VEGF agents was associated with initial visual improvements over 6 months but did not prevent the worsening of NAMD over 5 years. The BCVA at the initial visit was a strong predictor of the final BCVA. A more intensive injection schedule might improve long-term outcomes.

• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.141-146
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• 2019

Sparassis crispa is an edible mushroom that is distributed in Korea, Japan, Europe, and North America. It exerts various biological activities such as immunopotentiation, anti-diabetic, anti-cancer, and anti-inflammatory effects. Recently, we separated the health functional non-aqueous fraction from the chloroform extract of S. crispa (SCF4). In this study, we evaluated the antiangiogenic activity of SCF4 in human umbilical vein endothelial cells (HUVECs). SCF4 effectively inhibited vascular endothelial growth factor (VEGF)-induced cell growth at concentrations ($5-25{\mu}g/mL$) showing no cytotoxic effects. SCF4 inhibited VEGF-induced invasiveness and tube formation ability, which are in vitro angiogenic features of HUVECs, in a dose-dependent manner. In addition, SCF4 markedly suppressed in vivo angiogenesis of chorioallantoic membrane from growing chick embryos without cytotoxicity. Furthermore, SCF4 downregulated the phosphorylation of VEGFR2, AKT, and ERK1/2, which are major angiogenic signal mediators. These results suggest that SCF4 inhibited angiogenesis by suppressing the VEGFR2 signaling pathways without cytotoxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.453-461
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• 2007

Drynariae Rhizoma has been used for promotes mending of the sinews and bone, tonifies the kidney for such symptoms as weak low back and knees, and stimulates the growth of hair as a tinctute for alopecia in oriental medicine. This experiment examined the effect of an acetone extracts of Drynariae Rhizomas(GSB-1), its EtoAc fraction(GB-2) and n-buOH fraction(GSB-3), on hair growth activity of the C57BL/6L mice after topical application to skin. First, We examined on hair growth activity of extracts of Drynariae Rhizomas compare to control and 1 % minoxidil groups. Second, We investigated on the number of hair follicle and mast cells after topical application of extracts of the Drynariae Rhizomas to skin for 16 day. Third, We investigated immunoreactive density of vascular endothelial growth factor(VEGF), protein kinase C-${\alpha}$(PKC-${\alpha}$) and stem(mast) cell factor(SCF) in skin of C57BL/6N mice by immunohistochemical methods. The results were as follows : Hair growth effect of acetone extracts of Drynariae Rhizomas, its EtoAc fraction and n-BuOH fraction was observed in 98 %, 96 % and 60 % in hair removed skin area in 16 day respectively, Immunoreactive density of VEGF in skin of GSB-1 group was weakly stained compare to control group in 10 day, But GSB-2 and GSB-3 groups were mildy stained in bulge and root sheath of skin. Immunolocalization of SCF antigens was observed weakly stained density in epidermis, bulge, stem cells and dermal papilla of control gruop. but in experimental group, immunoreactivity of SCF antigens was observed mildly stained density in bulge, epidermis and root sheath of GSB-1 gruop, heavily stained density in epidermis, bulge and root sheath of GSB-2 and GSB-3 groups to the hair removal skin of C57BL/6N mice on day 10. These experiment suggest that acetone extracts of Drynariae Rhizomas and its EtoAc fraction may be used for topical treatment of alopecia areata.

• The Korean Journal of Food And Nutrition
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• v.22 no.4
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• pp.542-547
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• 2009

Brine mineral water(BMW) has recently gained attention as a new water resource due to its biological activities. In this study, BMW from the Geumjin area(Gangneung-city, Korea) was evaluated for its growth inhibition, anti-metastasis and anti-angiogenesis activity against cancer cells. The in vitro cytotoxicity was measured by CCK assay, and the anti-metastasis activity was estimated by lung metastasis in vivo. The in vitro incubation of mouse splenic cells with BMW that had been diluted more than 4-fold showed no effect on the cell growth when compared to a control group. Additionally, BMW inhibited the growth of the EL-4, L5178Y-R and colon26-M3.1 cancer cell lines in a dose-dependent manner. In vivo evaluation of the anti-metastasis activity of BMW in BALB/c mice inoculated with the colon26-M3.1 cell line revealed dose-dependent inhibition in response to treatment with samples that were diluted by up to 9 times. Finally, treatment with BMW effectively suppressed the growth of vascular endothelial growth factor(VEGF) added human umbilical vein endothelial cells. Overall, these results suggest that BMW has anti-cancer activity.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.166-173
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• 2010

Purpose : Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. Methods : Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. Results : The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/$D_0$ glucose) were $0.56{\pm}0.13$ and $0.43{\pm}0.11$, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007) and lower 4-hour D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037) than those without haplotype CTGGC. Conclusion : The VEGF genetic polymorphism may influence the peritoneal solute transport.