Daejeon, South Korea
Daejeon, South Korea

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Kang W.K.,Chungnam National University | Lee M.H.,Chungnam National University | Kim Y.H.,Chungnam National University | Kim M.Y.,AngioLab Inc. | Kim J.-Y.,Chungnam National University
Journal of Biotechnology | Year: 2013

Vascular endothelial growth factor (VEGF) mediates angiogenesis, which plays a critical role in the development and differentiation of the vascular system. VEGF is a homodimeric glycoprotein that contains one N-glycosylation site. In this study, we evaluated Saccharomyces cerevisiae expression systems producing glycosylated and non-glycosylated splice variants of human VEGF, VEGF121, and VEGF165. The pre region of the mating factor α1 (MFα1) signal sequence was found to perform better than the entire MFα1 prepro signal sequence in secreting glycosylated VEGF. Secretion of non-glycosylated VEGF165 was completely blocked, indicating the importance of glycosylation in VEGF165 secretion. Interestingly, non-glycosylated VEGF165 was secreted when guided by the MFα1 prepro signal sequence, albeit to a lesser degree, compared to glycosylated VEGF165. N-glycosylation in the pro region was required for the prepro sequence to promote VEGF secretion. Furthermore, substitution of asparagine at the VEGF glycosylation site with lysine or glutamic acid increased secretion of non-glycosylated VEGF, a finding not previously reported. Our findings suggest that S. cerevisiae could be a suitable host for secreting biologically active, non-glycosylated VEGF for clinical use. © 2013 Elsevier B.V.


Valiente Engelhorn A.L.D.,Angiolab Inc | Valiente Engelhorn A.L.D.,Pontifical Catholic University of Parana | Engelhorn C.A.,Angiolab Inc | Engelhorn C.A.,Pontifical Catholic University of Parana | And 5 more authors.
Ultrasound Quarterly | Year: 2012

Aim: Ultrasound tissue characterization (USTC) is a precursor of ultrasound virtual histology (USVH), already applied to B-mode images of coronary, carotid, and peripheral arteries, as well as venous thrombosis. Elevated echogenicity has been described for a rejected transplanted kidney. We analyzed data from healthy young adults as reference for further renal USTC. Methods: Ultrasound kidney images of 10 volunteers were analyzed. Pixel brightness in the 0-to-255 range was rescaled to zero for black and 200 for fascia brightness before automatic classification into 14 ranges, including "blood-like" (0-4), "fat-like" (8-26), "hypoechoic muscle-like" (41-60), "hyperechoic muscle-like" (61-76), 4 ranges of "fiber-like" (112-196), "calcium-like" (211-255) and intermediary intervals. Nomenclature was readapted using nonechoic, hypoechoic I to IV, echoic I to IV, hyperechoic I to IV, and saturated echoes to avoid inference to actual kidney tissue. Descriptive and comparative statistics were based on percentages of pixels in specific brightness ranges. Sample population: Eight women and 2 men, 26 ± 4 years (range, 22-34 years) old, were studied. Kidney length was 10.5 ± 0.9 cm (9.0-12.0 cm). Doppler US resistivity index was 0.67 ± 0.03 (0.62-0.71). Results: Original fascia brightness converted to 200 value had a mean ± SD of 206 ± 16 (range, 181-236). Kidney grayscale median averaged 37 ± 6 (27-48). Most pixels were hypoechoic II to IV (8-60), averaging 78% ± 6% (66%-87%). Percentages for fat-like, intermediary fat/muscle-like, and hypoechoic muscle-like intervals averaged 25%, 28%, and 25%, respectively. Conclusions: A reference database for USTC/USVH of normal young kidneys was created for future comparisons with transplanted and abnormal kidneys. Normal renal echoes have low brightness. Hyperechoic pixels may represent abnormalities. Copyright © 2012 by Lippincott Williams & Wilkins.


PubMed | AngioLab Inc., Korea University and Mokwon University
Type: | Journal: Journal of ethnopharmacology | Year: 2016

Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.


PubMed | AngioLab Inc., Korea University, Mokwon University and Korea Advanced Institute of Science and Technology
Type: Journal Article | Journal: PloS one | Year: 2015

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.


Hong Y.,Mokwon University | Kim M.-Y.,AngioLab Inc. | Yoon M.,Mokwon University
Pharmaceutical Biology | Year: 2011

Context: Growing adipose tissue is thought to require adipogenesis, angiogenesis, and extracellular matrix (ECM) remodeling. Close examination of developing adipose tissue microvasculature reveals that angiogenesis often precedes adipogenesis. Since our previous study demonstrated that Ob-X, the anti-angiogenic herbal composition composed of Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae), reduced adipose tissue mass in obese mice, we hypothesized that adipogenesis can be inhibited by Ob-X. Objective: To investigate the effects of the anti-angiogenic herbal extracts Ob-X on adipogenesis in 3T3-L1 adipocytes. Materials and methods: After differentiated 3T3-L1 adipocytes were treated with Ob-X, we studied the effects of Ob-X on triglyceride accumulation and expression of genes involved in adipogenesis, angiogenesis, and ECM remodeling. Results: Treatment of cells with Ob-X inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or monocyte differentiation-inducing (MDI) mix. Ob-X reduced mRNA levels of angiogenic factors (vascular endothelial growth factor-A, -B, -C, -D, and fibroblast growth factor-2) and matrix metalloproteinases (MMPs; MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors [(thrombospondin-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2)] in differentiated cells. MMP-2 and MMP-9 activities were also decreased in Ob-X-treated cells. Discussion and conclusion: These results suggest that the anti-angiogenic herbal composition Ob-X inhibits differentiation of preadipocytes into adipocytes. These events may be mediated by changes in the expression of genes involved in lipogenesis, angiogenesis, and the MMP system. Thus, by reducing adipogenesis, anti-angiogenic Ob-X provides a possible therapeutic approach for the prevention and treatment of human obesity and its related disorders. © 2011 Informa Healthcare USA, Inc.


Context: The growth and development of adipose tissue leading to obesity is suggested to depend on angiogenesis. Our previous study showed that Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are involved in the regulation of angiogenesis. We hypothesized that Ob-X, a mixture of three herbs, M. alba, M. officinalis, and A. capillaris, can regulate obesity. Objective: To investigate the inhibitory effect of Ob-X on obesity in genetically obese ob/ob mice. Materials and methods: The effect of Ob-X on angiogenesis was measured using a mouse Matrigel plug assay. The effects of Ob-X on obesity were investigated in ob/ob mice. Results: Ob-X inhibited angiogenesis in a dose-dependent manner, as evidenced by decreased blood vessel density in a mouse matrigel plug assay. Administration of Ob-X to ob/ob mice for 5 weeks produced a significant reduction in body weight gain by 27% compared with control (12.1±3.01 vs. 16.6±2.24g, respectively). Ob-X also significantly decreased visceral adipose tissue mass by 15% (0.87±0.12 vs. 1.02±0.15g, respectively). The size of adipocytes in visceral adipose tissue was reduced by 46% in Ob-X-treated mice. Ob-X treatment inhibited hepatic lipid accumulation and significantly decreased circulating glucose levels compared with controls (197±56.5 vs. 365±115mg/dL, respectively). Discussion and conclusion: These results suggest that Ob-X, which has an anti-angiogenic activity, reduces body weight gain and visceral adipose tissue mass in genetically obese mice, providing evidence that obesity can be prevented by angiogenesis inhibitors. © 2011 Informa Healthcare USA, Inc.


PubMed | Angiolab Inc
Type: Journal Article | Journal: Ultrasound quarterly | Year: 2012

Ultrasound tissue characterization (USTC) is a precursor of ultrasound virtual histology (USVH), already applied to B-mode images of coronary, carotid, and peripheral arteries, as well as venous thrombosis. Elevated echogenicity has been described for a rejected transplanted kidney. We analyzed data from healthy young adults as reference for further renal USTC.Ultrasound kidney images of 10 volunteers were analyzed. Pixel brightness in the 0-to-255 range was rescaled to zero for black and 200 for fascia brightness before automatic classification into 14 ranges, including blood-like (0-4), fat-like (8-26), hypoechoic muscle-like (41-60), hyperechoic muscle-like (61-76), 4 ranges of fiber-like (112-196), calcium-like (211-255) and intermediary intervals. Nomenclature was readapted using nonechoic, hypoechoic I to IV, echoic I to IV, hyperechoic I to IV, and saturated echoes to avoid inference to actual kidney tissue. Descriptive and comparative statistics were based on percentages of pixels in specific brightness ranges.Eight women and 2 men, 26 4 years (range, 22-34 years) old, were studied. Kidney length was 10.5 0.9 cm (9.0-12.0 cm). Doppler US resistivity index was 0.67 0.03 (0.62-0.71).Original fascia brightness converted to 200 value had a mean SD of 206 16 (range, 181-236). Kidney grayscale median averaged 37 6 (27-48). Most pixels were hypoechoic II to IV (8-60), averaging 78% 6% (66%-87%). Percentages for fat-like, intermediary fat/muscle-like, and hypoechoic muscle-like intervals averaged 25%, 28%, and 25%, respectively.A reference database for USTC/USVH of normal young kidneys was created for future comparisons with transplanted and abnormal kidneys. Normal renal echoes have low brightness. Hyperechoic pixels may represent abnormalities.


Trademark
AngioLab. Inc. | Date: 2016-06-13

Tea extracts for the food industry; tea extracts for use in the manufacture of pharmaceuticals and cosmetics; botanical extracts, plant extracts, and herb extracts, other than essential oils, for use in the manufacture of cosmetics; plant extracts, herb extracts, tea extracts for use in the manufacturing of dietary supplements, nutritional products, pharmaceuticals and cosmetics; phytochemicals for use in the manufacturing of dietary supplements, nutritional products, pharmaceuticals and cosmetics. Food and herbal supplements; dietary and nutritional supplements; nutraceuticals for use as dietary supplements; dietetic food supplements; dietary supplements for human consumption.


Trademark
Angiolab. Inc. | Date: 2012-09-11

Pharmaceutical preparations for the treatment of angiogenesis-dependent diseases, namely, obesity, cancer, arthritis, psoriasis, and ocular diseases, and diagnostic preparations for veterinary use for the treatment of angiogenesis-dependent diseases; dietary supplements and dietetic foods adapted for medical use for the treatment of angiogenesis-dependent diseases, namely, obesity, cancer, arthritis, psoriasis, and ocular diseases.


PubMed | AngioLab Inc
Type: Journal Article | Journal: International journal of obesity (2005) | Year: 2010

The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. As the composition of the herbal extract called Ob-X has been shown to have both anti-angiogenic and matrix metalloproteinase (MMP)-inhibiting activities, we hypothesized that growth of adipose tissue can be regulated by Ob-X.The effects of Ob-X on angiogenesis and extracellular matrix remodeling were measured using in vitro and ex vivo assays. The effects of Ob-X on adipose tissue growth were investigated in nutritionally obese mice.Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell tube formation assay in vitro and the rat aortic ring assay ex vivo. Ob-X also suppressed MMP activity in vitro. Administration of Ob-X to high fat diet-induced obese mice produced significant reductions in body weight gain and adipose tissue mass compared with control. The mass of both visceral (VSC) and subcutaneous (SC) fat was reduced in Ob-X-treated mice. The size of adipocytes in VSC and SC adipose tissues was also significantly reduced in Ob-X-treated mice. Ob-X treatment decreased the blood vessel density and MMP activity in VSC adipose tissues of nutritionally obese mice. Ob-X reduced mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1 and TIMP-2) in SC and VSC adipose tissues of nutritionally obese mice.Ob-X, which has anti-angiogenic and MMP-inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth and development may be prevented by inhibiting angiogenesis. In addition, these data suggest that regulation of adipose tissue growth by inhibiting angiogenesis may alter the expression of genes involved in angiogenesis and the MMP system.

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