• Title/Summary/Keyword: VEGF-D

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RK-270D and E, Oxindole Derivatives from Streptomyces sp. with Anti-Angiogenic Activity

  • Jang, Jun-Pil;Jang, Mina;Nogawa, Toshihiko;Takahashi, Shunji;Osada, Hiroyuki;Ahn, Jong Seog;Ko, Sung-Kyun;Jang, Jae-Hyuk
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.302-306
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    • 2022
  • A chemical investigation of a culture extract from Streptomyces sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and High-resolution electrospray ionization mass spectrometry (HRESIMS) experiments. Compound 1 exhibited anti-angiogenic activities against human umbilical vein endothelial cells (HUVECs) without cytotoxicity. Results of Western blot analysis revealed that 1 inhibits VEGF-induced angiogenesis in the HUVECs via VEGFR2/ p38 MAPK-mediated pathway.

Overexpression of Platelet-derived Growth Factor-D as a Poor Prognosticator in Endometrial Cancer

  • Ding, Jie;Li, Xiao-Mao;Liu, Sui-Ling;Zhang, Yu;Li, Tian
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3741-3745
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    • 2014
  • Background: Emerging evidence implicates the platelet-derived growth factor-D (PDGF-D) in many types of human solid tumors. We investigated whether PDGF-D plays an important role in endometrial cancer (EC) in relation to clinicopathologic phenotype, angiogenesis, and patient prognosis. Materials and Methods: We analyzed PDGF-D protein expression by Western blotting in twenty-seven human endometrial cancer tissues, and matched normal endometrial controls collected at the third Affiliated hospital of Sun Yat-sen University during 2012-2013 (n=27). Immunohistochemical staining was performed using a human PDGF-D antibody on the endometrial cancer patients collected in the same facility during January 2001 and October 2013 (n=152). Patients were followed from the time of primary surgery in 2001-2013 until death or last follow-up. We correlated the PDGF-D expression levels with clinicopathologic parameters and prognosis in human endometrial cancer patients. Results: Compared with matched normal endometrial cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D protein, found in 78% of the cases, was associated with nonendometrioid histologic type (p=0.028), FIGO stage III/IV (p=0.039), >50% solid tumor growth (p=0.048), pelvic LN metastasis (p=0.035) and ER and PR negativity (p=0.04 and 0.002). PDGF-D expression was also significantly associated with expression of VEGF-A (p=0.021). In multivariate analysis, PDGF-D expression proved to be an independent prognostic factor in addition to histologic grade and FIGO stage. Patients with high expression levels of PDGF-D had a significantly poorer overall survival rate compared with patients with no expression. Conclusions: PDGF-D expression is frequently up-regulated in endometrial cancer, and is associated with aggressive features and poor prognosis.

Fermented Jeju Soybean Extract Promotes Hair Growth in Human Hair Follicle Organ Culture and Clinical Trial (모낭기관배양과 임상에서 제주푸른콩발효추출물의 육모 효능에 미치는 영향)

  • Lee, Yonghee;Shin, Seung Hyun;Kim, Sehyun;Jeong, Gyusang;Hong, Min Jung;Park, Hyeokgon;Kim, Seung Hun;Kim, Eun Joo;Kang, Young-Gyu;Park, Byung Cheol;Park, Won Seok;Kim, Su Na;Kim, Hyoung-June
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.3
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    • pp.255-263
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    • 2021
  • Soybean extract is known to play an important role in preventing and treating diseases associated with aging, cancer, obesity, and cardiovascular disease. A recent has revealed that soybean extract has a potent effect on hair growth in in vitro, in vivo, and clinical studies. Recently, it has been reported that their fermented extracts exhibit numerous and high efficacy, as compared to general extracts. However, the underlying mechanisms that induce hair growth after using fermented soybean extract are not well understood. The present study aimed to determine the effects of fermented Jeju soybean (FJS) extract on hair growth, with a focus on the underlying mechanisms similar to those of minoxidil. We conducted in vitro and ex vivo investigations and clinical studies. FJS extract enhanced dermal papilla cell proliferation, VEGF levels, and potassium channel opening. Moreover, it promoted human hair follicle elongation. These effects were comprehensively demonstrated in the clinical results, in which FJS extract-containing shampoo improved hair density after 24 weeks of utilization. Collectively, the results of this study demonstrate that FJS extract promotes hair growth and inhibits hair loss through a mechanism similar to that of minoxidil in hair follicles.

Bevacizumab accelerates corneal wound healing by inhibiting TGF-βexpression in alkali-burned mouse cornea

  • Lee, Sung-Ho;Leem, Hyun-Sung;Jeong, Seon-Mi;Lee, Koon-ja
    • BMB Reports
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    • v.42 no.12
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    • pp.800-805
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    • 2009
  • This study investigated the effect of subconjunctival injections of bevacizumab, an anti-VEGF antibody, on processes involved in corneal wound healing after alkali burn injury. Mice were divided into three groups: Group 1 was the saline-treated control, group 2 received subconjunctival injection of bevacizumab 1hr after injury and group 3 received bevacizumab 1 hr and 4 days after injury. Cornea neovascularization and opacity were observed using a slit lamp microscope. Corneal repair was assessed through histological analysis and immunostaining for CD31, $\alpha$-SMA, collagen I, and TGF-$\beta$2 7 days post-injury. In group 3, injection of bevacizumab significantly lowered neovascularization and improved corneal transparency. Immunostaining analysis demonstrated a reduction in CD31, $\alpha$-SMA and TGF-$\beta$2 levels in stroma compared to group 1. These results indicate that bevacizumab may be useful in reducing neovascularization and improving corneal transparency following corneal alkali burn injury by accelerating regeneration of the basement membrane.

Neuroprotective effect of modified Boyanghwano-Tang and the major medicinal plants, Astragali Radix and Salviae Miltiorrhizae Radix on ischemic stroke in rats (허혈성뇌졸중 흰쥐모델에서 가미보양환오탕(加味補陽還五湯)와 주요 구성약재인 황기(黃芪), 단삼(丹蔘)의 뇌신경보호효과에 대한 연구)

  • Son, Hye-Young;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.25 no.2
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    • pp.71-79
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    • 2010
  • Objectives : In this study, the neuroprotective effects of modified Boyanghwano-Tang (mBHT) and the major medicinal plants, Astragali Radix(AR) and Salviae Miltiorrhizae Radix(SMR) were investigated in transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke of rats. Methods : mBHT(400 mg/kg) and AR(154 mg/kg) or SMR(62 mg/kg) water extract orally injected in rats after 90 min occlusion of MCA and then allow reperfusion to 24 h. Brain infarction was measured by TTC staining and the expressions of NOS isoforms and apoptotic molecules were determined in ischemic brain by Western blot. Results : The results showed that mBHT has stronger neuropreotective property through inhibitions of the PARP cleaved and caspase-3 activation in ischemic rats, and could reduced infarction volumes comparison of those of AR or SMR, respectively. While, AR extract has an angiogenic property through increasing the expressions of eNOS and VEGF, and SMR extract has a strong anti-inflammatory effects through inhibition of iNOS expression in ischemic brains. Conclusions : These results suggest that mBHT has multifactorial therapeutic advantages through anti-apoptosis, anti-inflammation and angiogenesis for ischemic stroke based on a synergistic combination of ingradients rather than monotherapy.

Wound Healing Effect of Low Molecular PDRN on Experimental Surgical Excision Rat Model (저분자화된 Polydeoxynucleotide (PDRN)의 흰쥐에 대한 외과적 창상 치유 효과)

  • Yun, Jong-Kuk;Yoon, Hye-Eun;Park, Jeong-Kyu;Kim, Mi Ryeo;Kim, Dae-Ik
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.4
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    • pp.401-411
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    • 2015
  • This study was performed to investigate the wound healing effect of skin regeneration cosmetics utilizing low molecular weight Polydeoxynucleotide (PDRN). High purity PDRN was prepared from salmon testes poly-deoxy-ribonucleotide through protein and toxin removal process and molecular weight reduction. In order to evaluate the wound healing effect of PDRN in SD rats, 4 sites of dorsal skin of each animal were excised by using biopsy punch and $500{\mu}L$ of test solution was topically applied once daily for 4 weeks. The tissue changes were observed for every week during the application periods. After applying the PDRN to the wound, the skin was cut flower and contraction of the wounds more quickly, and the coating of PDRN in the wound area was reduced significantly as compared to the positive control group $Fucidin^{(R)}$ applied. The microscopic observation of stained tissue showed that a positive control was most rapid in re-epithelialization ability followed by the PH group, PDRN group, HA group. In addition, transforming growth factor ($TGF-{\beta}$) and vascular endothelial growth factor (VEGF), such as in the growth factor was similar to the results of staining of tissue lesions. In conclusion, it is determined that the low molecular weight PDRN has the therapeutic effect to the wound, and could be used as a functional material of cosmetics and medical industries.

In Vitro Anti-aging and Hair Follicle Dermal Papilla Cells Activation Effects of Usnea diffracta Vain Extract (송라 추출물의 세포 수준에서 항노화 및 모유두세포 활성화 효과)

  • Min Jeong Kim;Won Yeoung Choi;Hyun Woo Shim;Eun Jin Shin;Jung No Lee;Sung Min Park;Hwa Sun Ryu
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.1
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    • pp.37-48
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    • 2024
  • Songla (Usnea diffracta Vain.) is one of the lichens belonging to the genus Usnea, and pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory, anti-tumor and cardiovascular protection have been reported in previous studies, but its efficacy in skin and hair is not well known. In this study, the effect of Usnea diffracta extract (UDE) on anti-aging and dermal papilla cell proliferation was verified in vitro. As a result of the experiment, it was confirmed that the UDE significantly reduced the expression of MMP-1 and the activity of MAPKs (ERK, p38, JNK) and AP-1 (c-Fos, c-Jun), which were increased by UVA in HDFn. In addition, the UDE significantly increased the proliferation of HFDPC and significantly increased the mRNA expression of VEGF and KGF, which are hair growth factors. Accordingly, the phosphorylation of ERK/CREB involved in hair proliferation and expression of growth factors was increased in a concentration-dependent manner. The main component represented by the main peak was separated and purified using Prep LC by concentrating the UDE, which was confirmed as diffractaic acid through NMR and Mess analysis. Isolated diffractaic acid significantly reduced the expression of MMP-1 increased by UVA in HDFn and increased the proliferation of HFDPC in a concentration-dependent manner. The result suggest that UDE proved its usability as a natural cosmetic material with anti-aging and dermal papilla cell activation effects.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

  • Kim, Young Eun;Choi, Hyung Chul;Lee, In-Chul;Yuk, Dong Yeon;Lee, Hyosung;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.572-580
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    • 2016
  • 3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

Vitexin, an HIF-1α Inhibitor, Has Anti-metastatic Potential in PC12 Cells

  • Choi, Hwa Jung;Eun, Jae Soon;Kim, Bang Geul;Kim, Sun Yeou;Jeon, Hoon;Soh, Yunjo
    • Molecules and Cells
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    • v.22 no.3
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    • pp.291-299
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    • 2006
  • Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.

Anti-oxidative and Anti-hyperglycemia Effects of Dung Beetle Extracts on the High Fat Diet SD Rats (고지방식이로 유발한 흰쥐에서 쇠똥구리 추출물의 항산화 효과 및 혈당강하에 미치는 영향)

  • Kim, Ha Jeong;Kim, Ban Ji;Ahn, Mi Young
    • Journal of Life Science
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    • v.26 no.7
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    • pp.772-781
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    • 2016
  • Dung beetle (Catharsius molossus, CA) is a well-known group of insects thanks to their exploitation of animal feces, a behavioral trait with a global impact on earth′s ecosystems. This study was conducted to investigate the effect of CA extract on a high-fat diet in SD rats. Male rats were divided into 5 groups. Animals were fed on a high-fat diet for seven weeks before and dung beetle extract for a month during the administration. Weight gain was decreased in ethanol extract from CA group. Administration of CA extract reduced the organ weight of testis and kidney, and adipose tissue weight. Lipid oxidative stress was evaluated measuring malondialdehyde level in liver. There were no significant differences in groups. Protein oxidative stress was evaluated measuring protein carbonyl content in blood. The protein carbonyl in blood was significantly decreased in ethanol and acetone extracted dung beetle groups (p<0.05). Meanwhile, the protein carbonyl in hepatocyte was not significant among the groups. Fibronectin and laminin by using D-HUVEC cell in vitro were measured by ELISA assay. There was significance in CA extract. The level of IL-10, IL-1β, VEGF, eNOS was evaluated by ELISA. There was significance in IL-10 compared to control (p<0.05). SOD and GPx tended to increase by CA extract. Furthermore, CAT was increased significantly by CA extract (p<0.05). After administration of CA extracts the composition of saturated fatty acid in adipose tissue tend to decrease, while unsaturated fatty acid increases. In conclusion, dung beetle had anti-hyperglycemia effects of oxidative stress and antioxidant activity.