• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• 동의생리병리학회지
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• 제25권1호
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• Archives of Plastic Surgery
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• 제35권2호
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• pp.121-126
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• 2008

Purpose: Poly-N-acetyl glucosamine(PGlcNAc) nanofiber-based materials, produced by a marine microalga, have been characterized as effective hemostatic and angiogenic agents. The similarity between PGlcNAc patch and the natural extracellular matrix allows it to support new healthy tissue growth in an injured area and to encourage fluid absorption. In this study, we hypothesized that a poly-N-acetyl glucosamine fiber patch(PGlcNAc patch) may enhance wound healing in the db/db mouse. Methods: PGlcNAc patches were applied on one square centimeter, full-thickness, skin wounds in the db/db mouse model. Wounds(n=15 per group) were dressed with a PGlcNAc nanofiber patch for 1 hour(1 h), 24 hours(24 h) or left untreated(NT). After the application time, patches were removed and wounds were allowed to heal spontaneously. The rate of wound closure was evaluated by digital analysis of unclosed wound area in course of time. At day 10, wounds(n=7 per group) were harvested and quantified with immunohistochemical markers of proliferation(Ki-67) and vascularization (platelet endothelial cell adhesion molecule, PECAM-1). Results: Wounds dressed with PGlcNAc patches for 1 hour closed faster than control wounds, reaching 90% closure in 16.6 days, nine days faster than untreated wounds. Granulation tissue showed higher levels of proliferation and vascularization following 1 h treatment than the 24 h and NT groups. In addition to its hemostatic properties, the PGlcNAc material also appears to accelerate wound closure in healing-impaired genetically diabetic mice. Conclusion: This material, with its combination of hemostatic and wound healing properties, has the potential to be effective agent for the treatment of complicated wounds.

• 동의생리병리학회지
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• 제17권4호
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• pp.1059-1064
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• 2003

Oldenlandiae Herba has been used for the prevention or treatment of cancer in oriental medicine for years. Experimentally its antitumor activity was reported. However, in order to develop new Korean original plants. we tried to study the antitumor activity of Chinese and Korean origin Oldenlandiae Herba. We first evaluated the cytotoxicity of Oldenlandiae Herba originated from China and Korea on HT1080, U937 and SK-mel tumor cells. MeOH extract of Chinese Oldelandiae Herba was more effective than MeOH extract of Korean Oldenlandiae Herba. Approixmately IC50 of two species of Oldelandiae Herba was 380-450 ug/ml. For evaluation of antiangiogenic activity, proliferation assay with HUVECs(Human umblical vein endothelial cells) was done with three samples. Chinese Herba and Korean Herba and root. Korean root and herba was more effective than Chinese Herba. Thus, we found Korean Oldenlandiae was more effective on angigenic activity than Chiness Oldenlandiae. In an anlytical study on effective compounds from Oldenlandiae, the spot of ursolic acid was more marked by Korean Oldenlandiae than by Chinese Oldenlandiae. whereas the spot of asperuloside was more pronounced by Chinese Oldenlandiaethan by Korean Oldenlandiae by TLC analysis.

• 방사선산업학회지
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• 제4권1호
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• pp.7-11
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• 2010

Clotrimazole [1-{(2-chlorophenyl)-diphenylmethyl}-1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [$^{18}F$]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [$^{18}F$]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/$K_2CO_3$ for 10 min at $80^{\circ}C$. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove $^{18}F^-$. The [$^{18}F$]F-clotrimazole derivatives were synthesized with a 20~25% yield. In the radiofluorination step, we used acetonitrile and DMSO as a solvent and observed a higher yield at the acetonitrile (25%) reaction compared with the DMSO reaction (5%).

• Journal of Ginseng Research
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• 제46권3호
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• pp.408-417
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• 2022

Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O₂ consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O₂ consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

• 한국축산식품학회지
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• 제44권1호
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• pp.204-215
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• 2024

This study was designed to examine the effect of Lactilactobacillus curvatus LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle dermal papilla cells and hair germinal matrix cells (hGMCs). Moreover, the expression levels of hair growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 7 were significantly elevated in hGMCs co-cultured with LB-P9. After time-synchronized depilation, mice were orally administered with either 4×10⁷ colony forming unit (CFU) of LB-P9 (low dose) or 4×10⁸ CFU of LB-P9 (high dose), once daily for 4 weeks. Compared with the vehicle (phosphate-buffered saline)-administrated group, the LB-P9-treated groups exhibited accelerated hair regrowth rate and enhanced hair thickness in a dose-dependent manner. Supporting this observation, both hair follicle numbers and the dermal thickness in skin tissues of the LB-P9-treated groups were increased, compared to those of the vehicle-treated group. These results might be explained by the increased level of β-catenin and number of hair follicle stem cells (CD34⁺ CD49f⁺ cells) in the skin tissues of mice administered with LB-P9, compared to the vehicle-treated mice. Also, increased serum levels of hair growth factors such as VEGF and insulin-like growth factor-1, and superoxide dismutase were found in the LB-P9-treated groups, compared to those of the vehicle-treated group. Taken together, these results might demonstrate that the oral administration of LB-P9 promotes hair regeneration by the enhancement of dermal papilla proliferation through the stimulation of hair growth factor production.

• Radiation Oncology Journal
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• 제15권1호
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• pp.37-47
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• 1997

목적 : 방사선량에 EK른 급성폐손상을 병리조직학적으로 분석하고 예방목적으로 투요한 스테로이드의 효과를 확인하여 방사선에 의한 폐손상의 감소방안을 모색하고자 한다. 대상 및 방법 : 생후 30일 정도인 체중 25+2g의 ICR 마우스 120마리를 암수 구별없이 사용하였고, 대조군은 전폐선량이 각각 8Gy와 12Gy인 방사선조사만 시행한 군과 방사선조사와 생리식염수를 투여한 또다른 군으로 하엿으며, 실험군은 방사선조사와 스테로이드를 복강내로 투여한 군으로 하여 방사선량과 스테로이드투여에 따른 급성폐손상의 양상을 광학 현미경 및 투과 전자현미경을 이용하여 병리조직학적으로 분석하였다. 결과 : 8Gy 대조군에서는 경미한 염증세포의 침윤, I형 폐포상피세포는 세포질이 파괴되거나 폐포강내로 돌출하였으며, 폐포 모세혈관은 경미하게 확장되었고 내피세포의 세포질과 간질은 경한 부종을 보였다. 8Gy 실험군에서 대조군에 보였던 폐포상피세포 및 내피 세포의 변화가 정도가 매우 약하였으나 섬유모세포의 증식과 기저판의 파괴정도는 대조군과 비슷하였다. 12Gy 대조군에서는 8Gy 대조군과 비교하여 염증세포의 침윤이 증가되었고 폐포강내에는 파기된 조직 파편이 산재해 있었으며 폐실질의 출혈과 무기폐가 관찰되었다. 12Gy 실험군에서는 대조군에서 보이던 현저한 염증변화가 많이 감소하였으며 폐포벽의 부종과 무기폐는 대조군과 비교하여 많이 감소되었으나 섬유모세포의 증식과 기저판의 왜곡 및 파괴는 차이가 없었다. 결론 : 방사선조사에 의한 급성폐손상은 전폐조사량이 8Gy에서 12Gy로 증가함에 따라 염증 세포의 침윤, 페포상피세포의 손상, 모세혈관 내피세포의 손상, 간질의 부종정도가 증가하였으며, 방사선조사후 스테로이드를 2주일에서 4주일간 투여한 결과 이들 소견이 많이 감소하였으나 섬유모세포의 증식정도와 기저판의 변화는 조사된 방사선량이나 스테로이드 투여여부와 무관하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.353-357
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• 2001

The pathogenesis of the nasal polyp is multifactorial and choanal polyps can be defined by its origin of genesis: antrochoanal (maxillochoanal), ethmochoanal and sphenochoanal polyp. Transforming growth $factor-{\beta}\;(TGF-{\beta})$ has various biologic activities, including the regulation of epithelial proliferation, the promotion of extracellular matrix formation and the induction of angiogenesis, hence closely related to pathogenesis of nasal polyp. Twenty cases of choanal polyps (13 antrochoanal, 4 ethmochoanal and 3 sphenochoanal polyps) were included in this study. Each polyp was subdivided into its origin, pedicle and choanal part. Hematoxylin and eosin stain for routine histopathology and immunohistochemistry were employed to detect expression of $TGF-{\beta}1.$ According to polyp type, edematous type is common at origin part and fibrous type at choanal part, and showed no difference at pedicle part in frequency. In ethmochoanal and sphenochoanal polyps, glandulocystic and edematous type is more common than fibrous type. $TGF-{\beta}1$ was expressed in epithelial cells, endothelial cells, eosinophils and lymphocytes. There was no different expression of $TGF-{\beta}1$ in each kind of choanal polyps and separate parts in each polyp. But histologic finding of choanal polyp is different between origin, pedicle and choanal part. Also infiltration of inflammatory cells including eosinophils has no difference between origin site. The expression of $TGF-{\beta}1$ was observed at all the choanal polyps and no difference between origin site and each portions was noted.