• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.1-15
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• 2015

Objectives The aim of this study was to investigate the effects of Cannabis Fructus on exercise capacity and cognitive function in chronic hypoperfusion induced vascular dementia rat model. Methods Vascular dementia rat models were induced by chronic cerebral hypoperfusion through bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal group; control group; CF I group (feeding Cannabis Fructus 100 mg/kg); CF II group (feeding Cannabis Fructus 300 mg/kg). In order to study the effects of oral administration of Cannabis Fructus on vascular dementia rat models, corner turn test, hole board test, radial arm maze test, passive avoidance test were taken and Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, serum of Vascular endothelial growth factor (VEGF) protein level were measured. Also histological findings of the liver, kidney, brain and the change of Tau immunoreactive neurons in hippocampus were observed. Results CF I and CF II showed significant improvement in corner turn test, hole board test, radial arm maze test, passive avoidance test, Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, the serum of Vascular endothelial growth factor (VEGF) protein level and the change of Tau immunoreactive neurons in hippocampus. CF I showed more significant effect than CF II in these tests. However in histological observations of the liver and kidney both CF I and CF II showed glomerular injury and hepatotoxicity. Conclusions These results suggest that Cannabis Fructus was helpful in improving exercise capacity and cognitive function on Chronic hypoperfusion induced Vascular Dementia rats. However Cannabis Fructus affects the liver and kidney, therefore suggest that this is an area for further study.

• Journal of Chest Surgery
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• v.24 no.3
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• pp.229-244
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• 1991

A bioassay technique and organ bath study were performed to analyze the effects of extracellular $Ca^{2+}$ and $Ca^{2+}$-antagonists on endothelium-derived relaxing factor[s][EDRF] released from the endothelial cells of rabbit aorta. Transverse strips with intact endothelium or damaged endothelium were used for the mechanical contraction experiment using organ bath. Long segment including thoracic and abdominal aorta with endothelium [EDRF donor aorta] was perfused with Tyrode solution which was aerated with 95% $O_2-5%$ $CO_2$ mixed gas and kept at 35oC. The perfusate was bioassayed with a transverse strip of thoracic aorta with damaged endothelium. The test strip was contracted with nor-epinephrine and acetylcholine was used to stimulate the release of EDRF from endothelial cells. The results obtained were as follows; 1] The endothelium-dependent relaxation[EDR] induced by acetylcholine was biphasic; an initial rapid relaxation followed by a slow relaxation. 2] EDR induced by acetylcholine was reduced gradually with the decrease in the concentration of extracellular $Ca^{2+}$. The effect of extracellular $Ca^{2+}$ on EDR was more prominent in the late slow relaxation phase. 3] EDR to acetylcholine was not altered by acute exposure to organic $Ca^{2+}$-antagonists. Pretreatment with verapamil to the EDRF donor aortic segment did not alter the magnitude of EDR. 4] Among the inorganic $Ca^{2+}$-antagonists $Mn^{2+}$ and $Cd^{2+}$ did not inhibit EDR, whereas $Co^{2+}$ and $La^{3+}$ inhibited EDR. 5] The inhibitory response of $Co^{2+}$ to EDR developed when infused directly on the test strip. That of $La^{3+}$, however, was evoked when added to solution perfusing the donor aortic segment. The above results suggest that $Ca^{2+}$-antagonists do not affect EDR and the inhibitory effect of $Ca^{2+}$ results from influencing the action of EDRF on vascular smooth muscle, whereas that of $La^{3+}$ results from its action on the release of EDRF from endothelial cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.645-649
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• 2013

Objective: The prognostic role of vascular endothelial growth factor (VEGF) in bladder cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Methods: We systematically searched for studies investigating the relationships between VEGF expression and outcome of bladder cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). Results: A total of 1,285 patients from 11 studies were included in the analysis. Our results showed that tissue VEGF overexpression in patients with bladder cancer was associated with poor prognosis in terms of OS (HR, 1.843; 95% CI, 1.231-2.759; P = 0.003), DFS (HR, 1.498; 95% CI, 1.255-1.787; P = 0.000) and DSS (HR, 1.562; 95% CI, 0.996-1.00; P = 0.052), though the difference for DSS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg's and Egger's tests except for DFS (Begg's test, P = 0.221; Egger's test, P = 0.018). Conclusion: The present meta-analysis indicated elevated VEGF expression to be associated with a poor prognosis in patients with bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5665-5669
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• 2012

Background: The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis. However, the prognostic value of VEGF in patients with prostate cancer remains controversial. Objectives: The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF. Methods: In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated. Results: The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg's, Egger's test and funnel plots, we confirmed lack of publication bias in our analysis. Conclusion: VEGF might be regarded as a prognostic maker for prostate cancer, as supported by our meta-analysis. To achieve a more definitive conclusion enabling the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.

• Journal of Life Science
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• v.14 no.2
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• pp.263-268
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• 2004

The sprouting of vascular endothelial cells is an initial step in angiogenesis. Matrix metalloproteinases can associate with integrin on the surface of endothelial cells, thereby promoting angiogenesis. The purpose of this study was to test if fibroblast growth factor-2 (FGF-2) can regulate the sprouting in porcine pulmonary artery endothelial cells. FGF-2 induced sprouting and secretion of MMP-2 and plasmin. FGF-2 also induced the expression of integrin Mac-1, which is inhibited IS20I. Addition of BB-94, a 2-antiplasmin and IS20I inhibited FGF-2-induced sprouting activity. Therefore, FGF-2-induced sprouting activity in PPAECs may be accomplished by secretion of proteinases such as MMP-2 and plasmin and integrin expression.

• Molecules and Cells
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• v.39 no.3
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• pp.195-203
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• 2016

Copper is an essential element required for a variety of functions exerted by cuproproteins. An alteration of the copper level is associated with multiple pathological conditions including chronic ischemia, atherosclerosis and cancers. Therefore, copper homeostasis, maintained by a combination of two copper ions ($Cu^+$ and $Cu^{2+}$), is critical for health. However, less is known about which of the two copper ions is more toxic or functional in endothelial cells. Cubic-shaped $Cu_2O$ and CuO crystals were prepared to test the role of the two different ions, $Cu^+$ and $Cu^{2+}$, respectively. The $Cu_2O$ crystal was found to have an effect on cell death in endothelial cells whereas CuO had no effect. The $Cu_2O$ crystals appeared to induce p62 degradation, LC3 processing and an elevation of LC3 puncta, important processes for autophagy, but had no effect on apoptosis and necrosis. $Cu_2O$ crystals promote endothelial cell death via autophagy, elevate the level of reactive oxygen species such as superoxide and nitric oxide, and subsequently activate AMP-activated protein kinase (AMPK) through superoxide rather than nitric oxide. Consistently, the AMPK inhibitor Compound C was found to inhibit $Cu_2O$-induced AMPK activation, p62 degradation, and LC3 processing. This study provides insight on the pathophysiologic function of $Cu^+$ ions in the vascular system, where $Cu^+$ induces autophagy while $Cu^{2+}$ has no detected effect.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.293-298
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• 2012

The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.4
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• pp.340-349
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• 2007

Free flap transplantation with microvascular anastomosis has been successfully performed by development of surgical technique, materials and postoperative monitoring equipments of flap. But success rate of microvascular anastomosis is influenced by various factors, and failure rate is about 5-10%. The most influential factor for success rate is surgical technique and other factors that influence failure of microvascular anastomosis are ischemic time of free flap, thrombus formation of anastomosis region and vascular spasm. In this study, vascular patency and thrombus formation in experimental micro-venous anastomosis, and endothelial repair were observed with histologic analysis, scanning electron microscopy, transmission electron microscopic examination. The results were obtained as follows: 1. In vascular patency test in 30 minute and 7 days after micro-venous anastomosis with heparin irrigation, all of 12 anastomosis site were good vascular patency. 2. In thrombus formation in 2 weeks group(Experimental I), 2 site of 6 cases were observed thrombus, and in 4 weeks group(Experimental II), 1 site of 6 cases were observed thrombus. 3. In histologic examination, normal vein(Control Group) showed continued internal elastic lamina, well formed thick smooth muscle layer and connective tissue. The group of 2 weeks after microvenous anastomosis(Experimental I) showd locally recovered internal lamina, discontinued internal lamina, disorganized smooth muscle cells and granulation tissue around suture silk. In the group of 4 weeks after micro-venous anastomosis(Experimental II), anastomosis site showed almostly continued internal lamina, disorganized smooth muscle cells and cicartrized tissue around suture silk. 4. In scanning electron microscope examination in 2 weeks(Experimental I) after micro-venous anastomosis, mesh fibrin formation showed near to endothelial cells, and in 4 weeks after micro-venous anastomosis(EXperimental II), numerous blood cells and fibrin mesh formation was seen associated with irregular endothelial cell arrangement. 5. In transmission electron microscope examination in 2 weeks after micro-venous anastomosis(Experimental I), irregular arrangement of smooth muscle cells was seen adjacent to collagenized tissue around suture silk. In 4 weeks after micro-venous anastomosis(Experimental II), denuded venous wall composed of relatively well arranged smooth muscle cells was covered by endothelial cells, but fibroblast cells and foreign body giant cells near to suture silk was remained. From the results obtained in this study, results of good vascular patiency and anti-thrombotic effect of heparin were obtained as a local irrigation solution, and repair of venous endothelial cell was observed in 2 weeks after micro-venous anastomosis.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.699-708
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• 2022

Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring. The antibiotic group offspring showed lower sociability and spatial learning and memory than control. To determine the role of the gut microbiota and their metabolites in the changes in offspring behavior, fecal samples of 6-week-old offspring rats were sequenced. The composition of dominant gut microbial taxa differed between the control and antibiotic groups. KEGG pathway analysis showed that S24-7 exerted its effects through the metabolic pathways including mineral absorption, protein digestion and absorption, Valine, leucine, and isoleucine biosynthesis. Correlation analysis showed that S24-7 abundance was negatively correlated with the level of VEGF, and metabolites associated with S24-7-including 3-aminobutanoic acid, dacarbazine, L-leucine, 3-ketosphinganine, 1-methylnicotinamide, and N-acetyl-L-glutamate-were also significantly correlated with VEGF levels. The findings suggest that antibiotic exposure during pregnancy, specifically ceftriaxone sodium, will adversely affects the behavior of offspring rats due to the imbalance of gut microbiota, especially S24-7, via VEGF and various metabolic pathways.

• Macromolecular Research
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• v.17 no.7
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• pp.458-463
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• 2009

Polyurethane (PU) is widely used as a cardiovascular biomaterial due to its good mechanical properties and hemocompatibility, but it is not adhesive to endothelial cells (ECs). Cell adhesive peptides, GRGDS and YIGSR, were found to promote adhesion and spreading of ECs and showed a synergistic effect when both of them were used. In this study, a surface modification was designed to fabricate an EC-active PU surface capable of promoting endothelialization using the peptides and poly(ethylene glycol) (PEG) spacer, The modified PU surfaces were characterized in vitro. The density of the grafted PEG on the PU surface was measured by acid-base back titration to the terminal-free isocyanate groups. The successful immobilization of pep tides was confirmed by amino acid analysis, following hydrolysis, and contact angle measurement. The uniform distribution of peptides on the surface was observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). To evaluate the EC adhesive property, cell viability test using human umbilical vein EC (HUVEC) was investigated in vitro and enhanced endothelialization was characterized by the introduction of cell adhesive peptides, GRGDS and YIGSR, and PEG spacer. Therefore, GRGDS and YIGSR co-immobilized PU surfaces can be applied to an EC-specific vascular graft with long-term patency by endothelialization.