Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.
Haggag, Basma S.;Hasanin, Amany H.;Raafat, Mona H.;Kawy, Hala S. Abdel
The Korean Journal of Physiology and Pharmacology
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v.18
no.3
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pp.269-278
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2014
Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.
BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.
Minerals from marine materials such as deep ocean water and Dead Sea water have been used since ancient times. We made a mask pack sheet including deep ocean water and salt from the Dead Sea and evaluated the function of the mask pack sheet through animal study. Three full-thickness skin defects were made on the backs of Sprague-Dawley rats. The wounds were left untreated in group Con, and mask pack sheets including deep ocean water or deep ocean water and Dead Sea water were used as treatment for 20 min on the skin of animals in groups DP and DDP, respectively. We analyzed the gross, histological and biochemical findings. Groups DDP and DP showed decreases in wound size, as compared to group Con at 7 days after wound infliction. The histological findings revealed that wound healing had progressed further in groups DP and DDP than in group Con, with more rapid collagen deposition and regression of neutrophils. Also, the expression of vascular endothelial growth factor and transforming growth factor ${\beta}1$ were increased in groups DDP and DP compared with those in group Con at 3 days after wound infliction. Mask sheet packs including deep ocean water and Dead Sea salt affected wound healing by reducing the inflammatory phase and stimulated wound contracture by facilitating the deposition of collagen.
Bae, Hyun Kyung;Lee, Hyeryon;Kim, Kwan Chang;Hong, Young Mi
Clinical and Experimental Pediatrics
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v.59
no.6
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pp.262-270
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2016
Purpose: Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods: The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results: The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-${\alpha}$, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion: Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function.
Alzheimer's disease is a neurodegenerative disorder associated with progressive loss of cognitive function and memory. Amyloid beta peptide ($A{\beta}$) is the major component of senile plaques and is known to exert its cytotoxic effect mainly by producing $H_2O_2$. Vascular endothelial growth factor (VEGF) is elevated in the cerebrospinal fluid (CSF) and brain of AD patients, and $H_2O_2$ is one of the factors that induce VEGF. Therefore, we tested whether $A{\beta}$ might be responsible for the increased VEGF synthesis. We found that $A{\beta}$ induced the production of $H_2O_2$ in vitro. Comparison of the amount of $H_2O_2$ required to induce VEGF synthesis in HN33 cells and the amount of $H_2O_2$ produced by $10{\mu}M\;A{\beta}_{1-42}$ in vitro suggested that a toxic concentration of $A{\beta}$ might induce VEGF synthesis in these cells. However, toxic concentrations of $A{\beta}$ failed to induce VEGF synthesis in several cell systems. They also had no effect on antioxidant enzymes such as glutathione peroxidase, catalase, and peroxiredoxin in HN33 cells. $Cu^{2+}$, $Zn^{2+}$ and $Fe^{3+}$ are known to accumulate in the brains of AD patients and promote aggregation of $A{\beta}$, and $Cu^{2+}$ by itself induces synthesis of VEGF. However, there was no synergistic effect between $Cu^{2+}$ and $A{\beta}_{1-42}$ in the induction of VEGF synthesis and $Zn^{2+}$ and $Fe^{3+}$ also had no effect on the synthesis of VEGF, alone or in combination with $A{\beta}$.
Yeo, Hyeonjung;Kim, Hyodong;Son, Daegu;Hong, Changbae;Kwon, Sun Young
Archives of Plastic Surgery
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v.44
no.2
/
pp.95-100
/
2017
Background Intima-to-intima microanastomotic vascular remodeling was explored, utilizing a polylactide-caprolactone absorbable vein coupler model (PAVCM), which was designed to simulate a non-absorbable counterpart system with the sole exception of being absorbable. Methods Six New Zealand white rabbits were used. After transection of the jugular vein, 2 PAVCMs were placed, 1 at each transected end. The stumps were slipped through the PAVCMs, and the venous wall was everted $90^{\circ}$ to achieve intima-to-intima contact. Reanastomosis of the transected jugular vein was performed bilaterally in 3 rabbits. In the other 3 rabbits, the jugular vein (20 mm) harvested from one side was interpositionally grafted to the jugular vein on the opposite side to ease the anastomotic tension. Patency testing, ultrasonography, and histologic assessments were conducted postoperatively at weeks 2, 4, 12, 16, 22, and 26. Results All anastomotic sites were patent, without stenosis, occlusion, or dilatation. In the histologic sections, immature endothelial regeneration was observed at week 2, which was completed by week 4. Regeneration of the tunica media was noted at week 12. Between week 22 and week 26, the tunica media fully regenerated and the coupler dissipated entirely. Conclusions Despite the absence of a coupler to act as an anastomotic buttress, the structure and function of all the vessels appeared normal, even histologically. These outcomes are true milestones in the development of an absorbable vein coupler.
Intravenous administration of saponin extracted from the root of Panax ginseng lowered the blood pressure dose-dependently (10-200 mg/kg, B.W) in anesthetized rats. Therefore, experiments were designed to study the hypothesis that the lowering of blood pressure is associated with the release of endothelium-derived relaxing factor and the accumulation of guanosine 3, 5-cyclic monophosphate (cGMP). Rings of thoracic aorta with and without endothelium were suspended for the measurement of isometric tension in organ chamber and the tissue content of cGMP was measured by radioimmunoassay. All experiments were performed in the presence of $indomethacin(10^{-5}M).$ Ginseng saponin $(10^{-5}-3{\times}10^{-6}g/ml)$ relaxed contractions induced by phenylephrine $10^{-6}M)$ in the aorta with endothelium but not in that without endothelium. Treatment of aortic rings with $N^G$ monomethyl-L-arginine (L-NMMA, $10^{-4}M$ for 30 min), a competitive inhibitor of nitric oxide synthase, and methylene blue $(MB,\;3{\times}10^{-7}M$ for 30 min). an inhibitor of soluble guanylate cyclase, diminished the relaxation induced by Ginseng saponin. Ginseng saponin $10^{-4}g/ml$ for 2 min) increased the accumulation of cGMP in rings with endothelium. L-NMMA and MB inhibited the accumulation of cGMP induced by Ginseng saponin. These data suggest that vascular relaxations induced by Ginseng saponin are mediated by release of endothelium-derived relaxing factor and the accumulation of cGMP. The effect of Ginseng saponin on endothelial function in hypercholesterolemic rabbits was examined. In hypercholesterolemic rabbits fed with $2\%$ cholesterol for 8 weeks, relaxation of aortic rings to acetylcholine was impaired. The impaired relaxations of aortic rings in hypercholesterolemic rabbits were improved by dietary supplementation of Ginseng saponin, probably because of an improved release of endothelium - derived relaxing factor.
Photobiomodulation (PBM) using organic light emitting diodes (OLEDs) surface light sources have recently been claimed to be the next generation of PBM light sources. However, the differences between light emitting diodes (LEDs) and OLED mechanisms in vitro and in vivo have not been well studied. In vivo mouse models were used to investigate the effects of OLED irradiation on cellular function and cutaneous wound healing compared to LED irradiation. Mice in the LED- and OLED-irradiated groups were subjected to irradiation with 6 J/㎠ LED and OLED (630 nm), respectively, for 14 days after wounding, and some mice were sacrificed for the experiments on days 3, 7, 10, and 14. To evaluate wound healing, we performed hematoxylin-eosin and Masson's trichrome staining and quantified collagen density by computerized image analysis. The results showed that the size of the wound, collagen density, neo-epidermis thickness, number of new blood vessels, and number of fibroblasts and neutrophils was significantly influenced by LED and OLED irradiation. The tissue levels of interleukin (IL)-β, IL-6 and tumor necrosis factor (TNF)-α were investigated by immunohistochemical staining. LED and OLED irradiation resulted in a significant increase in the tissue IL-β and IL-6 levels at the early stage of wound healing (P < 0.01), and a decrease in the tissue TNF-α level at all stages of wound healing (P < 0.05), compared to the no-treatment group. The expression levels of the genes encoding vascular endothelial growth factor and transforming growth factor-beta 1 were significantly increased in LED and OLED-irradiated wound tissue at the early stage of wound healing (P < 0.01) compared to the no-treatment group. Thus, OLED as well as LED irradiation accelerated wound healing by modulating the synthesis of anti-inflammatory cytokines and the expression levels of genes encoding growth factors, promoting collagen regeneration and reducing scarring. In conclusion, this suggests the possibility of OLED as a new light source to overcome the limitations of existing PBMs.
Journal of the korean academy of Pediatric Dentistry
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v.36
no.4
/
pp.586-590
/
2009
Leukocyte adhesion deficiency is rare inherited defect on phagocytic function resulting lack of leukocyte cell surface expression of $\beta2$ integrin molecule that are essential for leukocyte adhesion to endothelial cells and chemotaxis. Clinical features of patients with leukocyte adhesion deficiency type I include recurrent necrotic infection of the skin mucous membranes, and intestinal tract with septicemia, and omphalitis arising from delayed umbilical cord separation. Oral manifestations are severe progressive periodontitis with alveolar bone loss, periodontal pockets, and partial and total premature loss of the deciduous and permanent dentitions. We report a case of leukocyte adhesion deficiency type I in a 5-year-old child with severe periodontitis. In order to prevent local and systemic infection, we controlled periodontal disease with periodic oral prophylaxis. Oral swabs and blood cultures were perfomed for suspected infection, so that optimal measures were taken through the use of appropriate antibiotics.
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