Ferulic acid grafted into ß-cyclodextrin nanosponges ameliorates Paraquat-induced human MRC-5 fibroblast injury.

Paraquat (PQ) is a commercially important and effective herbicide in the world. Nevertheless, it has higher toxicity causing acute organ damage and different complications, mainly in the lungs and kidneys. Ferulic acid (FA), 4-hydroxy-3-methoxycinnamic acid imposes multiple pharmacological impacts. No protective effect of FA on PQ poisoning-caused human embryonic lung fibroblast damage has not been reported. Despite their many beneficial effects, FA is characterized by poor water solubility, low bioavailability, and phytochemical instability. To solve the problem, ß-cyclodextrin nanosponge (ß-CD NSs) was utilized to increase the solubility of FA so that it was grafted into ß-CD NSs to establish ß-CD@FA NSs. The purpose of this work was to examine for the first time the protective effect of ß-CD@FA NS on MRC-5 human lung cells damages induced by PQ poisoning. MTS assay was performed to investigate the viability of MRC-5 cells at different concentrations of FA/ß-CD@FA NSs when cells were co-cultured with 0.2 µg/mL PQ. The flow cytometry study was carried out to determine apoptosis. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were detected using appropriate biochemistry kits. Compared with the PQ group, the cell activity, CAT, and SOD levels were significantly increased in the FA and chiefly in ß-CD@FA NSs intervention groups, whereas apoptosis and MDA levels were markedly decreased. The inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 22 (IL-22) were detected. The results demonstrate that ß-CD@FA NSs can inhibit PQ-induced cell damage by enhancing antioxidant stress capacity and regulation of inflammatory responses.

Potential anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on B16-F10 murine melanoma: In vitro and in vivo studies.

Melanoma is the major type of skin cancer, which its treatment is still a challenge in the world. In recent years, interest in hibernation-based therapeutic approaches for various biomedical applications has been increased. Many studies indicated that some factors in the blood plasma of hibernating animals such as alpha-2-macroglobulin (A2M) cause anti-proliferative effects. Considering that, the present study was conducted to investigate the anti-cancer effects of hibernating common carp plasma (HCCP) on murine melanoma (B16-F10) in vitro and in vivo. The effect of HCCP on cell viability, migration, apoptosis rate, and cell cycle distribution of B16-F10 cells, tumor growth, and rate of survival were evaluated. To investigate the role of A2M in the anti-cancer effects of HCCP, the gene of interest and proteins in HCCP and non-hibernating common carp plasma (NHCCP) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry analysis. Based on our findings, HCCP significantly decreased B16-F10 cell viability. Moreover, HCCP caused morphological alternations, inhibition of migration, induction of apoptosis, and significantly induced the cell cycle arrest at the G2/M phase. In addition, A2M level was significantly increased in HCCP compared with NHCCP. Taken together, our findings suggested that HCCP had the potential to be a promising novel therapeutic target for cancer treatment because of its anti-cancer properties.

In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer.

Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.

Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial.

AIM: The effectiveness of nanofibers containing human placenta-derived mesenchymal stem cells (hPDMSCs) plus platelet-rich plasma (PRP) for healing of diabetic foot ulcers (DFUs) was investigated. METHODS: hPDMSCs were isolated from human donor placentas, and cultured in electrospun gelatin nanofibrous scaffolds (GNS). Twenty-eight patients with DFUs were randomized into three groups in a 12-week trial: (A) Treated with hPDMSCs; (B) Treated with hPDMSCs after coating the ulcer with PRP gel; (C) Control group received standard wound care. Wound area and pain freewalkingdistance were measured every 2 weeks. RESULTS: Flow cytometry showed the expression of mesenchymal markers. SEM images and DAPI staining indicated significantly higher levels of hPDMSC proliferation on GNS after 3 and 7 days of culture. The MTS assay showed a significant increase in proliferation on GNS, compared to controls. Wound size reduction was 66% in group A, 71% in group B, and 36% in control group C. A significant difference in wound closure and pain-free walking distance was observed between groups A and B, compared to control group C (p < 0.05), but no difference between groups A and B. Biopsy of the implanted tissue showed the development of new capillary formation in groups A and B. CONCLUSION: Implantation of hPDMSCs in GNS accelerated wound healing and improved clinical parameters in DFU patients.

An injectable carboxymethyl chitosan-methylcellulose-pluronic hydrogel for the encapsulation of meloxicam loaded nanoparticles.

Hydrogel scaffolds have been frequently utilized due to their ability to absorb water and develop similar body cell conditions. Specific drug delivery to the tissues ensures less adverse side effects and more efficiency. In the present study, carboxymethyl chitosan (CMC)-methylcellulose (MC)-pluronic (P) and zinc chloride hydrogels containing meloxicam loaded into nanoparticles were developed and characterized. Nanoparticles were incorporated at 3.5, 4.5 and 5.5% (w/v). Hydrogels containing the same amounts of the meloxicam solution were also prepared. Gelation time, swelling and degradation of the hydrogels were investigated. Hydrogels were characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, and rheological analysis. Meloxicam release, chondrocytes attachment and growth on the hydrogels were also studied. Gelation time, swelling and the degradation rate of the hydrogels were found to be decreased by nanoparticles and increased with the addition of the meloxicam solution. SEM images also showed three-dimensional networks. The ATR-FTIR bands were shifted to the lower wave numbers in the hydrogels containing nanoparticles and shifted to the upper ones in the hydrogels containing meloxicam solution. Storage (G') and loss (G″) modulus were increased by the nanoparticles and reduced by the meloxicam solution. 100% of meloxicam was released from the hydrogels containing the meloxicam solution within 20 days, but it was released slowly from the hydrogels containing nanoparticles in 37days. Chondrocytes metabolic activity was increased on the 6th and 10th days for all hydrogels. Hydrogel containing nanoparticles showed good biocompatibility, bioadhesion, cell growth and expansion. The hydrogel could be, therefore, suitable as a new composite biomaterial for the regeneration of articular cartilage and meloxicam delivery to control the pain and inflammation in osteoarthritis.

The anti-tumor activity of exopolysaccharides from Pseudomonas strains against HT-29 colorectal cancer cell line.

The anti-tumor activity of extracted exopolysaccharides (EPSs) (without any side effects) of Pseudomonas aeruginosa on HT-29 colorectal cancer cell line has not been previously investigated. The extraction and partial characterization of EPS from the strains of P. aeruginosa including A (CIP A22(PTCC1310)), and B (a clinical strain) were performed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays as well as microscopy were used to estimate the cell viability and morphological changes in HT-29 cells subjected to EPS at 0, 7.6, 15.8, 31.2, 62.5 and 125 µg/ml. The apoptotic effects of EPS were also examined by flow cytometry. The EPSs were found to be cytotoxic against HT-29 cells with IC50 values at 44.8 (EPS-A) and 12.7 (EPS-B) µg/ml. The counteraction of 125 µg/ml of EPS-A (87.5 and 56.7%) and EPS-B (86.7 and 59.2%) resulted in the highest repressive rates using the MTT and SRB assays, respectively. Flow cytometric results showed that EPS-A and EPS-B could induce apoptosis (33% and 39%) and necrosis (65% and 59%). The extracted EPSs of both bacterial strains can be used as natural, effective, efficient and anti-cancer drugs. However, more characterization at molecular and structural levels in this respect may be required.

Efficient co-cultivation of human fibroblast cells (HFCs) and adipose-derived stem cells (ADSs) on gelatin/PLCL nanofiber.

In this study, we investigated whether the nanofibers produced by natural-synthetic polymers can probably promote the proliferation of co-cultured adipose-derived stem cells/human fibroblast cells (ADSs/HFCs) and synthesis of collagen. Nanofiber was fabricated by blending gelatin and poly (L-lactide co-ɛ-caprolactone) (PLCL) polymer nanofiber (Gel/PLCL). Cell morphology and the interaction between cells and Gel/PLCL nanofiber were evaluated by FESEM and fluorescent microscopy. MTS assay and quantitative real-time polymerase chain reaction were applied to assess the proliferation of co-cultured ADSs/HFCs and the collagen type I and III synthesis, respectively. The concentrations of two cytokines including fibroblast growth factor-basic and transforming growth factor-ß1 were also measured in culture medium of co-cultured ADSs/HDCs using enzyme-linked immunosorbent assay assay. Actually, nanofibers exhibited proper structural properties in terms of stability in cell proliferation and toxicity analysis processes. Gel/PLCL nanofiber promoted the growth and the adhesion of HFCs. Our results showed in contact co-culture of ADSs/HFCs on the Gel/PLCL nanofiber increased cellular adhesion and proliferation synergistically compared to non-coated plate. Also, synthesis of collagen and cytokines secretion of co-cultured ADSs/HFCs on Gel/PLCL scaffolds is significantly higher than non-coated plates. To conclude, the results suggest that Gel/PLCL nanofiber can imitate physiological characteristics in vivo and enhance the efficacy of co-cultured ADSs/HFCs in wound healing process.

Improving the solubility and in vitro cytotoxicity (anticancer activity) of ferulic acid by loading it into cyclodextrin nanosponges.

Purpose: Ferulic acid (FA) is a poorly water-soluble natural antioxidant with anticancer activity. This poor solubility limits the application of FA in the food and pharmaceutical industry. Cyclodextrin nanosponges (CD-NSs) are a novel group of cross-linked CD derivatives which can be used to enhance the solubility of low-soluble bioactive compounds. Methods: In this study, FA was encapsulated into the NSs in the proportion of 1:4 (FA:NS). Diphenyl carbonate was used as a cross-linker in different proportions with ß-CD. Characterization of obtained NSs was performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis. Results: Our results revealed that the solubility of encapsulated FA was increased up to fifteenfold compared with pure FA in the proportion of 1:4 (CD:cross-linker). The results of FTIR, XRD, and DSC confirmed the interaction of FA with NSs. The cytotoxicity of encapsulated FA against MCF7 and 4T1 breast cancer cell lines was investigated using different concentrations of FA in 24, 48, and 72 hrs. The cytotoxicity assay indicated that FA treatment reduced viability and enhanced apoptosis of cancer cells. IC50 value of encapsulated FA (250 ppm) was decreased by threefold when compared with pure FA (750 ppm). Conclusion: In general, CD-NS was found to be a suitable delivery system for poorly soluble bioactives such as FA.

Differentiation of Human Scalp Adipose-Derived Mesenchymal Stem Cells into Mature Neural Cells on Electrospun Nanofibrous Scaffolds for Nerve Tissue Engineering Applications.

OBJECTIVES: This study aimed to isolate and culture SADS cells, investigate their neurogenic capacity and evaluate their application for nerve tissue engineering. MATERIALS AND METHODS: In this experimental study, SADS cells were isolated from human adipose tissue. After 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, neurogenic differentiation of SADS cells was investigated. During this study, Poly (ε-caprolactone) (PCL) and PCL/gelatin nanofibrous scaffolds were fabricated using electrospinning and subsequently nanofibrous scaffolds were coated with platelet-rich plasma (PRP). SADS cells were also seeded on nanofibrous scaffolds and neurogentic differentiation of these cells on nanofibers was also evaluated. Effect of PRP on proliferation and differentiation of SADS cells on scaffolds was also studied. RESULTS: Our results showed that after 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, SADS cells expressed markers characteristic of neural cells such as nestin and neuron specific nuclear protein (NEUN) (as early neuronal markers) as well as microtubule-associated protein 2 (MAP2) and neuronal microtubule-associated (TAU) (as mature neuronal markers) while mature astrocyte maker (GFAP) was not expressed. MTT assay and SEM results showed that incorporation of gelatin and PRP into the structure of nanofibrous scaffolds has a significant positive influence on the bioactivity of scaffolds. Our results also showed neurogentic differentiation of SADS cells on scaffolds. CONCLUSIONS: Our results demonstrated that SADS cells have potential to differentiate into early and mature progenitor neurons, in vitro. PCL/gelatin/PRP was found to be a promising substrate for proliferation of SADS cells and differentiation of these cells into neural cells which make these scaffolds a candidate for further in vivo experiments and suggest their application for nerve tissue engineering.

Gold nanoparticles in combination with megavoltage radiation energy increased radiosensitization and apoptosis in colon cancer HT-29 cells.

PURPOSE: Gold nanoparticles (GNP) act as a radiosensitizer in radiation therapy. However, recent studies have shown contradictory evidence in terms of radiosensitization in the presence of GNP combined with X-ray megavoltage energy (MV) on different cell types. In this study, the effect of GNP on radiosensitization enhancement of HT-29 human colorectal cancer cells at MV X-ray energy was evaluated. MATERIALS AND METHODS: The cytotoxicity and radiosensitization of GNP were evaluated in HT-29 human colorectal cancer cells by MTS-assay and multiple MTS-assay, respectively. Cellular uptake was assayed using graphite furnace atomic absorption spectrometry (GFAAS). Apoptosis and cell cycle progression were determined by an Annexin V-FITC/propidium iodide (PI) kit and PI/RNase solution with flow cytometry, respectively. RESULTS: Results showed that the cell viability of the HT-29 cells was not influenced by exposure to different concentrations of GNP (10-100 µM). GNP alone did not affect the cell cycle progression and apoptosis. In contrast, GNP, in combination with radiation (9 MV), induced more apoptosis. The interaction of GNP with MV energy resulted in a significant radiosensitization enhancement compared with irradiation alone. CONCLUSION: It was concluded that GNP may work as bio-inert material on HT-29 cancer cells and their enhancement of radiosensitization may be due to increase in the absorbed irradiation dose.

Culturing in serum-free culture medium on collagen type-I-coated plate increases expression of CD133 and retains original phenotype of HT-29 cancer stem cell.

BACKGROUND: A sub-population of tumor cells termed cancer stem cells (CSCs) has an important role in tumor initiation, progression, and recurrence. Selecting a suitable procedure for isolation and enrichment of CSCs is the biggest challenge in the study of CSCs. In the present study, the role of the combination of stem cell culture medium and collagen type-I was evaluated for successful isolation and enrichment of HT-29 CSCs. MATERIALS AND METHODS: HT-29 cells were cultured in serum-containing medium (parental culture medium: Medium + 10% fetal bovine serum) and serum-free medium (stem cell culture medium); both on collagen-coated plates. Spheres forming ability and CD133 expression, as a potential marker of colorectal CSCs, were evaluated in two culture mediums. RESULTS: The results show spheroids usually give rise completely within 15 days in the stem cell culture medium on the collagen-coated plate. CD133 expression in spheroid cells (84%) is extensively higher than in parental cells (25%). Moreover, relative to parental cells, spheroid cells were more radioresistance. CONCLUSION: Finding of this study suggested that CSCs derived from colon cancer cell line (HT-29) can be propagated and form colonospheres in serum-free culture medium on collagen type-I. According to maintenance of their original phenotype in these conditions, it seems serum-free culture medium on collagen type-I is a suitable way to drug screening of HT-29 CSCs.

Multiple MTS Assay as the Alternative Method to Determine Survival Fraction of the Irradiated HT-29 Colon Cancer Cells.

A multiple colorimetric assay has been introduced to evaluate the proliferation and determination of survival fraction (SF) of irradiated cells. The estimation of SF based on the cell-growth curve information is the major advantage of this assay. In this study, the utility of multiple-MTS assay for the SF estimation of irradiated HT-29 colon cancer cells, which were plated before irradiation, was evaluated. The SF of HT-29 colon cancer cells under irradiation with 9 MV photon was estimated using multiple-MTS assay and colony assay. Finally, the correlation between two assays was evaluated. Results showed that there are no significant differences between the SF obtained by two assays at different radiation doses (P > 0.05), and the survival curves have quite similar trends. In conclusion, multiple MTS-assay can be a reliable method to determine the SF of irradiated colon cancer cells that plated before irradiation.

Effect of the co-administration of glucose with morphine on glucoregulatory hormones and causing of diabetes mellitus in rats.

BACKGROUND: Morphine is related to dysregulation of serum hormone levels. In addition, addict subjects interest to sugar intake. Therefore, this study investigated the effect of co-administration of glucose with Mo on the glucoregulatory hormones and causing of diabetes mellitus in rats. MATERIALS AND METHODS: Male rats were randomly divided into four groups including, control, morphine, Morphine-Glucose and diabetes groups. Morphine was undergone through doses of 10, 20, 30, 40, 50, and 60 mg/kg, respectively on days 1, 2, 3, 4, 5, and 6. Then, dose of 60 mg/kg was used repeated for 20 extra days. The Morphine-Glucose group received the same doses of morphine plus 1 g/kg glucose per day. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. At the end of experiment, the serum insulin, glucagon, growth hormone (GH), cortisol, and glucose levels were measured. The homeostasis model assessment (HOMA) indexes concluding the HOMA-insulin resistance (HOMA-IR) and HOMA-ß were evaluated. RESULTS: Morphine insignificantly induced a hyperglycemia condition and insulin resistance. Whereas, the beta-cell functions significantly (P < 0.05) decreased only in morphine group. The co-administration of glucose slightly increased the GH, and increased insulin and cortisol levels significantly (P < 0.05 and P < 0.01; respectively) in the Morphine-Glucose group. Furthermore, the co-administration of glucose with morphine could nearly modulate the morphine effects on body weight, glucose, and glucagon levels. CONCLUSION: It is probable that the co-administration of glucose with morphine modulate the serum glucose levels by stimulating the beta-cell functions and to increase insulin secretion.

Initial clinical outcomes of intracoronary infusion of autologous progenitor cells in patients with acute myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is an irreversible cardiomyocytes injury which begins after 15-20 minutes of coronary artery occlusion. The extent of infarction is modulated by a number of factors including collateral blood supplies, medications, and ischemic preconditioning. Although angioplasty and thrombolytic agents can relieve the cause of the infarction, the time from the occlusion onset to reperfusion determines the degree of irreversible myocardial injury. Experimental studies suggested that stem cells and progenitor cells derived from bone marrow can be used in the repair of cardiac tissue after acute MI. This study was designed to investigate the feasibility, safety and initial clinical outcome of intracoronary infusion of autologous progenitor cells in patients with acute MI. METHODS: Patients with a history of anterior MI and a left ventricular ejection fraction (LVEF) less than 35 % who were candidates for coronary angioplasty were randomly allocated in a 1:1 ratio to either control or bone marrow cell groups (each including 16 patients). Thallium scan and 17-segment echocardiography analysis for regional wall motion abnormality were performed before and 1 and 6 months after intracoronary infusion of bone marrow cells. The same tests were also conducted for the control group at identical time intervals. Quantitative variables were compared by independent t-test and paired t-test. Statistical significance was assumed at a value of P < 0.05. RESULTS: LVEF in the case and control groups increased to 39.37 ± 2.47% and 31.00 ± 1.87%, respectively (P = 0.069 and 0.1, respectively). Wall motion abnormality index (WMAI) decreased insignificantly in both groups. Perfusion defect scores (PDSs) decreased significantly in the case group. CONCLUSION: In this study, autologous mesenchymal stem cell transplantation by intracoronary catheter during angioplasty in patients with a history of severe LV dysfunction caused mild increases in LVEF.

Treatment of full thickness cartilage defects in human knees with Autologous Chondrocyte Transplantation.

BACKGROUND: Although a variety of strategies have been employed for managing articular cartilage defects in the knee, overall outcomes have not been satisfactory. An alternative option may be autologous chondrocyte transplantation (ACT). However, as this method is still under investigation, here we assessed the efficacy of ACT for human knee defect cartilage repair. METHODS: In a randomized clinical trial study, eleven patients (mean age 31.09 years) were enrolled in the study with full thickness cartilage defects in the knee. Arthroscopically, healthy cartilage was obtained, chondrocytes expanded for 2-3 weeks and ACT performed. Clinical status was evaluated before ACT, 6 and 12 months after ACT using the Brittberg-Peterson functional assessment and modified Cincinnati rating score. Magnetic resonance imaging (MRI) findings were evaluated based on the scoring systems used by Sally Roberts and by Henderson. RESULTS: Modified Cincinnati rating indicated significant improvement of clinical score before ACT compared to 6 (p = 0.000) and 12 (p = 0.000) months after ACT (from 2.73 before ACT to 7.27, 8.36 and 9.5 at 6, 12, and 48 months after ACT, respectively). Brittberg-Peterson functional assessment indicated a decline from 79.27 to 25.82 and 19.27 at 6 and 12 months post ACT. Further, statistical test demonstrated significant differences 6, 12 and 48 months post ACT (p = 0.007). Evaluation of MRI revealed a score of 6.5 for Henderson criteria and a score of 2.5 for Robert criteria. CONCLUSIONS: Our study demonstrated that ACT of the knee provides an excellent treatment for full thickness cartilage defects with outstanding clinical and radiological outcomes.

The thickness of electrospun poly (epsilon-caprolactone) nanofibrous scaffolds influences cell proliferation.

Nanofibrous scaffolds have morphological similarities to native extracellular matrix and have been considered as candidate scaffolds in tissue engineering. However, there is no report on the effect of the thickness of nanofibrous scaffold on cell behavior. In this study poly (epsilon-caprolactone) (PCL) nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm were fabricated by electrospinning. Properties of PCL nanofibrous scaffolds were measured by contact angle and air permeability measurements while the morphology of the nanofibers was observed by SEM. Mouse embryonal carcinoma stem cells (P19), monkey epithelial kidney cells (Vero), Chinese hamster ovary cells (CHO) and mouse mesenchymal stem cells (MSCs) were seeded on PCL nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm. Air permeability measurements showed that air permeability decreases with the increase in the thickness of nanofibrous scaffolds, and contact angle measurements revealed a contact angle of 118 degrees for electrospun PCL nanofibers. The MTT assays showed that the proliferation of the cells was influenced by the thickness of the nanofibrous scaffold. Scaffolds with a thickness of 0.6 mm were found to provide a better substrate for cell proliferation, possibly due to more dimensional stability. Therefore, regardless of cell origin, thicker scaffolds provide a better substrate for cell proliferation, possibly due to the higher dimensional stability and tightness of thicker scaffolds.

Reactive oxygen metabolites and anti-oxidative defenses in aspirin-induced gastric damage in rats: Gastroprotection by Vitamin E.

OBJECTIVE: It has been proposed that neutrophil infiltration and oxygen radicals may be the important prime events that lead to mucosal injury induced by aspirin. Vitamin E acts as a potent antioxidant, and is capable of scavenging free radicals. The aim of this study was to evaluate the oxygen metabolites and anti-oxidative defenses in acute gastric damage induced by aspirin and to find the effects of Vitamin E. METHODS: Ninety-six Wistar rats were divided into four groups of 24 rats each as follows: (1) the control group; (2) the ASA group that received 300mg/kg of ASA; (3) the Vitamin E plus ASA group and (4) the Vitamin E group that received Vitamin E (75 units) alone. At 3, 6, 9 and 24h after the drug administration, six rats were randomly selected from each group and gastric mucosal injury, prostaglandin E2, and the activities of myeloperoxidase, xanthine-oxidase, superoxide dismutase, glutathione peroxidase as well as glutathione level were measured and compared between the groups. RESULTS: Oral administration of ASA caused acute gastric erosions and an increase in myeloperoxidase activity. It also decreased prostaglandin E2, superoxide dismutase activity, glutathione peroxidase activity and glutathione level. Concomitant administration of Vitamin E and ASA restored all the changes toward the control levels. CONCLUSION: Free radicals and suppression of anti-oxidizing enzymes play important roles in gastric damage induced by aspirin. Increased myeloperoxidase activity suggests that activated neutrophils may be a major source of free radicals. Vitamin E protects against ASA-induced damage due to its anti-oxidizing activity.