Chitosan/Gold Hybrid Nanoparticles Enriched Electrospun PVA Nanofibrous Mats for the Topical Delivery of Punica granatum L. Extract: Synthesis, Characterization, Biocompatibility and Antibacterial Properties.

PURPOSE: Intending to obtain Punica granatum L. extract (PE)-loaded drug delivery system of better impact and biomedical applicability, the current study reports the use of crosslinked PVA nanofibers (NFs) as platforms incorporating different amounts of biosynthesized PE-CS-gold nanoparticles (PE-CS-Au NPs). METHODS: PE-conjugated CS-Au nanoparticles (PE-CS-Au NPs) were synthesized via green chemistry approach. The formation of PE-CS-Au NPs was confirmed by UV spectroscopy, DLS, SEM and STEM. PE-CS-Au NPs were then dispersed into polyvinyl alcohol (PVA) solution at different ratios, where the optimized ratios were selected for electrospinning and further studies. Crosslinking of PE-CS-Au NPs loaded PVA nanofibers (NFs) was performed via glutaraldehyde vapor. The morphology, chemical compositions, thermal stability and mechanical properties of PE-CS-Au NPs loaded NFs were evaluated by SEM, FTIR and DSC. Swelling capacity, biodegradability, PE release profiles, release kinetics, antibacterial and cell biocompatibility were also demonstrated. RESULTS: By incorporating PE-CS-Au NPs at 0.6% and 0.9%, the diameters of the nanofibers decreased from 295.7±83.1 nm in neat PVA to 165.6±43.4 and 147.8±42.7 nm, respectively. It is worth noting that crosslinking and incorporation of PE-CS-Au NPs improved thermal stability and mechanical properties of the obtained NFs. The release of PE from NFs was controlled by a Fickian diffusion mechanism (n value ˂0.5), whereas Higuchi was the mathematical model which could describe this release. The antibacterial activity was found to be directly proportional to the amount of the incorporated PE-CS-Au NPs. The human fibroblasts (HFF-1) showed the highest viability (123%) by seeding over the PVA NFs mats containing 0.9% PE-CS-Au NPs. CONCLUSION: The obtained results suggest that the electrospun PVA NFs composites containing 0.9% PE-CS-Au NPs can be used as antibacterial agents against antibiotic-resistant bacteria, and as suitable scaffolds for cell adhesion, growth and proliferation of fibroblast populations.

alpha-Tocopherol supplementation reduces inflammation and apoptosis in high cholesterol mediated nonalcoholic steatohepatitis.

Inflammation and apoptosis signaling are crucial steps in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Alpha-tocopherol, the most active form of vitamin E, is an important modulator of signaling mechanisms, but its involvement to cholesterol-induced NASH pathogenesis remains poorly defined. Herein we have reported a novel effect of α-tocopherol in the transition from hepatic steatosis to NASH. High cholesterol diet alone (without α-tocopherol) in rabbits elevated NASH development as indicated by increased inflammatory response, apoptotic activity and liver fibrosis. Such elevation results from induction of signaling mechanisms since the expressions of IL1ß, phospho c-Jun/c-Jun ratio, JNK, caspase 9, CHOP and Bax were increased, and recruitment of macrophage, α-smooth muscle actin (α-SMA) and COL1A1 into the liver tissue were induced. Alpha-tocopherol supplementation inhibited inflammatory response, apoptosis and fibrosis development without affecting lipid accumulation in high cholesterol-induced NASH. Specifically, α-tocopherol lowered the inflammatory level as observed by reduced macrophage infiltration and JNK/c-Jun signaling. Lower inflammatory status co-occurred with the reduction of CHOP and Bax expressions as well as fibrosis-related COL1A1 and α-SMA levels. Taken together, α-tocopherol supplementation inhibits cholesterol-induced NASH development by lowering JNK/c-Jun/inflammation axis in addition to JNK/CHOP/apoptosis signaling, which might contribute to resistance against NAFLD/NASH transition.

High Cholesterol Diet-Induced Changes in Oxysterol and Scavenger Receptor Levels in Heart Tissue.

Involvement of high cholesterol and oxidative stress in cardiovascular diseases is well studied, as it can be hypothesized that various products originated from lipid peroxidation, such as oxysterols, or affected protein expression might lead to cardiomyocyte damage followed by the pathological modifications. Although oxidation of excessive cholesterol to oxysterols in elevated stress conditions is identified by a number of studies, the role of a high cholesterol diet in regulating fatty acid and oxysterol accumulation, together with scavenger receptor mRNA levels, in the heart remains little investigated. Our study provides a detailed analysis of the changes in fatty acid, oxysterol, and scavenger receptor profiles and its relation with histological alterations in the heart tissue. We evaluated alterations of fatty acid composition, by the GC-MS method, while 4ß-, 25-, and 27-hydroxycholesterol and 7-ketocholesterol levels by means of LC-MS/MS in high cholesterol diet-fed rabbits. Additionally, a number of proteins related to lipid metabolism and scavenger receptor mRNA expressions were evaluated by Western blotting and RT-PCR. According to our in vivo results, a high cholesterol diet enhances a number of unsaturated fatty acids, oxysterols, and LXRα, in addition to CD36, CD68, CD204, and SR-F1 expressions while α-tocopherol supplementation decreases LXRα and SR expressions together with an increase in 27-hydroxycholesterol and ABCA1 levels. Our results indicated that the high cholesterol diet modulates proteins related to lipid metabolism, which might result in the malfunction of the heart and α-tocopherol shows its beneficial effects. We believe that this work will lead the generation of different theories in the development of heart diseases.

Antitumor and antimetastatic effects of walnut oil in esophageal adenocarcinoma cells.

BACKGROUND: Walnuts contain many components including specific fatty acids, which could be active against cancer. Even though the anticarcinogenic effect of some of the individual fatty acids in walnut oil has been described, the effect of walnut oil itself on esophageal cancer cells hasn't yet been investigated. OBJECTIVE: We aimed to investigate whether walnut oil affects tumor growth and metastatic potential in esophageal cancer cells. METHODS: The human esophageal adenocarcinoma cell line, OE19, was treated with different doses of walnut oil and cell viability, apoptosis/necrosis and cell cycle analyses were performed using WST-1 assay and flow cytometry respectively. Adhesion, colony formation and wound healing assays were performed to assess the antimetastatic effects of walnut oil. NFkB expression was evaluated with western blot analysis. RESULTS: Walnut oil decreased the cell viability of esophageal cancer cells in a dose-dependent manner. 20 mg/mL walnut oil reduced cell viability by ∼50% when compared with control. The analysis revealed that necrosis and accumulation of cells in G0/G1 phase was induced in the cells treated with high doses of walnut oil. It also down-regulated the protein levels of NFkB. Walnut oil suppressed the adhesion, migration and colony formation of the cells. CONCLUSIONS: High-dose short-term administration of walnut oil reduces the cell viability and metastatic ability of esophageal cancer cells, while exhibiting anticarcinogenic effect by inducing necrosis and cell cycle arrest at the G0/G1 phase, probably through suppression of the NFkB pathway. These data indicate that walnut oil, and by extension walnut consumption, may have beneficial effects in esophageal cancer in humans. This should be tested by clinical trials in the future.

Distal ureteral stricture: An unexpected complication of further adjuvant intravesical mitomycin C thermotherapy.

We present a case of distal ureteral obstruction in relation to further adjuvant intravesical thermochemotherapy with mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). We also discuss the diagnostic procedures and management of this recurrent case.

Hippophae rhamnoides L. and dexpanthenol-bepanthene on blood flow after experimental skin burns in rats using 133Xe clearance technique.

UNLABELLED: The aim of the present experimental study was to determine and compare the effect of Hippophae rhamnoides L. extract (HRe-1) and of dexpanthenol on the blood flow of a wound region, in rats using xenon-133 ((133)Xe) clearance technique. METHODS: Burn wounds were made on both thighs of rats and, HRe-1 and dexpanthenol were applied topically on the wound region only in the right thigh for a period of 8 days. The effect of HRe-1 and of dexpanthenol on blood flow of the wound region was assessed before and after their topical application by using the (133)Xe clearance technique. RESULTS: HRe-1 increased significantly blood flow of the wound region (P<0.05). Dexpanthenol showed a smaller increase in blood flow. In conclusion, our results in rats suggest that HRe-1 increases blood flow of the wound area and can be used for the treatment of skin wound healing, preferably than dexpanthenol.

Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.