Pulsatile versus non-pulsatile perfusion in coronary artery bypass operation: The comparison of laboratory and clinical outcomes.

INTRODUCTION: The superiority of pulsatile or non-pulsatile perfusion in cardiopulmonary bypass (CPB) regarding morbidity and mortality is still debated. Therefore, we aimed to investigate the effect of different pulse rates in pulsatile perfusion in patients undergoing coronary artery bypass graft (CABG) and compared it with non-pulsatile perfusion. MATERIALS AND METHODS: In this randomized clinical trial, 90 patients who were all candidates for CABG under CPB were enrolled. Patients in groups A and B received pulsatile perfusion with 30 and 70 pulses per minute, and group C received non-pulsatile perfusion. The biochemical and clinical parameters in the ICU were evaluated in the study groups. RESULTS: There was no statistically significant difference between patients' clinical outcomes and kidney and liver function markers (all Ps> 0.05). Mean serum lactate level increased but did not show a statistically significant difference between the study groups (p = 0.8). The mean urine volume at 12 and 24 h after surgery was higher in group A, but there was no statistically significant difference between the three groups during the study period (p = 0.3). No significant difference was found in the length of the ICU stay between the study groups (p = 0.2). CONCLUSION: Our studied parameters demonstrated no significant difference between pulsatile and non-pulsatile and between 30 and 70 pulse rate pulsatile perfusion methods. Our findings support that pulsatile perfusion with different pulse rates has no advantages over non-pulsatile perfusion in selected CABG cases.

In Vitro Self-Assembly of a Modified Diphenylalanine Peptide to Nanofibers Induced by the Eye Absent Enzyme and Alkaline Phosphatase and Its Activity against Breast Cancer Cell Proliferation.

Drug-resistant breast cancers such as Triple negative breast cancer (TNBC) do not respond successfully to chemotherapy treatments because they lack the expression of receptor targets. Drug-resistant anti-cancer treatments require innovative approaches to target these cells without relying on the receptors. Intracellular self-assembly of small molecules induced by enzymes is a nanotechnology approach for inhibiting cancer cell growth. In this approach, enzymes will induce the self-assembly of small molecules to nanofibers, which leads to cell death. Here, we investigate the self-assembly of a modified small peptide induced by two different phosphatases: alkaline phosphatase (ALP) and eye absent tyrosine phosphatase (EYA). ALPs are expressed in many adult human tissues and are critical for many cellular functions. EYAs are embryonic enzymes that are over-expressed in drug-resistant breast cancers. We synthesized a small diphenylalanine-based peptide with a tyrosine phosphate end group as the substrate of phosphatase enzymes. Peptides were synthesized with solid phase techniques and were characterized by HPLC and MALDI-TOF. To characterize the self-assembly of peptides exposed to enzymes, different techniques were used such as scattering light intensity, microscopes, and phosphate detection kit. We then determined the toxicity effect of the peptide against normal breast cancer cells, MCF-7, and drug-resistant breast cancer cells, MDA-MB-231. The results showed that the EYA enzyme is able to initiate self-assembly at lower peptide concentration with higher self-assembling intensity compared to ALP. A significant decrease in the TNBC cell number was observed even with a low peptide concentration of 60 µM. These results collectively support the exploration of enzyme self-assembly to treat TNBC.

Effects of Co-Solvents on Loading and Release Properties of Self- Assembled Di-Peptide Building Blocks, Towards Drug Delivery Applications.

BACKGROUND: Due to their solid-like porous structure, molecular organogel and microcrystal structures have the capabilities of loading drug molecules, encapsulation, and extended release, all considered as essential properties in drug delivery applications. Phases of these structures, however, depend on the solvent used during the gelation process. OBJECTIVE: Understanding the phase transition between organogel and microcrystal structures through adjusting the mixture ratio of different co-solvents. METHODS: Short peptide Diphenylalanine as the gelation building block was used due to its amino acid sequences that can be exactly selected at its molecular levels. Ethanol as a polar solvent was used in combination with four other co-solvents with different polarity levels, namely Xylene, Toluene, Acetone, and Dimethyl Sulfoxide. The morphology of molecular structures of each co-solvent combination at each ratio level was examined as well as the loading and release properties for a non-polar Flufenamic Acid drug. RESULTS: The resultant structure was affected by the polarity of the co-solvents; in particular, in the sample containing 25 µg/ml of the drug, 94% of the drug amount was loaded inside the organogel. By increasing the drug concentration to 50, 75, and 100 µg/ml, the loading capability decreased to 76%, 47%, and 33%, respectively. CONCLUSION: Molecular organogels have excellent capabilities of loading drug molecules, while microcrystal structures have higher release capacity. The findings of this study reveal how to best design a gelation method to obtain maximum loading or release properties for a particular peptide- based drug delivery application.

Diphenylalanine peptide nanotubes self-assembled on functionalized metal surfaces for potential application in drug-eluting stent.

This study focuses on the potential of diphenylalanine self-assembled peptide nanotubes (FF Nts) for delivery of flufenamic acid (FA) from metal implants. Self-assembly of FF Nts was studied in solution and on surfaces of glass, silicone and gold substrates. FA was loaded inside the shell of FF Nts and subsequently FF/FA Nts were attached to gold surfaces. The substrate were characterized by Field Emission Scanning Electron Microscopy (FESEM), fluorescence microscopy, confocal microscopy, and UV-vis spectroscopy. Release of FA from FF Nts were investigated by immersing coated metal substrates in phosphate-buffered saline for 12 days. Self-assembly of FF in water and solvent resulted in formation of nanotubes, which efficiently loaded 98% of FA with concentration of 20 µg/mL. FESEM images confirmed successful attachment of FF/FA Nts to functionalized gold substrates. In vitro release studies indicated using FF Nts has prolonged the release rate of FA for several days. Biocompatibility studied confirmed more than 50% of the cells were alive in concentration of 250-1000 µg/mL of FF Nts thus suggesting the potential of peptide based self-assemble nanostructures as an alternate system for polymer coating in drugs eluting stents. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2280-2290, 2016.

Immobilization of bacterial S-layer proteins from Caulobacter crescentus on iron oxide-based nanocomposite: synthesis and spectroscopic characterization of zincite-coated Fe2O3 nanoparticles.

Zinc oxide was coated on Fe2O3 nanoparticles using sol-gel spin-coating. Caulobacter crescentus have a crystalline surface layer (S-layer), which consist of one protein or glycoprotein species. The immobilization of bacterial S-layers obtained from C. crescentus on zincite-coated nanoparticles of iron oxide was investigated. The SDS PAGE results of S-layers isolated from C. crescentus showed the weight of 50 KDa. Nanoparticles of the Fe2O3 and zinc oxide were synthesized by a sol-gel technique. Fe2O3 nanoparticles with an average size of 50 nm were successfully prepared by the proper deposition of zinc oxide onto iron oxide nanoparticles surface annealed at 450 °C. The samples were characterized by field-emission scanning electron microscope (FESEM), atomic force microscopy (AFM), powder X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR).

Nanoengineered polymeric S-layers based capsules with targeting activity.

Nanostructured polymeric capsules are regarded as highly promising systems with different potential applications ranging from drug delivery, biosensing and artificial cells. To fully exploit this potential, it is required to produce bio-activated stable and biocompatible capsules. To this purpose, in present work we proposed the combination of the layer-by-layer self assembly method with bacterial S-layer technology to fabricate stable and biocompatible polymeric capsules having a well defined arrangement of functional groups allowing the covalent attachment of antibody molecules. Hollow microcapsules were obtained by the layer-by-layer self assembly of oppositely charged polyelectrolytes onto colloidal particles, followed by removal of the cores at acidic pH. S-layers were crystallized onto the shell of the obtained capsules. Quartz crystal microbalance was used to characterize the crystallization process onto planar surfaces. S-layer containing capsules were investigated by atomic force microscopy. Immunoenzymatic tests were performed to assess the effective modification of the S-layer with antibody molecules both on planar surfaces and on hollow capsules. Fluorescent microscopy was employed to visualize the presence of the antibody molecules onto the capsule shell and immunological tests used to assess the bioactivity of the immobilized antibodies. Finally, the in vitro cytotoxicity of fabricated S-layer containing capsules was studied. The obtained results demonstrated the possibility to fabricate bio-activated S-layer containing capsules with improved features in terms of biocompatibility.