Decellularized amniotic membrane Scaffolds improve differentiation of iPSCs to functional hepatocyte-like cells

Human-induced pluripotent stem cells-derived hepatocyte-like cells (hiPSCs-HLCs) holds considerable promise for future clinical personalized therapy of liver disease. However, the low engraftment of these cells in the damaged liver microenvironment is still an obstacle for potential application. In this study, we explored the effectiveness of decellularized amniotic membrane (dAM) matrices for culturing of iPSCs and promoting their differentiation into HLCs. The DNA content assay and histological evaluation indicated that cellular and nuclear residues were efficiently eliminated and the AM extracellular matrix component was maintained during decelluarization. DAM matrices were developed as three-dimensional scaffolds and hiPSCs were seeded into these scaffolds in defined induction media. In dAM scaffolds, hiPSCs-HLCs gradually took a typical shape of hepatocytes (polygonal morphology). HiPSCs-HLCs that were cultured into dAM scaffolds showed a higher level of hepatic markers than those cultured in tissue culture plates (TCPs). Moreover, functional activities in term of albumin and urea synthesis and CYP3A activity were significantly higher in dAM scaffolds than TCPs over the same differentiation period. Thus, based on our results, dAM scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited higher level of the hepatic marker and more stable metabolic functions.     

Delta-6 desaturase makes a different fatty acid profile of seed oil in Iranian borage (Echium amoenum Fisch. and Mey.)

Iranian borage (Echium amoenum) from Boraginaceae is a valuable medicinal plant native to Iran and Syria. We determined fatty acid profile and individual fatty acid contents in E. amoenum seed oil using gas chromatography. Nevertheless, the cumulative amount of ω-6 and ω-3 fatty acids in E. amoenum (78.5 %) was in great accordance with those of other species of Echium, Stearidonic acid (SDA, C18:4ω3) and gamma-linolenic acid (GLA, C18:3ω6) constituted only 9.7 % of seed oil in this plant. This observation elucidated the weak activity of delta-6 desaturase (D6DES) in E. amoenum compared with D6DESs of other species. As D6DES enzyme is responsible for converting linoleic acid (LA, C18:2ω6) and alpha-linolenic acid (ALA, C18:3ω3) to GLA and SDA, we isolated coding sequence of D6DES gene and characterized primary structure of the translated protein to probably find some evidences explaining the weak activity of D6DES enzyme in E. amoenum. Gene sequence from E. amoenum showed a high identity of 94–96 % with the other Echium species and the amino acid homology increased by 98 %. All the expected signatures including cytochrome b5 domain and three conserved histidine-rich motifs were found in the translated amino acid sequence. Protein alignment revealed that all the conserved motifs in D6DES sequence from E. amoenum are coincident with its counterparts from other Echium species. However, secondary structure of the enzyme deduced from its primary structure using computational simulation represented obvious differences with D6DES proteins of the other species.     

Theoretical study of electron transfer process between fullerenes and neurotransmitters; acetylcholine,dopamine, serotonin and epinephrine in nanostructures [neurotransmitters].C<Subscript><Emphasis Type="Italic">n</Emphasis></Subscript> complexes

Neurotransmitters are the compounds which allow the transmission of signals from one neuron to the next across synapses. They are the brain chemicals that communicate information throughout brain and body. Fullerenes are a family of carbonallotropes, molecules composed entirely of carbon, that take the forms of spheres, ellipsoids, and cylinders. Various empty carbon fullerenes (C_n) with different carbon atoms have been obtained and investigated. Topological indices have been successfully used to construct effective and useful mathematical methods to establish clear relationships between structural data and the physical properties of these materials. In this study, the number of carbon atoms in the fullerenes was used as an index to establish a relationship between the structures of neurotransmitters (NTs) acetylcholine (AC) 1, dopamine (DP) 2, serotonin (SE) 3, and epinephrine (EP) 4 as the well-known redox systems and fullerenes C_n (n = 60, 70, 76, 82, and 86) which create [NT].C_n; A-1 to A-5 up to D-1 to D-5. The relationship between the number of carbon atoms and the free energy of electron transfer (ΔG_et(n); n = 1–4) is assessed using the Rehm-Weller equation for A-1 to A-5 up to D-1 to D-5 supramolecular [NT].C_n complexes. The calculations are presented for the four reduction potentials (^Red.E₁ to ^Red.E₄) of fullerenes C_n. The results were used to calculate the four free energy values of electron transfer (ΔG_et(1) to ΔG_et(4)) of the supramolecular complexes A-1 to A-8 up to D-1 to D-8 for fullerenes C₆₀ to C₁₂₀. The first to fourth free activation energy values of electron transfer and the maximum wavelength of the electron transfers, ΔG^#_et(n) and λ_et (n = 1–4), respectively, were also calculated in this study for A-1 to A-8 up to D-1 to D-8 in accordance with the Marcus theory.     

Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors

1. Download high-res image (199KB)
2. Download full-size image

     

Heavy metals in the Rosetta estuary of the Nile and the adjoining Mediterranean waters: evidence of removal of dissolved heavy metals from waters as a result of possible binding to suspended matter

The Rosetta estuary was partially separated from the Rosetta branch of the Nile by Edfina Barrage, which controls the Nile discharge into the Mediterranean Sea. The study area covers the Rosetta estuary (lotic environment) and the adjoining seawaters (lentic environment) to investigate the local and seasonal distribution of dissolved and particulate copper and zinc, as well as dissolved cadmium in this estuary and to illustrate its influence on the distribution of these metal forms in the inshore seawaters. Besides, emphasis on the removal of dissolved heavy metals from waters by their adsorption onto suspended matter (SM) was also considered. Contrary to particulate copper (PCu), the vertical values of dissolved copper (DCu) decreased generally with depth. Planktonic scavenging and regeneration processes might determine the vertical profiles of the copper forms. The copper data suggest that the surface sources of DCu exceeded the bottom sources, contrary to the sources of PCu. The markedly high and maximum seasonal averages of DCu in the estuary and inshore seawater in July inspite of the high uptake in summer possibly reflect higher amounts of humic materials. The lowest seasonal average value of DCu in the inshore seawater in January suggests removal of copper in presence of maximum value of SM during highest discharge. The highest regional average of DCu at the estuarine mouth coincided with desorption process during mixing of the fresh and salt waters. The vertical values of dissolved zinc (DZn) and particulate zinc (PZn) showed irregular variations and their high concentrations in the surface of the estuarine and inshore seawater indicate possible land-based sources. The high bottom DZn values, however, resulted from its contribution from the interstitial water of the sediments. The data suggest that the surface sources of DZn exceeded the bottom sources and PZn showed the opposite trend in the open sea area. In the estuary, the maximum seasonal average value of DZn accompanied by the lowest seasonal average of PZn in April inspite of the high uptake in spring suggest that desorption was the dominant process. The minimum regional averages of both zinc forms at the estuarine opening and the highest average of PZn near Edfina Barage are correlated with the amounts of SM, which decreased toward the estuarine mouth. The vertical values of dissolved cadmium (DCd) were much lower in the estuary than the other metals. They showed in both environments irregular variations with depth. The bottom maximum value of DCd can be attributed mainly to contamination from the sediments. There was a distinct seasonal variation of DCd. The minimum seasonal average value of DCd in the estuary in April seems to be caused by its specific binding to living plankton found in abundance. The minimum regional average of DCd value was found at the estuarine mouth. The decrease in Cd concentration due to removal from dissolved state is most pronounced in the early stage of mixing. The correlation coefficients of DCd were positive with salinity and negative with SM, indicating that Cd increased seaward. Statistical correlation between Cd and Zn concludes that the factors affecting their distribution are generally the same.     

A Particle Model for Prediction of Cement Infiltration of Cancellous Bone in Osteoporotic Bone Augmentation

Femoroplasty is a potential preventive treatment for osteoporotic hip fractures. It involves augmenting mechanical properties of the femur by injecting Polymethylmethacrylate (PMMA) bone cement. To reduce the risks involved and maximize the outcome, however, the procedure needs to be carefully planned and executed. An important part of the planning system is predicting infiltration of cement into the porous medium of cancellous bone. We used the method of Smoothed Particle Hydrodynamics (SPH) to model the flow of PMMA inside porous media. We modified the standard formulation of SPH to incorporate the extreme viscosities associated with bone cement. Darcy creeping flow of fluids through isotropic porous media was simulated and the results were compared with those reported in the literature. Further validation involved injecting PMMA cement inside porous foam blocks — osteoporotic cancellous bone surrogates — and simulating the injections using our proposed SPH model. Millimeter accuracy was obtained in comparing the simulated and actual cement shapes. Also, strong correlations were found between the simulated and the experimental data of spreading distance (R² = 0.86) and normalized pressure (R² = 0.90). Results suggest that the proposed model is suitable for use in an osteoporotic femoral augmentation planning framework.     

Optimization of Bacillus subtilis natto growth parameters in glycerol-based medium for vitamin K (Menaquinone-7) production in biofilm reactors

Bioprocess and Biosystems Engineering - Menaquinone-7 (MK-7) is the key form of vitamin K used as a dietary supplement and its production revolves around Bacillus subtilis natto. Current...     

Probiotics with ameliorating effects on the severity of skin inflammation in psoriasis: Evidence from experimental and clinical studies

Experimental and clinical studies have confirmed safety and the medical benefits of probiotics as immunomodulatory medications. Recent advances have emphasized the critical effect of gastrointestinal bacteria in the pathology of inflammatory disorders, even, outside the gut. Probiotics have shown promising results for curing skin-influencing inflammatory disorders through modulating the immune response by manipulating the gut microbiome. Psoriasis is a complex inflammatory skin disease, which exhibits a microbiome distinct from the normal skin. In the present review, we considered the impact of gastrointestinal microbiota on the psoriasis pathogenesis, and through literature survey, attempted to explore probiotic species utilized for psoriasis treatment.     

Caspase-3 is a component of Fas death-inducing signaling complex in lipid rafts and its activity is required for complete caspase-8 activation during Fas-mediated cell death

Since its discovery, caspase-8 has been placed at the apex of the proteolytic cascade triggered by death receptor (DR) cross-linking. Because of its capacity to interact with the cytoplasmic portion of DR, it has been suggested that caspase-8 acts independently of other caspases in the initiation of Fas and other DR signaling. In this study, we demonstrate that in Jurkat cells, caspase-3 cleavage is an early step during Fas-induced apoptosis. We show that caspase-3 processing into its p20 occurs rapidly after Fas cross-linking, in the absence of mitochondrial depolarization and caspase-9 activation. Moreover, caspase-3 is present in lipid rafts of untreated Jurkat cells and peripheral T lymphocytes. Caspase-3, caspase-8, and Fas-associated death domain are further recruited to lipid rafts of Jurkat cells following anti-Fas treatment. Fas immunoprecipitation reveals that caspase-3 is a component of the death-inducing signaling complex, suggesting that this cysteine protease is in close proximity to caspase-8. Furthermore, transduction of Jurkat cells with a caspase-3 dominant-negative form inhibits caspase-8 processing and results in inhibition of apoptosis, suggesting that caspase-3 activity is required for caspase-8 activation. Overall, these findings support a model whereby caspase-3 is a component of the death-inducing signaling complex located in lipid rafts, and as such, is involved in the amplification of caspase-8 activity by the mitochondrion.