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

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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.     

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.     

Primordial germ cell differentiation of nuclear transfer embryonic stem cells using surface modified electroconductive scaffolds

A combination of nanotopographical cues and surface modification of collagen and fibronectin is a potential platform in primordial germ cells (PGCs) differentiation. In the present study, the synergistic effect of nanotopography and surface modification on differentiation of nuclear transfer embryonic stem cells (nt-ESCs) toward PGC lineage was investigated. In order to achieve this goal, poly-anyline (PANi) was mix within poly-l-lactic acid (PLLA). Afterward, the random composite mats were fabricated using PLLA and PANi mix solution. The nanofiber topography notably upregulated the expressions of prdm14, mvh and c-kit compared with tissue culture polystyrene (TCP). Moreover, the combination of nanofiber topography and surface modification resulted in more enhancement of PGCs differentiation compared with non-modified nanofibrous scaffold. Additionally, gene expression results showed that mvh and c-kit were expressed at higher intensity in cells exposed to collagen and fibronectin rather than collagen or fibronectin solitary. These results demonstrated the importance of combined effect of collagen and fibronectin in order to develop a functional extracellular matrix (ECM) mimic in directing stem cell fate and the potential of such biofunctional scaffolds for treatment of infertility.     

A preliminary biomechanical assessment of a polymer composite hip implant using an infrared thermography technique validated by strain gage measurements

With the resurgence of composite materials in orthopaedic applications, a rigorous assessment of stress is needed to predict any failure of bone-implant systems. For current biomechanics research, strain gage measurements are employed to experimentally validate finite element models, which then characterize stress in the bone and implant. Our preliminary study experimentally validates a relatively new nondestructive testing technique for orthopaedic implants. Lock-in infrared (IR) thermography validated with strain gage measurements was used to investigate the stress and strain patterns in a novel composite hip implant made of carbon fiber reinforced polyamide 12 (CF/PA12). The hip implant was instrumented with strain gages and mechanically tested using average axial cyclic forces of 840 N, 1500 N, and 2100 N with the implant at an adduction angle of 15 deg to simulate the single-legged stance phase of walking gait. Three-dimensional surface stress maps were also obtained using an IR thermography camera. Results showed almost perfect agreement of IR thermography versus strain gage data with a Pearson correlation of R(2) = 0.96 and a slope = 1.01 for the line of best fit. IR thermography detected hip implant peak stresses on the inferior-medial side just distal to the neck region of 31.14 MPa (at 840 N), 72.16 MPa (at 1500 N), and 119.86 MPa (at 2100 N). There was strong correlation between IR thermography-measured stresses and force application level at key locations on the implant along the medial (R(2) = 0.99) and lateral (R(2) = 0.83 to 0.99) surface, as well as at the peak stress point (R(2) = 0.81 to 0.97). This is the first study to experimentally validate and demonstrate the use of lock-in IR thermography to obtain three-dimensional stress fields of an orthopaedic device manufactured from a composite material.     

Quiescent hepatic stellate cells induce toxicity and sensitivity to doxorubicin in cancer cells through a caspase-independent cell death pathway: Central role of apoptosis-inducing factor

Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy.