624 research outputs found
Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential
The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility
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Controlled release nanoparticulate matter delivery system
A controlled release nanoparticulate matter delivery system includes a plurality of thermoresponsive modules containing a respective nanoparticulate matter. Each thermoresponsive module is selectively operable in at least one of a heating mode that releases the nanoparticulate matter and a cooling mode that inhibits release of the nanoparticulate matter. A control module is in electrical communication with the plurality of thermoresponsive modules. The control module is configured to determine a temperature of each thermoresponsive module and to select the at least one heating mode and cooling mode based on the temperature. The heating and cooling mode may be selected in response to a desired dosing profile and/or a biometric condition.Board of Regents, University of Texas Syste
Structural Verification of the First Orbital Wonder of the World - The Structural Testing and Analysis of the International Space Station (ISS)
The International Space Station (ISS) can be considered one of the structural engineering wonders of the world. On par with the World Trade Center, the Colossus of Rhodes, the Statue of Liberty, the Great Pyramids, the Petronas towers and the Burj Khalifa skyscraper of Dubai, the ambition and scope of the ISS structural design, verification and assembly effort is a truly global success story. With its on-orbit life projected to be from its beginning in 1998 to the year 2020 (and perhaps beyond), all of those who participated in its development can consider themselves part of an historic engineering achievement representing all of humanity. The structural design and verification of the ISS could be the subject of many scholarly papers. Several papers have been written on the structural dynamic characterization of the ISS once it was assembled on-orbit [1], but the ground-based activities required to assure structural integrity and structural life of the individual elements from delivery to orbit through assembly and planned on-orbit operations have never been totally summarized. This paper is intended to give the reader an overview of some of the key decisions made during the structural verification planning for the elements of the U.S. On-Orbit Segment (USOS) as well as to summarize the many structural tests and structural analyses that were performed on its major elements. An effort is made for this paper to be summarily comprehensive, but as with all knowledge capture efforts of this kind, there are bound to be errors of omission. Should the reader discover any of these, please feel free to contact the principal author. The ISS (Figure 1) is composed of pre-integrated truss segments and pressurized elements supplied by NASA, the Russian Federal Space Agency (RSA), the European Space Agency (ESA) and the Japanese Aerospace Exploration Agency (JAXA). Each of these elements was delivered to orbit by a launch vehicle and connected to one another either robotically or autonomously. The primary structure of each element was assembled and verified by teams of responsible structural engineers within and among their respective agencies and agency contractors
Search for the Production of Element 112 in the 48Ca + 238U Reaction
We have searched for the production of element 112 in the reaction of 231 MeV
48Ca with 238U. We have not observed any events with a "one event" upper limit
cross section of 1.6 pb for EVR-fission events and 1.8 pb for EVR-alpha events.Comment: 6 pages, 3 figures, submitted to Phys. Rev.
The Genetic Structure and History of Africans and African Americans.
Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies
Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA
Essentials The Royal disease (RD) is a form of hemophilia B predicted to be caused by a splicing mutation. We generated an iPSC-based model of the disease allowing mechanistic studies at the RNA level. F9 mRNA analysis in iPSC-derived hepatocyte-like cells showed the predicted abnormal splicing. Mutated F9 mRNA level was very low but we also found traces of wild type transcripts.
SUMMARY:
Background The royal disease is a form of hemophilia B (HB) that affected many descendants of Queen Victoria in the 19th and 20th centuries. It was found to be caused by the mutation F9 c.278-3A>G. Objective To generate a physiological cell model of the disease and to study F9 expression at the RNA level. Methods Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs). Both the patient's and mother's iPSCs were differentiated into hepatocyte-like cells (HLCs) and their F9 mRNA was analyzed using next-generation sequencing (NGS). Results and Conclusion We demonstrated the previously predicted aberrant splicing of the F9 transcript as a result of an intronic nucleotide substitution leading to a frameshift and the generation of a premature termination codon (PTC). The F9 mRNA level in the patient's HLCs was significantly reduced compared with that of his mother, suggesting that mutated transcripts undergo nonsense-mediated decay (NMD), a cellular mechanism that degrades PTC-containing mRNAs. We also detected small proportions of correctly spliced transcripts in the patient's HLCs, which, combined with genetic variability in splicing and NMD machineries, could partially explain some clinical variability among affected members of the European royal families who had lifespans above the average. This work allowed the demonstration of the pathologic consequences of an intronic mutation in the F9 gene and represents the first bona fide cellular model of HB allowing the study of rare mutations at the RNA level
Spallation Neutron Production by 0.8, 1.2 and 1.6 GeV Protons on various Targets
Spallation neutron production in proton induced reactions on Al, Fe, Zr, W,
Pb and Th targets at 1.2 GeV and on Fe and Pb at 0.8, and 1.6 GeV measured at
the SATURNE accelerator in Saclay is reported. The experimental
double-differential cross-sections are compared with calculations performed
with different intra-nuclear cascade models implemented in high energy
transport codes. The broad angular coverage also allowed the determination of
average neutron multiplicities above 2 MeV. Deficiencies in some of the models
commonly used for applications are pointed out.Comment: 20 pages, 32 figures, revised version, accepted fpr publication in
Phys. Rev.
A biophysical protein folding model accounts for most mutational fitness effects in viruses
Fitness effects of mutations fall on a continuum ranging from lethal to
deleterious to beneficial. The distribution of fitness effects (DFE) among
random mutations is an essential component of every evolutionary model and a
mathematical portrait of robustness. Recent experiments on five viral species
all revealed a characteristic bimodal shaped DFE, featuring peaks at neutrality
and lethality. However, the phenotypic causes underlying observed fitness
effects are still unknown, and presumably thought to vary unpredictably from
one mutation to another. By combining population genetics simulations with a
simple biophysical protein folding model, we show that protein thermodynamic
stability accounts for a large fraction of observed mutational effects. We
assume that moderately destabilizing mutations inflict a fitness penalty
proportional to the reduction in folded protein, which depends continuously on
folding free energy (\Delta G). Most mutations in our model affect fitness by
altering \Delta G, while, based on simple estimates, \approx10% abolish
activity and are unconditionally lethal. Mutations pushing \Delta G>0 are also
considered lethal. Contrary to neutral network theory, we find that, in
mutation/selection/drift steady-state, high mutation rates (m) lead to less
stable proteins and a more dispersed DFE, i.e. less mutational robustness.
Small population size (N) also decreases stability and robustness. In our
model, a continuum of non-lethal mutations reduces fitness by \approx2% on
average, while \approx10-35% of mutations are lethal, depending on N and m.
Compensatory mutations are common in small populations with high mutation
rates. More broadly, we conclude that interplay between biophysical and
population genetic forces shapes the DFE.Comment: Main text: 12 pages, 5 figures Supplementary Information: 10 pages, 5
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