Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

There are many areas in medicine and industry where it would be advantageous to orally deliver bioactive proteins and peptides (BPPs), including ACE inhibitors, antimicrobials, antioxidants, hormones, enzymes, and vaccines. A major challenge in this area is that many BPPs degrade during storage of the product or during passage through the human gut, thereby losing their activity. Moreover, many BPPs have undesirable taste profiles (such as bitterness or astringency), which makes them unpleasant to consume. These challenges can often be overcome by encapsulating them within colloidal particles that protect them from any adverse conditions in their environment, but then release them at the desired site-of-action, which may be inside the gut or body. This article begins with a discussion of BPP characteristics and the hurdles involved in their delivery. It then highlights the characteristics of colloidal particles that can be manipulated to create effective BPP-delivery systems, including particle composition, size, and interfacial properties. The factors impacting the functional performance of colloidal delivery systems are then highlighted, including their loading capacity, encapsulation efficiency, protective properties, retention/release properties, and stability. Different kinds of colloidal delivery systems suitable for encapsulation of BPPs are then reviewed, such as microemulsions, emulsions, solid lipid particles, liposomes, and microgels. Finally, some examples of the use of colloidal delivery systems for delivery of specific BPPs are given, including hormones, enzymes, vaccines, antimicrobials, and ACE inhibitors. An emphasis is on the development of food-grade colloidal delivery systems, which could be used in functional or medical food applications. The knowledge presented should facilitate the design of more effective vehicles for the oral delivery of bioactive proteins and peptides

Field-guided proton acceleration at reconnecting X-points in flares

An explicitly energy-conserving full orbit code CUEBIT, developed originally to describe energetic particle effects in laboratory fusion experiments, has been applied to the problem of proton acceleration in solar flares. The model fields are obtained from solutions of the linearised MHD equations for reconnecting modes at an X-type neutral point, with the additional ingredient of a longitudinal magnetic field component. To accelerate protons to the highest observed energies on flare timescales, it is necessary to invoke anomalous resistivity in the MHD solution. It is shown that the addition of a longitudinal field component greatly increases the efficiency of ion acceleration, essentially because it greatly reduces the magnitude of drift motions away from the vicinity of the X-point, where the accelerating component of the electric field is largest. Using plasma parameters consistent with flare observations, we obtain proton distributions extending up to gamma-ray-emitting energies (>1MeV). In some cases the energy distributions exhibit a bump-on-tail in the MeV range. In general, the shape of the distribution is sensitive to the model parameters.Comment: 14 pages, 4 figures, accepted for publication in Solar Physic

Numerical simulations of chromospheric hard X-ray source sizes in solar flares

X-ray observations are a powerful diagnostic tool for transport, acceleration, and heating of electrons in solar flares. Height and size measurements of X-ray footpoints sources can be used to determine the chromospheric density and constrain the parameters of magnetic field convergence and electron pitch-angle evolution. We investigate the influence of the chromospheric density, magnetic mirroring and collisional pitch-angle scattering on the size of X-ray sources. The time-independent Fokker-Planck equation for electron transport is solved numerically and analytically to find the electron distribution as a function of height above the photosphere. From this distribution, the expected X-ray flux as a function of height, its peak height and full width at half maximum are calculated and compared with RHESSI observations. A purely instrumental explanation for the observed source size was ruled out by using simulated RHESSI images. We find that magnetic mirroring and collisional pitch-angle scattering tend to change the electron flux such that electrons are stopped higher in the atmosphere compared with the simple case with collisional energy loss only. However, the resulting X-ray flux is dominated by the density structure in the chromosphere and only marginal increases in source width are found. Very high loop densities (>10^{11} cm^{-3}) could explain the observed sizes at higher energies, but are unrealistic and would result in no footpoint emission below about 40 keV, contrary to observations. We conclude that within a monolithic density model the vertical sizes are given mostly by the density scale-height and are predicted smaller than the RHESSI results show.Comment: 19 pages, 9 figures, accepted for publication in Ap

Electron Inertial Effects on Rapid Energy Redistribution at Magnetic X-points

The evolution of non-potential perturbations to a current-free magnetic X-point configuration is studied, taking into account electron inertial effects as well as resistivity. Electron inertia is shown to have a negligible effect on the evolution of the system whenever the collisionless skin depth is less than the resistive scale length. Non-potential magnetic field energy in this resistive MHD limit initially reaches equipartition with flow energy, in accordance with ideal MHD, and is then dissipated extremely rapidly, on an Alfvenic timescale that is essentially independent of Lundquist number. In agreement with resistive MHD results obtained by previous authors, the magnetic field energy and kinetic energy are then observed to decay on a longer timescale and exhibit oscillatory behavior, reflecting the existence of discrete normal modes with finite real frequency. When the collisionless skin depth exceeds the resistive scale length, the system again evolves initially according to ideal MHD. At the end of this ideal phase, the field energy decays typically on an Alfvenic timescale, while the kinetic energy (which is equally partitioned between ions and electrons in this case) is dissipated on the electron collision timescale. The oscillatory decay in the energy observed in the resistive case is absent, but short wavelength structures appear in the field and velocity profiles, suggesting the possibility of particle acceleration in oppositely-directed current channels. The model provides a possible framework for interpreting observations of energy release and particle acceleration on timescales down to less than a second in the impulsive phase of solar flares.Comment: 30 pages, 8 figure

Comparative Analysis of Non-thermal Emissions and Study of Electron Transport in a Solar Flare

We study the non-thermal emissions in a solar flare occurring on 2003 May 29 by using RHESSI hard X-ray (HXR) and Nobeyama microwave observations. This flare shows several typical behaviors of the HXR and microwave emissions: time delay of microwave peaks relative to HXR peaks, loop-top microwave and footpoint HXR sources, and a harder electron energy distribution inferred from the microwave spectrum than from the HXR spectrum. In addition, we found that the time profile of the spectral index of the higher-energy (\gsim 100 keV) HXRs is similar to that of the microwaves, and is delayed from that of the lower-energy (\lsim 100 keV) HXRs. We interpret these observations in terms of an electron transport model called {\TPP}. We numerically solved the spatially-homogeneous {\FP} equation to determine electron evolution in energy and pitch-angle space. By comparing the behaviors of the HXR and microwave emissions predicted by the model with the observations, we discuss the pitch-angle distribution of the electrons injected into the flare site. We found that the observed spectral variations can qualitatively be explained if the injected electrons have a pitch-angle distribution concentrated perpendicular to the magnetic field lines rather than isotropic distribution.Comment: 32 pages, 12 figures, accepted for publication in The Astronomical Journa

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.

Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage

Propagating EUV disturbances in the solar corona : two-wavelength observations

Quasi-periodic EUV disturbances simultaneously observed in 171 Å and 195 Å TRACE bandpasses propagating outwardly in a fan-like magnetic structure of a coronal active region are analysed. Time series of disturbances observed in the different bandpasses have a relatively high correlation coefficient (up to about 0.7). The correlation has a tendency to decrease with distance along the structure: this is consistent with an interpretation of the disturbances in terms of parallel-propagating slow magnetoacoustic waves. The wavelet analysis does not show a significant difference between waves observed in different bandpasses. Periodic patterns of two distinct periods: 2-3 min and 5-8 min are detected in both bandpasses, existing simultaneously and at the same distance along the loop, suggesting the nonlinear generation of the second harmonics

Plasma Amino Acids Metabolomics' Important in Glucose Management in Type 2 Diabetes

The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma samples from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p < 0.01, Lysine, p < 0.001, Phenylalanine, p < 0.01, Tryptophan, p < 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D (p < 0.01, p < 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls (p < 0.001, p < 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p < 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls (p < 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c (p < 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment (p < 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications