Luminal nutrients stimulate enteroendocrine cells through the activation of specific receptors to release hormones that inhibit appetite and promote glucose homeostasis. While food protein is the ...macronutrient with the highest effect on satiety, the signaling on the protein digestion products at the gut is poorly understood. This perspective aims to highlight the existing gaps in the study of protein digestion products as signaling molecules in gastrointestinal enteroendocrine cells. Because dietary protein digestion can be modulated by the technological processes applied to food, it is possible to target gut receptors to control food intake by formulating specific food ingredients or protein preloads.
The protein corona formed on the surface of a nanoparticle in a biological medium determines its behavior in vivo. Herein, iron oxide nanoparticles containing the same core and shell, but bearing two ...different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles’ protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months were investigated. Although both types of nanoparticles bound similar amounts of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro degradation studies demonstrated faster degradation for nanoparticles functionalized with glucose, whereas the in vivo results were opposite with accelerated biodegradation and clearance of the nanoparticles functionalized with poly(ethylene glycol). Therefore, the variation in the degradation rate observed in vivo could be related not only to the molecules attached to the surface, but also with the associated protein corona, as the key role of the adsorbed proteins on the magnetic core degradation has been demonstrated in vitro.
The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and ...photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated “hot” NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.
The interaction between protons and graphene is attracting a large interest due to recent experiments showing that these charged species permeate through the 2D material following a low barrier (∼ ...0.8 eV) activated process. A possible explanation involves the flipping of a chemisorbed proton (rotation of the CH+ bond from one to the other side of the carbon layer) and previous studies have found so far that the energy barriers (around 3.5 eV) are too high to explain the experimental findings. Contrarily to the previously adopted model assuming an isolated proton, in this work we consider protonated graphene at high local coverage and explore the role played by nearby chemisorbed protons in the permeation process. By means of density functional theory calculations exploiting large molecular prototypes for graphene it is found that, when various protons are adsorbed on the same carbon hexagonal ring, the permeation barrier can be reduced down to 1.0 eV. The related mechanism is described in detail and could shed a new light on the interpretation of the experimental observations for proton permeation through graphene.
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The butyric acid fermentation, responsible for late blowing of cheese, is caused by the outgrowth in cheese of some species of Clostridium, resulting in texture and flavor defects and economical ...losses. The aim of this study was to evaluate the effectiveness of different antimicrobial compounds against vegetative cells and spores of C. tyrobutyricum, C. butyricum, C. beijerinckii and C. sporogenes strains isolated from cheeses with late blowing defect. Minimal inhibitory concentration (MIC) for reuterin, nisin, lysozyme and sodium nitrite were determined against Clostridium strains in milk and modified RCM (mRCM) after 7d exposure. Although the sensitivity of Clostridium to the tested antimicrobials was strain-dependent, C. sporogenes and C. beijerinckii generally had higher MIC values than the rest of Clostridium species. The majority of Clostridium strains were more resistant to antimicrobials in milk than in mRCM, and vegetative cells exhibited higher sensitivity than spores. Reuterin (MIC values 0.51–32.5mM) and nisin (MIC values 0.05–12.5μg/ml) were able to inhibit the growth of vegetative cells and spores of all assayed Clostridium strains in milk and mRCM. Strains of C. tyrobutyricum exhibited the highest sensitivity to lysozyme (MIC values<0.20–400μg/ml) and sodium nitrite (MIC values 18.75–150μg/ml). These results suggest that reuterin and nisin, with a broad inhibitory activity spectrum against Clostridium spp. spores and vegetative cells, may be the best options to control Clostridium growth in dairy products and to prevent associated spoilage, such as late blowing defect of cheese. However, further studies in cheese would be necessary to validate this hypothesis.
•Clostridium sensitivity to antimicrobials was strain dependent and varied with the type of bacteria cell and growth media.•Reuterin and nisin, with the broadest anti-clostridial spectrum, inhibited all Clostridium strains.•Sodium nitrite and lysozyme had limited inhibitory effect against Clostridium strains.
•Egg white peptides are identified as main GLP-1 secretagogues.•CCK is released in response to peptides and free amino acids but not proteins.•Two hydrophobic negatively charged peptides were found ...to trigger CCK release.•The highest GLP-1 response was found with a hydrophobic positively charged peptide.
The effect of dietary protein on the induction of intestinal hormones is recognised. However, little is known about the nature of the digestion products involved in this intestinal signalling. Our aim was to characterise egg white protein digestion products and study their ability to induce CCK and GLP-1 release in enteroendocrine STC-1 cells. Intestinal digests triggered GLP-1 release at a higher rate than gastric digests. Peptides, but not free amino acids, showed a potent GLP-1 secretagogue effect, while proteins only had a modest effect. CCK was released in response to peptides and free amino acids but not proteins. Two hydrophobic negatively charged peptides triggered CCK release, while the highest GLP-1 response was found with a hydrophobic positively charged peptide, pointing to the involvement of different receptors or active sites. Identifying peptide sequences and receptors involved in hormonal secretion could open up new ways to control food intake and glucose metabolism.
Graphynes are novel two-dimensional carbon-based materials that have been proposed as molecular filters, especially for water purification technologies. We carry out first-principles electronic ...structure calculations at the MP2C level of theory to assess the interaction between water and graphyne, graphdiyne, and graphtriyne pores. The computed penetration barriers suggest that water transport is unfeasible through graphyne while being unimpeded for graphtriyne. For graphdiyne, with a pore size almost matching that of water, a low barrier is found that in turn disappears if an active hydrogen bond with an additional water molecule on the opposite side of the opening is considered. Thus, in contrast with previous determinations, our results do not exclude graphdiyne as a promising membrane for water filtration. In fact, present calculations lead to water permeation probabilities that are 2 orders of magnitude larger than estimations based on common force fields. A new pair potential for the water–carbon noncovalent component of the interaction is proposed for molecular dynamics simulations involving graphdiyne and water.
Recent progress in the production of new two-dimensional (2D) nanoporous materials is attracting considerable interest for applications to isotope separation in gases. In this paper we report a ...computational study of the transmission of 4He and 3He through the (subnanometer) pores of graphdiyne, a recently synthesized 2D carbon material. The He–graphdiyne interaction is represented by a force field parametrized upon ab initio calculations, and the 4He/3He selectivity is analyzed by tunneling-corrected transition state theory. We have found that both zero point energy (of the in-pore degrees of freedom) and tunneling effects play an extraordinary role at low temperatures (≈20–30 K). However, both quantum features work in opposite directions in such a way that the selectivity ratio does not reach an acceptable value. Nevertheless, the efficiency of zero point energy is in general larger, so that 4He tends to diffuse faster than 3He through the graphdiyne membrane, with a maximum performance at 23 K. Moreover, it is found that the transmission rates are too small in the studied temperature range, precluding practical applications. It is concluded that the role of the in-pore degrees of freedom should be included in computations of the transmission probabilities of molecules through nanoporous materials.
The impermeability of defect-free graphene to all gases has been recently contested since experimental evidence (see Nature 579, 229–232 (2020)) of hydrogen transmission through a two-dimensional ...carbon layer has been obtained. By means of density functional theory computations here we elucidate a flipping mechanism which involves the insertion of a chemisorbed hydrogen atom in the middle of a C–C bond via a transition state that is relatively stable due to a sp2 rehybridization of the implicated carbon atoms. Present results suggest that transmission for hydrogenated graphene at low local coverage is highly unlikely since other outcomes such as hydrogen diffusion and desorption exhibit quite lower activation enthalpies. However, at high local coverage, with a given graphenic ring tending to saturation, the proposed flipping mechanism becomes competitive leading to a significantly exothermic process. Moreover, for a specific arrangement of four neighboring chemisorbed hydrogen atoms the flipping of one of them becomes the most likely outcome with a low activation enthalpy (about 0.8 eV), which is in the range of the experimental estimation. The effect of charge doping is investigated and it is found that electron doping can help to reduce the related activation enthalpy and to slightly enhance its exothermicity. Finally, an analysis of corresponding results for deuterium substitution is also presented.
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