Effects of the intake of craft or industrial beer on serum homocysteine.

Beer is a source of folate, vitamin B6 and B12, molecules involved in the pathways of homocysteine (HCY), a risk factor for cardiovascular disease. This research evaluated if a consumption of craft or industrial beer could reduce serum HCY. In a randomised cross-over study, 12 men (28.7 ± 6.0 years) and 12 women (29.4 ± 7.5 years), healthy, omnivorous, with normal body mass index, non-smoking and not taking oral supplements or contraceptives, followed a free-living diet and received, daily, for 3 weeks, 330 ml of industrial (4.5% of alcohol) or craft beer (9% of alcohol). Anthropometric measures and blood samples were taken at the beginning and at the end of each period. The consumption of industrial beer reduced (p < 0.05) HCY (7.35 vs. 6.50 µmol/L) and increased folic acid (3.46 vs. 3.94 ng/mL). Craft beer increased gamma-gluamyl transpeptidase (GGT) (16.6 vs. 18.6 U/L) and reduced vitamin B6 (20.9 vs. 16.9 ng/mL).

Effect of biscuits formulated with high-amylose maize flour on satiety-related sensations and food intake.

The amount of amylose within a food may elicit lower glycemic and insulin postprandial responses and thus potentially modulate the satiating effect. In this context, the effect of biscuits formulated with high amylose starch (HAS) flour on satiety-related sensations and food intake was studied. Three types of biscuits were produced: control biscuit (CRT, 0% of HAS), Amy-25 (25% HAS), and Amy-50 (50% HAS). Fifteen healthy volunteers were enrolled to conduct two in vivo experiments. In experiment 1, volunteers consumed biscuits ad libitum and their sensations of satiety and food intake were evaluated. In experiment 2, volunteers received a quantity of biscuits equivalent to the 20% of the daily estimated energy requirements, and both satiety-related sensations and food intake were checked at subsequent meal. The Amy-50 significantly reduced food intake at subsequent meal (p ˂ 0.05), compared to Amy-25 and CRT. The satiety-related sensations were not significantly affected in both experiments, excepted for intra-meal hunger variation induced by Amy-25 which resulted significantly higher (p ˂ 0.05) than Amy-50 and CRT. These findings support the need to reformulate carbohydrate rich foods commonly consumed in a dietary context, to provide consumers healthier alternatives to prevent and tackle obesity and related chronic diseases.

Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration.

SmartBone® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-ß.

Influence of the Core Formulation on Features and Drug Delivery Ability of Carbamate-Based Nanogels.

In the last years, nanogels have emerged as one of the most promising classes of novel drug delivery vehicles since they can be employed in multiple fields, such as various therapeutics or diagnostics, and with different classes of compounds and active molecules. Their features, such as a high volume to surface ratio, excellent drug loading and release ability, as well as biocompatibility and tunable behavior, are unique, and, nowadays, great efforts are made to develop new formulations that can be employed in a wider range of applications. Polyethylene glycol (PEG)-polyethylenimine (PEI) nanogels probably represent the baseline of this class of biomaterials and they are still largely employed and studied. In any way, the possibility to exploit new core formulations for nanogels is certainly very interesting in order to understand the influence of different polymer chains on the final properties of the system. In this research, we explore and make a comparison between PEG-PEI nanogels and two other different formulations: pluronic F127-PEI nanogels and PEG-Jeffamine nanogels. We propose nanogels synthesis methods, their chemical and physical characterization, as well as their stability analysis, and we focus on the different drug delivery ability that these structures exhibit working with different typologies of drug mimetics.

Neurobiological Mechanisms of Responding to Injustice.

People are particularly sensitive to injustice. Accordingly, deeper knowledge regarding the processes that underlie the perception of injustice, and the subsequent decisions to either punish transgressors or compensate victims, is of important social value. By combining a novel decision-making paradigm with functional neuroimaging, we identified specific brain networks that are involved with both the perception of, and response to, social injustice, with reward-related regions preferentially involved in punishment compared with compensation. Developing a computational model of punishment allowed for disentangling the neural mechanisms and psychological motives underlying decisions of whether to punish and, subsequently, of how severely to punish. Results show that the neural mechanisms underlying punishment differ depending on whether one is directly affected by the injustice, or whether one is a third-party observer of a violation occurring to another. Specifically, the anterior insula was involved in decisions to punish following harm, whereas, in third-party scenarios, we found amygdala activity associated with punishment severity. Additionally, we used a pharmacological intervention using oxytocin, and found that oxytocin influenced participants' fairness expectations, and in particular enhanced the frequency of low punishments. Together, these results not only provide more insight into the fundamental brain mechanisms underlying punishment and compensation, but also illustrate the importance of taking an explorative, multimethod approach when unraveling the complex components of everyday decision-making.SIGNIFICANCE STATEMENT The perception of injustice is a fundamental precursor to many disagreements, from small struggles at the dinner table to wasteful conflict between cultures and countries. Despite its clear importance, relatively little is known about how the brain processes these violations. Taking an interdisciplinary approach, we combine methods from neuroscience, psychology, and economics to explore the neurobiological mechanisms involved in both the perception of injustice as well as the punishment and compensation decisions that follow. Using a novel behavioral paradigm, we identified specific brain networks, developed a computational model of punishment, and found that administrating the neuropeptide oxytocin increases the administration of low punishments of norm violations in particular. Results provide valuable insights into the fundamental neurobiological mechanisms underlying social injustice.

Bone grafts: which is the ideal biomaterial?

Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio-maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future. AIM: Within this narrative review, we discuss possible future biomaterials for bone replacement. SCIENTIFIC RATIONALE FOR STUDY: Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce. PRACTICAL IMPLICATIONS: In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG. RESULTS: We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision-making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations. CONCLUSIONS: We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling.

Differential effects of coconut versus soy oil on gut microbiota composition and predicted metabolic function in adult mice.

BACKGROUND: Animal studies show that high fat (HF) diet-induced gut microbiota contributes to the development of obesity. Oil composition of high-fat diet affects metabolic inflammation differently with deleterious effects by saturated fat. The aim of the present study was to examine the diversity and metabolic capacity of the cecal bacterial community in C57BL/6 N mice administered two different diets, enriched respectively with coconut oil (HFC, high in saturated fat) or soy oil (HFS, high in polyunsaturated fat). The relative impact of each hypercaloric diet was evaluated after 2 and 8 weeks of feeding, and compared with that of a low-fat, control diet (LF). RESULTS: The HFC diet induced the same body weight gain and fat storage as the HFS diet, but produced higher plasma cholesterol levels after 8 weeks of treatment. At the same time point, the cecal microbiota of HFC diet-fed mice was characterized by an increased relative abundance of Allobaculum, Anaerofustis, F16, Lactobacillus reuteri and Deltaproteobacteria, and a decreased relative abundance of Akkermansia muciniphila compared to HFS mice. Comparison of cecal microbiota of high-fat fed mice versus control mice indicated major changes that were shared between the HFC and the HFS diet, including the increase in Lactobacillus plantarum, Lutispora, and Syntrophomonas, while some other shifts were specifically associated to either coconut or soy oil. Prediction of bacterial gene functions showed that the cecal microbiota of HFC mice was depleted of pathways involved in fatty acid metabolism, amino acid metabolism, xenobiotic degradation and metabolism of terpenoids and polyketides compared to mice on HFS diet. Correlation analysis revealed remarkable relationships between compositional changes in the cecal microbiota and alterations in the metabolic and transcriptomic phenotypes of high-fat fed mice. CONCLUSIONS: The study highlights significant differences in cecal microbiota composition and predictive functions of mice consuming a diet enriched in coconut vs soy oil. The correlations established between specific bacterial taxa and various traits linked to host lipid metabolism and energy storage give insights into the role and functioning of the gut microbiota that may contribute to diet-induced metabolic disorders.

Microwave-assisted synthesis of TEMPO-labeled hydrogels traceable with MRI.

Polymer functionalization strategies have recently attracted considerable attention for several applications in biomaterials science. In particular, technological advancements in medical imaging have focused on the design of polymeric matrices to improve non-invasive approaches and diagnostic accuracy. In this scenario, the use of microwave irradiation of aqueous solutions containing appropriate combinations of polymers is gaining increasing interest in the synthesis of sterile hydrogels without using monomers, eliminating the need to remove unreacted species. In this study, we developed a method for the in situ fabrication of TEMPO-labeled hydrogels based on a one-pot microwave reaction that can then be tracked by magnetic resonance imaging (MRI) without using toxic compounds that could be hostile for the target tissue. Click chemistry was used to link TEMPO to the polymeric scaffold. In an in vivo model, the system was able to preserve its TEMPO paramagnetic activity up to 1 month after hydrogel injection, showing a clear detectable signal on T1-weighted MRI with a longitudinal relaxivity value of 0.29 mM s-1, comparable to a value of 0.31 mM s-1 characteristic of TEMPO application. The uncleavable conjugation between the contrast agent and the polymeric scaffold is a leading point to record these results: the use of TEMPO only physically entrapped in the polymeric scaffold did not show MRI traceability even after few hours. Moreover, the use of TEMPO-labeled hydrogels can also help to reduce the number of animals sacrificed being a longitudinal non-invasive technique.

Effect of omnivorous and vegan diets with different protein and carbohydrate content on growth and metabolism of growing rats.

The purpose of this study was to observe, in a rat animal model, the short and medium term effects of vegan (VEG) or omnivorous (OMNI) diets with different energy partition between nutrients (zone or classic). Six different diets were administered, for 72 days to 120 growing male Sprague-Dawley rats: (i) VEG zone diet; (ii) VEG classic diet; (iii) OMNI zone diet; (iv) OMNI classic diet; (v) OMNI zone diet with added fibre and (vi) OMNI classic diet with added fibre. Zone diets (high protein and low carbohydrates), resulted in better growth , feed efficiency, lower blood glucose and insulin responses. VEG diets have lowered cholesterol blood level. Histopathological analysis evidenced no damage to liver and kidney tissue by the intake of any of the diet types. Further longer animal and human duration studies should be performed to exclude detrimental effect of higher protein diet.

On the parallelism between the mechanisms behind chromatography and drug delivery: the role of interactions with a stationary phase.

A huge number of studies and work in the drug delivery literature are focused on understanding and modeling transport phenomena, the pivotal point for a good device design. The rationalization of all phenomena involved is fundamental, but several concerns arise leaving many issues unsolved. In order to change the point of view we decided to focus our attention on the parallelisms between two fields that seem to be very far from each other: chromatography and drug release. Taking advantages of the studies conducted by many researchers using chromatographic columns we decided to explain all the phenomena involved in drug delivery considering sodium ibuprofen (IP) molecules as analytes and hydrogel as a stationary phase. In particular, we considered not only diffusion, but also drug-polymer interactions as adsorption on the stationary phase and drug-drug interactions as aggregation of analytes. The hydrogel investigated is a promising formulation made of agarose and carbomer 974p (AC) loaded with IP, a non-steroidal common anti-inflammatory drug. The self-diffusion coefficient of IP in AC formulations was measured by using an innovative method based on a magic angle spinning NMR spectroscopic technique to produce high resolution (liquid-like) spectra. This method (HR-MAS NMR) is used in combination with pulsed field gradient spin echo (PGSE) liquid-state techniques. The model predictions satisfactorily match with the experimental data obtained in water and the gel environment, indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing the device behavior and could be used to rationalize the experimental activity.

The Role of Drug-Drug Interactions in Hydrogel Delivery Systems: Experimental and Model Study.

To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials able to incorporate cells and drugs. The interpretation of transport phenomena is a key step, but comprehensive theoretical data is still missing and many issues related to these systems are still unsolved. In particular, the contribution of solute-solute interactions is not yet completely understood. Here, we investigate a promising agar-carbomer (AC) hydrogel loaded with sodium fluorescein (SF), a commonly used drug mimetic. The self-diffusion coefficient of SF in AC formulations was measured by using high resolution magic angle spinning NMR spectroscopy (HR-MAS NMR). Starting from experimental data, a complete overview on SF transport properties is provided, in particular a mathematical model that describes and rationalizes the differences between gel and water environments is developed and presented. The hydrogel molecular environment is able to prevent SF aggregation, owing to the adsorption mechanism that reduces the number of monomers available for oligomer formation at low solute concentration. Then, when all adsorption sites are saturated free SF molecules are able to aggregate and form oligomers. The model predictions satisfactorily match with experimental data obtained in water and the gel environment, thus indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing device behavior and could be used to rationalize experimental activity.

Drug-Polymer Interactions in Hydrogel-based Drug-Delivery Systems: An Experimental and Theoretical Study.

In drug-delivery systems, drug transport is a key step, but the interpretation of the transport mechanism is still controversial. Here, we investigated a promising hydrogel library loaded with the anticonvulsant drug ethosuximide (ESM). The self-diffusion coefficient of ESM was measured using two methods: a direct and advanced measurement with a pulsed field gradient spin-echo (PFGSE) method, using an NMR spectrometer equipped with high-resolution magic angle spinning (HR-MAS) probe, and an indirect one based on fitting in vitro drug-delivery data. Starting from the experimental data a mathematical model without fitted parameters was developed and all the phenomena involved, that is, adsorption and diffusion, were considered. At low drug concentrations, adsorption prevails and consequently the diffusivity in the gels is lower than that in water. At high drug concentrations, where all adsorption sites are saturated, the diffusion in the gels is similar to that in a water solution. This study may pave the way for better device design.

Polymer hydrogel functionalized with biodegradable nanoparticles as composite system for controlled drug delivery.

The possibility to direct pharmacological treatments targeting specific cell lines using polymer nanoparticles is one of the main novelties and perspectives in nanomedicine. However, sometimes, the ability to maintain NPs localized at the site of the injection that work as a drug reservoir can represent a good and complementary option. In this direction we built a composite material made of polymeric hydrogel functionalized with polymer NPs. ϵ-caprolactone and polyethylene glycol have been copolymerized in a two-step synthesis of PEGylated NPs, while hydrogel was synthesized through polycondensation between NPs, agarose and branched polyacrylic acid. NP functionalization was verified with Fourier transform infrared spectroscopy (FTIR), high resolution magic angle spinning-nuclear magnetic resonance (HRMAS-NMR) spectroscopy and release kinetics from a hydrogel matrix and compared with NPs only physically entrapped into a hydrogel matrix. The characteristics of the resulting composite hydrogel-NPs system were studied both in terms of rheological properties and in its ability to sustain the release of To-Pro3, used as a drug mimetic compound to represent a promising drug delivery device.

Gut response induced by weaning in piglet features marked changes in immune and inflammatory response.

At weaning, piglets are exposed to many stressors, such as separation from the sow, mixing with other litters, end of lactational immunity, and a change in their environment and gut microbiota. The sudden change of feeding regime after weaning causes morphological and histological changes in the small intestine which are critical for the immature digestive system. Sixteen female piglets were studied to assess the effect of sorbic acid supplementation on the small intestine tissue transcriptome. At weaning day (T0, piglet age 28 days), four piglets were sacrificed and ileal tissue samples collected. The remaining 12 piglets were weighed and randomly assigned to different postweaning (T5, piglet age 33 days) diets. Diet A (n = 6) contained 5 g/kg of sorbic acid. In diet B (n = 6), the organic acids were replaced by barley flour. Total RNA was isolated and then hybridized to CombiMatrix CustomArray™ 90-K platform microarrays, screening about 30 K genes. Even though diet had no detectable effect on the transcriptome during the first 5 days after weaning, results highlighted some of the response mechanisms to the stress of weaning occurring in the piglet gut. A total of 205 differentially expressed genes were used for functional analysis using the bioinformatics tools BLAST2GO, Ingenuity Pathway Analysis 8.0, and Dynamic Impact Approach (DIA). Bioinformatic analysis revealed that apoptosis, RIG-I-like, and NOD-like receptor signaling were altered as a result of weaning. Interferons and caspases gene families were the most activated after weaning in response to piglets to multiple stressors. Results suggest that immune and inflammatory responses were activated and likely are a cause of small intestine atrophy as revealed by a decrease in villus height and villus/crypt ratio.

Se-(2-aminoalkyl)selenocysteines as biochemical redox agents. A tool to contrast cell injury induced by aflatoxin B1 in HepG2 cells.

Se-(2-aminoalkyl)selenocysteines were shown to have a chemoprotective activity towards HepG2 cells, contrasting the cell damage of aflatoxin B1. The results of this study suggest that our newly synthesized seleno-diamino acids are apparently endowed with a potent protective potential against cell damage caused by AFB1 similar to, or even higher than, that exerted by the reference compound Se-Me-SeCys. The protective effect does not seem to be absolute, i.e., merely determined by the presence of the chalcogen atom, but rather strictly related to the molecular structure of the new compounds tested. From this point of view, Se-(2-aminoalkyl)selenocysteines may represent a new class of biochemical redox agents fruitfully exploitable to contrast aflatoxin toxicity, at the same time a sound medical application and an economically relevant agricultural issue.

Mathematical modeling of PLGA microparticles: from polymer degradation to drug release.

The present work is focused on the development and the validation of a mechanistic model describing the degradation of drug-loaded polylactic-co-glycolic acid microparticles and the drug release process from such devices. Microparticles' degradation is described through mass conservation equations; the application of population balances allows a detailed description of the hydrolysis kinetics, which also takes into account the autocatalytic behavior that characterizes bulk eroding polymers. Drug release considers both drug dissolution and the diffusion of dissolved active principle through the polymeric matrix. The diffusion of oligomers, water, and drug is assumed to follow Fickian behavior; the use of effective diffusion coefficients takes into account the diffusivity increase due to polymer hydrolysis. The model leads to a system of partial differential equations, solved by means of the method of lines. The model predictions satisfactorily match with different sets of literature data, indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing the device behavior.

Biphasic Porous Bijel-Like Structures with Hydrogel Domains as Controlled Drug Delivery Systems.

Bijels are a peculiar type of Pickering emulsion that have a bicontinuous morphology and are stabilised by a jammed layer of nanoparticles (NPs). Due to their double nature, their usage has increased in recent years in various fields, such as biological and food applications. In fact, they can release both hydrophilic and hydrophobic compounds simultaneously. An improvement to this structure is the use of a hydrophobic monomer like polycaprolactone as the organic phase, which is able to polymerise during the formation of the structure. Unfortunately, the structures formed in this way always have some drawbacks, such as their thermal stability or degradation when submerged in an aqueous medium. A number of studies have been carried out in which some parameters, such as the NPs or the monomer, were changed and their effect on the final product evaluated. In this work, the effect of modifying the aqueous phase was studied. In particular, the effect of adding alginate, a biopolymer capable of forming a stable hydrogel in the presence of divalent cations, was analysed, as was the difference between soaking or not in CaCl2, the final system. Specific attention was paid to their swelling behaviour (150% vs. 25% of the blank sample), rheological properties (G' 100 kPa vs. 20 kPa of the blank sample) and their release performances. In this framework, complete release of hydrophilic drug vs. 20% in the blank sample was observed together with improved release of the hydrophobic one with 35% in 8 h vs. 5% in the case of the blank sample. This strategy has been proven to influence bijels' properties, opening the doors to many different uses.

Biomaterials and Cell Therapy Combination in Central Nervous System Treatments.

Current pharmacological and surgical therapies for the central nervous system (CNS) show a limited capacity to reduce the damage progression; that together with the intrinsic limited capability of the CNS to regenerate greatly reduces the hopes of recovery. Among all the therapies proposed, the tissue engineering strategies supplemented with therapeutic stem cells remain the most promising. Neural tissue engineering strategies are based on the development of devices presenting optimal physical, chemical, and mechanical properties which, once inserted in the injured site, can support therapeutic cells, limiting the effect of a hostile environment and supporting regenerative processes. Thus, this review focuses on the employment of hydrogel and nanofibrous scaffolds supplemented with stem cells as promising therapeutic tools for the central and peripheral nervous systems in preclinical and clinical applications.

From Basic Science to Clinical Practice: A Review of Current Periodontal/Mucogingival Regenerative Biomaterials.

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.

Magnetically Active Bicontinuous Polymer Structures for Multiple Controlled Drug Delivery.

The targeted delivery of drugs using wireless navigable magnetic robots allows the delivery of drug molecules to be controlled non only in time but also in space, improving medical outcomes. The main disadvantages behind their use lies in the low amount of drug that can be transported and the single nature of drug that can be loaded (hydrophilic or hydrophobic). These considerations limit their use in co-delivery systems, now recognized to be very promising for many different pathologies. A magnetic bijel-like structure is developed to load and release different types of molecules (hydrophilic and hydrophobic). In this work, the use of ε-caprolactone is explored, which can polymerize, forming hydrophobic domains (oil phase). After mixing with iron oxide nanoparticles (NPs), the water dispersion creates a magnetic biphasic porous structure without phase separation. The resulting device shows good performance both in magnetic actuation and as a drug delivery system.