Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family.

The Flaviviridae family consists of single-stranded positive-sense RNA viruses, which contains the genera Flavivirus, Hepacivirus, Pegivirus, and Pestivirus. Currently, there is an outbreak of viral diseases caused by this family affecting millions of people worldwide, leading to significant morbidity and mortality rates. Advances in computational chemistry have greatly facilitated the discovery of novel drugs and treatments for diseases associated with this family. Chemoinformatic techniques, such as the perturbation theory machine learning method, have played a crucial role in developing new approaches based on ML models that can effectively aid drug discovery. The IFPTML models have shown its capability to handle, classify, and process large data sets with high specificity. The results obtained from different models indicates that this methodology is proficient in processing the data, resulting in a reduction of the false positive rate by 4.25%, along with an accuracy of 83% and reliability of 92%. These values suggest that the model can serve as a computational tool in assisting drug discovery efforts and the development of new treatments against Flaviviridae family diseases.

Ficin-Cyclodextrin-Based Docking Nanoarchitectonics of Self-Propelled Nanomotors for Bacterial Biofilm Eradication.

Development of bioinspired nanomotors showing effective propulsion and cargo delivery capabilities has attracted much attention in the last few years due to their potential use in biomedical applications. However, implementation of this technology in realistic settings is still a barely explored field. Herein, we report the design and application of a multifunctional gated Janus platinum-mesoporous silica nanomotor constituted of a propelling element (platinum nanodendrites) and a drug-loaded nanocontainer (mesoporous silica nanoparticle) capped with ficin enzyme modified with ß-cyclodextrins (ß-CD). The engineered nanomotor is designed to effectively disrupt bacterial biofilms via H2O2-induced self-propelled motion, ficin hydrolysis of the extracellular polymeric matrix (EPS) of the biofilm, and controlled pH-triggered cargo (vancomycin) delivery. The effective synergic antimicrobial activity of the nanomotor is demonstrated in the elimination of Staphylococcus aureus biofilms. The nanomotor achieves 82% of EPS biomass disruption and a 96% reduction in cell viability, which contrasts with a remarkably lower reduction in biofilm elimination when the components of the nanomotors are used separately at the same concentrations. Such a large reduction in biofilm biomass in S. aureus has never been achieved previously by any conventional therapy. The strategy proposed suggests that engineered nanomotors have great potential for the elimination of biofilms.

Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy.

Cancer immunotherapy has emerged in the past decade as a promising strategy for treating many forms of cancer by stimulating the patient's immune system. Although immunotherapy has achieved some promising results in clinics, more efforts are required to improve the limitations of current treatments related to lack of effective and targeted cancer antigens delivery to immune cells, dose-limiting toxicity, and immune-mediated adverse effects, among others. In recent years, the use of nanomaterials has proven promising to enhance cancer immunotherapy efficacy and reduce side effects. Among nanomaterials, attention has been recently paid to mesoporous silica nanoparticles (MSNs) as a potential multiplatform for enhancing cancer immunotherapy by considering their unique properties, such as high porosity, and good biocompatibility, facile surface modification, and self-adjuvanticity. This review explores the role of MSN and other nano/micro-materials as an emerging tool to enhance cancer immunotherapy, and it comprehensively summarizes the different immunotherapeutic strategies addressed to date by using MSN.

Ultrafast Directional Janus Pt-Mesoporous Silica Nanomotors for Smart Drug Delivery.

Development of bioinspired nanomachines with an efficient propulsion and cargo-towing has attracted much attention in the last years due to their potential biosensing, diagnostics, and therapeutics applications. In this context, self-propelled synthetic nanomotors are promising carriers for intelligent and controlled release of therapeutic payloads. However, the implementation of this technology in real biomedical applications is still facing several challenges. Herein, we report the design, synthesis, and characterization of innovative multifunctional gated platinum-mesoporous silica nanomotors constituted of a propelling element (platinum nanodendrite face), a drug-loaded nanocontainer (mesoporous silica nanoparticle face), and a disulfide-containing oligo(ethylene glycol) chain (S-S-PEG) as a gating system. These Janus-type nanomotors present an ultrafast self-propelled motion due to the catalytic decomposition of low concentrations of hydrogen peroxide. Likewise, nanomotors exhibit a directional movement, which drives the engines toward biological targets, THP-1 cancer cells, as demonstrated using a microchip device that mimics penetration from capillary to postcapillary vessels. This fast and directional displacement facilitates the rapid cellular internalization and the on-demand specific release of a cytotoxic drug into the cytosol, due to the reduction of the disulfide bonds of the capping ensemble by intracellular glutathione levels. In the microchip device and in the absence of fuel, nanomotors are neither able to move directionally nor reach cancer cells and deliver their cargo, revealing that the fuel is required to get into inaccessible areas and to enhance nanoparticle internalization and drug release. Our proposed nanosystem shows many of the suitable characteristics for ideal biomedical destined nanomotors, such as rapid autonomous motion, versatility, and stimuli-responsive controlled drug release.

Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.

Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50 ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.

Electrostatic control of peptide side-chain reactivity using amphiphilic homopolymer-based supramolecular assemblies.

Supramolecular assemblies formed by amphiphilic homopolymers with negatively charged groups in the hydrophilic segment have been designed to enable high labeling selectivity toward reactive side chain functional groups in peptides. The negatively charged interiors of the supramolecular assemblies are found to block the reactivity of protonated amines that would otherwise be reactive in aqueous solution, while maintaining the reactivity of nonprotonated amines. Simple changes to the pH of the assemblies' interiors allow control over the reactivity of different functional groups in a manner that is dependent on the pKa of a given peptide functional group. The labeling studies carried out in positively charged supramolecular assemblies and free buffer solution show that, even when the amine is protonated, labeling selectivity exists only when complementary electrostatic interactions are present, thereby demonstrating the electrostatically controlled nature of these reactions.

Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study.

Elevated concentrations of plasma adenosine in obese children.

There are no data regarding adenosine levels in obese children, even though is a ubiquitous molecule implicated in the regulation of lipid metabolism in humans. To determinate whether adenosine plasma levels are related with anthropometric and biochemical markers in children, we studied 51 students belong to Ramon Belmar School in Linares, Chile. Review of clinical data and frequent food questionnaire were taken in order to collect the information. Plasma adenosine levels were measured by high-performance liquid chromatography and biochemical parameters including insulin, glucose, total proteins, and lipid profile by using standard colorimetric assays. Children with detectable (above 0.1 µM) adenosine plasma levels (n = 30; BMI, 22.3 ± 0.7) had higher total cholesterol (P < 0.05); triglycerides (P < 0.01) and LDL-cholesterol (P < 0.05) concentrations than children with undetectable adenosine levels (n = 21; BMI, 23.9 ± 0.61). Among the analyzed variables, only BMI and BMI standard deviation score (BMI-SDS) were positively correlated with adenosine levels. Besides, obese children (n = 10) showed significantly high adenosine levels compared to controls (n = 11; 1.8 ± 0.2 vs. 1.2 ± 0.1 µM/mg protein, respectively. P < 0.05), but not compared to overweight children (n = 9). In conclusion, obesity in children is associated to high adenosine plasma levels. This study opens a new perspective to investigate the role of adenosine in the regulation of lipid metabolism in obese children.

Adverse perinatal outcomes after the February 27th 2010 Chilean earthquake.

OBJECTIVE: To investigate whether the February 27th earthquake exposition was associated to adverse perinatal outcomes in Chilean pregnant women. METHODS: We analyzed all deliveries occurred in 2009 (n = 3,609) and 2010 (n = 3,279) in a reference hospital in the area of the earthquake. Furthermore, we investigated pregnant women who gave birth between March 1st and December 31st 2010 (n = 2,553) and we classified them according to timing of exposition. RESULTS: We found a 9% reduction in birth rate, but an increase in the rate of early preterm deliveries (<34 weeks), premature rupture of membranes (PROM), macrosomia, small for gestational age, and intrauterine growth restriction (IUGR) after the earthquake, in contrast to the previous year. Women exposed to the earthquake during her first trimester delivered smaller newborns (3,340 ± 712 g v/s 3,426 ± 576 g respectively, p = 0.007) and were more likely diagnosed with early preterm delivery, preterm delivery (<37 weeks) and PROM but were less likely diagnosed with IUGR and late delivery (42 weeks, p < 0.05) compared to those exposed at third trimester. Accordingly, IUGR and preterm deliveries presented elevated healthcare costs. CONCLUSION: Natural disasters such as earthquakes are associated to adverse perinatal outcomes that impact negatively the entire maternal-neonatal healthcare system.

Amphiphilic nanoassemblies for the detection of peptides and proteins using fluorescence and mass spectrometry.

Amphiphilic nanostructures provide unique environments for molecules that are incompatible with the solvent to be sequestered within their interior. These internal environments provide opportunities for concentrating an analyte or transducer molecule for detection, and the functional groups within the amphiphiles provide an opportunity for incorporating specificity or selectivity toward analytes. In this review, we discuss ways in which amphiphilic assemblies can be used to detect peptides and proteins with a particular emphasis on facially amphiphilic polymers and dendrimers.

Selective peptide binding using facially amphiphilic dendrimers.

Amphiphilic dendrimers, which contain both hydrophobic and hydrophilic groups in every repeat unit, exhibit environment-dependent assemblies both in hydrophilic solvent, water, and in lipophilic solvent, toluene. Upon investigating the status of these assemblies in a mixture of immiscible solvents, these dendrimers were found to be kinetically trapped in the solvent in which they are initially assembled. This property has been exploited to selectively extract peptides from aqueous solution into an organic phase, where the peptides bind to the interior functionalities of the dendritic inverse micelles. While the corresponding small molecule surfactant does not exhibit any selective binding toward peptides, all dendrons (G1-G3) are capable of this selective binding. We show that the inverse micelle-type assembly itself is crucial for the binding event and that the assembly formed by the G1 dendron has a greater capability for binding compared to the G2 or G3 dendrons. We have also shown that the average apparent pKa of the carboxylic acid functionalities varies with generation, and this could be the reason for the observed differences in binding capacity.