Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations.

Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.

Characterization of the Cell Wall Component through Thermogravimetric Analysis and Its Relationship with an Expansin-like Protein in Deschampsia antarctica.

Deschampsia antarctica Desv. (Poaceae) is one of the two vascular plants that have colonized the Antarctic Peninsula, which is usually exposed to extreme environmental conditions. To support these conditions, the plant carries out modifications in its morphology and metabolism, such as modifications to the cell wall. Thus, we performed a comparative study of the changes in the physiological properties of the cell-wall-associated polysaccharide contents of aerial and root tissues of the D. antarctica via thermogravimetric analysis (TGA) combined with a computational approach. The result showed that the thermal stability was lower in aerial tissues with respect to the root samples, while the DTG curve describes four maximum peaks of degradation, which occurred between 282 and 358 °C. The carbohydrate polymers present in the cell wall have been depolymerized showing mainly cellulose and hemicellulose fragments. Additionally, a differentially expressed sequence encoding for an expansin-like (DaEXLA2), which is characterized by possessing cell wall remodeling function, was found in D. antarctica. To gain deep insight into a probable mechanism of action of the expansin protein identified, a comparative model of the structure was carried out. DaEXLA2 protein model displayed two domains with an open groove in the center. Finally, using a cell wall polymer component as a ligand, the protein-ligand interaction was evaluated by molecular dynamic (MD) simulation. The MD simulations showed that DaEXLA2 could interact with cellulose and XXXGXXXG polymers. Finally, the cell wall component description provides the basis for a model for understanding the changes in the cell wall polymers in response to extreme environmental conditions.

Antimicrobial properties of novel ionic liquids derived from imidazolium cation with phenolic functional groups.

Bacterial infections are nowadays among the major threats to public health worldwide. Thus, there is an urgent and increased need for new antimicrobial agents. As a result, the exploration of the antimicrobial properties of different substances including ionic liquids (ILs) has recently attracted great attention. The present work is aimed at evaluating how the addition of halogens and hydrophobic substituents on alkylimidazolium units of ILs as well as the increase in their chain lengths affects the antimicrobial properties of such ILs. After their synthesis, the antibacterial activities of these compounds against Pseudomona aeruginosa, Escherichia coli, and Staphylococcus aureus are determined by measuring their minimal inhibitory concentrations (MICs). Key features in ILs-membrane interactions are also studied using long-term all-atom molecular dynamics simulations (MDs). The results show that these ILs have good antibacterial activity against S. aureus, E. coli, and P. aeruginosa, with MIC values range from <7.81 to 62.50 µM. The antimicrobial property of tert-butyl N-methylphenolimidazolium salts (denoted as 8b and 8c) is particularly better with MIC values of < 7.81 µM. The antibacterial efficacy is also found to depend on the alkyl chain length and substituents on the phenolic ring. Finally, MDs done for ILs in a phosphatidylcholine (POPC) bilayer show key features in the mechanism of IL-induced membrane disruption, where the ILs are inserted as clusters into one side of the bilayer until saturation is reached. This insertion increases "leaflet strain" up to critical threshold, likely triggering the morphological disruption of the membranes in the microbes.

Effect of Exogenous Auxin Treatment on Cell Wall Polymers of Strawberry Fruit.

The role of auxin in the fruit-ripening process during the early developmental stages of commercial strawberry fruits (Fragaria x ananassa) has been previously described, with auxin production occurring in achenes and moving to the receptacle. Additionally, fruit softening is a consequence of the depolymerization and solubilization of cell wall components produced by the action of a group of proteins and enzymes. The aim of this study was to compare the effect of exogenous auxin treatment on the physiological properties of the cell wall-associated polysaccharide contents of strawberry fruits. We combined thermogravimetric (TG) analysis with analyses of the mRNA abundance, enzymatic activity, and physiological characteristics related to the cell wall. The samples did not show a change in fruit firmness at 48 h post-treatment; by contrast, we showed changes in the cell wall stability based on TG and differential thermogravimetric (DTG) analysis curves. Less degradation of the cell wall polymers was observed after auxin treatment at 48 h post-treatment. The results of our study indicate that auxin treatment delays the cell wall disassembly process in strawberries.

Perspectives of Dendrimer-based Nanoparticles in Cancer Therapy.

Currently, cancer is the second most common cause of death in the United States, exceeded only by heart disease. Chemotherapy traditionally suffers from a non-specific distribution, with only a small fraction of the drug reaching the tumor, in this sense, the use of dendrimers incorporating drugs non-covalently encapsulated inside the dendrimer or covalently conjugated have proven to be effectives against different cancer cell lines. However, at present the dendrimers used as drug-carriers still do not meet the necessary characteristic to be considered as an ideal dendrimer for drug delivery; high toxicity, bio-degradability, low toxicity, biodistribution characteristics, and favorable retention with appropriate specificity and bioavailability have not been fully covered by the current available dendrimers. However, the development and study of new dendrimers drug-carriers continues to be an important tool in the cancer therapy as they can be functionalized with varied ligands to reach the tumor tissue through the different body barriers in the body with minimal loss of activity in the bloodstream, have the ability to selectively kill tumor cells without affecting the normal cells and most important with a release mechanism controlling actively. Given the continuous efforts and research in this area of interest, we presented in this review the work done with a special emphasis on the development of dendrimers as a major tool in the combination with drugs, as a potential adjunctive agent in anticancer therapy.

Fast detection of Listeria monocytogenes through a nanohybrid quantum dot complex.

Listeria monocytogenes is a recognized foodborne pathogen that causes listeriosis in susceptible consumers. Currently, the detection systems for Listeria in food detect live and dead bacteria, being the viable microorganisms most relevant for their ability to cause sickness in the population at risk. For this reason, a new nanohybrid compound was developed for the optical detection of Listeria that was based on polyamidoamine dendrimers functionalized with an auxotrophic cofactor (lipoic acid), together with the coupling of fluorescent semiconductor crystals (quantum dots). The nanohybrid sensor has a detection limit for viable L. monocytogenes of 5.19 × 103 colony-forming units per milliliter under epifluorescence microscopy. It was specific when used among other pathogens commonly found in food.

The Controlled Release of Abscisic Acid (ABA) Utilizing Alginate-Chitosan Gel Blends: A Synergistic Approach for an Enhanced Small-Molecule Delivery Controller.

The integration of abscisic acid (ABA) into a chitosan-alginate gel blend unveils crucial insights into the formation and stability of these two substances. ABA, a key phytohormone in plant growth and stress responses, is strategically targeted for controlled release within these complexes. This study investigates the design and characterization of this novel controlled-release system, showcasing the potential of alginate-chitosan gel blends in ABA delivery. Computational methods, including molecular dynamics simulations, are employed to analyze the structural effects of microencapsulation, offering valuable insights into complex behavior under varying conditions. This paper focuses on the controlled release of ABA from these complexes, highlighting its strategic importance in drug delivery systems and beyond. This controlled release enables targeted and regulated ABA delivery, with far-reaching implications for pharmaceuticals, agriculture, and plant stress response studies. While acknowledging context dependency, the paper suggests that the liberation or controlled release of ABA holds promise in applications, urging further research and experimentation to validate its utility across diverse fields. Overall, this work significantly contributes to understanding the characteristics and potential applications of chitosan-alginate complexes, marking a noteworthy advancement in the field of controlled-release systems.

Development and Evaluation of Cross-Linked Alginate-Chitosan-Abscisic Acid Blend Gel.

Abscisic acid (ABA) has been proposed to play a significant role in the ripening of nonclimacteric fruit, stomatal opening, and response to abiotic stresses in plants, which can adversely affect crop growth and productivity. The biological effects of ABA are dependent on its concentration and signal transduction pathways. However, due to its susceptibility to the environment, it is essential to find a suitable biotechnological approach to coat ABA for its application. One promising approach is to utilize alginate and chitosan, two natural polysaccharides known for their strong affinity for water and their ability to act as coating agents. In this study, an alginate-chitosan blend was employed to develop an ABA cover. To achieve this, an alginate-chitosan-abscisic acid (ALG-CS-ABA) blend was prepared by forming ionic bonds or complexes with calcium ions, or through dual cross-linking. This was done by dripping a homogeneous solution of alginate-chitosan and ABA into a calcium chloride solution, resulting in the formation of the blend. By combining the unique properties of alginate, chitosan, and ABA, the resulting ALG-CS-ABA blend can potentially offer enhanced stability, controlled release, and improved protection of ABA. These characteristics make it a promising biotechnological approach for various applications, including the targeted delivery of ABA in agricultural practices or in the development of innovative plant-based products. Further evaluation and characterization of the ALG-CS-ABA blend will provide valuable insights into its potential applications in the fields of biomedicine, agriculture, and tissue engineering.

Efficient production of a polyhydroxyalkanoate by Azotobacter vinelandii OP using apple residues as promising feedstock.

Fruit residues are attractive substrates for the production of bacterial polyhydroxyalkanoates due to the high contents of fermentable sugars and the fast, simple, and efficient pretreatment methods required. In this study, apple residues, mainly apple peel, were used as the sole carbon source in cultures of the bacterium Azotobacter vinelandii OP to produce poly-3-hydroxybutyrate (P3HB). Conversion from the residue to total sugars was highly effective, achieving conversions of up to 65.4 % w w-1 when using 1 % v v-1 sulfuric acid and 58.3 % w w-1 in the absence of acid (only water). The cultures were evaluated at the shake-flask scale and in 3-L bioreactors using a defined medium under nitrogen starvation conditions. The results showed the production of up to 3.94 g L-1 P3HB in a bioreactor, reaching an accumulation of 67.3 % w w-1 when using apple residues. For the PHB obtained from the cultures with apple residues, a melting point of 179.99 °C and a maximum degradation temperature of 274.64 °C were calculated. A P3HB production strategy is shown using easily hydrolysable fruit residues to achieve production yields comparable to those obtained with pure sugars under similar cultivation conditions.

Calcium-Alginate-Chitosan Nanoparticle as a Potential Solution for Pesticide Removal, a Computational Approach.

Pesticides have a significant negative impact on the environment, non-target organisms, and human health. To address these issues, sustainable pest management practices and government regulations are necessary. However, biotechnology can provide additional solutions, such as the use of polyelectrolyte complexes to encapsulate and remove pesticides from water sources. We introduce a computational methodology to evaluate the capture capabilities of Calcium-Alginate-Chitosan (CAC) nanoparticles for a broad range of pesticides. By employing ensemble-docking and molecular dynamics simulations, we investigate the intermolecular interactions and absorption/adsorption characteristics between the CAC nanoparticles and selected pesticides. Our findings reveal that charged pesticide molecules exhibit more than double capture rates compared to neutral counterparts, owing to their stronger affinity for the CAC nanoparticles. Non-covalent interactions, such as van der Waals forces, π-π stacking, and hydrogen bonds, are identified as key factors which stabilized the capture and physisorption of pesticides. Density profile analysis confirms the localization of pesticides adsorbed onto the surface or absorbed into the polymer matrix, depending on their chemical nature. The mobility and diffusion behavior of captured compounds within the nanoparticle matrix is assessed using mean square displacement and diffusion coefficients. Compounds with high capture levels exhibit limited mobility, indicative of effective absorption and adsorption. Intermolecular interaction analysis highlights the significance of hydrogen bonds and electrostatic interactions in the pesticide-polymer association. Notably, two promising candidates, an antibiotic derived from tetracycline and a rodenticide, demonstrate a strong affinity for CAC nanoparticles. This computational methodology offers a reliable and efficient screening approach for identifying effective pesticide capture agents, contributing to the development of eco-friendly strategies for pesticide removal.

Structural Effects of pH Variation and Calcium Amount on the Microencapsulation of Glutathione in Alginate Polymers.

Reduced glutathione (GSH) has a high antioxidant capacity and is present in nearly every cell in the body, playing important roles in nutrient metabolism, antioxidant defense, and regulation of cellular events. Conversely, alginate is a macromolecule that has been widely used in the food, pharmaceutical, biomedical, and textile industries due to its biocompatibility, biodegradability, nontoxicity, and nonimmunogenicity as well as for its capabilities of retaining water and stabilizing emulsions. The primary goal of this study was to characterize and optimize the formation of a molecular complex of calcium alginate with GSH using a computational approach. As methods, we evaluated the influence of varying the amount of calcium cations at two different pHs on the structural stability of Ca2+-alginate complexes and thus on GSH liberation from these types of nanostructures. The results showed that complex stabilization depends on pH, with the system having a lower Ca2+ amount that produces the major GSH release. The systems at pH 2.5 retain more molecules within the calcium-alginate complex, which release GSH more slowly when embedded in more acidic media. In conclusions, this study demonstrates the dependence of the amount of calcium and the stabilizing effect of pH on the formation and subsequent maintenance of an alginate nanostructure. The results presented in this study can help to develop better methodological frameworks in industries where the release or capture of compounds, such as GSH in this case, depends on the conditions of the alginate nanoparticle.

Ugni molinae Fruit as a Source of Bioactive Compounds with Good Quality Traits.

Since the intake of fruits and vegetables displays important effects on the incidence of several chronic diseases in humans, consumers' attention worldwide is focused on the identification of functional foods. In this sense, Ugni molinae (murtilla or murta fruit) is an important source of molecules with a strong antioxidant capacity that is widely used as a medicinal plant in Southern Argentina-Chile. Research on murtilla berries showed that this fruit and its leaves can be an excellent source of polyphenols and bioactive compounds with antibacterial and antioxidant capacity. This review is aimed at providing valuable information and discussing the available literature focused on four principal points: (i) fruit quality and plant physiology, (ii) compound content with bioactive properties, (iii) health properties for consumers of the fruit and leaves, and (iv) challenges for future research. Based on these four points, we propose that murtilla fruit can be a potential ingredient for new functional food products.

Combined effects of sulfur dioxide, glutathione and light exposure on the conservation of bottled Sauvignon blanc.

Oxygen exposure may trigger a series of changes that could be detrimental to the quality white wines. This study evaluated the combined effects of sulfur dioxide, glutathione and light exposure on the chemistry and sensory perception of bottled Sauvignon blanc. The wines were manually bottled into clear bottles, closed with low oxygen transfer rate stoppers, and stored for three months, either exposed or protected from light. The wines exposed to artificial light showed higher rates of sulfite loss and oxygen consumption, were significantly darker in color, exhibited significant changes in the concentration of phenolics and volatile compounds, were perceived as less fruity/floral, and had higher nuances of solvent, earthy and honey aromas than the ones protected from light. The treatments with higher amounts of initial sulfites and glutathione were able to delay some of these changes but were less significant than protecting the wines from artificial light.

Design and Optimization of a Self-Assembling Complex Based on Microencapsulated Calcium Alginate and Glutathione (CAG) Using Response Surface Methodology.

The aim of this work was to characterize and optimize the formation of molecular complexes produced by the association of calcium alginate and reduced glutathione (GSH). The influence of varying concentrations of calcium and GSH on the production of microcapsules was analyzed using response surface methodology (RSM). The microcapsules were characterized by thermogravimetric analysis (TGA-DTG) and infrared spectroscopy (FTIR) in order to assess the hydration of the complexes, their thermal stability, and the presence of GSH within the complexes. The optimum conditions proposed by RSM to reach the maximum concentration of GSH within complexes were a 15% w/v of GSH and 1.25% w/v of CaCl2, with which a theorical concentration of 0.043 mg GSH per mg of CAG complex was reached.

In Silico and In Vitro Analysis of the 4,4',4''-((1,3,5-Triazine-2,4,6-triyl)tris(azanediyl))triphenol), an Antioxidant Agent with a Possible Anti-Inflammatory Function.

Inflammation is a consequence of an array of biological reactions that occur in response to pain sensation, local injury, and cell damage. A large number of studies have demonstrated that quercetin and other flavonoids show anti-inflammatory effects; thus, in the present work, we evaluated a triazine-phenol derivative (TP derivative) compound as a possible drug candidate with anti-inflammatory activity. This compound was studied as a possible anti-inflammatory drug using synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and mass spectrometry (MS). The derivative of melamine was evaluated for its antioxidant activity and exhibited good DPPH and FRAP antioxidant activity. Additionally, we evaluated the putative effect of the molecule on the COX-2 enzyme through molecular dynamic simulation (MDS), and the result suggested that the TP derivative is a potential anti-inflammatory agent that can interact with the COX-2 enzyme because of the high number of protein-ligand interactions observed with MDS. Finally, the study of theoretical physicochemical properties, the observation of low toxicity (hemolysis assay), and the evaluation of oral bioavailability of the TP derivative showed that it is a possible anti-inflammatory drug candidate.

Molecular Insights into FaEG1, a Strawberry Endoglucanase Enzyme Expressed during Strawberry Fruit Ripening.

The endo-ß-1,4-glucanases (EGs) that belong to the glycosyl hydrolase family 9 (GH9) have roles in cell wall synthesis, remodeling and degradation. Previous studies have suggested that EGs may play a key role in the ripening of different fruits including strawberries. In this study, we used reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assays to determine the transcript accumulation of an endo-ß-1,4-glucanase (FaEG1) during fruit development in two different strawberry 'Camarosa' and 'Monterey' with contrasting softening ratios. Phylogenetic analyses suggest that FaEG1 belongs to the α group of the GH9 family with other proteins previously described with roles in elongation, abscission and ripening. Comparative modeling was used to obtain the FaEG1 structure. The model displays a α-barrel-type structure that is typical of the GH9 enzyme family, and comprises 12 α-helices, 2 310 helices and 6 ß-sheets. The catalytic residues were oriented to the solvent in the middle of an open groove. Protein-ligand interactions were explored with cellulose and two xyloglucans as ligands; the results suggest that the FaEG1-cellulose and FaEG1-XXXGXXXG (the most abundant xyloglucan in strawberries) complexes were more stable complexes than XXFGXXFG. The cell wall degradation was observed by scanning electron microscopy (SEM). The data are congruent with the probable role of the FaEG1 protein in the dissembly of the cellulose-hemicellulose fraction during the ripening of strawberry fruit.

Preparation of Hydrogel/Silver Nanohybrids Mediated by Tunable-Size Silver Nanoparticles for Potential Antibacterial Applications.

In this study, a versatile synthesis of silver nanoparticles of well-defined size by using hydrogels as a template and stabilizer of nanoparticle size is reported. The prepared hydrogels are based on polyvinyl alcohol and maleic acid as crosslinker agents. Three hydrogels with the same nature were synthesized, however, the crosslinking degree was varied. The silver nanoparticles were synthesized into each prepared hydrogel matrix achieving three significant, different-sized nanoparticles that were spherical in shape with a narrow size distribution. It is likely that the polymer network stabilized the nanoparticles. It was determined that the hydrogel network structure can control the size and shape of the nanoparticles. The hydrogel/silver nanohybrids were characterized by swelling degree, Thermal Gravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscope (TEM). Antibacterial activity against Staphylococcus aureus was evaluated, confirming antimicrobial action of the encapsulated silver nanoparticles into the hydrogels.

Protective Effect of Pitao (Pitavia punctata (R. & P.) Molina) Polyphenols against the Red Blood Cells Lipoperoxidation and the In Vitro LDL Oxidation.

The oxidative stress is characterized by an imbalance between the oxidizing agents and antioxidants; meanwhile, the consumption of antioxidants has been considered as an important tool in the prevention of oxidative stress and its consequences. Pitavia punctata (R. & P.) Molina is an endemic arboreal species from the Chilean Coast Range, in which a large amount of flavonoids has been described. This work focused on characterizing and evaluating, in human erythrocytes, the antioxidant capacity and membrane protection of P. punctata extracts and the in vitro protection of the oxidation of the Low Density Lipoprotein (LDL). The phytochemical screening revealed the presence of Quercetin derivatives and flavonoids, such as (-)-Epicatechin, Kaempferol, and derivatives. The methanolic extract presented an important antioxidant activity, protecting the membrane integrity of the red blood cells against the oxidative damage caused by Hypochlorous acid and inhibiting the oxidation of the LDL lipoprotein.

Rational Development of a Novel Hydrogel as a pH-Sensitive Controlled Release System for Nifedipine.

This work depicts the rational development (in-silico design, synthesis, characterization and in-vitro evaluation) of polyvinyl alcohol hydrogels (PVAH) cross-linked with maleic acid (MA) and linked to γ-cyclodextrin molecules (γ-CDPVAHMA) as systems for the controlled and sustained release of nifedipine (NFD). Through computational studies, the structural blocks (PVA chain + dicarboxylic acid + γ-CD) of 20 different hydrogels were evaluated to test their interaction energies (ΔE) with NFD. According to the ΔE obtained, the hydrogel cross-linked with maleic acid was selected. To characterize the intermolecular interactions between NFD and γ-CDPVAHMA, molecular dynamics simulation studies were carried out. Experimentally, three hydrogel formulations with different proportions of γ-CD (2.43%, 3.61% and 4.76%) were synthesized and characterized. Both loading and release of NFD from the hydrogels were evaluated at acid and basic pH. The computational and experimental results show that γ-CDs linked to the hydrogels were able to form 1:1 inclusion complexes with NFD molecules. Finally, γ-CDPVAHMA-3 demonstrated to be the best pH-sensitive release platform for nifedipine. Its effectiveness could significantly reduce the adverse effects caused by the anticipated release of NFD in the stomach of patients.

New polymer for removal of wine phenolics: Poly(N-(3-(N-isobutyrylisobutyramido)-3-oxopropyl)acrylamide) (P-NIOA).

The phenolic compounds of wine contribute to color and astringency, also are responsible for the oxidation state and bitterness. Due the importance of these molecules, different techniques have been used to modulate their concentration such as natural or synthetic polymeric agents. Among the polymeric agents, PVPP is one of the most used, but lacks of selectivity and has a limited pH range. Therefore, the aim of this study was the synthesis of a new polymer, poly(N-(3-(N-isobutyrylisobutyramido)-3-oxopropyl)acrylamide) (P-NIOA), for removal of phenolic compounds, as a potential agent for the fining of wine. The new polymer affinity was studied using HPLC-DAD for different polyphenols using PVPP as a control. The results showed that the new polymer has a similar removal as PVPP, but with lower affinity to resveratrol. The interactions established between polymers and polyphenols were studied using computational chemistry methods demonstrating a direct correlation with the experimental affinity data.