Machine Learning-Driven Discovery and Database of Cyanobacteria Bioactive Compounds: A Resource for Therapeutics and Bioremediation.

Cyanobacteria strains have the potential to produce bioactive compounds that can be used in therapeutics and bioremediation. Therefore, compiling all information about these compounds to consider their value as bioresources for industrial and research applications is essential. In this study, a searchable, updated, curated, and downloadable database of cyanobacteria bioactive compounds was designed, along with a machine-learning model to predict the compounds' targets of newly discovered molecules.

Structural insights of an LCP protein-LytR-from through biophysical and methods.

The rise of antibiotic-resistant bacterial strains has become a critical health concern. According to the World Health Organization, the market introduction of new antibiotics is alarmingly sparse, underscoring the need for novel therapeutic targets. The LytR-CpsA-Psr (LCP) family of proteins, which facilitate the insertion of cell wall glycopolymers (CWGPs) like teichoic acids into peptidoglycan, has emerged as a promising target for antibiotic development.

Advances in structure-based drug design targeting membrane protein markers in prostate cancer.

Prostate cancer (PCa) is one of the leading cancers in men and the lack of suitable biomarkers or their modulators results in poor prognosis. Membrane proteins (MPs) have a crucial role in the development and progression of PCa and can be attractive therapeutic targets. However, experimental limitations in targeting MPs hinder effective biomarker and inhibitor discovery.

LC-ESI-UHR-QqTOF-MS/MS profiling and anti-inflammatory potential of the cultivated Opuntia ficus-indica (L.) Mill. and the wild Opuntia stricta (Haw.) Haw. fruits from the Algerian region.

Opuntia plants are abundant but still underexplored edible resources of the Algerian region. This work chemically characterizes extracts of different parts of the fruit of the commercial Opuntia ficus-indica (L.) Mill.

In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin.

Context: Multiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation.

Heterologous expression and structure prediction of a xylanase identified from a compost metagenomic library.

Xylanases are key biocatalysts in the degradation of the β-1,4-glycosidic linkages in the xylan backbone of hemicellulose. These enzymes are potentially applied in a wide range of bioprocessing industries under harsh conditions. Metagenomics has emerged as powerful tools for the bioprospection and discovery of interesting bioactive molecules from extreme ecosystems with unique features, such as high temperatures.

Dual action of benzaldehydes: Inhibiting quorum sensing and enhancing antibiotic efficacy for controlling Pseudomonas aeruginosa biofilms.

Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations. Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate their ability to increase antibiotic efficacy in preventing and eradicating P.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa.

Aims: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control.

Methods And Results: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps.

Evaluation of the impact of two C5 genetic variants on C5-eculizumab complex stability at the molecular level.

Complement C5 is the target of the monoclonal antibody eculizumab, used in complement dysregulating disorders, like the rare disease Paroxysmal Nocturnal Hemoglobinuria (PNH). PNH is an acquired hematopoietic stem cell condition characterized by aberrant destruction of erythrocytes, chronic hemolytic anemia, and thromboembolism propensity. C5 is a protein component of the complement system which is part of the immune system of the body and plays a prominent role in the destruction of red blood cells, misidentifying them as a threat.

Correction: Exploiting as a source of bioactive peptides with anti-fibrosis properties using an approach.

Correction for 'Exploiting as a source of bioactive peptides with anti-fibrosis properties using an approach' by Carla S. S. Teixeira , , 2024, , 493-502, https://doi.

Substitution Models of Protein Evolution with Selection on Enzymatic Activity.

Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity.

Glucocorticoid receptor-dependent therapeutic efficacy of tauroursodeoxycholic acid in preclinical models of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models.

Exploiting as a source of bioactive peptides with anti-fibrosis properties using an approach.

Edible insects have been proposed as an environmentally and economically sustainable source of protein, and are considered as an alternative food, especially to meat. The migratory locust, , is an edible species authorised by the European Union as a novel food. In addition to their nutritional value, edible insects are also sources of bioactive compounds.

Crystal structures of Streptomyces tsukubaensis sigma factor SigG1 and anti-sigma RsfG.

Transcription of specific genes in bacteria under environmental stress is frequently initiated by extracytoplasmic function (ECF) σ factors. ECFs σ factors harbour two conserved domains, σ and σ, for transcription initiation by recognition of the promoter region and recruitment of RNA polymerase (RNAP). The crystal structure of Streptomyces tsukubaensis SigG1, an ECF56-family σ factor, was determined revealing σ, σ and the additional carboxi-terminal domain SnoaL_2 tightly packed in a compact conformation.

An in silico approach to unveil peptides from Acheta domesticus with potential bioactivity against hypertension, diabetes, cardiac and pulmonary fibrosis.

Entomophagy is a sustainable alternative source of proteins for human nutrition. Acheta domesticus is one of the three insect species that complies with the European Union Regulation on novel foods, but to date, there are no reports on their potential bioactive peptides. In this study, an in silico approach was applied to simulate the gastrointestinal (GI) digestion of six A.

The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant A Case of Two Soul Mates Meeting.

Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity.

In Silico Evaluation of Quercetin Methylated Derivatives on the Interaction with Secretory Phospholipases A2 from and .

Quercetin derivatives have already shown their anti-inflammatory potential, inhibiting essential enzymes involved in this process. Among diverse pro-inflammatory toxins from snake venoms, phospholipase A2 is one of the most abundant in some species, such as and from the Viperidae family. These enzymes can induce the inflammatory process through hydrolysis at the sn-2 position of glycerophospholipids.

The Buzz on Insecticides: A Review of Uses, Molecular Structures, Targets, Adverse Effects, and Alternatives.

Insecticides play a critical role in controlling the spread of insect-borne diseases and preserving crop health. These chemical substances are specifically formulated to kill or manage insect populations. Over the years, various types of insecticides have been developed, including organophosphates, carbamates, pyrethroids, and neonicotinoids, each with unique modes of action, physiological targets, and efficacy.

Receptor-Based Virtual Screening of Large Libraries in a Multi-Level In Silico Approach.

Structure-based drug design (SBDD) has become an alternative to high throughput screening (HTS) as it reduces experimental costs and time. It works like a funnel, filtering out compounds that do not show good affinity (or score) toward a particular target, with known 3D structure.Here, we describe a protocol for structure-based drug design using a multi-level in silico approach, combining Molecular Docking, Virtual Screening, Molecular Dynamics Simulations and Free energy calculations to find new lead molecules for experimental testing, predict binding affinities and characterize binding modes.

TargIDe: a machine-learning workflow for target identification of molecules with antibiofilm activity against Pseudomonas aeruginosa.

Bacterial biofilms are a source of infectious human diseases and are heavily linked to antibiotic resistance. Pseudomonas aeruginosa is a multidrug-resistant bacterium widely present and implicated in several hospital-acquired infections. Over the last years, the development of new drugs able to inhibit Pseudomonas aeruginosa by interfering with its ability to form biofilms has become a promising strategy in drug discovery.

Curcumin and 10-undecenoic acid as natural quorum sensing inhibitors of LuxS/AI-2 of Bacillus subtilis and LasI/LasR of Pseudomonas aeruginosa.

The quorum sensing (QS) system is related to cell-to-cell communication as a function of population density, which regulates several physiological functions including biofilm formation and virulence gene expression. QS inhibitors have emerged as a promising strategy to tackle virulence and biofilm development. Among a wide variety of phytochemicals, many of them have been described as QS inhibitors.

Special Issue on "Enzymes as Biocatalysts: Current Research Trends and Applications".

Enzymes are able to catalyze a wide diversity of chemical reactions in nature, and they do it at an amazing level [...

Liposomal Formulations Loaded with a Eugenol Derivative for Application as Insecticides: Encapsulation Studies and In Silico Identification of Protein Targets.

A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against () insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at the future application as insecticides. Compound-loaded DOPG liposomes have sizes of 274 ± 12 nm, while Egg-PC:Ch liposomes exhibit smaller hydrodynamic diameters (69.5 ± 7 nm), high encapsulation efficiency (88.