Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens.

Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria.

Impact of Leave-on Skin Care Products on the Preservation of Skin Microbiome: An Exploration of Ecobiological Approach.

Purpose: Skincare products are used daily to maintain a healthy skin, although their skin microbiome impact is still poorly known. Preserving the natural resources and mechanisms of the skin ecosystem is essential, and a novel approach based on these premises, called ecobiology, has recently emerged in skincare. We evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic solution, a micellar solution, and an oil-in-water emulsion.

Understanding microRNAs in the Context of Infection to Find New Treatments against Human Bacterial Pathogens.

The development of RNA-based anti-infectives has gained interest with the successful application of mRNA-based vaccines. Small RNAs are molecules of RNA of <200 nucleotides in length that may control the expression of specific genes. Small RNAs include small interference RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), or microRNAs (miRNAs).

Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration.

Alterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer's disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown.

Opportunities of super high-density olive orchard to improve soil quality: Management guidelines for application of pruning residues.

Applying pruning residues in the lanes of olive groves has become a popular practice because it is economical and accrues benefits for soil and water management. This study presents an analysis of the impact of different rates of pruning residue on soil properties, in particular related with soil quality. Over 4 annual campaigns, chopped pruning residues used as a mulch were analyzed in terms of composition, coverage and moisture content to evaluate their effects on the amount of soil organic carbon (-10 cm and -20 cm) and CO emissions, temperature and moisture.

Novel Methods to Identify Oxidative Stress-Producing Antibiotics.

Antibiotherapy is the main therapeutic strategy in the fight against bacterial pathogens. However, the misuse of antimicrobials has led to the appearance of antimicrobial-resistant strains. The rate at which we isolate multidrug-resistant bacteria is now much faster than the discovery rate of new antimicrobials.

Genome-wide association study of stage III/IV grade C periodontitis (former aggressive periodontitis) in a Spanish population.

Aim: To identify loci associated with stages III/IV, grade C periodontitis (PIII/IV-C) through a genome-wide association study (GWAS).

Materials And Methods: 441 Caucasian Spanish PIII/IV-C cases from the SEPA Network of Research Clinics and 1141 controls from the Banco Nacional de ADN were genotyped with "Axiom Spain Biobank Array," which contains 757836 markers, including rare and low-frequency Spanish variants. The analysis of the individual association and subsequently the gene-level analysis with Sequence Kernel Association Test (SKAT) were carried out adjusting for age, sex and PC1 covariates.

Novel Treatments and Preventative Strategies Against Food-Poisoning Caused by Staphylococcal Species.

Staphylococcal infections are a widespread cause of disease in humans. In particular, is a major causative agent of infection in clinical medicine. In addition, these bacteria can produce a high number of staphylococcal enterotoxins (SE) that may cause food intoxications.

Robots Under COVID-19 Pandemic: A Comprehensive Survey.

As a result of the difficulties brought by COVID-19 and its associated lockdowns, many individuals and companies have turned to robots in order to overcome the challenges of the pandemic. Compared with traditional human labor, robotic and autonomous systems have advantages such as an intrinsic immunity to the virus and an inability for human-robot-human spread of any disease-causing pathogens, though there are still many technical hurdles for the robotics industry to overcome. This survey comprehensively reviews over 200 reports covering robotic systems which have emerged or have been repurposed during the past several months, to provide insights to both academia and industry.

Efficacy of FF/UMEC/VI compared with FF/VI and UMEC/VI in patients with COPD: subgroup analysis of the Spain cohort in IMPACT.

Objectives: The IMPACT trial has compared the benefit in the reduction of moderate/severe exacerbations of single inhaler triple therapy (SITT) with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) dual therapy with FF/VI (ICS/LABA) and UMEC/VI (LAMA/LABA) in the treatment of patients with chronic obstructive disease (COPD). This study performs a subgroup analysis of the cohort from Spain in the IMPACT study.

Materials And Methods: In IMPACT, a 52-week randomized, double-blind, parallel-group, multicenter study ( = 10,355), patients ⩾40 years of age with COPD and ⩾1 moderate/severe exacerbations in the previous year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.

Alternative Anti-Infective Treatments to Traditional Antibiotherapy against Staphylococcal Veterinary Pathogens.

The genus encompasses many species that may be pathogenic to both humans and farm animals. These bacteria have the potential to acquire multiple resistant traits to the antimicrobials currently used in the veterinary or medical settings. These pathogens may commonly cause zoonoses, and the infections they cause are becoming difficult to treat due to antimicrobial resistance.

Novel Treatments against Based on Drug Repurposing.

Tuberculosis is the leading cause of death, worldwide, due to a bacterial pathogen. This respiratory disease is caused by the intracellular pathogen and produces 1.5 million deaths every year.

The Impact of Cognitive Anxiety and the Rating of Pain on Care Processes in a Vigilance Task: The Important Part Played by Age.

Chronic pain is a serious public health problem that has grown exponentially in recent years, which is why it has received the attention of numerous researchers. Most of the studies in the field of chronic pain have focused on care as a mediating variable on the perception of painful stimuli and emotions. Nevertheless, there are very few studies that have gone in the opposite direction.

Oxidative Stress-Generating Antimicrobials, a Novel Strategy to Overcome Antibacterial Resistance.

Antimicrobial resistance is becoming one of the most important human health issues. Accordingly, the research focused on finding new antibiotherapeutic strategies is again becoming a priority for governments and major funding bodies. The development of treatments based on the generation of oxidative stress with the aim to disrupt the redox defenses of bacterial pathogens is an important strategy that has gained interest in recent years.

A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen .

is a facultative intracellular pathogen that causes infections in foals and many other animals such as pigs, cattle, sheep, and goats. Antibiotic resistance is rapidly rising in horse farms, which makes ineffective current antibiotic treatments based on a combination of macrolides and rifampicin. Therefore, new therapeutic strategies are urgently needed to treat infections caused by antimicrobial resistant strains.

Methionine sulfoxide reductase B from catalyzes sulfoxide reduction via an intramolecular disulfide cascade.

is a human pathogen that causes diphtheria. In response to immune system-induced oxidative stress, expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation.

Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen .

is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we identified three mycoredoxin-encoding genes () in the genome of , and we investigated their role in virulence.

Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus.

During patient colonization, Staphylococcus aureus is able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes during S.

Host-directed kinase inhibitors act as novel therapies against intracellular Staphylococcus aureus.

Host-directed therapeutics are a promising anti-infective strategy against intracellular bacterial pathogens. Repurposing host-targeted drugs approved by the FDA in the US, the MHRA in the UK and/or regulatory equivalents in other countries, is particularly interesting because these drugs are commercially available, safe doses are documented and they have been already approved for other clinical purposes. In this study, we aimed to identify novel therapies against intracellular Staphylococcus aureus, an opportunistic pathogen that is able to exploit host molecular and metabolic pathways to support its own intracellular survival.

Structural snapshots of OxyR reveal the peroxidatic mechanism of HO sensing.

Hydrogen peroxide (HO) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward HO One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces HO In this study, we present crystallographic evidence for the HO-sensing mechanism and HO-dependent structural transition of OxyR by capturing the reduced and HO-bound structures of a serine mutant of the peroxidatic cysteine, and the full-length crystal structure of disulfide-bonded oxidized OxyR. In the HO-bound structure, we pinpoint the key residues for the peroxidatic reduction of HO, and relate this to mutational assays showing that the conserved active-site residues T107 and R278 are critical for effective HO reduction. Furthermore, we propose an allosteric mode of structural change, whereby a localized conformational change arising from HO-induced intramolecular disulfide formation drives a structural shift at the dimerization interface of OxyR, leading to overall changes in quaternary structure and an altered DNA-binding topology and affinity at the catalase promoter region.

Intracellular Staphylococcus aureus Modulates Host Central Carbon Metabolism To Activate Autophagy.

is a facultative intracellular pathogen that invades and replicates within many types of phagocytic and nonphagocytic cells. During intracellular infection, is capable of subverting xenophagy and escaping to the cytosol of the host cell. Furthermore, drug-induced autophagy facilitates the intracellular replication of , but the reasons behind this are unclear.

Spectroscopic analysis of corrosion products in a bronze cauldron from the Late Iberian Iron Age.

Selected bronze fragments unearthed at Cerro de la Cruz (Almedinilla, southern Spain) were analyzed to determine the chemical composition of the corrosion products formed on their surface. The fragments came from a large bronze cauldron used in an Iberian village that was devastated in the mid II century BCE - possibly around 141 BCE. The fragments were analyzed by using various instrumental techniques including electron scanning microscopy coupled to energy dispersive X-ray spectroscopy (SEM-EDS), X-ray fluorescence (XRF) spectroscopy, and also by X-ray diffraction (XRD) and micro-Raman spectroscopy.

The antibacterial prodrug activator Rv2466c is a mycothiol-dependent reductase in the oxidative stress response of .

The gene encodes an oxidoreductase enzyme annotated as DsbA. It has a CPWC active-site motif embedded within its thioredoxin fold domain and mediates the activation of the prodrug TP053, a thienopyrimidine derivative that kills both replicating and nonreplicating bacilli. However, its mode of action and actual enzymatic function in have remained enigmatic.