A series of 70 new 3,3'(α,ω-dioxaalkyl)bis(1-alkylimidazolium) chlorides were synthesized. They were characterized with respect to surface active properties and antimicrobial activity against the following pathogens: Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Candida krusei, and Candida albicans. In this article, besides description of the synthesis, we characterize a set of features of these compounds, concerning their structure (described by the length of the dioxaalkan spacer and the length of the alkyl substituent in the aromatic ring) and surface active properties (critical micelle concentration, value of surface tension at critical micelle concentration, value of surface excess, molecular area of a single particle, and free energy of adsorption of molecule). Then, we present a SAR study for Staphylococcus aureus, as one of the most widespread pathogenic strains, conducted with the help of the Dominance-based Rough Set Approach (DRSA), that involves identification of relevant features and relevant combinations of features being in strong relationship with a high antimicrobial activity of the compounds. The SAR study shows, moreover, that the antimicrobial activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds.
Metabolic syndrome (MetS) and erratic eating patterns are associated with circadian rhythm disruption which contributes to an increased cardiometabolic risks. Restricting eating period (time-restricted eating, TRE) can restore robust circadian rhythms and improve cardiometabolic health. We describe a protocol of the Time-Restricted Eating on Metabolic and Neuroendocrine homeostasis, Inflammation, and Oxidative Stress (TREMNIOS) pilot clinical trial in Polish adult patients with MetS and eating period of ≥14 h/day. The study aims to test the feasibility of TRE intervention and methodology for evaluating its efficacy for improving metabolic, neuroendocrine, inflammatory, oxidative stress and cardiac biomarkers, and daily rhythms of behavior for such population. Participants will apply 10-h TRE over a 12-week monitored intervention followed by a 12-week self-directed intervention. Changes in eating window, body weight and composition, biomarkers, and rhythms of behavior will be evaluated. Dietary intake, sleep, activity and wellbeing will be monitored with the myCircadianClock application and questionnaires. Adherence to TRE defined as the proportion of days recorded with app during the monitored intervention in which participants satisfied 10-h TRE is the primary outcome. TREMNIOS will also provide an exploratory framework to depict post-TRE changes in cardiometabolic outcomes and behavior rhythms. This protocol extends previous TRE-related protocols by targeting European population with diagnosed MetS and including long-term intervention, validated tools for monitoring dietary intake and adherence, and comprehensive range of biomarkers. TREMNIOS trial will lay the groundwork for a large-scale randomized controlled trial to determine TRE efficacy for improving cardiometabolic health in MetS population.
Cardiometabolic diseases (CMDs), including cardiovascular disease (CVD), metabolic syndrome (MetS), and type 2 diabetes (T2D), are associated with increased morbidity and mortality. The growing prevalence of CVD is mostly attributed to the aging population and common occurrence of risk factors, such as high systolic blood pressure, elevated plasma glucose, and increased body mass index, which led to a global epidemic of obesity, MetS, and T2D. Oxidant–antioxidant balance disorders largely contribute to the pathogenesis and outcomes of CMDs, such as systemic essential hypertension, coronary artery disease, stroke, and MetS. Enhanced and disturbed generation of reactive oxygen species in excess adipose tissue during obesity may lead to increased oxidative stress. Understanding the interplay between adiposity, oxidative stress, and cardiometabolic risks can have translational impacts, leading to the identification of novel effective strategies for reducing the CMDs burden. The present review article is based on extant results from basic and clinical studies and specifically addresses the various aspects associated with oxidant–antioxidant balance disorders in the course of CMDs in subjects with excess adipose tissue accumulation. We aim at giving a comprehensive overview of existing knowledge, knowledge gaps, and future perspectives for further basic and clinical research. We provide insights into both the mechanisms and clinical implications of effects related to the interplay between adiposity and oxidative stress for treating and preventing CMDs. Future basic research and clinical trials are needed to further examine the mechanisms of adiposity-enhanced oxidative stress in CMDs and the efficacy of antioxidant therapies for reducing risk and improving outcome of patients with CMDs.
The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds.
Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell membranes. Vitamin K reduces the level of reactive oxygen species by modulating the expression of antioxidant enzymes. Additionally, vitamin K decreases inflammation and potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) is associated with oxidant–antioxidant imbalance. Studies have shown that intensified ferroptosis occurs in various tissues and cells affected by COVID-19. Vitamin K supplementation during SARS-CoV-2 infection may have a positive effect on reducing the severity of the disease. Preliminary research suggests that vitamin K may reduce lipid peroxidation and inhibit ferroptosis, potentially contributing to its therapeutic effects in COVID-19 patients. The links between ferroptosis, vitamin K, and SARS-CoV-2 infection require further investigation, particularly in the context of developing potential treatment strategies for COVID-19.
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