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Drugs in Context 2024Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and... (Review)
Review
BACKGROUND
Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children.
METHODS
A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics.
RESULTS
and spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. is the principal spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins.
CONCLUSIONS
Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
PubMed: 38915918
DOI: 10.7573/dic.2023-9-2 -
Unveiling the potential of Pseudococcomyxa simplex: a stepwise extraction for cosmetic applications.Applied Microbiology and Biotechnology Jun 2024Microalgae are gaining attention as they are considered green fabrics able to synthesize many bioactive metabolites, with unique biological activities. However, their...
Microalgae are gaining attention as they are considered green fabrics able to synthesize many bioactive metabolites, with unique biological activities. However, their use at an industrial scale is still a challenge because of the high costs related to upstream and downstream processes. Here, a biorefinery approach was proposed, starting from the biomass of the green microalga Pseudococcomyxa simplex for the extraction of two classes of molecules with a potential use in the cosmetic industry. Carotenoids were extracted first by an ultrasound-assisted extraction, and then, from the residual biomass, lipids were obtained by a conventional extraction. The chemical characterization of the ethanol extract indicated lutein, a biosynthetic derivative of α-carotene, as the most abundant carotenoid. The extract was found to be fully biocompatible on a cell-based model, active as antioxidant and with an in vitro anti-aging property. In particular, the lutein-enriched fraction was able to activate Nrf2 pathway, which plays a key role also in aging process. Finally, lipids were isolated from the residual biomass and the isolated fatty acids fraction was composed by palmitic and stearic acids. These molecules, fully biocompatible, can find application as emulsifiers and softener agents in cosmetic formulations. Thus, an untapped microalgal species can represent a sustainable source for cosmeceutical formulations. KEY POINTS: • Pseudococcomyxa simplex has been explored in a cascade approach. • Lutein is the main extracted carotenoid and has antioxidant and anti-aging activity. • Fatty acids are mainly composed of palmitic and stearic acids.
Topics: Microalgae; Cosmetics; Carotenoids; Biomass; Antioxidants; Lutein; Humans; Fatty Acids
PubMed: 38910175
DOI: 10.1007/s00253-024-13229-9 -
Stem Cell Research & Therapy Jun 2024Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other...
BACKGROUND
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart.
METHODS
CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel.
RESULTS
In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA.
CONCLUSION
By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.
Topics: Humans; Tretinoin; Myocytes, Cardiac; Cell Differentiation; Induced Pluripotent Stem Cells; Heart Ventricles; Myosin Heavy Chains; Cardiac Myosins; Tissue Engineering; Homeobox Protein Nkx-2.5; T-Box Domain Proteins
PubMed: 38902843
DOI: 10.1186/s13287-024-03741-0 -
Acta Dermato-venereologica Jun 2024
Topics: Isotretinoin; Humans; Dermatologic Agents; Treatment Outcome; Male; Female; Adult
PubMed: 38899441
DOI: 10.2340/actadv.v104.40101 -
The ISME Journal Jun 2024The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities....
The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities. Currently, there is little knowledge on the nature and the function of the different metabolites released by rhizospheric microbes to facilitate colonization of this highly competitive environment. Here, we demonstrate how the production of galbonolides, a group of polyene macrolides that inhibit plant and fungal inositol phosphorylceramide synthase (IPCS), empowers the rhizospheric Streptomyces strain AgN23, to thrive in the rhizosphere by triggering the plant's defence mechanisms. Metabolomic analysis of AgN23-inoculated Arabidopsis roots revealed a strong induction in the production of an indole alkaloid, camalexin, which is a major phytoalexin in Arabidopsis. By using a plant mutant compromized in camalexin synthesis, we show that camalexin production is necessary for the successful colonization of the rhizosphere by AgN23. Conversely, hindering galbonolides biosynthesis in AgN23 knock-out mutant resulted in loss of inhibition of IPCS, a deficiency in plant defence activation, notably the production of camalexin, and a strongly reduced development of the mutant bacteria in the rhizosphere. Together, our results identified galbonolides as important metabolites mediating rhizosphere colonization by Streptomyces.
PubMed: 38896026
DOI: 10.1093/ismejo/wrae112 -
International Journal of Nanomedicine 2024To improve the bioavailability of resveratrol (-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier,...
INTRODUCTION
To improve the bioavailability of resveratrol (-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.
METHODS
A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in -Res release.
RESULTS
Under protection of Ngel, Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of Res in the intestine. Ngel and Ngel@Res increased the lifespan of to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of and , while downregulating the expression of and .
CONCLUSION
This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of Res.
Topics: Animals; Caenorhabditis elegans; Resveratrol; Reactive Oxygen Species; Alginates; Nanogels; Antioxidants; Polyethylene Glycols; Polyethyleneimine; Free Radical Scavengers; Intestinal Mucosa; Drug Carriers
PubMed: 38895150
DOI: 10.2147/IJN.S464849 -
Molecules (Basel, Switzerland) May 2024Yerba Mate drink made from dried and crushed leaves and twigs of Paraguayan holly ( A. St.-Hil.), which is a valuable source of bioactive substances, in particular...
Yerba Mate drink made from dried and crushed leaves and twigs of Paraguayan holly ( A. St.-Hil.), which is a valuable source of bioactive substances, in particular antioxidants. The available literature lacks data on changes in the content and profile of bioactive compounds such as tannins, caffeine, the phenolic acid profile of flavonoids and carotenoids, as well as total polyphenol content and antioxidant activity in Yerba Mate infusions depending on different brewing conditions, and how different brewing conditions affect the physicochemical properties of these infusions. Therefore, this study evaluated the physicochemical properties of dried and Yerba Mate infusions prepared via single and double brewing processes at 70 °C and 100 °C. The organoleptic evaluation, as well as the instrumental color measurement, showed significant changes in the total color difference (Δ) and the *** chromatic coordinates of dried Yerba Mate samples and their infusions. Moreover, the research showed higher contents of tannins (mean 1.36 ± 0.14 g/100 g d.m.), caffeine (mean 17.79 ± 3.49 mg/g d.m.), carotenoids (mean 12.90 ± 0.44 μg/g d.m.), phenolic acids (mean 69.97 ± 7.10 mg/g d.m.), flavonoids (mean 5.47 ± 1.78 mg/g d.m.), total polyphenols (mean 55.26 ± 8.51 mg GAE/g d.m.), and antioxidant activity (mean 2031.98 ± 146.47 μM TEAC/g d.m.) in single-brewed Yerba Mate infusions compared to double-brewed (0.77 ± 0.12 g/100 g d.m., 14.28 ± 5.80 mg/g d.m., 12.67 ± 0.62 μg/g d.m., 57.75 ± 8.73 mg/g d.m., 3.64 ± 0.76 mg/g d.m., 33.44 ± 6.48 mg GAE/g d.m. and 1683.09 ± 155.34 μM TEAC/g d.m., respectively). In addition, infusions prepared at a lower temperature (70 °C) were characterized by a higher content of total polyphenols and higher antioxidant activity, in contrast to the tannin and carotenoid contents, the levels of which were higher at 100 °C than at 70 °C. Considering the high amount of bioactive ingredients, in particular antioxidants, and a wide range of health benefits, it is worth including Yerba Mate in the daily diet.
Topics: Ilex paraguariensis; Antioxidants; Polyphenols; Tannins; Flavonoids; Carotenoids; Plant Extracts; Plant Leaves; Caffeine; Hydroxybenzoates; Beverages
PubMed: 38893465
DOI: 10.3390/molecules29112590 -
Molecules (Basel, Switzerland) May 2024This study investigates the process of long-term (bio)degradation of polyethylene (PE) in an old municipal waste landfill (MWL) and its implications for environmental...
This study investigates the process of long-term (bio)degradation of polyethylene (PE) in an old municipal waste landfill (MWL) and its implications for environmental and human health. Advanced techniques, such as ICP-ES/MS and IC-LC, were used to analyze heavy metals and anions/cations, demonstrating significant concentration deviations from control samples. The soil's chemical composition revealed numerous hazardous organic compounds, further indicating the migration of additives from PE to the soil. Toxicological assessments, including Phytotoxkit F, Microtox bioassay, and Ostracodtoxkit, demonstrated phytotoxicity, acute toxicity, and high mortality in living organisms (over 85% for ). An unusual concentration of contaminants in the MWL's middle layers, linked to Poland's economic changes during the 1980s and 1990s, suggests increased risks of pollutant migration, posing additional environmental and health threats. Moreover, the infiltration capability of microorganisms, including pathogens, into PE structures raises concerns about potential groundwater contamination through the landfill bottom. This research underscores the need for vigilant management and updated strategies to protect the environment and public health, particularly in older landfill sites.
Topics: Polyethylene; Waste Disposal Facilities; Humans; Soil Pollutants; Environmental Monitoring; Biodegradation, Environmental; Metals, Heavy; Soil
PubMed: 38893375
DOI: 10.3390/molecules29112499 -
Molecules (Basel, Switzerland) May 2024Six ionone glycosides (- and -), including three new ones, named capitsesqsides A-C (-), together with an eudesmane sesquiterpenoid glycoside () and three known...
Six ionone glycosides (- and -), including three new ones, named capitsesqsides A-C (-), together with an eudesmane sesquiterpenoid glycoside () and three known triterpenoid saponins (-) were isolated from . The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that has a favorable affinity for NLRP3 and iNOS.
Topics: Rhododendron; Mice; Glycosides; RAW 264.7 Cells; Animals; Molecular Docking Simulation; Anti-Inflammatory Agents; Norisoprenoids; Molecular Structure; Nitric Oxide Synthase Type II; Lipopolysaccharides; Plant Extracts
PubMed: 38893339
DOI: 10.3390/molecules29112462 -
Nutrients Jun 2024: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.
: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. : In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. : Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory ( = 0.037), but not for working memory ( = 0.418) or verbal learning ( = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire ( = 0.022), increased plasma brain-derived neurotrophic factor ( = 0.030), decreased plasma malondialdehyde ( = 0.040), and increased skin carotenoid concentrations ( = 0.006). However, there were no group differences in changes in the remaining outcome measures. : Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.
Topics: Humans; Dietary Supplements; Middle Aged; Double-Blind Method; Male; Female; Cognition; Adult; Aged; Brain-Derived Neurotrophic Factor; Vitamin E; Xanthophylls; Skin; Antioxidants; Interleukin-6; Self Report; Carotenoids; Tumor Necrosis Factor-alpha; Memory, Short-Term; Memory, Episodic; Fruit and Vegetable Juices; Malondialdehyde; Eye
PubMed: 38892705
DOI: 10.3390/nu16111770