Effects of hypothermia and hypoxia on cytochrome P450-mediated drug metabolism in neonatal Göttingen minipigs.

Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. As perinatal asphyxia and TH impact neonatal physiology, this could also influence enzyme functionality. Therefore, this study aimed to unravel the impact of age, hypothermia and hypoxia on porcine hepatic cytochrome P450 (CYP) gene expression, protein abundance and activity.

Drug Disposition in Neonatal Göttingen Minipigs: Exploring Effects of Perinatal Asphyxia and Therapeutic Hypothermia.

Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. Since both perinatal asphyxia (PA) and TH influence physiology, altered pharmacokinetics (PK) and pharmacodynamics (PD) are expected. Given that TH is the standard of care for PA with moderate to severe hypoxic-ischemic encephalopathy, disentangling the effect of PA versus TH on PK/PD is not possible in clinical settings.

GprC of the nematode-trapping fungus Arthrobotrys flagrans activates mitochondria and reprograms fungal cells for nematode hunting.

Initiation of development requires differential gene expression and metabolic adaptations. Here we show in the nematode-trapping fungus, Arthrobotrys flagrans, that both are achieved through a dual-function G-protein-coupled receptor (GPCR). A.

The Antioxidant and Hepatoprotective Potential of Berberine and Silymarin on Acetaminophen Induced Toxicity in L.

Berberine (BBR) and silymarin (SM) are natural compounds extracted from plants known for their antioxidant and chemoprotective effects on the liver. The present study aimed to investigate the beneficial properties of BBR and SM and the association of BBR with SM on liver function using fish as "in vivo" models. Moreover, the study investigated their hepatoprotective role after acetaminophen (APAP) exposure.

Complexity of fungal polyketide biosynthesis and function.

Where does one draw the line between primary and secondary metabolism? The answer depends on the perspective. Microbial secondary metabolites (SMs) were at first believed not to be very important for the producers because they are dispensable for growth under laboratory conditions. However, such compounds become important in natural niches of the organisms, and some are of prime importance for humanity.

Pharmacokinetics during therapeutic hypothermia in neonates: from pathophysiology to translational knowledge and physiologically-based pharmacokinetic (PBPK) modeling.

Introduction: Perinatal asphyxia (PA) still causes significant morbidity and mortality. Therapeutic hypothermia (TH) is the only effective therapy for neonates with moderate to severe hypoxic-ischemic encephalopathy after PA. These neonates need additional pharmacotherapy, and both PA and TH may impact physiology and, consequently, pharmacokinetics (PK) and pharmacodynamics (PD).

Streptomyces polyketides mediate bacteria-fungi interactions across soil environments.

Although the interaction between prokaryotic and eukaryotic microorganisms is crucial for the functioning of ecosystems, information about the processes driving microbial interactions within communities remains scarce. Here we show that arginine-derived polyketides (arginoketides) produced by Streptomyces species mediate cross-kingdom microbial interactions with fungi of the genera Aspergillus and Penicillium, and trigger the production of natural products. Arginoketides can be cyclic or linear, and a prominent example is azalomycin F produced by Streptomyces iranensis, which induces the cryptic orsellinic acid gene cluster in Aspergillus nidulans.

Development of a neonatal Göttingen Minipig model for dose precision in perinatal asphyxia: technical opportunities, challenges, and potential further steps.

Animal models provide useful information on mechanisms in human disease conditions, but also on exploring (patho)physiological factors affecting pharmacokinetics, safety, and efficacy of drugs in development. Also, in pediatric patients, nonclinical data can be critical for better understanding the disease conditions and developing new drug therapies in this age category. For perinatal asphyxia (PA), a condition defined by oxygen deprivation in the perinatal period and possibly resulting in hypoxic ischemic encephalopathy (HIE) or even death, therapeutic hypothermia (TH) together with symptomatic drug therapy, is the standard approach to reduce death and permanent brain damage in these patients.

Optical and Structural Properties of Composites Based on Poly(urethane) and TiO Nanowires.

This article's objective is the synthesis of new composites based on thermoplastic polyurethane (TPU) and TiO nanowires (NWs) as free-standing films, highlighting their structural and optical properties. The free-standing TPU-TiO NW films were prepared by a wet chemical method accompanied by a thermal treatment at 100 °C for 1 h, followed by air-drying for 2 h. X-ray diffraction (XRD) studies indicated that the starting commercial TiO NW sample contains TiO tetragonal anatase (A), cubic TiO (C), and orthorhombic TiO (OR), as well as monoclinic HTiO (M).

The Photoluminescence and Vibrational Properties of Black Phosphorous Sheets Chemically/Electrochemically Functionalized in the Presence of Diphenylamine.

In this work, new information concerning the optical properties of black phosphorus (BP) sheets chemically/electrochemically functionalized with diphenyl amine (DPA) and its macromolecular compound (poly(diphenylamine) (PDPA)) in the absence/presence of phosphotungstic acid (PTA) is reported. Raman scattering and FTIR spectroscopy studies indicate that the interaction of BP with PTA leads to the elimination of the PO layer onto the surface of the BP sheets. In the case of the chemical interaction of BP with DPA, the reaction product corresponds to DPA chemically functionalized BP sheets having an imino-phosphorane (IP) structure.

Bacterial marginolactones trigger formation of algal gloeocapsoids, protective aggregates on the verge of multicellularity.

Photosynthetic microorganisms including the green alga are essential to terrestrial habitats as they start the carbon cycle by conversion of CO to energy-rich organic carbohydrates. Terrestrial habitats are densely populated, and hence, microbial interactions mediated by natural products are inevitable. We previously discovered such an interaction between releasing the marginolactone azalomycin F in the presence of Whether the alga senses and reacts to azalomycin F remained unknown.

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only target the electrical abnormalities and not the underlying atrial myopathy. For the development of novel therapies, a reproducible large animal model of atrial myopathy is necessary.

Metabolome Database for Mass Spectrometry Metabolomics.

The Metabolome Database is a free online resource to perform metabolite annotation in mass spectrometry studies devoted to the genus . The database was created by retrieving and curating information on 2811 compounds present in 601 different species and subspecies of the genus . A total of 1514 scientific journals where these metabolites are mentioned were added as meta-information linked to their respective compounds in the database.

Poly(Vinyl Chloride) Spheres Coated with Graphene Oxide Sheets: From Synthesis to Optical Properties and Their Applications as Flame-Retardant Agents.

A new method to obtain poly(vinyl chloride) (PVC) spheres, which consists of an interaction between commercial PVC grains and hexyl ethyl cellulose and lauroyl peroxide at a temperature of 60 °C, is reported. The addition of the graphene oxide (GO) sheets dispersed in dimethylformamide to the reaction mixture leads to the generation of composites made of PVC spheres coated with GO sheets. Scanning electron microscopy studies have demonstrated that this method allows for the transformation of PVC grains with sizes between 75 and 227 μm into spheres with sizes varying from 0.

Optical, Structural, and Dielectric Properties of Composites Based on Thermoplastic Polymers of the Polyolefin and Polyurethane Type and BaTiO Nanoparticles.

In this work, new films containing composite materials based on blends of thermoplastic polymers of the polyurethane (TPU) and polyolefin (TPO) type, in the absence and presence of BaTiO nanoparticles (NPs) with the size smaller 100 nm, were prepared. The vibrational properties of the free films depending on the weight ratio of the two thermoplastic polymers were studied. Our results demonstrate that these films are optically active, with strong, broad, and adjustable photoluminescence by varying the amount of TPU.

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development.

Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point.

Reduced Graphene Oxide Sheets as Inhibitors of the Photochemical Reactions of α-Lipoic Acid in the Presence of Ag and Au Nanoparticles.

The influence of Ag and Au nanoparticles and reduced graphene oxide (RGO) sheets on the photodegradation of α-lipoic acid (ALA) was determined by UV-VIS spectroscopy. The ALA photodegradation was explained by considering the affinity of thiol groups for the metallic nanoparticles synthesized in the presence of trisodium citrate. The presence of excipients did not induce further changes when ALA interacts with Ag and Au nanoparticles with sizes of 5 and 10 nm by exposure to UV light.

The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in .

In order for eukaryotes to efficiently detect and respond to environmental stimuli, a myriad of protein signaling pathways are utilized. An example of highly conserved signaling pathways in eukaryotes are the mitogen-activated protein kinase (MAPK) pathways. In fungi, MAPK pathways have been shown to regulate a diverse array of biological processes, such as asexual and sexual development, stress responses and the production of secondary metabolites (SMs).

Optical Properties of Composites Based on Graphene Oxide and Polystyrene.

In this work, new optical properties of composites based on polystyrene (PS) microspheres and graphene oxide (GO) are reported. The radical polymerization of styrene in the presence of benzoyl peroxide, pentane and GO induces the appearance of new ester groups in the PS macromolecular chains remarked through an increase in the absorbance of the infrared (IR) band at 1743 cm. The decrease in the GO concentration in the PS/GO composites mass from 5 wt.

Human Neutrophils Produce Antifungal Extracellular Vesicles against Aspergillus fumigatus.

Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored.

Targeted induction of a silent fungal gene cluster encoding the bacteria-specific germination inhibitor fumigermin.

Microorganisms produce numerous secondary metabolites (SMs) with various biological activities. Many of their encoding gene clusters are silent under standard laboratory conditions because for their activation they need the ecological context, such as the presence of other microorganisms. The true ecological function of most SMs remains obscure, but understanding of both the activation of silent gene clusters and the ecological function of the produced compounds is of importance to reveal functional interactions in microbiomes.

Redox Proteomic Analysis Reveals Oxidative Modifications of Proteins by Increased Levels of Intracellular Reactive Oxygen Species during Hypoxia Adaptation of Aspergillus fumigatus.

Aspergillus fumigatus faces abrupt changes in oxygen concentrations at the site of infection. An increasing number of studies has demonstrated that elevated production of intracellular reactive oxygen species (ROS) under low oxygen conditions plays a regulatory role in modulating cellular responses for adaptation to hypoxia. To learn more about this process in A.

Chromatin mapping identifies BasR, a key regulator of bacteria-triggered production of fungal secondary metabolites.

The eukaryotic epigenetic machinery can be modified by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. We discovered that the bacterium triggered increased chromatin acetylation and thus activation of the silent secondary metabolism gene cluster in the fungus . Using this model, we aim understanding mechanisms of microbial communication based on bacteria-triggered chromatin modification.

Aspf2 From Recruits Human Immune Regulators for Immune Evasion and Cell Damage.

The opportunistic fungal pathogen can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first Factor H-binding protein.

Facile assembly and fluorescence-based screening method for heterologous expression of biosynthetic pathways in fungi.

Heterologous expression of multi-gene biosynthetic pathways in eukaryotic hosts is limited by highly regulated individual monocistrons. Dissimilar to prokaryotes, each eukaryotic gene is strictly controlled by its own regulatory elements, such as promoter and terminator. Consequently, parallel transcription can occur only when a group of genes is synchronously activated.