Search Results (132)

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic variations in the ABCB11 (ATP-binding cassette B11) gene encoding the canalicular bile salt export pump (BSEP). Some missense variants identified in patients with PFIC2 do not traffic properly to the canalicular membrane. However, 4-phenybutyrate (4-PB) has been shown in vitro to partially correct the mis-trafficking of selected variants, resulting in an improvement of the medical conditions of corresponding PFIC2 patients. Herein, we report the ability of 4-PB analogous or homologous drugs and of non-4-PB related chemical correctors to rescue the canalicular expression and the activity of the folding-defective Abcb11^R1128C variant. New compounds, either identified by screening a chemical library or designed by structural homology with 4-PB (or its metabolites) and synthesized, were evaluated in vitro for their ability to (i) correct the canalicular localization of Abcb11^R1128C after transfection in hepatocellular polarized cell lines; (ii) restore the ³H-taurocholate transport of the Abcb11^R1128C protein in Madin–Darby canine kidney (MDCK) cells stably co-expressing Abcb11 and the sodium taurocholate co-transporting polypeptide (Ntcp/Slc10A1). Glycerol phenylbutyrate (GPB), phenylacetate (PA, the active metabolite of 4-PB), 3-hydroxy-2-methyl-4-phenylbutyrate (HMPB, a 4-PB metabolite analog chemically synthesized in our laboratory) and 4-oxo-1,2,3,4-tetrahydro-naphthalene-carboxylate (OTNC, from the chemical library screening) significantly increased the proportion of canalicular Abcb11^R1128C protein. GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11^R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter’s traffic. Full article

Background: Diclofenac is a phenylacetic acid derivative classified as a non-selective COX inhibitor. Similar to other NSAIDs, it is characterized by anti-inflammatory, antipyretic, and analgesic effects. Long-term therapy with diclofenac might also lead to severe gastrointestinal, renal, or cardiovascular systems disorders. Aim of the study was to compare own formulation prepared from pharmaceutical raw materials with ready-to-use diclofenac product. Methods: In the in vitro permeation experiments, human skin was excised from the abdomen of living patients as a result of plastic surgery. The transdermal semi-solid formulations were compounded using Pentravan^®, a ready-to-use transdermal base and hydrophilic gel base (Celugel). In vitro Penetration Studies, HPLC analysis, optical microscopy imaging, and a spreadability test were conducted. Rheological analysis provided insights into flow behavior, structure, and thixotropy. Results: Combination of Celugel with diclofenac sodium and the addition of substances acting as absorption enhancers, e.g., menthol, may provide an interesting alternative for enteral drugs, especially in patients with multimorbidity and polypharmacy. Conclusions: Topical diclofenac sodium with of addition of permeation enhancers like menthol might provide higher drug concentrations in the surrounding tissues and better analgesic and anti-inflammatory effects in compare to commercially available product and may provide optimum effectiveness with minimal risk of adverse effects, particularly in elderly and polymedicated patients. Full article

Microbial communities in wastewater treatment plants (WWTPs) play a crucial role in the decontamination of polluted water. An uncultured order-level lineage AKYH767 of the phylum Bacteroidota has been consistently detected in microbial consortia of activated sludge at WWTPs worldwide, but its functional role remains elusive. Representatives of AKYH767 were also detected in soils and freshwater bodies, which may be their natural reservoirs. Here, we obtained ten high-quality metagenome-assembled genomes, including one closed circular genome, of AKYH767 bacteria from metagenomes of the wastewater and activated sludge and used genomic data to uncover the metabolic potential of these bacteria and to predict their functional role. The cells of the AKYH767 bacteria were inferred to be rod-shaped and non-motile. Genome-based metabolic reconstruction predicted the Embden–Meyerhof pathway, the non-oxidative stage of the pentose phosphate pathway, and the complete tricarboxylic acid cycle. A facultatively anaerobic chemoheterotrophic lifestyle with the capacity to oxidize low organic substrates through aerobic respiration was suggested. Under anaerobic conditions AKYH767 bacteria can perform different steps of denitrification. They have limited capacities to hydrolyze carbohydrates and proteinaceous substrates but can utilize fatty acids. A peculiar property of AKYH767 bacteria is the presence of the phenylacetyl-CoA pathway for the utilization of phenylacetate, and about half of the genomes encoded the benzoate degradation pathway. Apparently, in bioreactors at WWTPs, the AKYH767 bacteria could be involved in the denitrification and biodegradation of aromatic compounds. Based on phylogenetic and genomic analyses, the novel AKYH767 bacterium is proposed to be classified as Candidatus Pollutiaquabacter aromativorans, within the candidate order Pollutiaquabacterales. Full article

Plant-derived biopesticides are emerging as a promising and popular alternative for promoting cleaner and safer agricultural practices. The present work aims to explore Argyranthemum frutescens (Asteraceae) as a source of botanical pesticides and to validate this through a cultivation process. To this task, a bioassay-guided fractionation of the ethanolic root extracts from both wild and cultivated A. frutescens on phytopathogenic fungi of Botrytis cinerea, Fusarium oxysporum, and Alternaria alternata was conducted. This approach led to the identification of polyacetylenes with higher potency than commercial fungicides. Specifically, compounds 3 (capillin) and 5 (frutescinone) showed more than 90% growth inhibition at 0.05 mg/mL concentration on B. cinerea, while compounds 2 (capillinol) and 3 were also more active than positive controls, Fosbel-Plus and Azoxystrobin, against F. oxysporum. The structures of the isolated polyacetylenes (1–6, 9, and 10) and alkamides (7, 8, and 11) were determined through spectroscopic analysis, and the absolute configuration of stereocenter C1 of compounds 1, 2, 4 and 9 was determined by NMR-spectroscopy with (R)-(-)-α-methoxy-phenylacetic as a chiral derivatizing agent, and biogenetic considerations. Overall, this study supports the potential of polyacetylenes as promising agrochemical lead compounds against phytopathogens, and validates A. frutescens cultivation as a viable source of biopesticides. Full article

Microwave-assisted synthesis was applied to obtain fifteen hydrazide-hydrazones of phenylacetic acid. The chemical structure of the synthesized compounds was confirmed on the basis of the analysis of the IR, ¹H NMR and ¹³C NMR spectra. Experimental logP values for all obtained acylhydrazones were established with the use of chromatographic methods. The synthesized compounds were tested for potential antimicrobial activity in in vitro conditions against a panel of microorganisms, which included eight strains of Gram-positive bacteria and six strains of Gram-negative bacteria as well as six strains of yeasts belonging to Candida spp. The assays we performed revealed significant antibacterial activity of obtained hydrazide-hydrazones of phenylacetic acid. Some of the tested compounds possessed much higher activity than that of reference antimicrobial agents towards Gram-positive bacterial strains. It is also worth mentioning that some of synthesized compounds possessed significant activity towards MRSA strain—methicillin-resistant Staphylococcus aureus ATCC 43300 and MSSA strain—methicillin susceptible Staphylococcus aureus ATCC 6538 and ATCC 29213. Full article

The mechanism of egg yolk phosphatidylcholine (PC) in alleviating Alzheimer’s disease (AD) has not yet been clear. The fatty acid composition of PC, especially the ratio of polyunsaturated fatty acids (PUFA), may be a critical determinant of their structural and functional roles. This study aimed to conduct a comparative analysis of the unsaturation levels of egg yolk PC and their impact on neurological health in a murine model of AD. The results showed that oral administration of high and low unsaturation PC (HUP, LUP) enhanced learning and memory abilities in AD mice, with the HUP intervention demonstrating superior efficacy compared to the LUP. Follow-up biochemical analysis of the brain tissue also suggested that HUP intervention effectively mitigated oxidative-stress damage and inhibited tau hyperphosphorylation in AD mice. Meanwhile, lipidomic analyses of the mouse hippocampus revealed that HUP intervention substantially increased the levels of phospholipids, such as PEt (phosphatidylethanol) and BisMePA (bis(methylthio)phenylacetic acid), which are recognized as vital components of neuronal cell membranes. Furthermore, HUP intervention markedly elevated the levels of phospholipids incorporating PUFAs in the hippocampus. These results revealed a mitigating role for unsaturated egg yolk PC in AD prevention and offer new insights into AD prevention from a lipidomic perspective. Full article

Bioremediation induced by bacteria offers a promising alternative for the contamination of aromatic hydrocarbons due to their metabolic processes suitable for the removal of these pollutants, as many of them are carcinogenic molecules and dangerous to human health. Our research focused on isolating a bacterium from the rhizosphere of the tara tree with the ability to degrade polycyclic aromatic hydrocarbons, using draft genomic sequencing and computational analysis. Enterobacter sp. strain UNJFSC 003 possesses 4460 protein-coding genes, two rRNA genes, 77 tRNA genes, and a GC content of 54.38%. A taxonomic analysis of our strain revealed that it has an average nucleotide identity (ANI) of 87.8%, indicating that it is a new native Enterobacteria. Additionally, a pangenomic analysis with 15 strains demonstrated that our strain has a phylogenetic relationship with strain FDAARGOS 1428 (Enterobacter cancerogenus), with a total of 381 core genes and 4778 accessory genes. Orthologous methods predicted that strain UNJFSC 003 possesses genes with potential for use in hydrocarbon bioremediation. Genes were predicted in the sub-pathways for the degradation of homoprotocatechuate and phenylacetate, primarily located in the cytoplasm. Studies conducted through molecular modeling and docking revealed the affinity of the predicted proteins in the degradation of benzo[a]pyrene in the homoprotocatechuate sub-pathway, specifically hpcB, which has enzymatic activity as a dioxygenase, and hpcC, which functions as an aldehyde dehydrogenase. This study provides information on native strains from Lomas de Lachay with capabilities for the bioremediation of aromatic hydrocarbons and other compounds. Full article

This study investigates the impact of key factors on the formation of odorants and sensory properties in mead. The effects of the honey type (acacia, buckwheat, linden), wort heating, and the fermentation method (commercial Saccharomyces cerevisiae yeasts, spontaneous fermentation, Galactomyces geotrichum molds) were examined. Twelve model mead batches were produced, matured for 12 months, and analyzed using gas chromatography–olfactometry (GC–O) and headspace SPME-GC/MS to identify odor-active compounds. Results confirmed that the honey type plays a significant role in sensory profiles, with distinct aroma clusters for buckwheat, acacia, and linden honey. Compounds like phenylacetic acid, 2- and 3-methylbutanal, and butanoic acid were identified as the most important odorants, correlating with sensory attributes such as honey-like, malty, and fermented aromas. Univariate and multivariate analyses, followed by correlation analysis, highlighted how production parameters affect mead aroma, providing insights to optimize sensory quality. Full article

Root-knot nematodes (RKNs) are pathogens that endanger a wide range of crops and cause serious global agricultural losses. In this study, we investigated metabolites of the endoparasitic fungus Harposporium anguillulae YMF1.01751, with the expectation of discovering valuable Meloidogyne incognita biocontrol compounds. Based on results obtained by a liquid chromatograph coupled to a mass spectrometer (LC-MS) of crude extracts under five culture conditions and their nematicidal activity against M. incognita, corn meal agar (CMA) medium was determined as the scale-up fermentation medium. Twelve metabolites (1–12) were isolated from the fermentation products, and compound 1 was identified to be a new cyclic tetrapeptide. The activity assay results showed that phenylacetic acid (11) had good nematicidal activity at 400 μg/mL, and the mortalities of M. incognita were 89.76% and 96.05% at 12 and 24 h, respectively, while the mortality of canthin-6-one (2) against M. incognita was 44.26% at 72 h. In addition, the results of chemotaxis activity showed that 1-(1H-indol-3-yl)ethanone (10) possessed attraction activity towards M. incognita. At the tested concentrations, cyclo-(Arg-Pro) (4) and cyclo-(Val-Ile) (7) showed an avoidant response to M. incognita. This study provides insight into the nematode-active compounds of H. anguillulae origin and offers new opportunities for the development of RKN biocontrol products. Full article

Background: Glyoxal has been implicated as a significant contributor to the formation of secondary organic aerosols, which play a key role in our ability to estimate the impact of aerosols on climate. Elevated concentrations of glyoxal over open ocean waters suggest that there exists an additional source, different from urban and forest environments, which has yet to be identified. Methods: Based on mass spectrometric analyses of nascent sea spray aerosols (SSAs) and gas-phase molecules generated during the course of a controlled algal bloom, the work herein suggests that marine microorganisms are capable of excreting toluene in response to environmental stimuli. Additional culture flask experiments demonstrated that pathogenic attack could also serve as a trigger for toluene formation. Using solid-phase microextraction methods, the comparison of samples collected up-channel and over the breaking wave suggests it was transferred across the air–water interface primarily through SSA formation. Results: The presence and then absence of phenylacetic acid in the SSA days prior to the appearance of toluene support previous reports that proposed toluene is produced as a metabolite of phenylalanine through the Shikimate pathway. As a result, once in the atmosphere, toluene is susceptible to oxidation and subsequent degradation into glyoxal. Conclusions: This work adds to a minimal collection of literature that addresses the primary production of aromatic hydrocarbons from marine microorganisms and provides a potential missing source of glyoxal that should be considered when accounting for its origins in remote ocean regions. Full article

The valorization of coffee cherry waste through hydrothermal carbonization (HTC) was investigated using various organic and inorganic acid catalysts to produce platform chemicals. This study aimed to evaluate the effectiveness of these catalysts for enhancing reaction rates, improving yields, and promoting selectivity. The results showed that sulfuric acid and adipic acid were the most effective, each resulting in a 20% increase in the total yield, demonstrating the potential of organic acids as efficient catalysts in HTC. Other catalysts, such as benzoic acid and phenylacetic acid, also showed promising results, while butyric acid significantly decreased the total yield. The most abundantly produced platform chemicals were sugars, followed by formic acid, levulinic acid, HMF, and furfural. These findings highlight the potential of coffee cherry waste as a valuable resource for producing key chemicals, and the feasibility of hydrothermal carbonization as a sustainable approach for biomass valorization. This study emphasizes the importance of selecting the appropriate catalysts to optimize the conversion process and maximize the extraction of valuable chemicals. The environmental and economic implications of these findings are significant, as they can contribute to the development of sustainable and efficient biomass utilization technologies that could transform agricultural waste into high-value products while reducing waste and promoting a circular economy. Full article

Background/objective: Approximately one-third of pregnant individuals in the U.S. are affected by obesity, which can adversely impact the in utero environment and offspring. This study aimed to investigate the differences in urine metabolomics between children exposed and unexposed to maternal obesity. Methods: In a study nested within a larger pregnancy cohort of women–offspring pairs, we measured untargeted metabolomics using liquid chromatography–mass spectrometry in urine samples from 68 children at 4–8 years of age. We compared metabolite levels between offspring exposed to maternal obesity (body mass index [BMI] ≥ 30.0 kg/m²) vs. unexposed (maternal BMI 18.5–24.9 kg/m²) and matched them on covariates, using two-sample t-tests, with additional sensitivity analyses based on children’s BMI. This study reports statistically significant results (p ≤ 0.05) and potentially noteworthy findings (fold change > 1 or 0.05 < p < 0.15), considering compounds’ involvement in common pathways or similar biochemical families. Results: The mean (SD) maternal age at study enrollment was 28.0 (6.3) years, the mean child age was 6.6 (0.8) years, 56% of children were male, and 38% of children had a BMI in the overweight/obese range (BMI ≥ 85th percentile). Children exposed to maternal obesity had lower levels of 5-hydroxyindole sulfate and 7-hydroxyindole sulfate and higher levels of secondary bile acids. Phenylacetic acid derivatives were lower in offspring exposed to obesity and in offspring who had a current BMI in the overweight/obese range. Exposure to maternal obesity was associated with lower levels of androgenic steroid dehydroepiandrosterone sulfate (DHEA-S). Conclusions: In this preliminary study, children exposed to maternal obesity in utero had differences in microbiome-related metabolites in urine suggestive of altered microbial catabolism of tryptophan and acetylated peptides. Some of these differences were partially attributable to the offspring’s current BMI status. This study highlights the potential of urine metabolomics to identify biomarkers and pathways impacted by in utero exposure to maternal obesity. Full article

Cardiovascular disease is the main cause of mortality in industrialized countries, with over 500 million people affected worldwide. In this work, the roles of low-molecular-weight metabolites originating from the gut microbiome, such as short-chain fatty acids, hydrogen sulfide, trimethylamine, phenylacetic acid, secondary bile acids, indoles, different gases, neurotransmitters, vitamins, and complex lipids, are discussed in relation to their CVD-promoting or preventing activities. Molecules of mixed microbial and human hepatic origin, such as trimethylamine N-oxide and phenylacetylglutamine, are also presented. Finally, dietary agents with cardioprotective effects, such as probiotics, prebiotics, mono- and poly-unsaturated fatty acids, carotenoids, and polyphenols, are also discussed. A special emphasis is given to their gut microbiota-modulating properties. Full article

This study evaluates the physicochemical properties, phenolic and flavonoid content, antioxidant activity, and molecular docking interactions of honey from eastern Morocco. Analysis confirmed compliance with European Commission standards, with moisture content ranging from 15.39% to 19.74% and pH between 3.79 and 4.94. Carob honey exhibited the highest protein content (0.42%), polyphenol concentration (720.16 mg gallic acid/kg), flavonoid content (90.5 mg catechin/kg), and antioxidant activity (63.5% DPPH inhibition). Strong correlations were observed between phenolic and flavonoid content and antioxidant properties. Molecular docking identified ethyl phenylacetate and thymol as key compounds with significant interactions with cytochrome c peroxidase, suggesting potential therapeutic effects. DFT calculations supported these findings, indicating these compounds may enhance antioxidant activity. The study highlights the exceptional quality and antioxidant capacity of honey from eastern Morocco, reflecting its unique floral sources and potential as a natural source of antioxidants with therapeutic benefits. Full article

A density functional theory method was employed to conduct theoretical calculations on the pyrolysis reaction pathways of lignin monomer model compounds with an aldehyde or carboxyl group under the catalytic effect of alkali metal ions Na⁺ and K⁺, exploring their influence on the formation of the small molecular gaseous products CO and CO₂. The results indicate that Na⁺ and K⁺ can easily bind with the oxygen-containing functional groups of the lignin monomer model compounds to form stable and low-energy complexes. Except for benzaldehyde and p-hydroxybenzaldehyde, Na⁺ and K⁺ can facilitate the decarbonylation reactions of other benzaldehyde-based and phenylacetaldehyde-based lignin monomer model compounds during the pyrolysis process, thereby enhancing the generation of CO. When the characteristic functional groups on the benzene rings of benzaldehyde-based and phenylacetaldehyde-based lignin monomer model compounds are the same, the phenylacetaldehyde-based ones are more prone to undergo decarbonylation than the benzaldehyde-based ones. Additionally, both Na⁺ and K⁺ can inhibit the decarboxylation reactions of benzoic acid-based and phenylacetic acid-based lignin monomer model compounds, thereby restraining the formation of CO₂. When the characteristic functional groups on the benzene rings of benzoic acid-based and phenylacetic acid-based lignin monomer model compounds are the same, the phenylacetic acid-based ones are more difficult to undergo decarboxylation than the benzoic acid-based ones. Full article