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Environmental Toxicology Jun 2024Multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs) are widely used tubular-structured nanomaterials (NMs), but their cardiovascular effects are not...
Multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs) are widely used tubular-structured nanomaterials (NMs), but their cardiovascular effects are not clear. This study compared the effects of MWCNTs and HNTs on lipid profiles in mouse plasma and gene expression profiles in aortas and hearts. Mice were intravenously injected with 50 μg NMs, once a day, for 5 days. Then, the plasma was collected for lipidomics analysis, and aortas and hearts were collected for RNA-sequencing analysis. While MWCNTs or HNTs did not induce obvious pathological changes in aortas or hearts, the lipid profiles in mouse plasma were altered. Further analysis revealed that MWCNTs more effectively upregulated sphingolipids and sterol lipids, whereas HNTs more effectively upregulated glycerophospholipids and fatty acyls. Consistently, RNA-sequencing data indicated that MWCNTs and HNTs altered signaling pathways related with lipid synthesis and metabolism, as well as those related with endoplasmic reticulum, lysosomes and autophagy, more significantly in aortas than in hearts. We further verified the changes of proteins involved in autophagic lipolysis, that MWCNTs were more effectively to suppress the autophagic biomarker LC3, whereas HNTs were more effectively to affect lipid metabolism proteins. These results may provide novel understanding about the influences of MWCNTs and HNTs on lipid profiles and lipid signaling pathways in cardiovascular systems. Importantly, previous studies considered HNTs as biocompatible materials, but the results from this study suggested that both MWCNTs and HNTs were capable to affect lipid profiles and autophagic lipolysis pathways in cardiovascular systems, although their exact influences were different.
PubMed: 38856197
DOI: 10.1002/tox.24352 -
Communications Biology Jun 2024Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates....
Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins' involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.
Topics: Aspergillus fumigatus; Sirtuins; Virulence; Animals; Mice; Aspergillosis; Acetylation; Fungal Proteins; Gene Expression Regulation, Fungal; Virulence Factors; Moths
PubMed: 38851817
DOI: 10.1038/s42003-024-06383-3 -
Fitoterapia Jun 2024Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore,...
Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), and 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-β-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (-)-secoisolariciresinol-O-β-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner.
PubMed: 38851515
DOI: 10.1016/j.fitote.2024.106056 -
Phytomedicine : International Journal... Aug 2024Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin...
BACKGROUND
Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction.
PURPOSE
The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms.
STUDY DESIGN
The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice.
METHODS/RESULTS
Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC.
CONCLUSION
Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Mice, Inbred C57BL; Cardiomyopathies; Sepsis; Mice; Male; Inflammasomes; Lipoylation; Rats; Oxidative Stress; Cell Line; Lipopolysaccharides; Myocytes, Cardiac; Interleukin-1beta; Interleukin-18
PubMed: 38851101
DOI: 10.1016/j.phymed.2024.155771 -
Food Chemistry Jun 2024Dendrobium officinale Kimura & Migo (D. officinale) has been widely used as Chinese medicine and functional food. In present study, the structural characteristics of...
Dendrobium officinale Kimura & Migo (D. officinale) has been widely used as Chinese medicine and functional food. In present study, the structural characteristics of anthocyanins in D. officinale were investigated by ultra-performance liquid chromatography with diode array detector (UPLC-DAD) and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). Totally, 14 anthocyanins were detected and identified, and 13 of them were first reported in D. officinale. Results showed that the vast majority of anthocyanins had multi-glycosylated cyanidin core, with variable acylation pattern mainly comprising phenolic acids. The composition and content of anthocyanins in D. officinale stems with different cultivation modes and years have been compared. The anthocyanins showed potent antioxidant activity in terms of radicals scavenging capacity and reducing power, as well as superior α-amylase and α-glucosidase inhibitory activity. The results provided a complete profile of anthocyanins in D. officinale and laid a foundation for further utilizing them as functional foods.
PubMed: 38850968
DOI: 10.1016/j.foodchem.2024.139952 -
Organic & Biomolecular Chemistry Jun 2024This work demonstrates trivalent tris-(3--methyl--pyridyl propyl)amine (1) catalyzing the site-selective mono--acylation of glycopyranosides. Different acid anhydrides...
This work demonstrates trivalent tris-(3--methyl--pyridyl propyl)amine (1) catalyzing the site-selective mono--acylation of glycopyranosides. Different acid anhydrides were used for the acylation of monosaccharides, mediated by catalyst 1, at a loading of 1.5 mol%; the extent of site-selectivity and the yields of mono--acylation products were assessed. The reactions were performed between 2 and 10 h, depending on the nature of the acid anhydride, where the bulkier pivalic anhydride required a longer duration for acylation. The glycopyranosides are maintained as diols and triols, and from a set of experiments, the site-selectivity of acylations was observed to follow the intrinsic reactivities and stereochemistry of hydroxy functionalities. The trivalent catalyst 1 mediates the reactions with excellent site-selectivities for mono--acylation product formation in the studied glycopyranosides, in comparison to the monovalent ,-dimethylamino pyridine (DMAP) catalyst. This study illustrates the benefits of the multivalency of catalytic moieties in catalysis.
PubMed: 38847370
DOI: 10.1039/d4ob00599f -
Synthetic and Systems Biotechnology Dec 2024Four new -acylated aminoalkanoic acids, namely clonoroseins E-H (-), together with three previously identified analogs, clonoroseins A, B, and D (-), were identified...
Four new -acylated aminoalkanoic acids, namely clonoroseins E-H (-), together with three previously identified analogs, clonoroseins A, B, and D (-), were identified from the endophytic fungus strain 15020 (CR15020), using Feature-based Molecular Networking (FBMN). The elucidation of their chemical structures, including their absolute configurations, was achieved through spectroscopic analysis combined with quantum chemical calculations. Bioinformatics analyses suggested that an iterative type I HR-PKS (CrsE) generates the polyketide side chain of these clonoroseins. Furthermore, a downstream adenylate-forming enzyme of the PKS (CrsD) was suspected to function as an amide synthetase. CrsD potentially facilitates the transformation of the polyketide moiety into an acyl-AMP intermediate, followed by nucleophilic substitution with either β-alanine or γ-aminobutyric acid to produce amide derivatives. These findings significantly expand our understanding of PKS-related products originating from and also underscore the powerful application of FBMN analytical methods in characterization of new compounds.
PubMed: 38846337
DOI: 10.1016/j.synbio.2024.05.006 -
Journal of Cell Science Jun 2024An important mechanism of gene expression regulation is the epigenetic modification of histones. The cofactors and substrates for these modifications are often... (Review)
Review
An important mechanism of gene expression regulation is the epigenetic modification of histones. The cofactors and substrates for these modifications are often intermediary metabolites, and it is becoming increasingly clear that the metabolic and nutritional state of cells can influence these marks. These connections between the balance of metabolites, histone modifications and downstream transcriptional changes comprise a metabolic signaling program that can enable cells to adapt to changes in nutrient availability. Beyond acetylation, there is evidence now that histones can be modified by other acyl groups. In this Cell Science at a Glance article and the accompanying poster, we focus on these histone acylation modifications and provide an overview of the players that govern these acylations and their connections with metabolism.
Topics: Animals; Humans; Acylation; Epigenesis, Genetic; Histones; Protein Processing, Post-Translational
PubMed: 38842578
DOI: 10.1242/jcs.261250 -
Journal of the American Society For... Jul 2024In prior research, hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) has demonstrated applicability for characterizing...
Hyphenation of Liquid Chromatography and Trapped Ion Mobility - Mass Spectrometry for Characterization of Isomeric Phosphatidylethanolamines with Focus on -Acylated Species.
In prior research, hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) has demonstrated applicability for characterizing regioisomers in lipidomics studies, including phosphatidylglycerols (PG) and bis(monoacyl)glycerophosphates (BMP). However, there are other lipid regioisomers, such as phosphatidylethanolamines (PE) and lyso--acyl-PE (LNAPE), that have not been studied as extensively. Therefore, hyphenated mass spectrometric methods are needed to investigate PE and LNAPE regioisomers individually. The asymmetric structure of LNAPE favors isomeric species, which can result in coelution and chimeric MS/MS spectra. One way to address the challenge of chimeric MS/MS spectra is through mobility-resolved fragmentation using trapped ion mobility spectrometry (TIMS). Therefore, we developed a multidimensional HILIC-TIMS-MS/MS approach for the structural characterization of isomeric phosphatidylethanolamines in both negative and positive ionization modes. The study revealed the complementary fragmentation pattern and ion mobility behavior of LNAPE in both ionization modes, which was confirmed by a self-synthesized LNAPE standard. With this knowledge, a distinction of regioisomeric PE and LNAPE was achieved in human plasma samples. Furthermore, regioisomeric LNAPE species containing at least one unsaturated fatty acid were noted to exhibit a change in collision cross-section in positive ionization mode, leading to a lipid characterization with respect to fatty acyl positional level. Similar mobility behavior was also observed for the biological LNAPE precursor -acyl-PE (NAPE). Application of this approach to plasma and cereal samples demonstrated its effectiveness in regioisomeric LNAPE and NAPE species' elucidation.
Topics: Phosphatidylethanolamines; Tandem Mass Spectrometry; Humans; Isomerism; Ion Mobility Spectrometry; Chromatography, Liquid; Acylation; Hydrophobic and Hydrophilic Interactions
PubMed: 38842006
DOI: 10.1021/jasms.4c00162 -
Medicinal Chemistry (Shariqah (United... Jun 2024The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new...
BACKGROUND
The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species.
OBJECTIVE
This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency.
METHODS
A direct acylation method maintaining several conditions was used for esterification. In vitro tests, molecular docking, and in silico studies were conducted using standard procedures.
RESULTS
In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR).
CONCLUSION
This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.
PubMed: 38840400
DOI: 10.2174/0115734064292665240523113515