-
Free Radical Research Dec 2019Matrix metalloproteinases (MMPs), zinc-containing proteinases, play a critical role in tumour progression by degrading extracellular matrix components. MMP2 and MMP9 are...
Matrix metalloproteinases (MMPs), zinc-containing proteinases, play a critical role in tumour progression by degrading extracellular matrix components. MMP2 and MMP9 are secreted from tumour-associated macrophages as well as tumour cells and have been implicated in the formation of the tumour microenvironment. Therefore, the inhibition of these MMPs may suppress tumour progression and metastasis. 4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE) is known to cause apoptosis in the human lung cancer cell line A549 by inducing endoplasmic reticulum (ER) stress. However, the effects of HPO-DAEE on tumour progression remain unclear. HPO-DAEE pre-treatment significantly suppressed phorbol 12-myristate 13-acetate (TPA)-triggered MMP activation in human monocytic THP-1 cells. It also enhanced the expression of haem oxygenase-1, an antioxidant enzyme, and suppressed the TPA-triggered intracellular accumulation of reactive oxygen species (ROS). Furthermore, HPO-DAEE suppressed transforming growth factor-β1-triggered human prostate cancer PC3 cell migration and this was accompanied by the inhibition of MMP expression and activities. The present results indicate that HPO-DAEE may exert inhibitory effects on tumour progression by suppressing MMP expression and activities.
Topics: Antineoplastic Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esters; Fatty Acids; Fatty Acids, Monounsaturated; Humans; Male; Matrix Metalloproteinases; Phorbol Esters; Prostatic Neoplasms; Reactive Oxygen Species; Structure-Activity Relationship; Transforming Growth Factor beta1
PubMed: 31575304
DOI: 10.1080/10715762.2019.1675874 -
Frontiers in Microbiology 2015Many bacterial pathogens use quorum-sensing (QS) signaling to regulate the expression of factors contributing to virulence and persistence. Bacteria produce signals of...
Many bacterial pathogens use quorum-sensing (QS) signaling to regulate the expression of factors contributing to virulence and persistence. Bacteria produce signals of different chemical classes. The signal molecule, known as diffusible signal factor (DSF), is a cis-unsaturated fatty acid that was first described in the plant pathogen Xanthomonas campestris. Previous works have shown that human pathogen, Pseudomonas aeruginosa, also synthesizes a structurally related molecule, characterized as cis-2-decenoic acid (C10: Δ(2), CDA) that induces biofilm dispersal by multiple types of bacteria. Furthermore, CDA has been shown to be involved in inter-kingdom signaling that modulates fungal behavior. Therefore, an understanding of its signaling mechanism could suggest strategies for interference, with consequences for disease control. To identify the components of CDA signaling pathway in this pathogen, a comparative transcritpome analysis was conducted, in the presence and absence of CDA. A protein-protein interaction (PPI) network for differentially expressed (DE) genes with known function was then constructed by STRING and Cytoscape. In addition, the effects of CDA in combination with antimicrobial agents on the biofilm surface area and bacteria viability were evaluated using fluorescence microscopy and digital image analysis. Microarray analysis identified 666 differentially expressed genes in the presence of CDA and gene ontology (GO) analysis revealed that in P. aeruginosa, CDA mediates dispersion of biofilms through signaling pathways, including enhanced motility, metabolic activity, virulence as well as persistence at different temperatures. PPI data suggested that a cluster of five genes (PA4978, PA4979, PA4980, PA4982, PA4983) is involved in the CDA synthesis and perception. Combined treatments using both CDA and antimicrobial agents showed that following exposure of the biofilms to CDA, remaining cells on the surface were easily removed and killed by antimicrobials.
PubMed: 25972860
DOI: 10.3389/fmicb.2015.00383 -
Biomaterials Advances May 2022Graphene oxide quantum dots (GOQDs) have attracted substantial attention in numerous fields due to their unique physicochemical properties. However, their nanotoxicity...
Graphene oxide quantum dots (GOQDs) have attracted substantial attention in numerous fields due to their unique physicochemical properties. However, their nanotoxicity and potential for use in biomedicine still require further study. In this work, the effects of GOQD and trans- 10-hydroxy-2-decenoic acid (10-HDA) cotreatment on the immune function of macrophages (RAW264.7 cells) were investigated. In particular, LC/MS-based metabolomics was performed to evaluate the effects of GOQDs on the metabolism of LPS-stimulated macrophages. Herein, we fabricated GOQDs with good dispersibility and a uniform size distribution of approximately 7 nm using a polyimide-pyrolyzed carbon film as the working electrode, a high-voltage graphite electrode as the cathode, and HO as the oxidant. The GOQDs entered the macrophages and emitted green fluorescence under UV irradiation. Cotreatment with GOQDs and 10-HDA induced RAW 264.7 cell proliferation. GOQDs promoted the anti-inflammatory effect of 10-HDA on LPS-stimulated RAW264.7 cells and attenuated the secretion of TNF-α, IL-6, and IL-1β. The metabolites in RAW264.7 cells treated with GOQDs were significantly different from those in RAW264.7 cells treated with LPS. The enrichment analysis showed that treatment with GOQDs interfered with amino acid metabolism, and lipid metabolism. Our results demonstrate the role of GOQDs in macrophages and provide a basis for their further application in biomedical fields.
Topics: Anti-Inflammatory Agents; Fatty Acids, Monounsaturated; Graphite; Hydrogen Peroxide; Lipopolysaccharides; Macrophages; Quantum Dots
PubMed: 35929313
DOI: 10.1016/j.bioadv.2022.212774 -
Chembiochem : a European Journal of... Jul 2010In the human mouth, fungi and several hundred species of bacteria coexist. Here we report a case of interkingdom signaling in the oral cavity: A compound excreted by the...
In the human mouth, fungi and several hundred species of bacteria coexist. Here we report a case of interkingdom signaling in the oral cavity: A compound excreted by the caries bacterium Streptococcus mutans inhibits the morphological transition from yeast to hyphae, an important virulence trait, in the opportunistic fungus Candida albicans. The compound excreted by S. mutans was originally studied because it inhibited signaling by the universal bacterial signal autoinducer-2 (AI-2), determined by the luminescence of a Vibrio harveyi sensor strain. The inhibitor was purified from cell-free culture supernatants of S. mutans guided by its activity. Its chemical structure was elucidated by using NMR spectroscopy and GC-MS and proved to be trans-2-decenoic acid. We show that trans-2-decenoic acid does not inhibit AI-2-specific signaling, but rather the luciferase reaction used for its detection. A potential biological role of trans-2-decenoic acid was then discovered. It is able to suppress the transition from yeast to hyphal morphology in the opportunistic human pathogen Candida albicans at concentrations that do not affect growth. The expression of HWP1, a hyphal-specific signature gene of C. albicans, is abolished by trans-2-decenoic acid. trans-2-Decenoic acid is structurally similar to the diffusible signal factor (DSF) family of interkingdom-signaling molecules and is the first member of this family from a Gram-positive organism (Streptococcus DSF, SDSF). SDSF activity was also found in S. mitis, S. oralis, and S. sanguinis, but not in other oral bacteria. SDSF could be relevant in shaping multispecies Candida bacteria biofilms in the human body.
Topics: Biofilms; Candida albicans; Fatty Acids; Fatty Acids, Monounsaturated; Humans; Hyphae; Mouth; Signal Transduction; Streptococcus mutans
PubMed: 20572249
DOI: 10.1002/cbic.201000086 -
Applied and Environmental Microbiology Nov 2014Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is...
Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Escherichia coli; Fatty Acids, Monounsaturated; Isomerism; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Signal Transduction
PubMed: 25192989
DOI: 10.1128/AEM.01576-14 -
Journal of Food Science Sep 2019A rapid quantitative analysis model for determining the hydroxy-2-decenoic acid (10-HDA) content of royal jelly based on near-infrared spectroscopy combining with PLS...
A rapid quantitative analysis model for determining the hydroxy-2-decenoic acid (10-HDA) content of royal jelly based on near-infrared spectroscopy combining with PLS has been developed. Firstly, near-infrared spectra of 232 royal jelly samples with different 10-HDA concentrations (0.35% to 2.44%) were be collected. Second-order derivative processing of the spectra was carried out to construct a full-spectrum PLS model. Secondly, GA-PLS, CARS-PLS, and Si-PLS were used to select characteristic wavelengths from the second-order derivative spectrum to construct a PLS calibration model. Finally, 58 samples were used to select the best predictive model for 10-HDA content. The result show that the PLS model constructed after wavelength selection was significantly more accurate than the full spectrum model. The Si-PLS algorithm performed best and the corresponding characteristic wavelength range were: 980 to 1038, 1220 to 1278, 1340 to 1398, and 1688 to 1746 nm. The prediction results were RMSEP = 0.1496% and R = 0.9380. Hence, it is feasible to employ near-infrared spectra to analyze 10-HDA in royal jelly.
Topics: Algorithms; Animals; Bees; Calibration; Fatty Acids; Fatty Acids, Monounsaturated; Least-Squares Analysis; Spectroscopy, Near-Infrared
PubMed: 31483872
DOI: 10.1111/1750-3841.14748 -
PloS One 2014Biofilm formation by food-related bacteria and food-related pathogenesis are significant problems in the food industry. Even though much disinfection and mechanical...
Biofilm formation by food-related bacteria and food-related pathogenesis are significant problems in the food industry. Even though much disinfection and mechanical procedure exist for removal of biofilms, they may fail to eliminate pre-established biofilms. cis-2 decenoic acid (CDA), an unsaturated fatty acid messenger produced by Pseudomonas aeruginosa, is reportedly capable of inducing the dispersion of established biofilms by multiple types of microorganisms. However, whether CDA has potential to boost the actions of certain antimicrobials is unknown. Here, the activity of CDA as an inducer of pre-established biofilms dispersal, formed by four main food pathogens; Staphylococcus aureus, Bacillus cereus, Salmonella enterica and E. coli, was measured using both semi-batch and continuous cultures bioassays. To assess the ability of CDA combined biocides treatments to remove pre-established biofilms formed on stainless steel discs, CFU counts were performed for both treated and untreated cultures. Eradication of the biofilms by CDA combined antibiotics was evaluated using crystal violet staining. The effect of CDA combined treatments (antibiotics and disinfectants) on biofilm surface area and bacteria viability was evaluated using fluorescence microscopy, digital image analysis and LIVE/DEAD staining. MICs were also determined to assess the probable inhibitory effects of CDA combined treatments on the growth of tested microorganisms' planktonic cells. Treatment of pre-established biofilms with only 310 nM CDA resulted in at least two-fold increase in the number of planktonic cells in all cultures. While antibiotics or disinfectants alone exerted a trivial effect on CFU counts and percentage of surface area covered by the biofilms, combinational treatments with both 310 nM CDA and antibiotics or disinfectants led to approximate 80% reduction in biofilm biomass. These data suggests that combined treatments with CDA would pave the way toward developing new strategies to control biofilms with widespread applications in industry as well as medicine.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Physiological Phenomena; Biofilms; Disinfectants; Dose-Response Relationship, Drug; Drug Interactions; Fatty Acids, Monounsaturated; Food Microbiology; Plankton; Polystyrenes; Stainless Steel; Surface Properties
PubMed: 25000301
DOI: 10.1371/journal.pone.0101677 -
The Journal of Veterinary Medical... Sep 201710-Hydroxy-2-decenoic acid (10H2DA) is a fatty acid found in royal jelly (RJ). In healthy mice, it activates 5'-AMP-activated protein kinase (AMPK) and increases glucose...
10-Hydroxy-2-decenoic acid (10H2DA) is a fatty acid found in royal jelly (RJ). In healthy mice, it activates 5'-AMP-activated protein kinase (AMPK) and increases glucose transporter 4 (GLUT4) translocation. Therefore, we examined whether 10H2DA has a potential therapeutic effect against type 2 diabetes in obese/diabetic KK-Ay mice. 10H2DA (3 mg/kg body weight) was administered to female KK-Ay mice for 4 weeks by oral gavage. Phenotypes for body weight, plasma glucose by oral glucose tolerance test and insulin levels were measured. mRNA and protein levels were determined using qRT-PCR and Western blot analyses, respectively. Long-term administration of 10H2DA significantly improved hyperglycemia and insulin resistance in KK-Ay mice, but did not prevent obesity. 10H2DA increased the expression of phosphorylated AMPK (pAMPK) protein in skeletal muscles; however, this expression did not correlate with increased GLUT4 translocation. Furthermore, 10H2DA neither enhanced the expression of adiponectin receptor mRNA nor activated the insulin signaling cascade, such as GSK-3β phosphorylation, in the liver. We found that 10H2DA-treated mice had a significant increase in the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc-1α) mRNA in skeletal muscles compared with non-treated group (P=0.0024). These findings suggest that 10H2DA is involved in the improvement of type 2 diabetes, at least in part via activation of Pgc-1α expression, but does not prevent obesity.
Topics: Adiponectin; Adipose Tissue; Animals; Fatty Acids, Monounsaturated; Gene Expression Regulation, Enzymologic; Glucose Tolerance Test; Homeostasis; Hyperglycemia; Insulin Resistance; Liver; Mice; Mice, Inbred Strains; Obesity; RNA, Messenger
PubMed: 28740028
DOI: 10.1292/jvms.17-0348 -
Neurochemistry International Jan 2018Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress has...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress has been reported to be closely related to the pathogenesis and worsening of symptoms of PD. One therapeutic strategy is to alleviate neuronal injuries caused by oxidative stress. In this study, we investigated protective effects of royal jelly (RJ) fatty acids and their derivatives on oxidative stress-induced cell death using human neuroblastoma SH-SY5Y cells. 4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE), a synthesized RJ fatty acid derivative, markedly induced antioxidant enzymes such as heme oxygenase-1 (HO-1). Pretreatment with HPO-DAEE protected against 6-hydroxydopamine (6-OHDA)-induced cell death. NF-E2-related factor 2 (Nrf2), a master regulator of antioxidative responses, plays a key role in the acquisition of resistance to oxidative stress. HPO-DAEE elicited nuclear accumulation of Nrf2 and activated antioxidant response element (ARE), a cis-activating regulatory element, indicating that HPO-DAEE induced expression of antioxidant genes through Nrf2-ARE signaling. Recently, the activating transcription factor-4 (ATF4) has been shown to cooperate with Nrf2 and modulate antioxidant gene expression. We also found that HPO-DAEE promoted phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is an upstream effector of ATF4, and subsequent nuclear accumulation of ATF4. The eIF2α phosphatase inhibitor, salubrinal, augmented HPO-DAEE-induced HO-1 expression and protection against 6-OHDA-induced cell death. These results indicate that HPO-DAEE activates both the Nrf2-ARE and eIF2α-ATF4 pathways. Moreover, ROS generation occurred upon treatment of SH-SY5Y cells with HPO-DAEE, and the antioxidants N-acetylcysteine and glutathione suppressed HPO-DAEE-induced activation of the Nrf2-ARE and eIF2α-ATF4 pathways. Therefore, sublethal oxidative stress caused by HPO-DAEE is likely to activate both these pathways. Taken together, we conclude that HPO-DAEE elicits adaptive responses to oxidative stress through cooperative activation of the Nrf2-ARE and eIF2α-ATF4 pathways.
Topics: Activating Transcription Factor 4; Antioxidant Response Elements; Cell Death; Cell Line, Tumor; Cytoprotection; Dose-Response Relationship, Drug; Eukaryotic Initiation Factor-2; Fatty Acids; Humans; NF-E2-Related Factor 2; Oxidopamine; Signal Transduction
PubMed: 28823537
DOI: 10.1016/j.neuint.2017.08.011 -
Journal of Medical Microbiology Nov 2014The catheterized urinary tract provides ideal conditions for the development of biofilm populations. Catheter-associated urinary tract infections (CAUTIs) are...
The catheterized urinary tract provides ideal conditions for the development of biofilm populations. Catheter-associated urinary tract infections (CAUTIs) are recalcitrant to existing antimicrobial treatments; therefore, established biofilms are not eradicated completely after treatment and surviving biofilm cells will carry on the infection. Cis-2-decenoic acid (CDA), an unsaturated fatty acid, is capable of inhibiting biofilm formation by Pseudomonas aeruginosa and of inducing the dispersion of established biofilms by multiple types of micro-organisms. Here, the ability of CDA to induce dispersal in pre-established single- and dual-species biofilms formed by Escherichia coli and Klebsiella pneumoniae was measured by using both semi-batch and continuous cultures bioassays. Removal of the biofilms by combined CDA and antibiotics (ciprofloxacin or ampicillin) was evaluated using microtitre plate assays (crystal violet staining). The c.f.u. counts were determined to assess the potential of combined CDA treatments to kill and eradicate pre-established biofilms formed on catheters. The effects of combined CDA treatments on biofilm surface area and bacteria viability were evaluated using fluorescence microscopy, digital image analysis and live/dead staining. To investigate the ability of CDA to prevent biofilm formation, single and mixed cultures were grown in the presence and absence of CDA. Treatment of pre-established biofilms with only 310 nM CDA resulted in at least threefold increase in the number of planktonic cells in all cultures tested. Whilst none of the antibiotics alone exerted a significant effect on c.f.u. counts and percentage of surface area covered by the biofilms, combined CDA treatments led to at least a 78% reduction in biofilm biomass in all cases. Moreover, most of the biofilm cells remaining on the surface were killed by antibiotics. The addition of 310 nM CDA significantly prevented biofilm formation by the tested micro-organisms, even within mixed cultures, indicating the ability of CDA to inhibit biofilm formation by other types of bacteria in addition to Pseudomonas aeruginosa. These findings suggested that the biofilm-preventive characteristics of CDA make it a noble candidate for inhibition of biofilm-associated infections such as CAUTIs, which paves the way toward developing new strategies to control biofilms in clinical as well as industrial settings.
Topics: Anti-Bacterial Agents; Biofilms; Drug Therapy, Combination; Escherichia coli; Fatty Acids, Monounsaturated; Humans; Klebsiella pneumoniae; Urinary Catheters
PubMed: 25082943
DOI: 10.1099/jmm.0.075374-0