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Heliyon Feb 2024This study was conducted to mitigate the food safety risks related to biogenic amine (BA) by reducing the BA content in using applicable food additives. In -...
This study was conducted to mitigate the food safety risks related to biogenic amine (BA) by reducing the BA content in using applicable food additives. In - experiments, of the additives tested, tartaric acid (TA), potassium sorbate (PS), and sodium benzoate (SB) considerably inhibited tyramine production of strains of spp. and while less affecting their growth. In addition to these three additives, two additives, glycine (GL) and nicotinic acid (NA), reported to have significant inhibitory effects in previous studies, were applied to the fermentation with prolific tyramine-producing strains of and . The content of tyramine in the samples treated with TA, PS, SB, GL, and NA was significantly reduced by 27.5%, 50.7%, 51.4%, 76.1%, and 100.0%, respectively, compared to the control sample. Additionally, the content of polyamines (putrescine, cadaverine, spermidine, and spermine) in the GL-treated sample was reduced by 42.6%-62.4%. The mode of action could be attributed to inhibiting the bacterial decarboxylase activity and/or growth. Consequently, excluding NA that interfered with fermentation, GL was the most outstanding additive with an inhibitory effect on tyramine formation in food, followed by SB and PS, all of which showed a more than 50% reduction. Therefore, the use of appropriate additives could be one of the promising strategies to avoid the food safety issues implicated in BAs in .
PubMed: 38379996
DOI: 10.1016/j.heliyon.2024.e26135 -
Biochemistry Research International 2024Bacterial and mammalian cells are rich in putrescine, spermidine, and spermine. Polyamines are required for optimum fitness, but the biological function of these small...
Bacterial and mammalian cells are rich in putrescine, spermidine, and spermine. Polyamines are required for optimum fitness, but the biological function of these small aliphatic compounds has only been partially revealed. Known functions of polyamines include interaction with nucleic acids that alters gene expression and with proteins that modulate activity. Although polyamines can be incorporated into proteins, very few naturally occurring polyaminated proteins have been identified, which is due in part to the difficulty in detecting these adducts. In the current study, bovine albumin and the recombinant universal stress protein from were used as models for mass spectrometry analysis of polyaminated proteins. The proteins were covalently bound to putrescine, spermidine, or spermine by the action of carbodiimide or microbial transglutaminase. Tryptic peptides, subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS), were identified using Protein Prospector software. We describe the search parameters for identifying polyaminated peptides and show MS/MS spectra for adducts with putrescine, spermidine, and spermine. Manual evaluation led us to recognize signature ions for polyamine adducts on aspartate, glutamate, and glutamine, as well as neutral loss from putrescine, spermidine, and spermine during the fragmentation process. Mechanisms for the formation of signature ions and neutral loss are presented. Manual evaluation identified a false-positive adduct that had formed during trypsinolysis and resulted in peptide sequence rearrangement. Another false positive initially appeared to be a 71 kDa putrescine adduct on a cysteine residue. However, it was an acrylamide adduct on cysteine for a sample extracted from a polyacrylamide gel. The information presented in this report provides guidance and serves as a model for identifying naturally occurring polyaminated proteins.
PubMed: 38347948
DOI: 10.1155/2024/7120208 -
Biomedical Reports Mar 2024Ductal adenocarcinoma represents 90-95% of pancreatic cancer (PC) cases and it is an aggressive disease with asymptomatic evolution at early stages, non-specific...
Ductal adenocarcinoma represents 90-95% of pancreatic cancer (PC) cases and it is an aggressive disease with asymptomatic evolution at early stages, non-specific symptoms and a typical late diagnosis with a 5-year survival rate estimated to be 8%. A window of opportunity lies in early diagnosis as there are currently no reliable biomarkers. CA 19-9 is one of the most frequently used biomarkers of PC, with 75 and 77.6% sensitivity (Se) and specificity (Sp), respectively, and the carcinoembryonic antigen (CEA) shows 39.5 and 81.3% of Se and Sp, respectively. A case-control study was conducted including adult patients with a histological diagnosis of PC (n=11) without previous treatment at the Oncology Service of the CMNO-IMSS between 2019 and 2020, and a control group of adult volunteers (n=11) who were clinically healthy or with controlled disease including hypertension, hypothyroidism and diabetes. Clinical, laboratory and sociodemographic data as well as blood, urine and saliva samples were collected following patient consent. Polyamines were quantified using high-performance liquid chromatography with fluorescence detection, CA 19-9 and CEA were evaluated using enzyme-linked immunosorbent assay, and the protein expression of ornithine decarboxylase (ODC) was evaluated using western blotting. Polyamine metabolism and modulation by means of ODC were increased in the serum and saliva of patients with PC, and the expression of ODC alone was increased in peripheral blood mononuclear cells (PBMCs). The present study focused on the evaluation of putrescine, spermine, spermidine and ODC in PBMCs associated with CA 19-9 and CEA as an auxiliary tool in PC diagnosis.
PubMed: 38343658
DOI: 10.3892/br.2024.1726 -
Plants (Basel, Switzerland) Jan 2024Polyamines and ethylene are key regulators of the growth and development, quality formation, and stress response of cereal crops such as rice. However, it remains...
Polyamines and ethylene are key regulators of the growth and development, quality formation, and stress response of cereal crops such as rice. However, it remains unclear whether the application of these regulators could improve the nutritional quality via increasing amino acids in rice grains. This study examined the role of exogenous polyamines and ethylene in regulating amino acid levels in the milled rice of earlier-flowered superior grain (SG) and later-flowered inferior grain (IG). Two rice varieties were field grown, and either 1 mmol L spermidine (Spd) or 50 μmol L amino-ethoxyvinylglycine (AVG) was applied to panicles at the early grain-filling stage. The control check (CK) was applied with deionized water. The results showed that the Spd or AVG applications significantly increased polyamine (spermine (Spm) and Spd) contents and decreased ethylene levels in both SG and IG and significantly increased amino acid levels in the milled rice of SG and IG relative to the CK. Collectively, the application of Spd or AVG can increase amino acid-based nutritional quality and grain yield via increasing polyamine (Spm and Spd) contents and reducing ethylene levels in both SG and IG of rice.
PubMed: 38276774
DOI: 10.3390/plants13020316 -
Pathogens (Basel, Switzerland) Jan 2024Neglected tropical diseases transmitted by trypanosomatids include three major human scourges that globally affect the world's poorest people: African trypanosomiasis or... (Review)
Review
Neglected tropical diseases transmitted by trypanosomatids include three major human scourges that globally affect the world's poorest people: African trypanosomiasis or sleeping sickness, American trypanosomiasis or Chagas disease and different types of leishmaniasis. Different metabolic pathways have been targeted to find antitrypanosomatid drugs, including polyamine metabolism. Since their discovery, the naturally occurring polyamines, putrescine, spermidine and spermine, have been considered important metabolites involved in cell growth. With a complex metabolism involving biosynthesis, catabolism and interconversion, the synthesis of putrescine and spermidine was targeted by thousands of compounds in an effort to produce cell growth blockade in tumor and infectious processes with limited success. However, the discovery of eflornithine (DFMO) as a curative drug against sleeping sickness encouraged researchers to develop new molecules against these diseases. Polyamine synthesis inhibitors have also provided insight into the peculiarities of this pathway between the host and the parasite, and also among different trypanosomatid species, thus allowing the search for new specific chemical entities aimed to treat these diseases and leading to the investigation of target-based scaffolds. The main molecular targets include the enzymes involved in polyamine biosynthesis (ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermidine synthase), enzymes participating in their uptake from the environment, and the enzymes involved in the redox balance of the parasite. In this review, we summarize the research behind polyamine-based treatments, the current trends, and the main challenges in this field.
PubMed: 38251386
DOI: 10.3390/pathogens13010079 -
Cells Jan 2024Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate...
Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells' morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.
Topics: Animals; Cholestanes; Glucose; Horses; Insulin; Metabolic Syndrome; Mitochondrial Dynamics; Palmitates; Spermine; Insulin Resistance
PubMed: 38247843
DOI: 10.3390/cells13020152 -
Food Chemistry Jun 2024This study involved an investigation into the electrochemical characteristic of a few biogenic amines (BAs) occurring at the polarized interface between two immiscible...
This study involved an investigation into the electrochemical characteristic of a few biogenic amines (BAs) occurring at the polarized interface between two immiscible electrolyte solutions (ITIES) with ion transfer voltammetry (ITV). The main focus of this research was the comprehensive electroanalytical and physicochemical analysis of phenylethylamine (PEA), allowing the determined of the formal Galvani potential of the ion transfer reaction (ΔΦ), diffusion coefficients (D), formal free Gibbs energy of the ion transfer reaction (ΔG) and water-1,2-dichloroethane partition coefficient (logP). Furthermore, the collected data were employed to calculate analytical parameters, including voltametric detection sensitivity, limits of detection and the target analyte quantification. Moreover, the influence of the presence of 7 other BAs (histamine, spermine, spermidine, putrescine, cadaverine, tyramine and tryptamine) on the recorded signals originating from the PEA ion transfer was checked. The feasibility of the developed method was corroborated through experimentation with milk samples. Additionally, utilizing the devised methodology, an electrochemical assessment of the spoilage progression in milk samples was undertaken.
Topics: Animals; Milk; Electrochemistry; Biogenic Amines; Histamine; Water
PubMed: 38241999
DOI: 10.1016/j.foodchem.2024.138407 -
Scientific Reports Jan 2024Huntington's disease (HD) is increasingly recognized for diverse pathology outside of the nervous system. To describe the biology of HD in relation to functional... (Randomized Controlled Trial)
Randomized Controlled Trial
An exploratory metabolomic comparison of participants with fast or absent functional progression from 2CARE, a randomized, double-blind clinical trial in Huntington's disease.
Huntington's disease (HD) is increasingly recognized for diverse pathology outside of the nervous system. To describe the biology of HD in relation to functional progression, we previously analyzed the plasma and CSF metabolome in a cross-sectional study of participants who had various degrees of functional impairment. Here, we carried out an exploratory study in plasma from HD individuals over a 3-year time frame to assess whether differences exist between those with fast or absent clinical progression. There were more differences in circulating metabolite levels for fast progressors compared to absent progressors (111 vs 20, nominal p < 0.05). All metabolite changes in faster progressors were decreases, whereas some metabolite concentrations increased in absent progressors. Many of the metabolite levels that decreased in the fast progressors were higher at Screening compared to absent progressors but ended up lower by Year 3. Changes in faster progression suggest greater oxidative stress and inflammation (kynurenine, diacylglycerides, cysteine), disturbances in nitric oxide and urea metabolism (arginine, citrulline, ornithine, GABR), lower polyamines (putrescine and spermine), elevated glucose, and deficient AMPK signaling. Metabolomic differences between fast and absent progressors suggest the possibility of predicting functional decline in HD, and possibly delaying it with interventions to augment arginine, polyamines, and glucose regulation.
Topics: Humans; Huntington Disease; Cross-Sectional Studies; Polyamines; Arginine; Glucose; Disease Progression
PubMed: 38212353
DOI: 10.1038/s41598-023-50553-y -
Molecules (Basel, Switzerland) Dec 2023is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of revealed that ethyl acetate (EtOAc) was...
is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of revealed that ethyl acetate (EtOAc) was the most bioactive fraction. Bio-guided fractionation of EtOAc fraction afforded nine compounds isolated for the first time from the plant species. Macrocyclic spermine alkaloids (1,9), proanthocyanidins (2,4,5), quinoline alkaloids (7,8), phenolic (3), and nucleoside (6) were identified and elucidated by spectroscopic analyses including 1D and 2D NMR, ESI-MS-MS spectrometry. The tested compounds exhibited moderate anticancer activity, except for the kynurenic acid derivative (6-mKYNA) which showed significant cytotoxicity and remarkable inhibition of CA-19.9 and CA-125 tumor biomarkers. In-silico study was conducted to determine the anti-proliferative mechanism of 6-mKYNA by using the CK2 enzyme active site. Moreover, the ADME computational study suggested that 6-mKYNA is an effective candidate with a promising pharmacokinetic profile and therapeutic potential against various types of cancer.
Topics: Ephedra; Biological Assay; Biomarkers, Tumor; Alkaloids; Acetates
PubMed: 38202783
DOI: 10.3390/molecules29010199 -
Scientific Reports Jan 2024Leishmania amazonensis is a protozoan that primarily causes cutaneous leishmaniasis in humans. The parasite relies on the amino acid arginine to survive within...
Leishmania amazonensis is a protozoan that primarily causes cutaneous leishmaniasis in humans. The parasite relies on the amino acid arginine to survive within macrophages and establish infection, since it is a precursor for producing polyamines. On the other hand, arginine can be metabolized via nitric oxide synthase 2 (NOS2) to produce the microbicidal molecule nitric oxide (NO), although this mechanism does not apply to human macrophages since they lack NOS2 activity. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at posttranscriptional levels. Our previous work showed that mmu-miR-294 targets Nos2 favoring Leishmania survival in murine macrophages. Here, we demonstrate that human macrophages upregulate the hsa-miR-372, hsa-miR-373, and hsa-miR-520d, which present the same seed sequence as the murine mmu-miR-294. Inhibition of the miR-372 impaired Leishmania survival in THP-1 macrophages and the effect was further enhanced with combinatorial inhibition of the miR-372/373/520d family, pointing to a cooperative mechanism. However, this reduction in survival is not caused by miRNA-targeting of NOS2, since the seed-binding motif found in mice is not conserved in the human 3'UTR. Instead, we showed the miR-372/373/520d family targeting the macrophage's main arginine transporter SLC7A2/CAT2 during infection. Arginine-related metabolism was markedly altered in response to infection and miRNA inhibition, as measured by Mass Spectrometry-based metabolomics. We found that Leishmania infection upregulates polyamines production in macrophages, as opposed to simultaneous inhibition of miR-372/373/520d, which decreased putrescine and spermine levels compared to the negative control. Overall, our study demonstrates miRNA-dependent modulation of polyamines production, establishing permissive conditions for intracellular parasite survival. Although the effector mechanisms causing host cell immunometabolic adaptations involve various parasite and host-derived signals, our findings suggest that the miR-372/373/520d family may represent a potential target for the development of new therapeutic strategies against cutaneous leishmaniasis.
Topics: Humans; Animals; Mice; Leishmaniasis, Cutaneous; Leishmania; Arginine; Macrophages; MicroRNAs
PubMed: 38200138
DOI: 10.1038/s41598-024-51511-y