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Annals of Medicine Dec 2023N-myristoyltransferase 1 (NMT1) is an indispensable eukaryotic enzyme that catalyses the transfer of myristoyl groups to the amino acid terminal residues of numerous... (Review)
Review
N-myristoyltransferase 1 (NMT1) is an indispensable eukaryotic enzyme that catalyses the transfer of myristoyl groups to the amino acid terminal residues of numerous proteins. This catalytic process is required for the growth and development of many eukaryotes and viruses. Elevated expression and activity of NMT1 is observed to varying degrees in a variety of tumour types (e.g. colon, lung and breast tumours). Furthermore, an elevated level of NMT1 in tumours is associated with poor survival. Therefore, a relationship exists between NMT1 and tumours. In this review, we discuss the underlying mechanisms by which NMT1 is associated with tumour development from the perspective of oncogene signalling, involvement in cellular metabolism, and endoplasmic reticulum stress. Several NMT inhibitors used in cancer treatment are introduced. The review will provide some directions for future research.Key MessagesElevated expression and activity of NMT1 is observed to varying degrees in a variety of tumour types which creates the possibility of targeting NMT1 in tumours.NMT1-mediated myristoylation plays a pivotal role in cancer cell metabolism and may be particularly relevant to cancer metastasis and drug resistance. These insights can be used to direct potential therapeutic avenues for NMT1 inhibitors.
Topics: Humans; Myristic Acid; Acyltransferases; Lung; Neoplasms
PubMed: 37140999
DOI: 10.1080/07853890.2023.2193425 -
Molecules (Basel, Switzerland) Nov 2023Camphene, C12-C18 fatty acids, and titanium sulfate were used as raw materials to study the synthesis of long-chain fatty acid isobornyl esters. Products were analyzed...
Camphene, C12-C18 fatty acids, and titanium sulfate were used as raw materials to study the synthesis of long-chain fatty acid isobornyl esters. Products were analyzed quantitatively by gas chromatography (GC), characterized by nuclear magnetic resonance spectroscopy (hydrogen and carbon), and evaluated using toxicity tests. The optimum reaction conditions were as follows: n(lauric acid):n(camphene) = 2.5:1, m(titanium sulfate):m(camphene) = 0.25:1, reaction temperature of 80 °C, and reaction time of 25 h. Under these conditions, the content of isobornyl laurate in the product was 74.49%, and the content of purified product was 95.02%. The reaction kinetics for isobornyl laurate showed an apparent first-order reaction in the first 9 h with an activation energy of 31.01 kJ/mol. The reaction conditions of myristic acid, palmitic acid, and stearic acid were similar to those of lauric acid, but the reaction time had to be increased as the molecular weight of the fatty acid increased. Toxicity tests for four types of long-chain fatty acid isobornyl esters showed that the samples had low toxicity.
PubMed: 38005232
DOI: 10.3390/molecules28227510 -
Biomedicine & Pharmacotherapy =... Dec 2023The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by...
The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by symptoms of metabolic dysfunction. Cordycepin is a Chinese herbal medicine commonly used for its metabolism-enhancing effects. We aimed to investigate the dose-dependent effects of cordycepin on psycho-metabolic disorders induced by stress. Our behavioral tests revealed that 12.5 mg/kg cordycepin by oral gavage significantly attenuated the anxiety- and depression-like behaviors induced by stress in mice. At 25 mg/kg, cordycepin restored the reduced weight and cell size of adipose tissues caused by stress. Besides ameliorating the metabolic dysbiosis of gut microbiota due to stress, cordycepin significantly reduced the elevated contents of 5-hydroxyindoleacetic acid in the serum and prefrontal cortex at 12.5 mg/kg and reversed the decrease in adipose induced by stress at 25 mg/kg. Correlation analyses further revealed that 12.5 mg/kg cordycepin reversed stress-induced changes in the intestinal microbiome of NK4A214_group and decreased serum Myristic acid and PC(15:0/18:1(11Z)) and cytokines, such as IFN-γ and IL-1β. 25 mg/kg cordycepin reversed stress-induced changes in the abundances of Prevoteaceae_UCG-001 and Desulfovibrio, increased serum L-alanine level, and decreased serum Inosine-5'-monophosphate level. Cordycepin thereby ameliorated the anxiety- and depression-like behaviors as well as disturbances in the adipose metabolism of mice exposed to stress. Overall, these findings offer evidence indicating that the prominent effects of cordycepin in the brain and adipose tissues are dose dependent, thus highlight the importance of evaluating the precise therapeutic effects of different cordycepin doses on psycho-metabolic diseases.
Topics: Humans; Mice; Animals; Gastrointestinal Microbiome; Obesity; Brain; Deoxyadenosines; Depression
PubMed: 38294969
DOI: 10.1016/j.biopha.2023.115796 -
JACC. Basic To Translational Science Oct 2023Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac...
Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.
PubMed: 38094695
DOI: 10.1016/j.jacbts.2023.06.006 -
Materials (Basel, Switzerland) Aug 2023This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature...
This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature control. Encapsulated paraffin wax particles (EPWP) and encapsulated myristic acid particles (EMAP) were synthesized using acid-etched ceramsite (AECS) as the carrier, paraffin wax (PW) or myristic acid (MA) as the core material, and a combination of epoxy resin and cement as the encapsulation material. The investigation encompassed leakage tests on PCMs; rutting plate rolling forming tests; SEM, FTIR, XRD, and TG-DSC microscopic tests; as well as heat storage and release tests and temperature control assessments using a light heating device. The study revealed the following key findings. Both types of PCMs exhibited no PCM leakage even under high temperatures and demonstrated low crushing ratios during rut-forming tests. Microscopic evaluations confirmed the chemical stability and phase compatibility of the constituents within the two types of PCMs. Notably, the phase change enthalpies of EPWP and EMAP were relatively high, measuring 133.31 J/g and 138.52 J/g, respectively. The utilization of AECS as the carrier for PCMs led to a substantial 4.61-fold increase in the adsorption rate. Moreover, the PCMs showcased minimal mass loss at 180 °C, rendering them suitable for asphalt pavement applications. The heat storage and release experiments further underscored the PCMs' capacity to regulate ambient temperatures through heat absorption and release. When subjected to light heating, the maximum temperatures of the two types of phase change Marshall specimens were notably lower by 6.6 °C and 4.8 °C, respectively, compared to standard Marshall specimens. Based on comprehensive testing, EPWP displayed enhanced adaptability and demonstrated substantial potential for practical implementation in asphalt pavements.
PubMed: 37687694
DOI: 10.3390/ma16176002 -
Biomolecules Aug 2023Pollen germination in vivo on wet stigmas is assisted by the receptive fluid-stigma exudate. Its exact composition is still unknown because only some components have...
Pollen germination in vivo on wet stigmas is assisted by the receptive fluid-stigma exudate. Its exact composition is still unknown because only some components have been studied. For the first time, hormonal screening was carried out, and the fatty acid (FA) composition of lipid-rich () and sugar-rich () exudates was studied. Screening of exudate for the presence of plant hormones using HPLC-MS revealed abscisic acid (ABA) in tobacco stigma exudate at the two stages of development, at pre-maturity and in mature stigmas awaiting pollination, increasing at the fertile stage. To assess physiological significance of ABA on stigma, we tested the effect of this hormone in vitro. ABA concentration found in the exudate strongly stimulated the germination of tobacco pollen, a lower concentration had a weaker effect, increasing the concentration did not increase the effect. GC-MS analysis showed that both types of exudate are characterized by a predominance of saturated FAs. The lipids of tobacco stigma exudate contain significantly more myristic, oleic, and linoleic acids, resulting in a higher unsaturation index relative to lily stigma exudate lipids. The latter, in turn, contain more 14-hexadecenoic and arachidic acids. Both exudates were found to contain significant amounts of squalene. The possible involvement of saturated FAs, ABA, and squalene in various exudate functions, as well as their potential relationship on the stigma, is discussed.
Topics: Plant Growth Regulators; Lilium; Nicotiana; Fatty Acids; Squalene; Abscisic Acid; Exudates and Transudates
PubMed: 37759713
DOI: 10.3390/biom13091313 -
Archives Animal Breeding 2023The aim of the study was to compare carcass composition and physicochemical and sensory attributes of breast and leg meat from native Mexican guajolote () as influenced...
The aim of the study was to compare carcass composition and physicochemical and sensory attributes of breast and leg meat from native Mexican guajolote () as influenced by sex. For this, slaughter weight and carcass characteristics of male () and female () guajolotes raised traditionally under extensive systems with similar housing and feeding conditions were recorded. Also, physical characteristics, proximate composition, the fatty acid profile, and sensory attributes were determined in breast and leg meat using standard procedures. The results showed that males had higher () slaughter weight, hot and cold carcass weights, and dressing percentage, as well as carcass part weights, while females had higher () abdominal fat weights than males. The lightness (), yellowness (), and drip loss values of breast meat, as well as redness () and water-holding capacity values of leg meat, were significantly () influenced by sex. Male breast meat had higher () moisture content, crude protein, erucic acid (C22:1n9), MUFAs (total monounsaturated fatty acids), UFAs (unsaturated fatty acids), DFAs (desirable fatty acids), UFA SFA (total saturated fatty acid) ratio, PUFA (total polyunsaturated fatty acid) SFA ratio, and chewiness scores than females. Likewise, leg meat from males showed higher () ash content, myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9c), palmitoleic acid (C16:1n7), SFAs, OFAs (odd fatty acids), thrombogenic index, and atherogenic index, whereas females had high fat content. In conclusion, it would be suggested that, from a nutritional point of view, the meat from male guajolotes was preferable to the meat from females.
PubMed: 38111389
DOI: 10.5194/aab-66-341-2023 -
Animals : An Open Access Journal From... Jun 2023This meta-analysis aimed to investigate the effect of dietary fatty acid (FA) profile on milk fat production and FA profile in dairy cows. The study also aimed to...
This meta-analysis aimed to investigate the effect of dietary fatty acid (FA) profile on milk fat production and FA profile in dairy cows. The study also aimed to develop prediction models using a meta-regression approach. The database included 217 peer-reviewed articles on lactating dairy cows ( = 12,892), consisting of 515 treatment means. Effect size was assessed using the raw mean differences between diets with supplementary lipid sources and those without. Subgroup analyses were employed to assess heterogeneity. Diets rich in saturated FA (SFA) increased milk fat production and proportion, while reducing de novo FA in milk. Diets high in monounsaturated FA and polyunsaturated FA decreased mixed FA in milk. Most lipid-supplemented diets increase preformed FA in milk, except those rich in SFA. Prediction models were developed using meta-regression. Key predictors of milk fat production included neutral detergent fiber (NDF), dietary myristic acid, and milk production. Milk fat proportion was best predicted by dietary unsaturated FA, NDF, and forage. De novo FA in milk was predicted by dry matter intake (DMI) and dietary FA, while preformed FA was predicted by DMI, dietary oleic and linoleic acids. In conclusion, this study emphasizes the importance of the dietary FA profile in evaluating the effects of lipids on milk fat production and FA profile. Accurate and precise predictions of milk fat production, proportion, and FA profile can be achieved by considering cow production and dietary characteristics.
PubMed: 37443861
DOI: 10.3390/ani13132063 -
Frontiers in Nutrition 2023Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the...
OBJECTIVE
Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice.
METHODS
For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics.
RESULTS
By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism.
CONCLUSION
We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.
PubMed: 37492592
DOI: 10.3389/fnut.2023.1171806 -
Antibiotics (Basel, Switzerland) Jul 2023In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are...
In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are increased rates of morbidity and mortality due to fungal infections. Hence, a series of novel myristic acid derivatives were designed via molecular docking studies and ADMET studies by targeting NMT (N-Myristoyltransferase). The designed myristic acid derivatives were synthesized by converting myristic acid into myristoyl chloride and coupling it with aryl amines to yield corresponding myristic acid derivatives. The compounds were purified and characterized via FTIR, NMR and HRMS spectral analyses. In this study, we carried out a target NMT inhibition assay. In the NMT screening assay results, the compounds and showed better inhibition compared to the other myristic acid derivatives. In an in vitro antifungal evaluation, the myristic acid derivatives were assessed against and strains by determining their minimal inhibitory concentrations (MIC). The compounds , and displayed superior antifungal capabilities against , and the compounds and displayed superior antifungal capabilities against compared to the standard drug FLZ (fluconazole). Altogether, we identified a new series of antifungal agents.
PubMed: 37508263
DOI: 10.3390/antibiotics12071167