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The Journal of Biological Chemistry May 2024Aristolochic acids I and II (AA-I/II) are carcinogenic principles of Aristolochia plants, which have been employed in traditional medicinal practices and discovered as...
Aristolochic acids I and II (AA-I/II) are carcinogenic principles of Aristolochia plants, which have been employed in traditional medicinal practices and discovered as food contaminants. While the deleterious effects of AAs are broadly acknowledged, there is a dearth of information to define the mechanisms underlying their carcinogenicity. Following bioactivation in the liver, N-hydroxyaristolactam and N-sulfonyloxyaristolactam metabolites are transported via circulation and elicit carcinogenic effects by reacting with cellular DNA. In this study, we apply DNA adduct analysis, X-ray crystallography, isothermal titration calorimetry (ITC) and fluorescence quenching to investigate the role of human serum albumin (HSA) in modulating AA carcinogenicity. We find that HSA extends the half-life and reactivity of N-sulfonyloxyaristolactam-I with DNA, thereby protecting activated AAs from heterolysis. Applying novel pooled plasma HSA crystallization methods, we report high-resolution structures of myristic acid-enriched HSA (HSA) and its AA complexes (HSA/AA-I and HSA/AA-II) at 1.9 Å resolution. Whereas AA-I is located within HSA subdomain IB, AA-II occupies subdomains IIA and IB. ITC binding profiles reveal two distinct AA sites in both complexes with association constants of 1.5 and 0.5 · 10 M for HSA/AA-I versus 8.4 and 9.0 · 10 M for HSA/AA-II. Fluorescence quenching of the HSA Trp suggests variable impacts of fatty acids on ligand binding affinities. Collectively, our structural and thermodynamic characterizations yield significant insights into AA binding, transport, toxicity, and potential allostery, critical determinants for elucidating the mechanistic roles of HSA in modulating AA carcinogenicity.
PubMed: 38782206
DOI: 10.1016/j.jbc.2024.107358 -
Journal of Dairy Science May 2024Typically, Swiss-type cheese is made from cow's milk. However, in the present work an attempt to expand the sheep supply chain and product offering in this field was...
Typically, Swiss-type cheese is made from cow's milk. However, in the present work an attempt to expand the sheep supply chain and product offering in this field was made by developing a new type of cheese using Swiss-type cheese technology. The cheese was manufactured under industrial conditions, and fermentations were carried out using freeze-dried commercial starters that are traditionally used in the production of Swiss cheese. Two experimental "Ewiss cheese" (EC) products were produced using raw milk (RM-EC) and pasteurized milk (PM-EC), respectively. Fourteen microbial groups were investigated by plate counts from curd until ripened cheeses. According to microbiological analyses, no statistically significant differences were found between the 2 productions with respect to the group of lactic acid bacteria (LAB). The curds were mainly characterized by mesophilic LAB cocci (7.45 log cfu/g in RM-EC and 7.33 log cfu /g in PM-EC). However, at the end of the ripening period (9 mo), the cheeses exhibited a higher presence of mesophilic LAB rods. Undesired microbiological groups were found only in the curd of raw milk cheese in the range of 10-10 cfu/g, but reaching undetectable levels by plate count in the cheese at the end of ripening. RM-EC and PM-EC were characterized by 76% and 68% of dry matter, respectively. These cheeses contained 29.30% and 34.36% of protein, and 51.31% and 50.38% of fat, respectively. Textural analysis showed differences in terms of hardness, chewiness, and gumminess between the experimental cheeses and Swiss cheese sold on the market. These differences could be attributed to the higher protein content of ewe's milk. The main fatty acids in the cheeses were palmitic acid, myristic acid, oleic acid, and capric acid. Among the organic acids, RM-EC had higher concentrations of lactic acid, while PM-EC was higher in propionic acid. The ewe's cheeses emitted 46 volatile compounds, including acids, aldehydes, ketones, esters, alcohols, and other compounds. PM-EC was characterized by the main compounds of Swiss-type cheese: acetic acid, butyric acid, ethyl butyrate, ethyl caproate, propanoic acid, and tetramethylpyrazine. Sensory evaluation showed that the new dairy products were generally appreciated, and PM-EC was the most preferred by the judges. This research has enabled the development of new ewe's milk products, which could stimulate the valorization of a sector that has been long neglected and still has a large margin of improvement.
PubMed: 38754834
DOI: 10.3168/jds.2024-24711 -
Polymers May 2024It has been established that the wild-type B-10646 strain uses saturated fatty acids (SFAs) for growth and polyhydroxyalkanoate (PHA) synthesis. It uses lauric (12:0),...
It has been established that the wild-type B-10646 strain uses saturated fatty acids (SFAs) for growth and polyhydroxyalkanoate (PHA) synthesis. It uses lauric (12:0), myristic (14:0), palmitic (16:0) and stearic (18:0) acids as carbon sources; moreover, the elongation of the C-chain negatively affects the biomass and PHA yields. When bacteria grow on C12 and C14 fatty acids, the total biomass and PHA yields are comparable up to 7.5 g/L and 75%, respectively, which twice exceed the values that occur on longer C16 and C18 acids. Regardless of the type of SFAs, bacteria synthesize poly(3-hydroxybutyrate), which have a reduced crystallinity (C from 40 to 57%) and a molecular weight typical for poly(3-hydroxybutyrate) (P(3HB)) (M from 289 to 465 kDa), and obtained polymer samples demonstrate melting and degradation temperatures with a gap of about 100 °C. The ability of bacteria to assimilate SFAs opens up the possibility of attracting the synthesis of PHAs on complex fat-containing substrates, including waste.
PubMed: 38732762
DOI: 10.3390/polym16091294 -
Journal of Translational Medicine May 2024In humans, two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, catalyze myristate transfer to proteins to facilitate membrane targeting and signaling. We...
BACKGROUND
In humans, two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, catalyze myristate transfer to proteins to facilitate membrane targeting and signaling. We investigated the expression of NMTs in numerous cancers and found that NMT2 levels are dysregulated by epigenetic suppression, particularly so in hematologic malignancies. This suggests that pharmacological inhibition of the remaining NMT1 could allow for the selective killing of these cells, sparing normal cells with both NMTs.
METHODS AND RESULTS
Transcriptomic analysis of 1200 NMT inhibitor (NMTI)-treated cancer cell lines revealed that NMTI sensitivity relates not only to NMT2 loss or NMT1 dependency, but also correlates with a myristoylation inhibition sensitivity signature comprising 54 genes (MISS-54) enriched in hematologic cancers as well as testis, brain, lung, ovary, and colon cancers. Because non-myristoylated proteins are degraded by a glycine-specific N-degron, differential proteomics revealed the major impact of abrogating NMT1 genetically using CRISPR/Cas9 in cancer cells was surprisingly to reduce mitochondrial respiratory complex I proteins rather than cell signaling proteins, some of which were also reduced, albeit to a lesser extent. Cancer cell treatments with the first-in-class NMTI PCLX-001 (zelenirstat), which is undergoing human phase 1/2a trials in advanced lymphoma and solid tumors, recapitulated these effects. The most downregulated myristoylated mitochondrial protein was NDUFAF4, a complex I assembly factor. Knockout of NDUFAF4 or in vitro cell treatment with zelenirstat resulted in loss of complex I, oxidative phosphorylation and respiration, which impacted metabolomes.
CONCLUSIONS
Targeting of both, oxidative phosphorylation and cell signaling partly explains the lethal effects of zelenirstat in select cancer types. While the prognostic value of the sensitivity score MISS-54 remains to be validated in patients, our findings continue to warrant the clinical development of zelenirstat as cancer treatment.
Topics: Humans; Neoplasms; Cell Line, Tumor; Oxidative Phosphorylation; Acyltransferases; Myristic Acid; Proteomics; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Multiomics
PubMed: 38715059
DOI: 10.1186/s12967-024-05150-6 -
Chemosphere Jun 2024The accumulation of fat, oil and grease (FOG) deposits in sanitary sewer systems is a significant cause of sewer overflows, mainly due to their tendency to adhere to...
The accumulation of fat, oil and grease (FOG) deposits in sanitary sewer systems is a significant cause of sewer overflows, mainly due to their tendency to adhere to pipe walls. The aim of this study is to (i) develop laboratory-prepared FOG deposits using a mixture of iron (Fe) and aluminium (Al) metal ions, fatty acids, saccharides and cooked oils, in addition to various sanitary waste materials such as paper towels, wipes and pads and (ii) examine the characteristics of these FOG deposits. The goals of this study were to (i) gain a deeper understanding of the impact of sanitary waste on the formation of FOG deposits and (ii) discuss the detailed physiochemical properties of these FOG deposits. The findings revealed that FOG deposits can vary in nature, appearing as either a smooth, paste-like substance or a coarse, semi-solid material, depending on the types of waste present in the sewer. Analysis of the fatty acid profile indicated that the FOG deposits with wipes have the highest viscosity (3.2 × 10 Pa s) and larger composition of smaller chain saturated fatty acids (caprylic acid 0.64%, undecanoic acid 5.61%, lauric acid 4.65%, myristic acid 3.21% and palmitic 8.38%). In contrast, FOG deposits with Fe and Al metal impurities have higher heat resistance and thermal stability (melting point of 125 °C) and have larger composition of long chain fatty acids. Furthermore, FTIR analysis confirmed that these FOG deposits are composed of metallic salts of fatty acids, aligning with samples from sewer lines. Our results suggest that FOG deposit formation involves the aggregation of excess calcium, which compresses free fatty acid micelles, and a saponification reaction between the calcium aggregates and free fatty acids. This research illuminates the complex processes behind FOG deposit formation and their varied characteristics, providing valuable insights into potential strategies for preventing FOG-related sewer blockages.
Topics: Sewage; Fats; Fatty Acids; Oils; Iron; Waste Disposal, Fluid; Drainage, Sanitary
PubMed: 38685332
DOI: 10.1016/j.chemosphere.2024.142183 -
Physicochemical properties and fatty acid profile of oil extracted from black soldier fly larvae ().Veterinary World Mar 2024, a black soldier fly, is widely recognized for sustainable recycling of organic waste. Black soldier fly larvae (BSFLs) can consume various types of biowastes and...
BACKGROUND AND AIM
, a black soldier fly, is widely recognized for sustainable recycling of organic waste. Black soldier fly larvae (BSFLs) can consume various types of biowastes and convert them into nutrient-rich biomass, including proteins, lipids, chitin, and minerals. This study investigated the best extraction method by comparing the fatty acid profiles, percentage yield, and antioxidant properties of BSFL oil extracted using different extraction methods.
MATERIALS AND METHODS
The physicochemical properties, fatty acid profile, and free radical scavenging ability of BSFL oil were analyzed using six extraction methods.
RESULTS
Ultrasonic extraction with hexane resulted in the highest yields compared with different extraction methods. Lauric acid (28%-37%) was the most abundant fatty acid in all extracts, followed by palmitic acid, myristic acid, oleic acid, and linoleic acid. Compared with other methods, aqueous extraction showed the highest lauric acid composition and free radical scavenging activities. In addition, high-temperature aqueous extraction resulted in higher oil yield and free radical scavenging activities than low-temperature extraction.
CONCLUSION
High-temperature aqueous extraction is the best extraction method because it is rich in lauric acid, has antioxidant ability, and can be further developed to produce novel sustainable biomaterials for humans and animals.
PubMed: 38680136
DOI: 10.14202/vetworld.2024.518-526 -
The Journal of Nutrition, Health & Aging Apr 2024Hip fractures are associated with a high burden of morbidity and mortality. Diet is essential for preventing fragility fractures, but the role of dietary fatty acids on...
OBJECTIVES
Hip fractures are associated with a high burden of morbidity and mortality. Diet is essential for preventing fragility fractures, but the role of dietary fatty acids on the risk of hip fracture is uncertain. The aim was to investigate how intake of different dietary fatty acids relates to the risk of hip fracture. A relative validation of the long-term intake of dietary fatty acids estimated from food frequency questionnaires (FFQs) was also performed.
DESIGN, SETTINGS AND PARTICIPANTS
We used data collected in two population-based cohorts, the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men, aged 45-82 years). Data from the repeated investigations in the cohorts and cross-sectional data from their clinical sub-cohorts were used.
MEASUREMENTS
Diet data was collected in FFQs. Incident hip fractures were gathered by individual linkage to national registers. We performed Cox regression analysis to investigate associations between dietary fatty acids and hip fracture. Follow-up time was between January 1st, 1998 and December 31st, 2020. The validation was performed using correlation analyses, comparing fatty acids measured in adipose tissue with estimated fatty acid intakes from FFQs.
RESULTS
During up to 23 years of follow-up (mean 18 years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. A low linoleic acid (LA) and high intakes of long-chain n-3 fatty acids were associated with higher hip fracture risk in a non-linear way. In quartile 4 compared to quartile 1 of LA, the multivariable-adjusted hazard ratio of hip fracture was 0.89 (95% Confidence Interval: 0.81, 0.97). The study confirmed the validity of FFQs to capture the intake of the specific dietary long-chain n-3 fatty acids. The estimated intake of LA, α-linolenic acid, and myristic acid were also adequately captured by the FFQs. Validity was confirmed in both women and men.
CONCLUSION
A low to moderate intake of linoleic acid and a higher intake of long-chain n-3 fatty acids were associated with a higher risk of hip fractures. The results indicate that attention should be paid to dietary fatty acid composition for the optimal prevention of fragility fractures.
PubMed: 38669838
DOI: 10.1016/j.jnha.2024.100247 -
Heliyon Apr 2024, commonly known as the African Baobab plant is used widely in traditional medicine for treating of many diseases. The current study investigates the antioxidant and...
, commonly known as the African Baobab plant is used widely in traditional medicine for treating of many diseases. The current study investigates the antioxidant and antimicrobial properties, and nutritional composition of the pulp and seeds from the fruit of African Baobab plant. Matured fruits were harvested and processed by separating the fruit pulp and seeds. Water, 70 % Ethanol/water mixture, and Hexane were used as solvents for extraction. Antioxidant properties of extracts in this study were investigated using the 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxidescavenging assays., Total Flavonoid Content, Total Phenolic Content, Total Tannin Content, and Total Antioxidant Capacity were also investigated. Agar Well Diffusion and Broth Dilution methods were used to estimate the antimicrobial properties of the extracts. The proximate composition of the seeds and fruit pulps was also determined. GC-MS was employed to determine the fatty acid composition. Results obtained showed the presence of Total phenolics (range 4.1-5.5 mg GAE/g), Total flavonoids (range 10.1-16.5 mg QE/g), Total Tannins (range 1.7-15.6 mg CE/g), and Antioxidants (range 2.0-14.5 mg AAE/g). The HO and DPPH assays gave ICs in the ranges of 300-1800 mg/L and 700-1600 mg/L respectively. Extract from the fruit pulp was found to inhibit the growth of a panel of 2 g-positive bacteria, 2 g-negative bacteria, and two fungi microorganisms. Fatty acids such as myristic acid, palmitic acid, and stearic acid were found to be present in oil from the seeds. Proximate components such as crude protein, crude fat, and crude fibre were found to be high. From the results, seeds and the fruit pulp of the African Baobab plant have significant antioxidant properties and can inhibit microbial growth.
PubMed: 38665573
DOI: 10.1016/j.heliyon.2024.e29660 -
Frontiers in Medicine 2024Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the...
BACKGROUND
Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC).
METHODS
EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and isolation was analyzed, which may relate to the severity of bronchiectasis disease.
RESULTS
Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in (+) group compared to the (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with isolation.
CONCLUSION
The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.
PubMed: 38633315
DOI: 10.3389/fmed.2024.1345165 -
PloS One 2024The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable...
The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable N-terminal extension of the G domain modified with myristate. Arf proteins, including Arf1, have roles in membrane trafficking and cytoskeletal dynamics. While screening for Arf1:small molecule co-crystals, we serendipitously solved the crystal structure of the non-myristoylated engineered mutation [L8K]Arf1 in complex with a GDP analogue. Like wild-type (WT) non-myristoylated Arf1•GDP, we observed that [L8K]Arf1 exhibited an N-terminal helix that occludes the hydrophobic cavity that is occupied by the myristoyl group in the GDP-bound state of the native protein. However, the helices were offset from one another due to the L8K mutation, with a significant change in position of the hinge region connecting the N-terminus to the G domain. Hypothesizing that the observed effects on behavior of the N-terminus affects interaction with regulatory proteins, we mutated two hydrophobic residues to examine the role of the N-terminal extension for interaction with guanine nucleotide exchange factors (GEFs) and GTPase Activating Proteins (GAPs. Different than previous studies, all mutations were examined in the context of myristoylated Arf. Mutations had little or no effect on spontaneous or GEF-catalyzed guanine nucleotide exchange but did affect interaction with GAPs. [F13A]myrArf1 was less than 1/2500, 1/1500, and 1/200 efficient as substrate for the GAPs ASAP1, ARAP1 and AGAP1; however, [L8A/F13A]myrArf1 was similar to WT myrArf1. Using molecular dynamics simulations, the effect of the mutations on forming alpha helices adjacent to a membrane surface was examined, yet no differences were detected. The results indicate that lipid modifications of GTPases and consequent anchoring to a membrane influences protein function beyond simple membrane localization. Hypothetical mechanisms are discussed.
Topics: GTPase-Activating Proteins; Myristates; Point Mutation; Myristic Acid; ADP-Ribosylation Factor 1; ADP-Ribosylation Factors; Guanine Nucleotide Exchange Factors
PubMed: 38574162
DOI: 10.1371/journal.pone.0295103