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Veterinary Parasitology Apr 2020The aim of the present study was to test the in vitro acaricidal activity of saturated fatty acids (hexanoic, octanoic, decanoic, lauric, myristic, palmitic,...
The aim of the present study was to test the in vitro acaricidal activity of saturated fatty acids (hexanoic, octanoic, decanoic, lauric, myristic, palmitic, octadecanoic, eicosanoic, docosanoic and tetracosanoic) against Rhipicephalus microplus and select a candidate compound for the subsequent determination of its clinical safety for mice and bovines as well as its in vivo efficacy (ethical clearance number 507/2013). None of the compounds exhibited in vitro larvicidal effectiveness, but acaricidal effectiveness was greater than 95 % in the adult immersion test at 40 mg/ml (hexanoic, octanoic, decanoic, lauric, myristic, palmitic and eicosanoic acids). After a second AIT evaluation of serial concentrations of the fatty acids, lauric and myristic acids were selected for the safety and in vivo efficacy assays. No adverse effect was found in the local lymph node assay in mice treated with lauric or myristic acid. Moreover, no clinical signs of systemic poisoning or dermatological, hematological or biochemical abnormalities were found in cattle after the topical application of 1 % lauric acid. In the dose determination test, the 1% solution of this compound exhibited 86% efficacy in cattle naturally infested by a field population of Rhipicephalus microplus susceptible to all chemical groups, except synthetic pyrethroids. The efficacy of 1 % lauric acid was 53.4 % in the dose confirmation test performed on another herd with a field R. microplus population resistant to all chemical groups of acaricides. In conclusion, fatty acids are potential bioactive compounds for the control of R. microplus. Topically applied lauric acid (C12) exhibits in vivo acaricide activity against adults, nymphs and larvae of R. (B) microplus and is safe for cattle.
Topics: Acaricides; Animals; Cattle; Cattle Diseases; Female; Larva; Lauric Acids; Nymph; Rhipicephalus; Tick Infestations
PubMed: 32251919
DOI: 10.1016/j.vetpar.2020.109095 -
ACS Omega May 2022Thermal properties, stability, and reliability of lauric acid-based binary eutectic mixtures for building energy efficiency were studied. The eutectic points and phase...
Thermal properties, stability, and reliability of lauric acid-based binary eutectic mixtures for building energy efficiency were studied. The eutectic points and phase change performance of these binary PCMs were obtained as follows: (1) For lauric acid-myristic acid, the mass eutectic point is 70 wt % LA/30 wt % MA. (2) For lauric acid-palmitic acid, the eutectic point is 79 wt % LA/21 wt % PA. (3) For lauric acid-stearic acid, the eutectic point is 82 wt % LA/18 wt % SA. The eutectic PCMs have a melting enthalpy of 166.18, 183.07, and 189.50 J·g and a melting temperature of 35.10, 37.15, and 39.29 °C for lauric-myristic acid, lauric-palmitic acid, and lauric-stearic acid binary eutectic PCMs, respectively. The experimental results are very close to the theoretical results. Moreover, from FT-IR and XRD investigations, we realized that during the preparation of the lauric acid-based binary eutectic fatty acids, no new functional groups were produced. Besides, the TG illustrated that the LA-MA eutectic PCMs, LA-PA eutectic PCMs, and LA-SA eutectic PCMs exhibit excellent thermal stability below 126.51, 135.7, and 110.08 °C, respectively. Finally, lauric acid-based binary eutectic PCMs still show excellent thermal properties and chemical structure after 500 hot and cold cycles. All in all, as a novel material for building energy conservation, lauric acid-based binary eutectic PCMs have broad prospects and good practicability.
PubMed: 35571813
DOI: 10.1021/acsomega.2c01420 -
Nature Communications Feb 2018Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor...
Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, a long-acting parenteral DTG was created through chemical modification to improve treatment outcomes. A hydrophobic and lipophilic modified DTG prodrug is encapsulated into poloxamer nanoformulations (NMDTG) and characterized by size, shape, polydispersity, and stability. Retained intracytoplasmic NMDTG particles release drug from macrophages and attenuate viral replication and spread of virus to CD4+ T cells. Pharmacokinetic tests in Balb/cJ mice show blood DTG levels at, or above, its inhibitory concentration of 64 ng/mL for 56 days, and tissue DTG levels for 28 days. NMDTG protects humanized mice from parenteral challenge of the HIV-1 strain for two weeks. These results are a first step towards producing a long-acting DTG for human use by affecting drug apparent half-life, cell and tissue drug penetration, and antiretroviral potency.
Topics: Animals; Drug Delivery Systems; Drug Evaluation, Preclinical; HIV Infections; HIV Integrase Inhibitors; Heterocyclic Compounds, 3-Ring; Humans; Male; Mice, Inbred BALB C; Myristic Acid; Nanoparticles; Oxazines; Piperazines; Pyridones
PubMed: 29402886
DOI: 10.1038/s41467-018-02885-x -
Biochimica Et Biophysica Acta.... Jul 2019Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of...
Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of type 2 diabetes. We recently found that free myristic acid (14:0), but not free palmitic acid (16:0), increased the DGKδ protein levels and enhanced glucose uptake in C2C12 myotube cells. However, it has been unclear how myristic acid regulates the level of DGKδ2 protein. In the present study, we characterized the myristic acid-dependent increase of DGKδ protein. A cycloheximide chase assay demonstrated that myristic acid, but not palmitic acid, markedly stabilized DGKδ protein. Moreover, other DGK isozymes, DGKη and ζ, as well as glucose uptake-related proteins, such as protein kinase C (PKC) α, PKCζ, Akt and glycogen synthase kinase 3β, failed to be stabilized by myristic acid. Furthermore, DGKδ was not stabilized in cultured hepatocellular carcinoma cells, pancreas carcinoma cells or neuroblastoma cells, and only a moderate stabilizing effect was observed in embryonic kidney cells. A proteasome inhibitor and a lysosome inhibitor, MG132 and chloroquine, respectively, partly inhibited DGKδ degradation, suggesting that myristic acid prevents, at least in part, the degradation of DGKδ by the ubiquitin-proteasome system and the autophagy-lysosome pathway. Overall, these results strongly suggest that myristic acid attenuates DGKδ protein degradation in skeletal muscle cells and that this attenuation is fatty acid-, protein- and cell line-specific. These new findings provide novel insights into the molecular mechanisms of the pathogenesis of type 2 diabetes mellitus.
Topics: Animals; Cell Line; Diabetes Mellitus, Type 2; Diacylglycerol Kinase; Glucose; Humans; Isoenzymes; Mice; Muscle, Skeletal; Myristic Acid; Protein Stability; Proteolysis
PubMed: 30980919
DOI: 10.1016/j.bbalip.2019.04.003 -
Methods in Enzymology 2023Protein N-terminal myristoylation is a lipidic modification typically occurring to the α-amino group of N-terminal glycine residues of proteins. It is catalyzed by the...
Protein N-terminal myristoylation is a lipidic modification typically occurring to the α-amino group of N-terminal glycine residues of proteins. It is catalyzed by the N-myristoyltransferase (NMT) enzyme family. Many studies in the past three decades have highlighted the importance of N-terminal glycine myristoylation as it affects protein localization, protein-protein interaction, and protein stability, thereby regulating multiple biological processes, including immune cell signaling, cancer progression, and infections. This book chapter will present protocols for using alkyne-tagged myristic acid to detect the N-myristoylation of targeted proteins in cell lines and compare global N-myristoylation levels. We then described a protocol of SILAC proteomics that compare the levels of N-myristoylation on a proteomic scale. These assays allow for the identification of potential NMT substrates and the development of novel NMT inhibitors.
Topics: Myristic Acid; Proteomics; Proteins; Acyltransferases; Indicators and Reagents; Glycine
PubMed: 37230589
DOI: 10.1016/bs.mie.2023.02.019 -
Bioorganic & Medicinal Chemistry Letters Oct 2023Promysalin is an amphipathic antibiotic isolated from Pseudomonas promysalinigenes (previously Pseudomonas putida RW10S1) which shows potent antibacterial activities...
Promysalin is an amphipathic antibiotic isolated from Pseudomonas promysalinigenes (previously Pseudomonas putida RW10S1) which shows potent antibacterial activities against Gram-negative pathogens by inactivating succinate dehydrogenase. Based on the in-vivo studies, promysalin is hypothesized to be assembled from three building blocks: salicylic acid, proline, and myristic acid via a proposed but uncharacterized hybrid NRPS-PKS biosynthetic pathway. So far, no in-vitro biosynthetic studies have been reported for this promising antibiotic. Here, we report the first in-vitro reconstitution and biochemical characterization of two early enzymes on the pathway: PpgH, an isochorismate synthase (IS), and PpgG, an isochorismate pyruvate lyase (IPL) which are involved in the biosynthesis of salicylic acid, the polar fragment of promysalin. We also report a secondary chorismate mutase (CM) activity for PpgG. Based on our biochemical experiments, preliminary mechanistic proposals have been postulated for PpgH and PpgG. We believe this study will lay a strong foundation for elucidating the functions and mechanisms of other intriguing enzymes of the promysalin biosynthesis pathway, which may potentially unravel interesting enzyme chemistries and promote pathway engineering in the future.
Topics: Pyrrolidines; Salicylamides; Salicylic Acid; Anti-Bacterial Agents
PubMed: 37567320
DOI: 10.1016/j.bmcl.2023.129440 -
Nature Communications Oct 2020Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often...
Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often have increased N-myristoyltransferase (NMT) expression, NMTs were proposed as anti-cancer targets. To systematically investigate this, we performed robotic cancer cell line screens and discovered a marked sensitivity of hematological cancer cell lines, including B-cell lymphomas, to the potent pan-NMT inhibitor PCLX-001. PCLX-001 treatment impacts the global myristoylation of lymphoma cell proteins and inhibits early B-cell receptor (BCR) signaling events critical for survival. In addition to abrogating myristoylation of Src family kinases, PCLX-001 also promotes their degradation and, unexpectedly, that of numerous non-myristoylated BCR effectors including c-Myc, NFκB and P-ERK, leading to cancer cell death in vitro and in xenograft models. Because some treated lymphoma patients experience relapse and die, targeting B-cell lymphomas with a NMT inhibitor potentially provides an additional much needed treatment option for lymphoma.
Topics: Acyltransferases; Adenine; Aminopyridines; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dasatinib; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Female; Humans; Lymphoma, B-Cell; Mice; Mice, SCID; Models, Biological; Myristic Acid; Piperidines; Pyrazoles; Pyrimidines; Receptors, Antigen, B-Cell; Signal Transduction; Sulfonamides; Xenograft Model Antitumor Assays; src-Family Kinases
PubMed: 33093447
DOI: 10.1038/s41467-020-18998-1 -
Journal of Food Science and Technology Feb 2020The fatty acid (FA) composition of raw, salted, and fermented fish products prepared from two populations of Baikal omul () was determined. Total lipid content in the...
The fatty acid (FA) composition of raw, salted, and fermented fish products prepared from two populations of Baikal omul () was determined. Total lipid content in the raw, salted, and fermented fish products was 3.85, 4.04, and 3.76%, respectively. Overall, the most abundant fatty acids were 14:0 (myristic acid), 16:0 (palmitic acid), 16:1n-7 (palmitoleic acid), 18:1n-9 (oleic acid), 20:5n-3 (eicosapentaenoic acid), and 22:6n-3 (docosahexaenoic acid, DHA). Polyunsaturated FAs were the main fatty acid group. Among unsaturated FA, n-3 forms dominated. The highest amounts of n-3 FAs were found in raw fish, followed by fermented and salted fish. Salting significantly increased the content of some FAs (15:0, 16:2n-4, 18:3n-3, 20:3n-3) compared with raw fish and decreased the DHA content. The FA composition of fermented fish did not differ from that of raw fish. The n-3:n-6 ratio did not differ between raw, salted, and fermented fish from population A, while the ratio was higher in raw fish from population B. Overall, thiobarbituric acid reactive substances, and thereby oxidation, were significantly lower in raw fish than in salted and fermented fish. Salting, but not fermentation, affected the FA composition of fish.
PubMed: 32116369
DOI: 10.1007/s13197-019-04091-z -
Advanced Biosystems May 2020Sub-nanoscaled polyalkoxyvanadates (PAOVs) functionalized with various aliphatic acids are evaluated for their insulin-sensitizing activity in lowering the blood glucose...
Sub-nanoscaled polyalkoxyvanadates (PAOVs) functionalized with various aliphatic acids are evaluated for their insulin-sensitizing activity in lowering the blood glucose levels of diabetic mice in typical glucose tolerance tests. All the PAOVs can restore the blood glucose to normal levels after a single oral administration of PAOVs. Among them, the myristic acid-modified PAOVs enable the response of insulin to the repeated glucose challenges, lasting for up to 13 h. The combined administration of PAOVs exerts better glucose control over insulin alone, while the capric acid- and myristic acid-modified ones can enhance the responsiveness of insulin to glucose challenge and is comparable to a clinical-used derivative of insulin. Interestingly, continuous glucose monitoring shows that myristic acid-modified PAOV derivatives sensitize the responsiveness of insulin, almost matching with that of a healthy pancreas. These discoveries open up new opportunities for the application of PAOVs to promote glucose-responsive and long-lasting activity of insulin, which are expected to aid the accurate blood glucose control in insulin therapy while reducing the number of insulin administrations.
Topics: Animals; Blood Glucose; Decanoic Acids; Diabetes Mellitus, Experimental; Insulin; Male; Mice; Myristic Acid; Vanadates
PubMed: 32402119
DOI: 10.1002/adbi.201900281 -
Early Human Development Dec 2017A mixture of eight fatty acids (lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, and linoleic acid) that are...
BACKGROUND
A mixture of eight fatty acids (lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, and linoleic acid) that are contained in human amniotic fluid, colostrum, and milk produces appetitive responses in newborns, suggesting the existence of a transition of sensorial cues that guide newborns to the maternal breast.
OBJECTIVE
To explore the ability of each of these eight fatty acids individually to produce appetitive responses in newborns.
METHODS
The study included 12 healthy human newborns<24h after birth. Using a longitudinal design, cotton swabs that were impregnated with each of the eight fatty acids and control substances (i.e., vehicle, saline, and vanilla) were placed approximately 1cm from the newborns' nostrils for 30s. Positive responses that were suggestive of acceptance included appetitive movements (i.e., suckling) and sniffing that were directed toward the cotton swab. Lateral movements of the head away from the swab were considered negative responses. Remaining stationary with no changes in facial expressions was considered indifference.
RESULTS
Compared with controls (i.e., vehicle, saline, and vanilla) and the other fatty acids tested, myristic acid produced the longest duration of positive facial responses (suckling and sniffing). No significant differences in negative facial responses were observed in response to the odoriferous stimuli. No reactions that were suggestive of disgust were observed.
CONCLUSION
A complex combination of stimuli, including the odor of myristic acid, may integrate sensory cues that guide newborns to the maternal breast.
Topics: Adolescent; Adult; Amniotic Fluid; Appetite; Female; Humans; Infant, Newborn; Male; Myristic Acid; Odorants; Sucking Behavior
PubMed: 28886572
DOI: 10.1016/j.earlhumdev.2017.08.009