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1.
Carbohydr Polym ; 337: 122187, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710543

ABSTRACT

The effects of different electron beam irradiation doses (2, 4, 8 KGy) and various types of fatty acids (lauric acid, stearic acid, and oleic acid) on the formation, structure, physicochemical properties, and digestibility of starch-lipid complex were investigated. The complexing index of the complexes was higher than 85 %, indicating that the three fatty acids could easily form complexes with starch. With the increase of electron beam irradiation dose, the complexing index increased first and then decreased. The highest complexing index was lauric acid (97.12 %), stearic acid (96.80 %), and oleic acid (97.51 %) at 2 KGy radiation dose, respectively. Moreover, the microstructure, crystal structure, thermal stability, rheological properties, and starch solubility were analyzed. In vitro digestibility tests showed that adding fatty acids could reduce the content of hydrolyzed starch, among which the resistant starch content of the starch-oleic acid complex was the highest (54.26 %). The lower dose of electron beam irradiation could decrease the digestibility of starch and increase the content of resistant starch.


Subject(s)
Electrons , Fatty Acids , Solubility , Starch , Starch/chemistry , Fatty Acids/chemistry , Lauric Acids/chemistry , Rheology , Hydrolysis , Oleic Acid/chemistry , Lipids/chemistry
2.
Food Microbiol ; 121: 104498, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38637069

ABSTRACT

Organic acids are widely used in foodstuffs to inhibit pathogen and spoiler growth. In this study, six organic acids (acetic, lactic, propionic, phenyllactic, caprylic, and lauric acid) and monolaurin were selected based on their physicochemical properties: their molecular structure (carbon chain length), their lipophilicity (logP), and their ability to dissociate in a liquid environment (pKa). The relation between these physicochemical properties and the inhibitory efficacy against B. weihenstephanensis KBAB4 growth was evaluated. After assessing the active form of these compounds against the strain (undissociated, dissociated or both forms), their MIC values were estimated in nutrient broth at pH 6.0 and 5.5 using two models (Lambert & Pearson, 2000; Luong, 1985). The use of two models highlighted the mode of action of an antibacterial compound in its environment, thanks to the additional estimation of the curve shape α or the Non-Inhibitory Concentration (NIC). The undissociated form of the tested acids is responsible for growth inhibition, except for lauric acid and monolaurin. Moreover, long-carbon chain acids have lower estimated MICs, compared to short-chain acids. Thus, the inhibitory efficacy of organic acids is strongly related to their carbon chain length and lipophilicity. Lipophilicity is the main mechanism of action of a membrane-active compound, it can be favored by long chain structure or high pKa in an acid environment like food.


Subject(s)
Bacillus , Laurates , Monoglycerides , Monoglycerides/pharmacology , Monoglycerides/chemistry , Acids , Lauric Acids/pharmacology , Carbon
3.
Sci Rep ; 14(1): 9270, 2024 04 23.
Article in English | MEDLINE | ID: mdl-38649421

ABSTRACT

The present study explored the anticancer activity of a Chitosan-based nanogel incorporating thiocolchicoside and lauric acid (CTL) against oral cancer cell lines (KB-1). Cell viability, AO/EtBr dual staining and Cell cycle analysis were done to evaluate the impact of CTL nanogel on oral cancer cells. Real-time PCR was performed to analyze proapoptotic and antiapoptotic gene expression in CTL-treated KB-1 cells. Further, molecular docking analysis was conducted to explore the interaction of our key ingredient, thiocolchicoside and its binding affinities. The CTL nanogel demonstrated potent anticancer activity by inhibiting oral cancer cell proliferation and inducing cell cycle arrest in cancer cells. Gene expression analysis indicated alterations in Bax and Bcl-2 genes; CTL nanogel treatment increased Bax mRNA expression and inhibited the Bcl-2 mRNA expression, which showed potential mechanisms of the CTL nanogel's anticancer action. It was found that thiocolchicoside can stabilize the protein's function or restore it as a tumour suppressor. The CTL nanogel exhibited excellent cytotoxicity and potent anticancer effects, making it a potential candidate for non-toxic chemotherapy in cancer nanomedicine. Furthermore, the nanogel's ability to modulate proapoptotic gene expression highlights its potential for targeted cancer therapy. This research contributes to the growing interest in Chitosan-based nanogels and their potential applications in cancer treatment.


Subject(s)
Antineoplastic Agents , Apoptosis , Chitosan , Colchicine , Colchicine/analogs & derivatives , Lauric Acids , Mouth Neoplasms , Nanogels , Polyethyleneimine , Humans , Chitosan/analogs & derivatives , Chitosan/chemistry , Chitosan/pharmacology , Lauric Acids/chemistry , Lauric Acids/pharmacology , Cell Line, Tumor , Nanogels/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Colchicine/pharmacology , Apoptosis/drug effects , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Molecular Docking Simulation , Cell Proliferation/drug effects , Cell Survival/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology
4.
J Mater Chem B ; 12(16): 3947-3958, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38586917

ABSTRACT

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for Fn-associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat Fn, inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for Fn-associated drug-resistant colorectal tumor. Both in vitro and in vivo studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.


Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Fluorouracil , Lauric Acids , Fluorouracil/pharmacology , Fluorouracil/chemistry , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Humans , Lauric Acids/chemistry , Lauric Acids/pharmacology , Animals , Mice , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Fusobacterium nucleatum/drug effects , Oxaliplatin/pharmacology , Oxaliplatin/chemistry , Drug Delivery Systems , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Prodrugs/chemistry , Prodrugs/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Mice, Inbred BALB C , Particle Size , Drug Carriers/chemistry
5.
Bioprocess Biosyst Eng ; 47(3): 313-323, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38438572

ABSTRACT

Molecular docking is an important computational analysis widely used to predict the interaction of enzymes with several starting materials for developing new valuable products from several starting materials, including oils and fats. In the present study, molecular docking was used as an efficient in silico screening tool to select biocatalysts with the highest catalytic performance in butyl esters production in a solvent-free system, an eco-friendly approach, via direct esterification of free fatty acids from Licuri oil with butanol. For such purpose, three commercial lipase preparations were used to perform molecular docking studies such as Burkholderia cepacia (BCL), Porcine pancreatic (PPL), and Candida rugosa (CRL). Concurrently, the results obtained in BCL and CRL are the most efficient in the esterification process due to their higher preference for catalyzing the esterification of lauric acid, the main fatty acid found in the licuri oil composition. Meanwhile, PPL was the least efficient because it preferentially interacts with minor fatty acids. Molecular docking with the experimental results indicated the better performance in the synthesis of esters was BCL. In conclusion, experimental results analysis shows higher enzymatic productivity in esterification reactions of 1294.83 µmol/h.mg, while the CRL and PPL demonstrated the lowest performance (189.87 µmol / h.mg and 23.96 µmol / h.mg, respectively). Thus, molecular docking and experimental results indicate that BCL is a more efficient lipase to produce fatty acids and esters from licuri oil with a high content of lauric acid. In addition, this study also demonstrates the application of molecular docking as an important tool for lipase screening to achieve more sustainable production of butyl esters with a view synthesis of biolubricants.


Subject(s)
Fatty Acids , Lipase , Animals , Swine , Lipase/chemistry , Molecular Docking Simulation , Catalytic Domain , Fatty Acids/chemistry , Esterification , Esters , Lauric Acids , Enzymes, Immobilized/metabolism
6.
Plant Signal Behav ; 19(1): 2332019, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38527068

ABSTRACT

Tobacco black shank (TBS), caused by Phytophthora nicotianae, is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However, the specific interaction between key secondary metabolites present in root exudates and the mechanisms of disease resistance remains poorly understood. This study conducted a comprehensive comparison via quasi-targeted metabolomic analysis on the root exudate metabolites from the tobacco cultivar Yunyan87 and K326, both before and after inoculation with P. nicotianae. The results showed that the root exudate metabolites changed after P. nicotianae inoculation, and the root exudate metabolites of different tobacco cultivar was significantly different. Furthermore, homovanillic acid, lauric acid, and isoliquiritigenin were identified as potential key compounds for TBS resistance based on their impact on the mycelium growth of the pathogens. The pot experiment showed that isoliquiritigenin reduced the incidence by 55.2%, while lauric acid reduced it by 45.8%. This suggests that isoliquiritigenin and lauric acid have potential applications in the management of TBS. In summary, this study revealed the possible resistance mechanisms of differential metabolites in resistance of commercial tobacco cultivar, and for the first time discovered the inhibitory effects of isoliquiritigenin and homovanillic acid on P. nictianae, and attempt to use plants secondary metabolites of for plant protection.


Subject(s)
Chalcones , Lauric Acids , Homovanillic Acid , Lauric Acids/pharmacology , Nicotiana
7.
J Complement Integr Med ; 21(1): 101-112, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38353231

ABSTRACT

OBJECTIVES: Lauric acid has been investigated for its effects on various human cancer cell types, although limited research has been dedicated to its impact on oral cancer. In light of this, the objective of our study was to comprehensively assess the anticancer properties of lauric acid specifically in the context of oral cancer. This evaluation was achieved through an in-silico approach, leveraging network analysis techniques. By employing this methodology, we aimed to gain valuable insights into the potential therapeutic benefits of lauric acid for treating oral cancer. METHODS: The in-silico analysis involved determination of drug-likeness prediction, prediction of common targets between oral cancer and LA, protein-protein interactions (PPI), hub genes, top 10 associated pathways by gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, molecular docking experiments. RESULTS: Our study pinpointed 23 common genes involved in critical cellular processes, including proliferation, apoptosis regulation, PI3K AKT cascade, and cell cycle control. Among them, CXCL8, MMP9, PPARA, MAPK1, and AR stood out in the top 10 pathways, particularly in the PI3K/AKT signaling pathway. This highlights the potential role of lauric acid in oral cancer treatment through the PI3K/AKT pathway and calls for further exploration of this mechanism. CONCLUSIONS: Our study highlights lauric acid's promising anticancer properties through computational analysis, offering a foundation for future research in cancer treatment development. This approach combines molecular insights with in-silico methods, paving the way for identifying therapeutic compounds and understanding their mechanisms. Lauric acid holds potential as a chemotherapeutic agent, opening up new avenues for cancer therapy exploration.


Subject(s)
Drugs, Chinese Herbal , Lauric Acids , Mouth Neoplasms , Humans , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Mouth Neoplasms/drug therapy
8.
Nutrition ; 121: 112362, 2024 May.
Article in English | MEDLINE | ID: mdl-38354680

ABSTRACT

BACKGROUND: Fatty acids (FAs) in human milk are important nutrients for infants. They play important roles in energy supply, nervous system development, and metabolic function maintenance. However, how the composition of major milk FAs change with lactation stages remains controversial. OBJECTIVES: To systematically review the concentration range of major FAs in human milk at various lactation stages. METHODS: A total of 12 papers involving 50 sets of data with 3507 participants were reviewed according to the PRISMA checklist and flow diagram. The inclusion criteria was the literatures had the FAs contents in breast milk of healthy lactation mothers at three lactation stages and the dietary patterns could be calculated. The exclusion criteria were: the studies were duplicates, were unrelated to dietary patterns or breast milk composition, and/or the study populations were unhealthy. We searched PubMed, the China National Knowledge Infrastructure, WanFang, and Web of science. Agency for Health Care Research and Quality (AHRQ) was used to assess the bias of studies. The mean values of polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), linoleic acid (LA), monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs, including lauric acid and palmitic acid), in human milk at three lactation stages (colostrum 1-7 d, transitional milk 8-14 d, mature milk 15 d-3 mo) of healthy lactating women were investigated in terms of the high protein dietary pattern. Publication biases were evaluated by Egger's test. RESULTS: According to the percentage in total fat of colostrum, transitional milk, and mature milk (% wt/wt), respectively, the results showed that PUFA (25.72%, 24.92%, and 22.69%), AA (0.85%, 0.76%, and 0.59%), DHA (0.53%, 0.47%, and 0.39%), EPA (0.15%, 0.10%, and 0.10%), and MUFA (37.39%, 37.21%, and 36.14%) contents in breast milk decreased with lactation, while another two PUFA forms, LA (17.47%, 17.82%, and 17.48%), and ALA (1.09%, 1.39%, and 1.24%) arrived at a peak in the transitional milk and then decreased in the mature milk, SFA (37.46%, 38.64%, and 40.52%), and lauric acid contents (2.78%, 4.91%, and 4.97%) increased with the lactation stages. CONCLUSION: These findings could shed light on the dynamic change progress of major FA metabolism, potentially enhancing the knowledge of lactation biology, and improving infant feeding practices to meet their needs.


Subject(s)
Fatty Acids , Lactation , Infant , Humans , Female , Fatty Acids/analysis , Lactation/metabolism , Dietary Patterns , Milk, Human/chemistry , Fatty Acids, Unsaturated , Arachidonic Acid/analysis , Linoleic Acid , Docosahexaenoic Acids/analysis , Lauric Acids/analysis , Lauric Acids/metabolism
9.
J Drug Target ; 32(4): 433-443, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38385752

ABSTRACT

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.


Subject(s)
Antineoplastic Agents , Head and Neck Neoplasms , Animals , Mice , Squamous Cell Carcinoma of Head and Neck/drug therapy , Lauric Acids , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Head and Neck Neoplasms/drug therapy
10.
Ecotoxicol Environ Saf ; 272: 116054, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38310819

ABSTRACT

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fatty Acids , Fluorocarbons , Lauric Acids , Prenatal Exposure Delayed Effects , Pregnancy , Infant , Humans , Male , Female , Cohort Studies , Bayes Theorem , China , Gonadal Steroid Hormones , Testosterone , Fluorocarbons/toxicity , Environmental Pollutants/toxicity
11.
Int J Hyg Environ Health ; 257: 114339, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38401404

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic organic chemicals with potential endocrine-disrupting effects, and have been found to impair the physical growth of offspring in both experimental and epidemiological studies. We aimed to investigate the effects of prenatal PFAS exposure on repeated measurements of multiple anthropometric indicators in infants. METHOD: PFAS were measured in serum samples collected from pregnant women at 12-16 gestational weeks. We calculated z-scores for the weight-for-age (WAZ), weight-for-length (WLZ), head circumference-for-age (HCZ), arm circumference-for-age (ACZ), triceps skinfold-for-age (TSZ), and subscapular skinfold-for-age (SSZ) at birth, 6 months, and 12 months of age according to the child growth standards of the World Health Organization (WHO) for anthropometric indicators. A total of 964 mother-infant pairs were included. A multivariate linear regression was performed to examine the associations between prenatal PFAS concentrations and anthropometric indicators at each time point. A generalized estimating equation (GEE) model was used to examine the longitudinal effects of PFAS exposure on repeated measurements of anthropometric indicators. Ultimately, a Bayesian kernel machine regression (BKMR) model was used to assess the joint effects of the PFAS mixture on anthropometric indicators. RESULTS: In GEE models, perfluorododecanoic acid (PFDoA) in the high tertile group was associated with increased WAZ/WLZ, with ß values (95% confidence intervals (CI)) of 0.12 (0.00, 0.23) and 0.18 (0.03, 0.32), respectively. Perfluorononanoic acid (PFNA) was associated with increased ACZ in the middle and high tertile groups. The BKMR models also presented the associations of the PFAS mixture with increased WAZ/WLZ throughout infancy, with more profound effects in females. Meanwhile, a pattern of inverse associations was observed between the perfluorooctanoic acid (PFOA) concentrations in the high tertile group and decreased WAZ, WLZ, and HCZ in males. In addition, the associations between PFAS and increased TSZ/SSZ at birth were identified by both linear regression and BKMR models. CONCLUSION: Prenatal PFAS exposure (PFNA and PFDoA) was associated with increased infant anthropometry, especially in female infants, while prenatal PFOA exposure was associated with decreased weight, and head and arm circumference in male infants. The findings indicate that prenatal PFAS exposure may impair the growth trajectory of offspring.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fatty Acids , Fluorocarbons , Lauric Acids , Prenatal Exposure Delayed Effects , Infant, Newborn , Infant , Child , Humans , Male , Female , Pregnancy , Prospective Studies , Bayes Theorem , Anthropometry
12.
Toxicol Mech Methods ; 34(4): 454-467, 2024 May.
Article in English | MEDLINE | ID: mdl-38166588

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin. Moreover, lauric acid significantly elevated the levels of SOD, GSH, catalase, and IL-10. Additionally, it lowered the hepatic levels of MDA, ROS, MPO, 4-HNE, interleukin (IL)-1ß, and tumor necrosis factor (TNF-α). Furthermore, lauric acid significantly up-regulated the hepatic expression of IRS1, AMPK, PI3K, and SIRT1 genes. In parallel, lauric acid could improve the histopathological picture of the liver and reduce the liver apoptosis via decreasing the expression of annexin V (Anx V). Finally, our data proposed that lauric acid could be an effective candidate for the NAFLD treatment.


Subject(s)
Lauric Acids , Non-alcoholic Fatty Liver Disease , Rats , Male , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/etiology , Diet, High-Fat/adverse effects , Rats, Sprague-Dawley , Liver , Tumor Necrosis Factor-alpha/metabolism
13.
J Oleo Sci ; 73(1): 113-119, 2024.
Article in English | MEDLINE | ID: mdl-38171727

ABSTRACT

Cluster of differentiation 36 (CD36) is a scavenger receptor expressed in various vertebrate cells that contains diverse ligands, including long-chain fatty acids. This receptor has recently been suggested as a captor of specific volatile odorants (e.g., aliphatic acetates) in the mammalian nasal epithelium. This study used a fluorescence-intensifying assay to produce the first evidence that lauric acid, an odorous fatty acid, directly binds to CD36. This expansion of the repertoire of volatile ligands supports potential applications for nasal CD36. Our present findings could promote future research aimed at understanding the mechanisms of fatty acid interactions with CD36.


Subject(s)
CD36 Antigens , Fatty Acids , Animals , CD36 Antigens/metabolism , Fluorescence , Odorants , Lauric Acids , Mammals/metabolism
14.
EMBO J ; 43(4): 507-532, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38191811

ABSTRACT

Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis of metabolic syndrome by recruiting an essential patient cohort and performing extensive gene expression profiling. The mitochondrial fatty acid metabolism enzyme acyl-CoA synthetase medium-chain family member 3 (ACSM3) was identified to be significantly lower expressed in the peripheral blood of metabolic syndrome patients. In line, hepatic ACSM3 expression was decreased in mice with metabolic syndrome. Furthermore, Acsm3 knockout mice showed glucose and lipid metabolic abnormalities, and hepatic accumulation of the ACSM3 fatty acid substrate lauric acid. Acsm3 depletion markedly decreased mitochondrial function and stimulated signaling via the p38 MAPK pathway cascade. Consistently, Acsm3 knockout mouse exhibited abnormal mitochondrial morphology, decreased ATP contents, and enhanced ROS levels in their livers. Mechanistically, Acsm3 deficiency, and lauric acid accumulation activated nuclear receptor Hnf4α-p38 MAPK signaling. In line, the p38 inhibitor Adezmapimod effectively rescued the Acsm3 depletion phenotype. Together, these findings show that disease-associated loss of ACSM3 facilitates mitochondrial dysfunction via a lauric acid-HNF4a-p38 MAPK axis, suggesting a novel therapeutic vulnerability in systemic metabolic dysfunction.


Subject(s)
Lauric Acids , Metabolic Syndrome , Humans , Mice , Animals , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Liver/metabolism , Fatty Acids/metabolism , Coenzyme A Ligases/genetics , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/pharmacology
15.
Int J Biol Macromol ; 260(Pt 2): 129526, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38242387

ABSTRACT

A model system of gelatinized wheat starch (GWS) and lauric acid (LA) was used to examine the effect of residual short-range molecular order in GWS on the formation of starch-lipid complexes. The extent of residual short-range molecular order, as determined by Raman spectroscopy, decreased with increasing water content or heating duration of gelatinization. The enthalpy changes, crystallinity, short-range molecular order and the in vitro enzymic digestion of GWS-LA complexes increased initially to a maximum and then declined as the short-range molecular order in GWS decreased, showing that there was an optimal amount of residual short-range molecular order in GWS for maximizing GWS-LA complexes formation. Below this optimum amount, the limited disruption of short-range molecular order may constrain the mobility of amylose chains for complexation with LA, whereas with excessive disruption above this amount the amylose chains may be too disorganized or entangled to form complexes with LA. The susceptibility of GWS-LA complexes to enzymatic hydrolysis was influenced by both long- and short-range structural order, and to a lesser extent the amounts of complexes. This study showed clearly the role of short-range molecular order in gelatinized starch in influencing the formation of GWS-LA complexes.


Subject(s)
Amylose , Starch , Starch/chemistry , Amylose/chemistry , Lauric Acids/chemistry , Hydrolysis
16.
Mol Nutr Food Res ; 68(2): e2300535, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38039428

ABSTRACT

SCOPE: Butyric acid (C4) and lauric acid (C12) are recognized as functional fatty acids, while the health benefits of the structural lipids they constitute remain unclear. METHODS AND RESULTS: In this study, lauric acid-butyric structural lipid (SLBL ) is synthesized through ultrasound-assisted enzyme-catalyzed acidolysis and its health benefits are evaluated in a high-fat diet-induced obesity mouse model. SLBL and its physical mixture (MLBL ) do not significantly inhibit obesity in mice. However, SLBL treatment increases the ratio of n3/n6 fatty acids in the liver and improves obesity-induced hepatic lipid metabolism disorders. Furthermore, the expression of liver pro-inflammatory cytokines (interleukin [IL]-6, IL-1ß, TNF-α) are significantly suppressed by SLBL , while the expression of anti-inflammatory cytokine (IL-10) is increased. Moreover, SLBL ameliorates the dysbiosis of small intestinal microbes induced by high-fat diet and regulates microbial community structure to be close to the control group. Especially, SLBL significantly alleviates the high-fat diet-induced decrease in Dubosiella and Bifidobacterium abundance. Correlation analysis reveals that SLBL treatment increases the abundance of microorganisms with potential anti-inflammatory function and decreases the abundance of potentially pathogenic bacteria. CONCLUSION: In all, small intestinal microbes may be a significant bridge for the positive anti-inflammatory effects of SLBL , while the exact mechanism remains to be clarified.


Subject(s)
Gastrointestinal Microbiome , Animals , Mice , Inflammation/metabolism , Obesity/metabolism , Diet, High-Fat/adverse effects , Liver/metabolism , Fatty Acids/metabolism , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Lauric Acids/pharmacology , Mice, Inbred C57BL , Lipid Metabolism
17.
Int J Biol Macromol ; 256(Pt 2): 128376, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38007029

ABSTRACT

As polyhydroxybutyrate (P(3HB)) was struggling with mechanical properties, efforts have been directed towards increasing mole fraction of 3-hydroxyhexanoate (3HHx) in P(3HB-co-3HHx) to improve the properties of polyhydroxyalkanoates (PHAs). Although genetic modification had significant results, there were several issues related to cell growth and PHA production by deletion of PHA synthetic genes. To find out easier strategy for high 3HHx mole fraction without gene deletion, Cupriavidus necator H16 containing phaC2Ra-phaACn-phaJ1Pa was examined with various oils resulting that coconut oil gave the highest 3HHx mole fraction. When fatty acid composition analysis with GC-MS was applied, coconut oil was found to have very different composition from other vegetable oil containing very high lauric acid (C12) content. To find out specific fatty acid affecting 3HHx fraction, different fatty acids from caproic acid (C6) to stearic acid (C18) was evaluated and the 3HHx mole fraction was increased to 26.5 ± 1.6 % using lauric acid. Moreover, the 3HHx mole fraction could be controlled from 9 % to 31.1 % by mixing bean oil and lauric acid with different ratios. Produced P(3HB-co-3HHx) exhibited higher molecular than P(3HB-co-3HHx) from phaB-deletion mutant. This study proposes another strategy to increase 3HHx mole fraction with easier way by modifying substrate composition without applying deletion tools.


Subject(s)
Cupriavidus necator , Polyhydroxyalkanoates , Polyhydroxybutyrates , Caproates/chemistry , 3-Hydroxybutyric Acid/chemistry , Cupriavidus necator/genetics , Coconut Oil , Hydroxybutyrates , Polyhydroxyalkanoates/chemistry , Lauric Acids
18.
Dev Comp Immunol ; 153: 105126, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38160872

ABSTRACT

The medium-chain fatty acid receptor GPR84, a member of the G protein-coupled receptor family, is mainly expressed in macrophages and microglia, and is involved in the regulation of inflammatory responses and retinal development in mammals and amphibians. However, structure, tissue distribution, and pharmacology of this receptor have rarely been reported in fish. In this study, we cloned the coding sequence (CDS) of common carp GPR84 (ccGPR84), examined its tissue distribution, and explored its cellular signaling function. The results showed that the CDS of ccGPR84 is 1191 bp and encodes a putative protein with 396 amino acids. Phylogenetic and chromosomal synteny analyses revealed that ccGPR84 was evolutionarily conserved with Cyprinids. Real-time quantitative PCR (qPCR) indicated that ccGPR84 was predominantly expressed in the intestine and spleen. Luciferase reporter assay demonstrated that nonanoic acid, capric acid (decanoic acid), undecanoic acid and lauric acid could inhibit cAMP signaling pathway and activate MAPK/ERK signaling pathway, while the potencies of these four fatty acids on the two signaling pathways were different. Lauric acid has the highest inhibitory potency on cAMP signaling pathway, followed by undecanoic acid, nonanoic acid, and capric acid. While for MAPK/ERK signaling pathway, nonanoic acid has the highest activation potency, followed by undecanoic acid, capric acid, and lauric acid. These findings lay the foundation for revealing the roles of different medium-chain fatty acids in the inflammatory response of common carp.


Subject(s)
Carps , Animals , Carps/genetics , Carps/metabolism , Phylogeny , Fatty Acids/metabolism , Decanoic Acids , Lauric Acids , Mammals
19.
Article in English | MEDLINE | ID: mdl-37967739

ABSTRACT

Lauric acid (LA) induces apoptosis in cancer and promotes the proliferation of normal cells by maintaining cellular redox homeostasis. Earlier, we postulated LA-mediated regulation of the NF-κB pathway by an epigenetic mechanism. However, the molecular mechanism and possible epigenetic events remained enigmatic. Herein, taking the lead from the alteration in cellular energetics in cancer cells upon LA exposure, we investigated whether LA exposure can epigenetically influence lncRNA HOTAIR, regulate glucose metabolism, and shift the cellular energetic state. Our results demonstrate LA induced modulation of lncRNA HOTAIR in a dose and time dependent manner. In addition, HOTAIR induces the expression of glucose transporter isoform 1 (GLUT1) and is regulated via NF-κB activation. Silencing HOTAIR by siRNA-mediated knockdown suppressed GLUT1 expression suggesting the key role of HOTAIR in LA-mediated metabolic reprogramming. Further, from our ChIP experiments, we observed that silencing HOTAIR subdues the recruitment of NF-κB on the GLUT1 (SLC2A1) promoter region. In addition, by performing western blot and immunocytochemistry studies, we found a dose dependent increase in Histone 3 Lysine 4 tri-methylation (H3K4me3) in the chromatin landscape. Taken together, our study demonstrates the epigenetic regulation in LA-treated SH-SY5Y cancer cells orchestrated by remodeling chromatin H3K4me3 and modulation of lncRNA HOTAIR that apparently governs the GLUT1 expression and regulates glucose uptake by exerting transcriptional control on NF-κB activation. Our work provides insights into the epigenetic regulation and metabolic reprogramming of LA through modulation of lncRNA HOTAIR, remodeling chromatin H3K4 tri-methylation, and shifting the energy metabolism in SH-SY5Y neuroblastoma cells.


Subject(s)
Neuroblastoma , RNA, Long Noncoding , Humans , Methylation , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Epigenesis, Genetic , Chromatin/genetics , NF-kappa B/metabolism , Macrophage Activation , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Cell Line, Tumor , Neuroblastoma/genetics , Lauric Acids , Glucose
20.
J Environ Manage ; 351: 119788, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38100857

ABSTRACT

A novel rare earth separation system composed of lauric acid (LA) and primary ammonium (RNH2) was studied. Compared with individual LA and RNH2, the mixed extraction system can significantly improve the extraction and separation ability of rare earth (RE). When LA and RNH2 are mixed in an equal molar ratio, the synergistic coefficient for extracting Nd(III) in the system reaches 136.85. Effective separation of Nd from Co and Ni can be achieved, with the separation coefficients of 1503 and 2762 for Nd/Co and Nd/Ni, respectively. The ion association mechanism of developed extraction system can avoid the generation of saponification wastewater. Thus, the negative impact of saponification wastewater on the economy and environment can be reduced. The extraction system is simple to be prepared and easy to be stripped, which helps to reduce acid and alkali consumption. Application of this extraction system can effectively realize the separation of RE elements La, Ce, Pr, Nd and transition metals Co, Ni, Mn in nickel-metal hydride (NiMH) battery. This paper provides a new strategy for the development of ionic liquid saponification technology without saponified wastewater.


Subject(s)
Lauric Acids , Metals, Rare Earth , Nickel , Amines , Wastewater , Metals
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