-
In Vivo (Athens, Greece) 2023Acute liver injury is the hallmark of organ failure in sepsis. Enteral nutrition (EN) is an important clinical therapeutic measure in septic patients. However, the...
BACKGROUND/AIM
Acute liver injury is the hallmark of organ failure in sepsis. Enteral nutrition (EN) is an important clinical therapeutic measure in septic patients. However, the therapeutic effect of EN alone is not obvious. Here, we investigated whether octanoic acid (OA)-rich EN alleviated acute liver injury through PPARγ/STAT-1/MyD88 pathway in endotoxemic rats.
MATERIALS AND METHODS
First, rats were randomly divided into four groups: Sham, Lipopolysaccharide (LPS), LPS+EN and LPS+EN+OA groups to investigate the effect of OA-rich EN on LPS-induced acute liver injury in endotoxemic rats. Then rats were randomly divided into five groups: Sham, LPS, LPS+EN+OA, LPS+EN+OA+SR202 (SR) and LPS+ pioglitazone (PI) groups to examine whether OA-rich EN alleviated acute liver injury through the PPARγ/STAT-1/MyD88 pathway. Rats received nutrition support via a gastric tube for 3 days. We evaluated the liver histology, apoptosis, liver enzymes and inflammatory cytokine levels in the liver and serum. PPARγ/STAT-1/MyD88 pathway was also measured.
RESULTS
OA-rich EN inhibited the phosphorylation of STAT-1 and the activity of MyD88 by activating PPARγ and alleviating LPS-induced acute liver injury more effectively than EN alone in endotoxemic rats. The use of SR counteracted the effect of OA-rich EN on acute liver injury. Meanwhile, PI showed effects similar to OA-rich EN in endotoxemic rats.
CONCLUSION
OA-rich EN alleviated acute liver injury through PPARγ/STAT-1/MyD88 pathway in endotoxemic rats.
Topics: Rats; Animals; Enteral Nutrition; Lipopolysaccharides; Myeloid Differentiation Factor 88; PPAR gamma; Liver
PubMed: 37369501
DOI: 10.21873/invivo.13246 -
The Journal of Prevention of... 2023Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1)...
OBJECTIVE
Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1) whether plasma caprylic acid (C8:0) is associated with risk of incident mild cognitive impairment (MCI) among baseline cognitively normal (CN) participants, and incident Alzheimer's Disease (AD) among baseline MCI participants; and 2) whether these associations differ by sex, comorbidity of cardiometabolic diseases, apolipoprotein E (APOE) ε4 alleles, and ADAS-Cog 13.
METHODS
Within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, plasma C8:0 was measured at baseline in 618 AD-free participants aged 55 to 91. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs with incident MCI and AD as dependent variables, separately.
RESULTS
The inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among CN participants with ≥1 cardiometabolic diseases [OR (95% CI): 0.75 (0.58-0.98) (P=0.03)], those with one copy of APOE ε4 alleles [OR (95% CI): 0.43 (0.21-0.89) (P=0.02)], female [OR (95% CI): 0.60 (0.38-0.94) (P=0.02)], and ADAS-Cog 13 above the median [OR (95%CI): 0.69 (0.50-0.97)(P=0.03)] after adjusting for all covariates.
CONCLUSION
The inverse associations were present only among subgroups of CN participants, including female individuals, those with one or more cardiometabolic diseases, or one APOE ε4 allele, or higher ADAS-Cog 13 scores. If confirmed, this finding will facilitate precision prevention of MCI, in turn, AD among CN older adults.
Topics: Humans; Female; Aged; Alzheimer Disease; Apolipoprotein E4; Caprylates; Neuroimaging; Cognitive Dysfunction; Cardiovascular Diseases
PubMed: 37357292
DOI: 10.14283/jpad.2023.37 -
ACS Omega Jun 2023A simple and sensitive preconcentration method, namely, effervescence-assisted liquid-liquid microextraction based on the ternary deep eutectic solvent method, was...
Trace-Level Determination of Triazole Fungicides Using Effervescence-Assisted Liquid-Liquid Microextraction Based on Ternary Deep Eutectic Solvent Prior to High-Performance Liquid Chromatography.
A simple and sensitive preconcentration method, namely, effervescence-assisted liquid-liquid microextraction based on the ternary deep eutectic solvent method, was developed for enrichment of triazole fungicide residues prior to their determination by high-performance liquid chromatography coupled with UV detection. In this method, a ternary deep eutectic solvent (as extractant) was prepared by combination of octanoic acid, decanoic acid, and dodecanoic acid. The solution was well dispersed with sodium bicarbonate (as effervescence powder) without using auxiliary devices. In order to obtain relatively high extraction efficiency, analytical parameters were investigated and optimized. Under optimum conditions, the proposed method showed good linearity within the range of 1-1000 μg L with a coefficient for determination () greater than 0.997. The low limits of detection (LODs) were in the range of 0.3-1.0 μg L. The precisions were assessed from the relative standard deviations (RSDs) of retention time and peak area obtained from intra- ( = 3) and inter-day ( = 5 × 5) experiments, which were greater than 1.21 and 4.79%, respectively. Moreover, the proposed method provided high enrichment factors ranging from 112 to 142 folds. A matrix-match calibration method was used for analysis of real samples. Finally, the developed method was successfully applied for determination of the triazole fungicide in environmental water (near agricultural area), honey, and bean samples, and it represents a promising alternative method for analysis of triazoles. The recoveries of the studied triazoles were obtained in the range of 82-106% with an RSD less than 4.89.
PubMed: 37323407
DOI: 10.1021/acsomega.3c02919 -
International Journal of Molecular... May 2023Innovations in biocatalysts provide great prospects for intolerant environments or novel reactions. Due to the limited catalytic capacity and the long-term and...
Innovations in biocatalysts provide great prospects for intolerant environments or novel reactions. Due to the limited catalytic capacity and the long-term and labor-intensive characteristics of mining enzymes with the desired functions, de novo enzyme design was developed to obtain industrial application candidates in a rapid and convenient way. Here, based on the catalytic mechanisms and the known structures of proteins, we proposed a computational protein design strategy combining de novo enzyme design and laboratory-directed evolution. Starting with the constructed using a quantum-mechanical approach, the theoretical enzyme-skeleton combinations were assembled and optimized via the Rosetta "inside-out" protocol. A small number of designed sequences were experimentally screened using SDS-PAGE, mass spectrometry and a qualitative activity assay in which the designed enzyme 1a8uD exhibited a measurable hydrolysis activity of 24.25 ± 0.57 U/g towards p-nitrophenyl octanoate. To improve the activity of the designed enzyme, molecular dynamics simulations and the RosettaDesign application were utilized to further optimize the substrate binding mode and amino acid sequence, thus keeping the residues of intact. The redesigned lipase 1a8uD-M8 displayed enhanced hydrolysis activity towards p-nitrophenyl octanoate-3.34 times higher than that of 1a8uD. Meanwhile, the natural skeleton protein (PDB entry 1a8u) did not display any hydrolysis activity, confirming that the hydrolysis abilities of the designed 1a8uD and the redesigned 1a8uD-M8 were devised from scratch. More importantly, the designed 1a8uD-M8 was also able to hydrolyze the natural middle-chained substrate (glycerol trioctanoate), for which the activity was 27.67 ± 0.69 U/g. This study indicates that the strategy employed here has great potential to generate novel enzymes exhibiting the desired reactions.
Topics: Lipase; Hydrolysis; Caprylates; Proteins; Fatty Acids; Substrate Specificity; Esters
PubMed: 37239928
DOI: 10.3390/ijms24108581 -
ACS Pharmacology & Translational Science May 2023Pathological fibrosis is distinguished from physiological wound healing by persistent myofibroblast activation, suggesting that therapies that induce myofibroblast...
Pathological fibrosis is distinguished from physiological wound healing by persistent myofibroblast activation, suggesting that therapies that induce myofibroblast apoptosis selectively could prevent progression and potentially reverse the established fibrosis, such as for scleroderma (a heterogeneous autoimmune disease characterized by multiorgan fibrosis). Navitoclax (NAVI) is a BCL-2/BCL-xL inhibitor with antifibrotic properties and has been investigated as a potential therapeutic for fibrosis. NAVI makes myofibroblasts particularly vulnerable to apoptosis. However, despite NAVI's significant potency, clinical translation of BCL-2 inhibitors, NAVI in this case, is hindered due to the risk of thrombocytopenia. Therefore, in this work, we utilized a newly developed ionic liquid formulation of NAVI for direct topical application to the skin, thereby avoiding systemic circulation and off-target-mediated side effects. The ionic liquid composed of choline and octanoic acid (COA) at a 1:2 molar ionic ratio increases skin diffusion and transportation of NAVI and maintains their retention within the dermis for a prolonged duration. Topical administration of NAVI-mediated BCL-xL and BCL-2 inhibition results in the transition of myofibroblast to fibroblast and ameliorates pre-existing fibrosis, as demonstrated in a scleroderma mouse model. We have observed a significant reduction of α-SMA and collagen, which are known as fibrosis marker proteins, as a result of the inhibition of anti-apoptotic proteins BCL-2/BCL-xL. Overall, our findings show that COA-assisted topical delivery of NAVI upregulates apoptosis specific to myofibroblasts, with minimal presence of the drug in the systemic circulation, resulting in an accelerated therapeutic effect with no discernible drug-associated toxicity.
PubMed: 37200808
DOI: 10.1021/acsptsci.3c00039 -
Scientific Reports May 2023We found that Drosophila species vary in their susceptibility to the broad-spectrum entomopathogen, Metarhizium anisopliae (strain Ma549). Generalist species were...
We found that Drosophila species vary in their susceptibility to the broad-spectrum entomopathogen, Metarhizium anisopliae (strain Ma549). Generalist species were generally more resistant than dietary specialists, with the cactophilic Drosophila buzzatii and Drosophila sechellia, a specialist of the Morinda citrifolia (Morinda) fruit, being most susceptible. Morinda fruit is reported to be toxic to most herbivores because it contains Octanoic Acid (OA). We confirmed that OA is toxic to Drosophila spp., other than D. sechellia, and we also found that OA is highly toxic to entomopathogenic fungi including Ma549 and Beauveria bassiana. Drosophila sechellia fed a diet containing OA, even at levels much less than found in Morinda fruit, had greatly reduced susceptibility to Ma549. This suggests that specializing to Morinda may have provided an enemy-free space, reducing adaptive prioritization on a strong immune response. Our results demonstrate that M. anisopliae and Drosophila species with divergent lifestyles provide a versatile model system for understanding the mechanisms of host-pathogen interactions at different scales and in environmental context.
Topics: Animals; Drosophila; Disease Resistance; Caprylates; Genetic Variation; Metarhizium
PubMed: 37179396
DOI: 10.1038/s41598-023-34976-1 -
BMC Cancer May 2023In previous study, we found that the content of medium-chain fatty acid Caprylic Acid (FFA C8:0) may be an important risk factor of obesity induced prostate cancer...
BACKGROUND
In previous study, we found that the content of medium-chain fatty acid Caprylic Acid (FFA C8:0) may be an important risk factor of obesity induced prostate cancer (PCa). However, the relationship between FFA C8:0 and PCa has not been reported. In this study, we explored whether the FFA C8:0 can promotes the progression of PCa by up-regulating Krüppel-like factor 7 (KLF7).
METHODS
We collected tissues from PCa patients and Benign Prostate Hyperplasia (BPH), constructed a primary-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, CCK8 assay, plate cloning, Transwell and scratch experiment were used to detect the changes in biological behavior of PCa cells stimulated by FFA C8:0.
RESULTS
First, we found that the expression level of KLF7 is higher in PCa tissues of patients, and the expression of KLF7 is positively correlated with tumour-promoting gene IL-6, while it is negative correlated with another tumour-suppressor gene p21. Then, this study found that PCa cells were more likely to form tumors in diet induced obese mice. Compared with the normal diet group (ND), the expression levels of KLF7 in tumor tissues in high-fat diet group (HFD) were higher. Futhermore, we verified that high concentrations of FFA C8:0 can promote the biological behavior of PCa cells by activating KLF7/IL-6/p21 signaling pathway, which is mediated by the GPR84.
CONCLUSIONS
Our research may provide a potential target for clinical prevention and treatment of PCa which induced by obesity.
Topics: Humans; Male; Mice; Animals; Cell Line, Tumor; Interleukin-6; Prostatic Neoplasms; Kruppel-Like Transcription Factors; Receptors, G-Protein-Coupled; Obesity
PubMed: 37170248
DOI: 10.1186/s12885-023-10841-2 -
Food Science and Biotechnology Jun 2023In this study, gas chromatography-mass spectrometry (GC-MS) coupled with Partial least squares Discriminant Analysis (PLS-DA) was used to analyze the volatiles in...
UNLABELLED
In this study, gas chromatography-mass spectrometry (GC-MS) coupled with Partial least squares Discriminant Analysis (PLS-DA) was used to analyze the volatiles in Chinese breast milk from different cities (Wuhan, Qingdao and Hohhot) and different lactation stages (colostrum and mature milk). The results showed that breast milk contained 122 volatile substances in 9 major groups, with the largest number of olefins (36) and the highest content of acids. The different volatile compounds of breast milk in three cities were heptanal, 2-pentylfuran, (E)-2,4-decadienal, (E)-2-heptenal, (E)-2-nonenal and 1-octen-3-one, colostrum and mature milk were (E)-2-heptenal, (E)-2-decenal, lauric acid, -decanoic acid, (E)-2-nonenal and octanoic acid. This study might provide scientific data for the development and optimization of formulas that were more suitable for the health of Chinese infants.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10068-022-01235-4.
PubMed: 37123065
DOI: 10.1007/s10068-022-01235-4 -
Biotechnology For Biofuels and... Apr 2023Medium-chain fatty acids are molecules with applications in different industries and with growing demand. However, the current methods for their extraction are not...
BACKGROUND
Medium-chain fatty acids are molecules with applications in different industries and with growing demand. However, the current methods for their extraction are not environmentally sustainable. The reverse β-oxidation pathway is an energy-efficient pathway that produces medium-chain fatty acids in microorganisms, and its use in Saccharomyces cerevisiae, a broadly used industrial microorganism, is desired. However, the application of this pathway in this organism has so far either led to low titers or to the predominant production of short-chain fatty acids.
RESULTS
We genetically engineered Saccharomyces cerevisiae to produce the medium-chain fatty acids hexanoic and octanoic acid using novel variants of the reverse β-oxidation pathway. We first knocked out glycerolphosphate dehydrogenase GPD2 in an alcohol dehydrogenases knock-out strain (△adh1-5) to increase the NADH availability for the pathway, which significantly increased the production of butyric acid (78 mg/L) and hexanoic acid (2 mg/L) when the pathway was expressed from a plasmid with BktB as thiolase. Then, we tested different enzymes for the subsequent pathway reactions: the 3-hydroxyacyl-CoA dehydrogenase PaaH1 increased hexanoic acid production to 33 mg/L, and the expression of enoyl-CoA hydratases Crt2 or Ech was critical to producing octanoic acid, reaching titers of 40 mg/L in both cases. In all cases, Ter from Treponema denticola was the preferred trans-enoyl-CoA reductase. The titers of hexanoic acid and octanoic acid were further increased to almost 75 mg/L and 60 mg/L, respectively, when the pathway expression cassette was integrated into the genome and the fermentation was performed in a highly buffered YPD medium. We also co-expressed a butyryl-CoA pathway variant to increase the butyryl-CoA pool and support the chain extension. However, this mainly increased the titers of butyric acid and only slightly increased that of hexanoic acid. Finally, we also tested the deletion of two potential medium-chain acyl-CoA depleting reactions catalyzed by the thioesterase Tes1 and the medium-chain fatty acyl CoA synthase Faa2. However, their deletion did not affect the production titers.
CONCLUSIONS
By engineering the NADH metabolism and testing different reverse β-oxidation pathway variants, we extended the product spectrum and obtained the highest titers of octanoic acid and hexanoic acid reported in S. cerevisiae. Product toxicity and enzyme specificity must be addressed for the industrial application of the pathway in this organism.
PubMed: 37101299
DOI: 10.1186/s13068-023-02317-z -
Frontiers in Immunology 2023Dietary high soybean oil (SO) levels might cause hepatic lipid deposition, induce oxidative stress and inflammatory response in aquatic animals, while octanoate (OCT) is...
Effects of supplemental octanoate on hepatic lipid metabolism, serum biochemical indexes, antioxidant capacity and inflammation-related genes expression of large yellow croaker () fed with high soybean oil diet.
Dietary high soybean oil (SO) levels might cause hepatic lipid deposition, induce oxidative stress and inflammatory response in aquatic animals, while octanoate (OCT) is beneficial to metabolism and health in mammals. However, the effect of OCT has been studied rarely in aquatic animals. In this study, a 10-week feeding trial was conducted to investigate the effect of supplemental OCT on hepatic lipid metabolism, serum biochemical indexes, antioxidant capacity and inflammatory response of large yellow croaker () fed with high SO levels diet. The negative control diet contained 7% fish oil (FO), while the positive control diet contained 7% SO. The other four experimental diets were supplemented with 0.7, 2.1, 6.3 and 18.9 g/kg sodium octanoate (OCT) based on the positive control diet. Results showed that OCT supplementation effectively reduced the hepatic crude lipid, triglyceride (TG), total cholesterol (TC) and non-esterified free fatty acids contents, and alleviated lipid accumulation caused by the SO diet. Meanwhile, OCT supplementation decreased the serum TG, TC, alanine transaminase, aspartate transaminase and low-density lipoprotein cholesterol levels, increased the serum high-density lipoprotein cholesterol level, improved the serum lipid profiles and alleviated hepatic injury. Furthermore, with the supplementation of OCT, the mRNA expression of genes related to lipogenesis (, , , , and ) and fatty acid (FA) transport ( and ) were down-regulated, while the mRNA expression of genes related to lipolysis (, and ) and FA β-oxidation ( and ) were up-regulated. Besides that, dietary OCT increased the total antioxidant capacity, activities of peroxidase, catalase and superoxide dismutase and the content of reduced glutathione, decreased the content of 8-hydroxy-deoxyguanosine and malondialdehyde and relieved hepatic oxidative stress. Supplementation of 0.7 and 2.1 g/kg OCT down-regulated the mRNA expression of genes related to pro-inflammatory cytokines (, and ), and suppressed hepatic inflammatory response. In conclusion, supplementation with 0.7-2.1 g/kg OCT could reduce hepatic lipid accumulation, relieve oxidative stress and regulate inflammatory response in large yellow croaker fed the diet with high SO levels, providing a new way to alleviate the hepatic fat deposition in aquatic animals.
Topics: Animals; Antioxidants; Soybean Oil; Caprylates; Lipid Metabolism; Diet; Inflammation; Perciformes; RNA, Messenger; Cholesterol; Mammals
PubMed: 37051230
DOI: 10.3389/fimmu.2023.1162633