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Antimicrobial Agents and Chemotherapy Jul 2022Metronidazole (Met) is the first choice for treating Helicobacter pylori (). However, is easy to resistant, making Met unable to be widely used. How to overcome 's Met...
Metronidazole (Met) is the first choice for treating Helicobacter pylori (). However, is easy to resistant, making Met unable to be widely used. How to overcome 's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to were 2~4 μg/mL, 8~16 μg/mL. Moreover, experiments, Lla-Met significantly reduced the colonization of drug-resistant in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 μg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, G27 continued for 18 days with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non- species with 128 μg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive , with a capability of overcoming the metronidazole resistance of
Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Drug Resistance; Helicobacter Infections; Helicobacter pylori; Metronidazole; Mice; alpha-Linolenic Acid
PubMed: 35758720
DOI: 10.1128/aac.00073-22 -
Molecules (Basel, Switzerland) Jan 2022Water shortage caused by long-term drought is one of the most serious abiotic stress factors in maize. Different drought conditions lead to differences in growth,...
Water shortage caused by long-term drought is one of the most serious abiotic stress factors in maize. Different drought conditions lead to differences in growth, development, and metabolism of maize. In previous studies, proteomics and genomics methods have been widely used to explain the response mechanism of maize to long-term drought, but there are only a few articles related to metabolomics. In this study, we used transcriptome and metabolomics analysis to characterize the differential effects of drought stress imposed at seedling or flowering stages on maize. Through the association analysis of genes and metabolites, we found that maize leaves had 61 and 54 enriched pathways under seedling drought and flowering drought, respectively, of which 13 and 11 were significant key pathways, mostly related to the biosynthesis of flavonoids and phenylpropanes, glutathione metabolism and purine metabolism. Interestingly, we found that the α-linolenic acid metabolic pathway differed significantly between the two treatments, and a total of 10 differentially expressed genes and five differentially abundant metabolites have been identified in this pathway. Some differential accumulation of metabolites (DAMs) was related to synthesis of jasmonic acid, which may be one of the key pathways underpinning maize response to different types of long-term drought. In general, metabolomics provides a new method for the study of water stress in maize and lays a theoretical foundation for drought-resistant cultivation of silage maize.
Topics: Droughts; Flowers; Gene Expression Regulation, Plant; Genes, Plant; Metabolomics; Seedlings; Stress, Physiological; Zea mays; alpha-Linolenic Acid
PubMed: 35164035
DOI: 10.3390/molecules27030771 -
BMC Genomics Apr 2021Paeonia ostii is a potentially important oilseed crop because its seed yield is high, and the seeds are rich in α-linolenic acid (ALA). However, the molecular...
BACKGROUND
Paeonia ostii is a potentially important oilseed crop because its seed yield is high, and the seeds are rich in α-linolenic acid (ALA). However, the molecular mechanisms underlying ALA biosynthesis during seed kernel, seed testa, and fruit pericarp development in this plant are unclear. We used transcriptome data to address this knowledge gap.
RESULTS
Gas chromatograph-mass spectrometry indicated that ALA content was highest in the kernel, moderate in the testa, and lowest in the pericarp. Therefore, we used RNA-sequencing to compare ALA synthesis among these three tissues. We identified 227,837 unigenes, with an average length of 755 bp. Of these, 1371 unigenes were associated with lipid metabolism. The fatty acid (FA) biosynthesis and metabolism pathways were significantly enriched during the early stages of oil accumulation in the kernel. ALA biosynthesis was significantly enriched in parallel with increasing ALA content in the testa, but these metabolic pathways were not significantly enriched during pericarp development. By comparing unigene transcription profiles with patterns of ALA accumulation, specific unigenes encoding crucial enzymes and transcription factors (TFs) involved in de novo FA biosynthesis and oil accumulation were identified. Specifically, the bell-shaped expression patterns of genes encoding SAD, FAD2, FAD3, PDCT, PDAT, OLE, CLE, and SLE in the kernel were similar to the patterns of ALA accumulation in this tissue. Genes encoding BCCP, BC, KAS I- III, and FATA were also upregulated during the early stages of oil accumulation in the kernel. In the testa, the upregulation of the genes encoding SAD, FAD2, and FAD3 was followed by a sharp increase in the concentrations of ALA. In contrast, these genes were minimally expressed (and ALA content was low) throughout pericarp development.
CONCLUSIONS
We used three tissues with high, moderate, and low ALA concentrations as an exemplar system in which to investigate tissue-specific ALA accumulation mechanisms in P. ostii. The genes and TFs identified herein might be useful targets for future studies of ALA accumulation in the tree peony. This study also provides a framework for future studies of FA biosynthesis in other oilseed plants.
Topics: Fruit; Gene Expression Profiling; Gene Expression Regulation, Plant; Paeonia; Plant Proteins; Seeds; Transcriptome; alpha-Linolenic Acid
PubMed: 33892636
DOI: 10.1186/s12864-021-07594-2 -
Toxicology Research Jul 2020α-Linolenic acid (ALA, 18:3-3) and γ-gamma linolenic acid (GLA, 18:3-6) are polyunsaturated fatty acids (PUFA) that improve the human health. The present study focused...
α-Linolenic acid (ALA, 18:3-3) and γ-gamma linolenic acid (GLA, 18:3-6) are polyunsaturated fatty acids (PUFA) that improve the human health. The present study focused on testing the antitumor actions of pure ALA and GLA on the HT-29 human colorectal cancer cell line. Cell viability was checked by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, cell membrane damage by the lactate dehydrogenase assay, apoptosis was tested by both caspase-3 activity trial and transmission electron microscopy images, and protein composition was analyzed by quantitative proteomics analysis. MTT test revealed IC values of 230 and 255 μM for ALA and GLA, respectively, at 72 h. After 24 h of incubation, both ALA and GLA induced apoptosis on HT-29 colorectal cancer cells according to the caspase-3 assay and microscopy images. SWATH/MS analysis evidenced that ALA significantly affected the mitochondrial protein import pathway and the citric acid cycle pathway, while GLA did not significantly affect any particular pathway. In summary, both ALA and GLA showed concentration-dependent inhibitory effects on HT-29 cells viability and induced cell death by apoptosis. ALA significantly affected cellular pathways, while GLA does not have specific actions on either pathway. Both -3 and -6 C18 PUFA are bioactive food components useful in the colorectal cancer prevention.
PubMed: 32905142
DOI: 10.1093/toxres/tfaa046 -
Acta Biomaterialia Mar 2022Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived...
Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived lipid mediators remains unclear. Skin substitutes were engineered according to the self-assembly method with a culture medium supplemented with 10 μM of both α-linolenic acid (ALA) and linoleic acid (LA). The supplementation with ALA and LA decreased testosterone absorption through a tissue-engineered reconstructed skin model, thus indicating an improved skin barrier function following supplementation. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes. Indeed, the dual supplementation increased the levels of eicosapentaenoic acid (EPA) (15-fold), docosapentaenoic acid (DPA) (3-fold), and LA (1.5-fold) in the epidermal phospholipids while it increased the levels of ALA (>20-fold), DPA (3-fold) and LA (1.5-fold) in the epidermal triglycerides. The bioactive lipid mediator profile of the skin substitutes, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols, was next analyzed using liquid chromatography-tandem mass spectrometry. The lipid supplementation further modulated bioactive lipid mediator levels of the reconstructed skin substitutes, leading to a lipid mediator profile more representative of the one found in normal human skin. These findings show that an optimized supply of PUFAs via culture media is essential for the establishment of improved barrier function in vitro. STATEMENT OF SIGNIFICANCE: Supplementation of the culture medium with 10 μM of both α-linolenic acid (ALA) and linoleic acid (LA) improved the skin barrier function of a tissue-engineered skin model. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes and further modulated bioactive lipid mediator levels, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols. These findings highlight the important role of ALA and LA in skin homeostasis and show that an optimized supply of polyunsaturated fatty acids via culture media is essential for the establishment of improved barrier function in vitro.
Topics: Eicosapentaenoic Acid; Humans; Linoleic Acid; Lipidomics; Skin; alpha-Linolenic Acid
PubMed: 34808417
DOI: 10.1016/j.actbio.2021.11.021 -
Acta Neuropathologica Communications Dec 2020Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and...
Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson's disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8% D-linoleic and 0.3% H-linolenic, produced significant disease-modifying beneficial effects against α-syn-induced motor deficits, synaptic pathology, oxidative damage, mitochondrial dysfunction, disrupted trafficking along axons, inflammation and DA neuronal loss. These findings support the clinical evaluation of D-PUFAs as a neuroprotective therapy for PD.
Topics: Animals; Axonal Transport; Behavior, Animal; Brain; Deuterium; Dopaminergic Neurons; Exploratory Behavior; Humans; Inflammation; Linoleic Acid; Mitochondria; Oxidative Stress; Parkinson Disease; Postural Balance; Rats; Rats, Transgenic; Substantia Nigra; alpha-Linolenic Acid; alpha-Synuclein
PubMed: 33308320
DOI: 10.1186/s40478-020-01090-6 -
Molecules (Basel, Switzerland) Oct 2022Gas chromatography (GC) with flame ionization detection (FID) and mass spectrometry (MS) detection were used to characterize the fatty acid (FA) compositions of ten...
Gas chromatography (GC) with flame ionization detection (FID) and mass spectrometry (MS) detection were used to characterize the fatty acid (FA) compositions of ten commonly consumed (i.e., market class) pulses. Lipids from ground pulses were extracted using a classical chloroform/methanol extraction and quantified by GC-FID with structural confirmation by GC-MS. Principal component analysis (PCA) was applied to FA compositions of the pulse extracts, and the pulses clustered into three distinct groups: one rich in linolenic acid, 18:3 (carbon number:unsaturation, C:U), one rich in 16:0, and one in which 18:1 was highest, along with predominant 18:2. These ten pulses averaged 46.1% linoleic acid (18:2), 22.7% oleic acid (18:1), 18.0% palmitic acid (16:0), and 7.6% linolenic acid (18:3). Individual values ranged widely, with 18:2 ranging from 26.0% in black beans to 48.4% in garbanzo beans. The greatest difference was in 18:3, which ranged from 2.2% in garbanzo beans to 38.8% in pinto beans. Oxo-FA were observed in all ten samples, and the distribution of oxo-FA in the samples also varied. Overall, the very different FA compositions of pulses lead to the possibility of breeding and genetic modification between pulses to produce the most desirable FA composition for nutritional benefit.
Topics: Fatty Acids; Gas Chromatography-Mass Spectrometry; alpha-Linolenic Acid; Plant Breeding; Flame Ionization; Fabaceae
PubMed: 36364086
DOI: 10.3390/molecules27217260 -
Nutrients Nov 2022Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing...
Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.
Topics: Humans; Alzheimer Disease; Blood-Brain Barrier; alpha-Linolenic Acid; Brain; Apolipoprotein E4
PubMed: 36501121
DOI: 10.3390/nu14235091 -
Nutrients Oct 2019Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets... (Review)
Review
Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.
Topics: Diet, Vegan; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Linoleic Acid; Nutritional Status; Nutritive Value; Recommended Dietary Allowances; alpha-Linolenic Acid
PubMed: 31590264
DOI: 10.3390/nu11102365 -
Frontiers in Nutrition 2021The association between α-linolenic acid (ALA) and mortality is inconsistent and has not been summarized systematically. The purpose was to conduct a meta-analysis...
The association between α-linolenic acid (ALA) and mortality is inconsistent and has not been summarized systematically. The purpose was to conduct a meta-analysis that synthesized the results of prospective cohort studies to investigate associations between ALA intake and mortality. We conducted a comprehensive search on PubMed, Embase, and Web of Science databases on May 1, 2021, for relevant prospective cohort studies which reported associations of ALA (assessed by dietary surveys and/or ALA concentrations in body tissues) with mortality from all-cause, cardiovascular disease (CVD), and other diseases. Multivariable-adjusted relative risks (RRs) were pooled by a random or fixed-effects model. A total of 34 prospective cohort studies, of which 17 reported dietary ALA intake, 14 for ALA biomarkers, and the remaining 3 reported both of intake and biomarkers. The studies included 6,58,634 participants, and deaths were classified into all-cause mortality (56,898), CVD mortality (19,123), and other diseases mortality (19,061). Pooled RRs of ALA intake were 0.93 (95% CI: 0.86, 1.01, = 71.2%) for all-cause mortality, 0.90 (95% CI: 0.83, 0.98, = 22.1%) for CVD mortality, and 0.94 (95% CI: 0.83, 1.06, = 73.3%) for other diseases mortality. The two-stage random-effects dose-response analysis showed a linear relationship between dietary ALA intake and CVD-mortality and each 0.5% energy increment of ALA intake was associated with a 5% lower risk of CVD-mortality (RR: 0.95; 95% CI: 0.90, 1.00). Pooled RRs per SD increment of ALA biomarkers were 0.99 (95% CI: 0.96, 1.01, = 27%) for all-cause mortality, 1.00 (95% CI: 0.98, 1.03, = 0%) for CVD mortality and 0.98 (95% CI: 0.95, 1.01, = 0%) for other diseases mortality. This meta-analysis summarizing the available prospective cohort studies indicated that ALA intake was associated with reduced risk of mortality, especially CVD mortality. Our findings suggest that ALA consumption may be beneficial for death prevention. https://www.crd.york.ac.uk/PROSPERO; identifier: CRD42021264532.
PubMed: 34805241
DOI: 10.3389/fnut.2021.743852