Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har...Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.展开更多
Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied...Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.展开更多
Aim To separate high purity linolenic acid from the oil of Lithospermumerythrorhizon growing in the Northeast of China. Methods Urea inclusion and column chromatographywere used. Results Unsaturated fatty acid was sep...Aim To separate high purity linolenic acid from the oil of Lithospermumerythrorhizon growing in the Northeast of China. Methods Urea inclusion and column chromatographywere used. Results Unsaturated fatty acid was separated, with a purity of 99.30 wt% of linolenicacid. Conclusion The experiment shows excellent reproducibility and high feasibility for industrialproduction.展开更多
[Objective] The aim was to investigate the anti-inflammatory effect and the mechanism of gamma-linolenic acid on lipopolysaccharide-induced RAW264.7 cells.[Method] Macrophagic system RAW 264.7 cells were cultured in v...[Objective] The aim was to investigate the anti-inflammatory effect and the mechanism of gamma-linolenic acid on lipopolysaccharide-induced RAW264.7 cells.[Method] Macrophagic system RAW 264.7 cells were cultured in vitro,when cells grew to fusion state,they were pretreated with 0,12.5,25.0,50.0 μmol/L of GLA for 4 h,and then 100 ng/ml of LPS were added to induce for 12 h or 30 min.Meanwhile,the blank control and LPS control were set.And the expression of iNOS,COX-2 and the effect of GLA on IκBα,p-JNK/SAPK(Thr183/Tyr185),p38 MAPK,p-p38 MAPK(Thr180/Tyr182),ERK1/2,p-ERK1/2 were detected by Western blot.[Result] GLA significantly inhibited the expression of iNOS and COX-2 in RAW264.7 cells induced by LPS,and in the range of 0-50 μmol/L of GLA,the inhibition effect was concentration-dependent(P0.05).GLA could significantly inhibited the degradation of IκBα(P0.05),thereby inhibited the activation of NF-κB.GLA could significantly inhibited the phosphorylation of LPS-induced JNK1/2 and ERK1/2(P0.05),while it had not significantly effect on the phosphorylation of p38(P0.05).[Conclusion] GLA had excellent anti-inflammation effect.The inhibition of the phosphorylation of JNK1/2,ERK1/2 and the inhibition of activation of NF-κB might be the important mechanism for the educing of its biological effect.展开更多
Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-(3-dimethylami- nopropyyl) carbodiimide (EDC)-mediated reaction. The degree of substitution 1.8% ( i.e. 1.8 linolenic acid g...Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-(3-dimethylami- nopropyyl) carbodiimide (EDC)-mediated reaction. The degree of substitution 1.8% ( i.e. 1.8 linolenic acid group per 100 anhydroglucose units) was measured by ^1H NMR. The critical aggregation concentration (CAC) of the self-aggregate of hydrophobically modified chitosan was determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe. The CAC value in phosphate-buffered saline (PBS) solution (pH 7.4) was 5 × 10^-2 mg mL^-1. The average particle size of selfaggregates of hydrophobically modified chitosan in PBS solution (pH7.4) was 210.8 nm with a unimodal size distribution ranging from 100 to 500 nm. Transmission electron microscopy (TEM) study showed that the formation of near spherical shape nanoparticles has enough structural integrity. The loading ability of hydrophibically modified chitosan (LA-chitosan) was investigated by using bovine serum albumin (BSA) as the model. The loading capacity of self-aggregated nanoparticles increases ( 19.85 % ± 0.04 % to 37.57 % ± 0.25 % ) with the concentration of BSA (0.1-0.5 mg mL^-1 ).展开更多
Linolenic acid has great effects on the structure and function of chloroplast. We studied the effects of Ce3+ on the improvement of chloroplast spectral characteristics and oxygen evolution damaged by linolenic acid ...Linolenic acid has great effects on the structure and function of chloroplast. We studied the effects of Ce3+ on the improvement of chloroplast spectral characteristics and oxygen evolution damaged by linolenic acid in spinach. Results showed that Ce3+ could decrease the light absorption increased by linolenic acid and promote the distribution of excitation energy to PS II and alleviate the decrease of PS Ⅱ fluo- rescence yield caused by linolenic acid. The linolenic acid treatments in various concentrations reduced the oxygen-evolving rate of chloroplasts, but the rate was accelerated since adding Ce3+.展开更多
A 90-day experiment was conducted to investigate the effects of different dietary linoleic acid (LA; 18:2n-6) and linolenic acid ratios (LNA; 18:3n-3) on growth induces, feed utilization and tissue fatty acid pr...A 90-day experiment was conducted to investigate the effects of different dietary linoleic acid (LA; 18:2n-6) and linolenic acid ratios (LNA; 18:3n-3) on growth induces, feed utilization and tissue fatty acid profile of freshwater prawn, Macrobrachium rosenbergii post-larvae (PL). The experiment was conducted in cubic indoor fiberglass tanks, each holding 700 L in triplicate. Post-larvae with an average weight of 20.8 ± 0.20 mg were stocked at 80 PL m2. Five experimental isocaloric (15.06 MJ kgl digestible energy), and isonitrogenous (30.45% digestible protein) diets were formulated by blending of soybean oil and linseed oil to containing five dietary LA/LNA ratios (7.80, 2.75, 1.28, 0.65 and 0.30). The highest survival values were recorded for prawn PL fed diet containing 0.65 LA/LAN ratios. Growth indices of PL significantly increased (P 〈 0.05) with decreased dietary LA/LAN ratios to 0.65. The same trend was observed for the highest (P ≤ 0.05) protein efficiency ratio, protein productive value, fat retention, energy retention and best feed conversion ratio. The total whole tissue polyunsaturated fatty acid composition of M. rosenbergii PL was dominated by LA followed by LAN. Post larvae fed the diets containing higher LA/LNA ratios showed a higher tissue LA/LNA ratio. The obtained findings revealed that fatty acid patterns ofM. rosenbergii PL were influenced by fatty acid profiles of diets. The diet containing 0.65 LA/LNA ratio is recommended to obtaining optimum growth performance and feed utilization for M. rosenbergii PL.展开更多
Objective: To evaluate a new pharmacological activity/effect of linolenic acid(α- and γ-form) and conjugated-linoleic acid(CLA) causing antibacterial activity against Mycobacterium tuberculosis(Mtb). Methods: The an...Objective: To evaluate a new pharmacological activity/effect of linolenic acid(α- and γ-form) and conjugated-linoleic acid(CLA) causing antibacterial activity against Mycobacterium tuberculosis(Mtb). Methods: The anti-Mtb activity/effect of linolenic acid and CLA were determined using different anti-Mtb indicator methods such as resazurin microtiter assay(REMA) and MGIT 960 system assay. The Mtb was incubated with various concentrations(12.5–200) μg/m L of the compounds and anti-Mtb first-line drugs for 5 d in the REMA, and for 3 wk in MGIT 960 system assay. Results: Linolenic acid and CLA obviously indicated their anti-Mtb activity/effect by strongly inhibiting the growth/proliferation of Mtb in a dosedependent manner in the REMA and the MGIT 960 system assay. Interestingly, linolenic acid and CLA consistently induced anti-Mtb activity/effect by effectively inhibiting the growth/proliferation of Mtb in MGIT 960 system for 21 d with a single-treatment, and their minimum inhibitory concentrations were measured as 200 μg/m L respectively. Conclusions: These results demonstrate that linolenic acid and CLA not only have effective anti-Mtb activity/properties, but also induce the selective-anti-Mtb effects by strongly inhibiting and blocking the growth/proliferation of Mtb through a new pharmacological activity/action. Therefore, this study provides novel perspectives for the effective use of them and the potential that can be used as potent anti-Mtb candidate drugs, as well as suggests the advantage of reducing the cost and/or time for developing a new/substantive drug by effectively repurposing the existing drugs or compounds as one of new strategies for the global challenge of tuberculosis.展开更多
Linolenic acid has great effects on the structure and function of chloroplast. The function of Ce^3+ on the improvement of chloroplast photoreduction activity and oxygen evolution damaged by linolenic acid in spinach...Linolenic acid has great effects on the structure and function of chloroplast. The function of Ce^3+ on the improvement of chloroplast photoreduction activity and oxygen evolution damaged by linolenic acid in spinach by in vitro investigation was studied. Results showed that adding Ce^3+ to the linolenic acid treated chloroplast could greatly decrease the reduction linolenic acid exerted on the whole chain electron transport rate and the photoreduction activity of photosystem Ⅱ (PSII) and photosystem Ⅰ (PSI) as well as the oxygen evolution rate of chloroplast. It indicated that Ce^3+ had the ability to relieve the inhibition of the photochemical reaction of chloroplast caused by linolenic acid to some extent.展开更多
A novel class ofα-linolenic acid-in-water microemulsion free of co-surfactant was investigated as potential food delivery systems.Rough demarcation within the transparent region was deduced from the results of conduc...A novel class ofα-linolenic acid-in-water microemulsion free of co-surfactant was investigated as potential food delivery systems.Rough demarcation within the transparent region was deduced from the results of conductivity and polarizing optical microscopy.The microemulsion mean hydrodynamic diameter and characterization were determined by dynamic light scattering and negative-staining TEM.The location of ALA molecules in the microemulsion formulations was determined by ~1H NMR spectroscopy.展开更多
Background:In ruminants,dietary C18:3n-3 can be lost through biohydrogenation in the rumen;and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle,theoretically reducing the deposition of C...Background:In ruminants,dietary C18:3n-3 can be lost through biohydrogenation in the rumen;and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle,theoretically reducing the deposition of C18:3n-3,the substrate for synthesis of poly-unsaturated fatty acids(n-3 LCPUFA)in muscle.In vitro studies have shown that rumen hydrogenation of C18:3n-3 is reduced by supplementation with palm oil(rich in cis-9 C18:1).In addition,in hepatocytes,studies with neonatal rats have shown that cis-9 C18:1 inhibits the oxidation of C18:3n-3.It therefore seems likely that palm oil could reduce both rumen biohydrogenation of C18:3n-3 and muscle oxidation of C18:3n-3.The present experiment tested whether the addition of palm oil to a linseed oil supplement for goat kids would prevent the losses of C18:3n-3 and thus improve the FA composition in two muscles,Longissimus dorsi and Biceps femoris.To investigate the processes involved,we studied the rumen bacterial communities and measured the mRNA expression of genes related to lipid metabolism in Longissimus dorsi.Sixty 4-month-old castrated male Albas white cashmere kids were randomly allocated among three dietary treatments.All three diets contained the same ingredients in the same proportions,but differed in their fat additives:palm oil(PMO),linseed oil(LSO)or mixed oil(MIX;2 parts linseed oil plus 1 part palm oil on a weight basis).Results:Compared with the LSO diet,the MIX diet decreased the relative abuandance of Pseudobutyrivibrio,a bacterial species that is positively related to the proportional loss rate of dietary C18:3n-3 and that has been reported to generate the ATP required for biohydrogenation(reflecting a decrease in the abundance of rumen bacteria that hydrogenate C18:3n-3 in MIX kids).In muscle,the MIX diet increased concentrations of C18:3n-3,C20:5n-3,C22:6n-3,and n-3 LCPUFA,and thus decreased the n-6/n-3 ratio;decreased the mRNA expression of CPT1β(a gene associated with fatty acid oxidation)and increased the mRNA expression of FADS1 and FADS2(genes associated with n-3 LCPUFA synthesis),compared with the LSO diet.Interestingly,compared to Longissimus dorsi,Biceps femoris had greater concentrations of PUFA,greater ratios of unsaturated fatty acids/saturated fatty acids(U/S),and poly-unsaturated fatty acids/saturated fatty acids(P/S),but a lesser concentration of saturated fatty acids(SFA).Conclusions:In cashmere goat kids,a combination of linseed and palm oils in the diet increases the muscle concentration of n-3 LCPUFA,apparently by decreasing the relative abundance of rumen bacteria that are positively related to the proportional loss rate of dietary C18:3n-3,by inhibiting mRNA expression of genes related to C18:3n-3 oxidation in muscle,and by up-regulating mRNA expression of genes related to n-3 LCPUFA synthesis in muscle,especially in Longissimus dorsi.展开更多
Genetic modifi cation is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be...Genetic modifi cation is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be used to modify fatty acid metabolism. S ynechococcus sp. PCC7002, a fast-growing cyanobacterium, does not contain a Δ6 desaturase gene and is therefore unable to synthesize γ-linolenic acid(GLA) and stearidonic acid(SDA), which are important in human health. In this work, we constructed recombinant vectors Syd6 D, Syd15 D and Syd6Dd15 D to express the Δ15 desaturase and Δ6 desaturase genes from Synechocystis PCC6803 in Synechococcus sp. PCC7002, with the aim of expressing polyunsaturated fatty acids. Overexpression of the Δ15 desaturase gene in S ynechococcus resulted in 5.4 times greater accumulation of α-linolenic acid compared with the wild-type while Δ6 desaturase gene expression produced both GLA and SDA. Co-expression of the two genes resulted in low-level accumulation of GLA but much larger amounts of SDA, accounting for as much to 11.64% of the total fatty acid content.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
Aluminum has been associated with neurodegenerative diseases.ALA(α-linolenic acid),an essential dietary component for human health,possesses prominent biological activities.Herein,we aim to explore the neuroprotectiv...Aluminum has been associated with neurodegenerative diseases.ALA(α-linolenic acid),an essential dietary component for human health,possesses prominent biological activities.Herein,we aim to explore the neuroprotective effects of ALA on aluminum toxicity and reveal the underlying mechanism.Results show that aluminum chloride(denoted as Al)enabled cell viability decline and apoptosis with oxidative stress and mitochondrial damage in differentiated rat pheochromocytoma cells(PC12)for 24 h incubation.Compared with Al(10 mmol/L)treatment alone,ALA(50μmol/L)pretreatment for 24 h significantly enhanced cell viability by 28.40%,and hindered cell apoptosis by 12.35%,together with recovering redox state balance and alleviating mitochondrial damage.It was measured that ALA treatment upregulated Bcl-2 expression and down-regulated Bax level,accompanied with an expression decline of caspase-3 and caspase-9.Meanwhile,ALA pretreatment was proved to increase protein kinase A(PKA)expression and to promote phosphorylation of cAMP response element-binding protein(p-CREB),resulting in elevation on the level of brain-derived neurotrophic factor(BDNF).The above results showed that ALA attenuated Al toxicity in PC12 cells by mediating the PKA-CREBBDNF signaling pathway.展开更多
The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
In the present feeding trial,responses of laying hens that were kept at high ambient temperature and Fed with various dietary ratios of linoleic acid(LNA)toα-linolenic acid(ALA)and vitamin A levels on production perf...In the present feeding trial,responses of laying hens that were kept at high ambient temperature and Fed with various dietary ratios of linoleic acid(LNA)toα-linolenic acid(ALA)and vitamin A levels on production performance and egg quality traits were evaluated.A total of 360 Leghorn laying hens at 40th week of age(average initial body weight;1.79±0.23 kg)were fed with various combinations of canola oil and linseed oil containing diets to achieve LNA to ALA dietary ratios of 20:1,10:1,4:1,2:1,1:1 and 1:2,each supplemented with 3000 or 10000 IU of vitamin A/kg of diet.The experiment was designed as a 6×2 factorial Completely Randomized Design that continued for 12 weeks.Feed intake,body weight gain,egg production and egg quality traits were recorded during the trial.Decreasing dietary LNA to ALA ratio or increasing poly unsaturated fatty acids(PUFA)in the diet decreased(P<0.05)body weight gain and yolk percentage in laying hens.Feed intake,hen-day and hen-housed egg production,feed conversion ratio(FCR)per dozen of eggs and shell quality remained unaffected(P>0.05)by dietary treatments.Feed conversion ratio per kg eggs,egg weight and egg-shell thickness showed a curvilinear(P<0.05)response to decreasing dietary LNA to ALA ratio.Although the dietary ratio of LNA to ALA of 4:1 or less could produce eggs by the hens with desirable quantities of n-6 and n-3 PUFA–that are characteristics of functional diets–the performance of laying hens in terms of body weight gain and egg-yolk percentage was slightly compromised.Therefore,a 4:1 or 2:1 LNA to ALA combination can make a borderline between the production traits and the feed economics.展开更多
The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke ...The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorec...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.展开更多
Alpha linolenic acid ( ALA), a kind of polyunsaturated fatty acid extracted from plants and fruits, has a variety of biological functions. In recent years, ALA has attracted much attention as a natural green feed ad...Alpha linolenic acid ( ALA), a kind of polyunsaturated fatty acid extracted from plants and fruits, has a variety of biological functions. In recent years, ALA has attracted much attention as a natural green feed additive. The physical and chemical properties, metabolic process, physiological function of ALA as well as its application and mechanisms in livestock and poultry production are summarized in the paper.展开更多
基金The study was financially supported by Projects from Shaanxi Province(2021LLRH-07-03-01 and 2023-ZDLNY-07)Yangling Seed Industry Innovation(YLzy-yc2021-01).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.
基金supported by the National Natural Science Foundation of China(31930115,32173007)China Agriculture Research System of MOF and MARA(CARS-47-G16)Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515010595)。
文摘Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.
文摘Aim To separate high purity linolenic acid from the oil of Lithospermumerythrorhizon growing in the Northeast of China. Methods Urea inclusion and column chromatographywere used. Results Unsaturated fatty acid was separated, with a purity of 99.30 wt% of linolenicacid. Conclusion The experiment shows excellent reproducibility and high feasibility for industrialproduction.
文摘[Objective] The aim was to investigate the anti-inflammatory effect and the mechanism of gamma-linolenic acid on lipopolysaccharide-induced RAW264.7 cells.[Method] Macrophagic system RAW 264.7 cells were cultured in vitro,when cells grew to fusion state,they were pretreated with 0,12.5,25.0,50.0 μmol/L of GLA for 4 h,and then 100 ng/ml of LPS were added to induce for 12 h or 30 min.Meanwhile,the blank control and LPS control were set.And the expression of iNOS,COX-2 and the effect of GLA on IκBα,p-JNK/SAPK(Thr183/Tyr185),p38 MAPK,p-p38 MAPK(Thr180/Tyr182),ERK1/2,p-ERK1/2 were detected by Western blot.[Result] GLA significantly inhibited the expression of iNOS and COX-2 in RAW264.7 cells induced by LPS,and in the range of 0-50 μmol/L of GLA,the inhibition effect was concentration-dependent(P0.05).GLA could significantly inhibited the degradation of IκBα(P0.05),thereby inhibited the activation of NF-κB.GLA could significantly inhibited the phosphorylation of LPS-induced JNK1/2 and ERK1/2(P0.05),while it had not significantly effect on the phosphorylation of p38(P0.05).[Conclusion] GLA had excellent anti-inflammation effect.The inhibition of the phosphorylation of JNK1/2,ERK1/2 and the inhibition of activation of NF-κB might be the important mechanism for the educing of its biological effect.
基金National Natural Science Foundation of China(30370344)Korea Science and Engineering Foundation(19992-220-009-4)supported this study
文摘Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-(3-dimethylami- nopropyyl) carbodiimide (EDC)-mediated reaction. The degree of substitution 1.8% ( i.e. 1.8 linolenic acid group per 100 anhydroglucose units) was measured by ^1H NMR. The critical aggregation concentration (CAC) of the self-aggregate of hydrophobically modified chitosan was determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe. The CAC value in phosphate-buffered saline (PBS) solution (pH 7.4) was 5 × 10^-2 mg mL^-1. The average particle size of selfaggregates of hydrophobically modified chitosan in PBS solution (pH7.4) was 210.8 nm with a unimodal size distribution ranging from 100 to 500 nm. Transmission electron microscopy (TEM) study showed that the formation of near spherical shape nanoparticles has enough structural integrity. The loading ability of hydrophibically modified chitosan (LA-chitosan) was investigated by using bovine serum albumin (BSA) as the model. The loading capacity of self-aggregated nanoparticles increases ( 19.85 % ± 0.04 % to 37.57 % ± 0.25 % ) with the concentration of BSA (0.1-0.5 mg mL^-1 ).
基金supported by the National Natural Science Foundation of China (30800068)
文摘Linolenic acid has great effects on the structure and function of chloroplast. We studied the effects of Ce3+ on the improvement of chloroplast spectral characteristics and oxygen evolution damaged by linolenic acid in spinach. Results showed that Ce3+ could decrease the light absorption increased by linolenic acid and promote the distribution of excitation energy to PS II and alleviate the decrease of PS Ⅱ fluo- rescence yield caused by linolenic acid. The linolenic acid treatments in various concentrations reduced the oxygen-evolving rate of chloroplasts, but the rate was accelerated since adding Ce3+.
文摘A 90-day experiment was conducted to investigate the effects of different dietary linoleic acid (LA; 18:2n-6) and linolenic acid ratios (LNA; 18:3n-3) on growth induces, feed utilization and tissue fatty acid profile of freshwater prawn, Macrobrachium rosenbergii post-larvae (PL). The experiment was conducted in cubic indoor fiberglass tanks, each holding 700 L in triplicate. Post-larvae with an average weight of 20.8 ± 0.20 mg were stocked at 80 PL m2. Five experimental isocaloric (15.06 MJ kgl digestible energy), and isonitrogenous (30.45% digestible protein) diets were formulated by blending of soybean oil and linseed oil to containing five dietary LA/LNA ratios (7.80, 2.75, 1.28, 0.65 and 0.30). The highest survival values were recorded for prawn PL fed diet containing 0.65 LA/LAN ratios. Growth indices of PL significantly increased (P 〈 0.05) with decreased dietary LA/LAN ratios to 0.65. The same trend was observed for the highest (P ≤ 0.05) protein efficiency ratio, protein productive value, fat retention, energy retention and best feed conversion ratio. The total whole tissue polyunsaturated fatty acid composition of M. rosenbergii PL was dominated by LA followed by LAN. Post larvae fed the diets containing higher LA/LNA ratios showed a higher tissue LA/LNA ratio. The obtained findings revealed that fatty acid patterns ofM. rosenbergii PL were influenced by fatty acid profiles of diets. The diet containing 0.65 LA/LNA ratio is recommended to obtaining optimum growth performance and feed utilization for M. rosenbergii PL.
文摘Objective: To evaluate a new pharmacological activity/effect of linolenic acid(α- and γ-form) and conjugated-linoleic acid(CLA) causing antibacterial activity against Mycobacterium tuberculosis(Mtb). Methods: The anti-Mtb activity/effect of linolenic acid and CLA were determined using different anti-Mtb indicator methods such as resazurin microtiter assay(REMA) and MGIT 960 system assay. The Mtb was incubated with various concentrations(12.5–200) μg/m L of the compounds and anti-Mtb first-line drugs for 5 d in the REMA, and for 3 wk in MGIT 960 system assay. Results: Linolenic acid and CLA obviously indicated their anti-Mtb activity/effect by strongly inhibiting the growth/proliferation of Mtb in a dosedependent manner in the REMA and the MGIT 960 system assay. Interestingly, linolenic acid and CLA consistently induced anti-Mtb activity/effect by effectively inhibiting the growth/proliferation of Mtb in MGIT 960 system for 21 d with a single-treatment, and their minimum inhibitory concentrations were measured as 200 μg/m L respectively. Conclusions: These results demonstrate that linolenic acid and CLA not only have effective anti-Mtb activity/properties, but also induce the selective-anti-Mtb effects by strongly inhibiting and blocking the growth/proliferation of Mtb through a new pharmacological activity/action. Therefore, this study provides novel perspectives for the effective use of them and the potential that can be used as potent anti-Mtb candidate drugs, as well as suggests the advantage of reducing the cost and/or time for developing a new/substantive drug by effectively repurposing the existing drugs or compounds as one of new strategies for the global challenge of tuberculosis.
基金supported by the National Natural Science Foundation of China (30800068, 30470150)
文摘Linolenic acid has great effects on the structure and function of chloroplast. The function of Ce^3+ on the improvement of chloroplast photoreduction activity and oxygen evolution damaged by linolenic acid in spinach by in vitro investigation was studied. Results showed that adding Ce^3+ to the linolenic acid treated chloroplast could greatly decrease the reduction linolenic acid exerted on the whole chain electron transport rate and the photoreduction activity of photosystem Ⅱ (PSII) and photosystem Ⅰ (PSI) as well as the oxygen evolution rate of chloroplast. It indicated that Ce^3+ had the ability to relieve the inhibition of the photochemical reaction of chloroplast caused by linolenic acid to some extent.
基金supported by National Natural Scientific Foundation of China(No.20676051)Major Project Regarding Scientific and Technological Development of Shanghai Municipal Science and Technology Commission (No.07DZ 19508)the Technology Standard Project of Shanghai Municipal Science and Technology Commission (No.07DZ05019).
文摘A novel class ofα-linolenic acid-in-water microemulsion free of co-surfactant was investigated as potential food delivery systems.Rough demarcation within the transparent region was deduced from the results of conductivity and polarizing optical microscopy.The microemulsion mean hydrodynamic diameter and characterization were determined by dynamic light scattering and negative-staining TEM.The location of ALA molecules in the microemulsion formulations was determined by ~1H NMR spectroscopy.
基金supported by the National Science Foundation of China(Project No.31760685)the National Key R&D Program of China(Project No.2017YFD0500504).
文摘Background:In ruminants,dietary C18:3n-3 can be lost through biohydrogenation in the rumen;and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle,theoretically reducing the deposition of C18:3n-3,the substrate for synthesis of poly-unsaturated fatty acids(n-3 LCPUFA)in muscle.In vitro studies have shown that rumen hydrogenation of C18:3n-3 is reduced by supplementation with palm oil(rich in cis-9 C18:1).In addition,in hepatocytes,studies with neonatal rats have shown that cis-9 C18:1 inhibits the oxidation of C18:3n-3.It therefore seems likely that palm oil could reduce both rumen biohydrogenation of C18:3n-3 and muscle oxidation of C18:3n-3.The present experiment tested whether the addition of palm oil to a linseed oil supplement for goat kids would prevent the losses of C18:3n-3 and thus improve the FA composition in two muscles,Longissimus dorsi and Biceps femoris.To investigate the processes involved,we studied the rumen bacterial communities and measured the mRNA expression of genes related to lipid metabolism in Longissimus dorsi.Sixty 4-month-old castrated male Albas white cashmere kids were randomly allocated among three dietary treatments.All three diets contained the same ingredients in the same proportions,but differed in their fat additives:palm oil(PMO),linseed oil(LSO)or mixed oil(MIX;2 parts linseed oil plus 1 part palm oil on a weight basis).Results:Compared with the LSO diet,the MIX diet decreased the relative abuandance of Pseudobutyrivibrio,a bacterial species that is positively related to the proportional loss rate of dietary C18:3n-3 and that has been reported to generate the ATP required for biohydrogenation(reflecting a decrease in the abundance of rumen bacteria that hydrogenate C18:3n-3 in MIX kids).In muscle,the MIX diet increased concentrations of C18:3n-3,C20:5n-3,C22:6n-3,and n-3 LCPUFA,and thus decreased the n-6/n-3 ratio;decreased the mRNA expression of CPT1β(a gene associated with fatty acid oxidation)and increased the mRNA expression of FADS1 and FADS2(genes associated with n-3 LCPUFA synthesis),compared with the LSO diet.Interestingly,compared to Longissimus dorsi,Biceps femoris had greater concentrations of PUFA,greater ratios of unsaturated fatty acids/saturated fatty acids(U/S),and poly-unsaturated fatty acids/saturated fatty acids(P/S),but a lesser concentration of saturated fatty acids(SFA).Conclusions:In cashmere goat kids,a combination of linseed and palm oils in the diet increases the muscle concentration of n-3 LCPUFA,apparently by decreasing the relative abundance of rumen bacteria that are positively related to the proportional loss rate of dietary C18:3n-3,by inhibiting mRNA expression of genes related to C18:3n-3 oxidation in muscle,and by up-regulating mRNA expression of genes related to n-3 LCPUFA synthesis in muscle,especially in Longissimus dorsi.
基金Supported by the International S&T Cooperation Program of China(No.2012DFA30450)the National Natural Science Foundation of China(No.30871541)+1 种基金the Taishan Scholar Foundation of Shandong Province(No.tshw20091014)the Innovation Program of the University Institutes of Jinan,Shandong Province(No.201004044)
文摘Genetic modifi cation is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be used to modify fatty acid metabolism. S ynechococcus sp. PCC7002, a fast-growing cyanobacterium, does not contain a Δ6 desaturase gene and is therefore unable to synthesize γ-linolenic acid(GLA) and stearidonic acid(SDA), which are important in human health. In this work, we constructed recombinant vectors Syd6 D, Syd15 D and Syd6Dd15 D to express the Δ15 desaturase and Δ6 desaturase genes from Synechocystis PCC6803 in Synechococcus sp. PCC7002, with the aim of expressing polyunsaturated fatty acids. Overexpression of the Δ15 desaturase gene in S ynechococcus resulted in 5.4 times greater accumulation of α-linolenic acid compared with the wild-type while Δ6 desaturase gene expression produced both GLA and SDA. Co-expression of the two genes resulted in low-level accumulation of GLA but much larger amounts of SDA, accounting for as much to 11.64% of the total fatty acid content.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
基金supported by the National Natural Science Foundation of China (31972041, 32101955)the China Agriculture Research System of MOF and MARA (CARS-12)+1 种基金the Agricultural Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences (CAASASTIP-2016-OCRI)the Key Scientific Research Projects of Hubei Province (2020BCA086)
文摘Aluminum has been associated with neurodegenerative diseases.ALA(α-linolenic acid),an essential dietary component for human health,possesses prominent biological activities.Herein,we aim to explore the neuroprotective effects of ALA on aluminum toxicity and reveal the underlying mechanism.Results show that aluminum chloride(denoted as Al)enabled cell viability decline and apoptosis with oxidative stress and mitochondrial damage in differentiated rat pheochromocytoma cells(PC12)for 24 h incubation.Compared with Al(10 mmol/L)treatment alone,ALA(50μmol/L)pretreatment for 24 h significantly enhanced cell viability by 28.40%,and hindered cell apoptosis by 12.35%,together with recovering redox state balance and alleviating mitochondrial damage.It was measured that ALA treatment upregulated Bcl-2 expression and down-regulated Bax level,accompanied with an expression decline of caspase-3 and caspase-9.Meanwhile,ALA pretreatment was proved to increase protein kinase A(PKA)expression and to promote phosphorylation of cAMP response element-binding protein(p-CREB),resulting in elevation on the level of brain-derived neurotrophic factor(BDNF).The above results showed that ALA attenuated Al toxicity in PC12 cells by mediating the PKA-CREBBDNF signaling pathway.
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
文摘In the present feeding trial,responses of laying hens that were kept at high ambient temperature and Fed with various dietary ratios of linoleic acid(LNA)toα-linolenic acid(ALA)and vitamin A levels on production performance and egg quality traits were evaluated.A total of 360 Leghorn laying hens at 40th week of age(average initial body weight;1.79±0.23 kg)were fed with various combinations of canola oil and linseed oil containing diets to achieve LNA to ALA dietary ratios of 20:1,10:1,4:1,2:1,1:1 and 1:2,each supplemented with 3000 or 10000 IU of vitamin A/kg of diet.The experiment was designed as a 6×2 factorial Completely Randomized Design that continued for 12 weeks.Feed intake,body weight gain,egg production and egg quality traits were recorded during the trial.Decreasing dietary LNA to ALA ratio or increasing poly unsaturated fatty acids(PUFA)in the diet decreased(P<0.05)body weight gain and yolk percentage in laying hens.Feed intake,hen-day and hen-housed egg production,feed conversion ratio(FCR)per dozen of eggs and shell quality remained unaffected(P>0.05)by dietary treatments.Feed conversion ratio per kg eggs,egg weight and egg-shell thickness showed a curvilinear(P<0.05)response to decreasing dietary LNA to ALA ratio.Although the dietary ratio of LNA to ALA of 4:1 or less could produce eggs by the hens with desirable quantities of n-6 and n-3 PUFA–that are characteristics of functional diets–the performance of laying hens in terms of body weight gain and egg-yolk percentage was slightly compromised.Therefore,a 4:1 or 2:1 LNA to ALA combination can make a borderline between the production traits and the feed economics.
基金supported by MICIU(grant number PID2021-128133NB-100/AEI/FEDER10.13039/501100011033 to JMHG)by the National Institutes of Health(grant number R01 NS083858 to SAK)+1 种基金the Intramural Grants Program IGPP00057(to SAK)VIC enjoys a FPU contract from the Comunidad de Madrid(PIPF-2022/SAL-GL-25948)。
文摘The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.
基金Supported by Romanian Ministry of Research,Innovation and Digitization,No.PN23.16.02.04 and No.31PFE/30.12.2021.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.
基金Supported by Key Scientific Research Project of Colleges and Universities in Henan Province(15A230012)
文摘Alpha linolenic acid ( ALA), a kind of polyunsaturated fatty acid extracted from plants and fruits, has a variety of biological functions. In recent years, ALA has attracted much attention as a natural green feed additive. The physical and chemical properties, metabolic process, physiological function of ALA as well as its application and mechanisms in livestock and poultry production are summarized in the paper.