NMR Studies of a New Binding Mode of the Amino Acid Esters by Porphyrinatozinc(Ⅱ)

The binding mode of the amino acid ethyl esters(guest) by 5 (2 carboxylphenyl) 10,15,20 triphenylporphyrinatozinc(Ⅱ)(host 1) was studied by means of 1H NMR spectra. The binding mode is the hydrogen bonding between the amino group of the guest and the carboxyl group of host 1 plus the coordination between the zinc atom of porphyrinatozinc(Ⅱ) and the carbonyl group of the guest. This is a novel binding mode of the metalloporphyrin to amino acid derivatives.

Studies on Models,Patterns and Requirements of Digestible Amino Acids for Layers by Nitrogen Metabolism

The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 4348 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid requirements. The regression relationship of nitrogen retention vs amino acid intake was estimated for each amino acid by giving, at rate of N intake of 091, 052, 015 and 0007gkg-1 body-weight (W075) per d, the semi-synthetic diets was made specially deficient in one amino acid. From the regression coefficients, it was calculated that, for the accretion of 1 g protein, the dietary digestible amino acid requirements were (mg) Thr 631, Val 1004, Met 399, Ile 886, Leu 1143, Phe 632, Lys 870, His 205, Arg 879, Trp 214, Met+Cys 776, and Phe+Tyr 1143. Daily amino acid requirements for N equilibrium were estimated to be (mgkg-1W075 per day) Thr 506, Val 747, Met 303, ILe 667 Leu 814, Phe 448, Lys 605 His 147, Arg 739 ,Trp 173, Met+Cys 586, and Phe+Tyr 839 The dietary degestible amino acid patterns for protein accretion and N equilibrium were also proposed. The models of estimating digestible amino acid requirements for the different productions were developed.

Direct Electron Transfer Reactions of Glucose Oxidase and D-Amino Acid Oxidase at a Glassy Carbon Electrode in Organic Media

Cyclic voltammetry is employed to demonstrate feasibility of direct electron transfer of glucose oxidase and D amino acid oxidase at a glassy carbon electrode in organic media. The reversible slight conformational change of glucose oxidase is observed by changing 0.1 mol/L phosphate buffer to acetonitrile containing 10% v/v of water and 0.05 mol/L tetrabutyalammonium perchlorate, and vice versa.

Effects of Nerve Growth Factor on Excitatory Amino Acid Content in Spinal Cord Neuron after Spinal Cord Injury

To investigate the protective mechanism of nerve growth factor (NGF) on spinal cord injury (SCI), surgical spinal cord injury in Wistar rats was performed by a 10 g2.5 cm impact on the posterior spinal cord at T8 level, and a thin plastic tube was placed in subarachoid space below the injury level for perfusion of solution. To the experimental animals were given 60 g (20 l liquid) NGF, purified from bovine seminal plasma, at the moment of injury and 1,2,3,4,8,12,24 h after injury. An equal volume of normal saline was given to rats of the control group at the same time. In the expermental group, the injured spinal cord tissue was taken following treatment. The contents of the excitatory amino acids (Glu, Asp) were determined by high performance liquid chromatography (HPLC). Excitatory amino acid contents in the injured spinal cord were significantly increased at 10 min and 8 h after the injury as compared with those in the control group. However, The peak values of the excitatory amino acid contents in NGF group were obviously lowered. NGF might protect spinal cord against injury in vivo. One of the possible mechanisms is that NGF prohibits neurotoxicity of the exitatory amino acids.

Analysis of amino acid constituents of gallstones

IM To seek effective drugs to dissolve bilirubin, glycoprotein and black stones and better lithotriptics for cholesterol stones, and study the amino acid constituents of gallstones.METHODS According to the characteristics of infrared spectrum and the contents of bilirubin tested by semiquantitative chemical analysis, 30 of 148 cases of gallstones were selected and divided into 5 groups. Amino acids of the 30 cases were detected by high speed chromatography.RESULTS The quantity of amino acids in black stones was the highest (2269mg/g) and that of pure cholesterol stones was the lowest, only 14mg/g in a case. In five groups of gallstones, the contents of amino acids were: black stone > mixed bilirubin stone and glucoprotein stone > mixed cholesterol stone > pure cholesterol stone. The proportions were: 9595∶2902 and 2805∶578∶1. Aliphatic amino acids accounted for about 50% of the total amino acids in gallstones and glycine 153% of the total amount of 17 kinds of amino acids.CONCLUSION In mixed stones, the higher level of bilirubin, the higher contents of amino acids. The acidic amino acids of bilirubin stones were relatively higher than those of cholesterol stones.

Protective Effect of Tetrandrine against Excitatory Amino Acids induced Neuronal Injury in Cortical Culture

The ability of tetrandrine (Tet), an alkaloid isolated from Radix Stephaniae Tetrandrae, to reduce cortical neuronal injury in cortical cultures derived from fetal rats was quantitatively assessed by examination of morphological changes and measurement of lactate dehydrogenase (LDH) released to the extracellular bathing media Cell cultures exposed to the excitatory amino acids (EAA) 50 μmol L 1 glutamate (Glu), 20 μmol L 1 N methyl D aspartate (NMDA), 300 μmol·L 1 β N oxalylamino L alanine (BMAA, NMDA receptor agonist) or 20 μmol·L 1 β N oxaly lamino L alanine (BOAA, non NMDA receptor agonist) for 24 h at 37℃ showed widespread neuronal injury Tet had little effect on the injury induced by 20 μmol·L 1 NMDA but 10 7 and 10 6 μmol·L 1 Tet did partially attenuate the neuronal degeneration, neuronal loss and LDH efflux resulting from prolonged exposures to 100 μmol·L 1 Glu, 300 μmol·L 1 BMAA and 20 μmol·L 1 BOAA respectively The ability of Tet to reduce the neuronal injury induced by prolonged exposure to EAA may contribute, at least in part, to the reduction of Ca 2+ influx through inhibiting the opening of voltagegated Ca 2+ channels Another mechanism that Tet might have a little inhibitory effect on NMDA receptor on neuronal membrane cannot be excluded, as BMAA has been considered to act as a weak NMDA receptor agonist

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Metagenomic analysis revealing the metabolic role of microbial communities in the free amino acid biosynthesis of Monascus rice vinegar during fermentation

Free amino acid(FAA)is the important component of vinegar that infl uences quality perception and consumer acceptance.FAA is one of the major metabolites produced by microorganisms;however,the microbial metabolic network on FAA biosynthesis remains unclear.Through metagenomic analysis,this work aimed to elucidate the roles of microbes in FAA biosynthesis during Monascus rice vinegar fermentation.Taxonomic profiles from functional analyses showed 14 dominant genera with high contributions to the metabolism pathways.The metabolic network for FAA biosynthesis was then constructed,and the microbial distribution in different metabolic pathways was illuminated.The results revealed that 5 functional genera were closely involved in FAA biosynthesis.This study illuminated the metabolic roles of microorganisms in FAA biosynthesis and provided crucial insights into the functional attributes of microbiota in vinegar fermentation.

Effect of different drying methods on the amino acids,α-dicarbonyls and volatile compounds of rape bee pollen

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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.

Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows

Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown.Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets(10.80 MJ/kg net energy):control(CON;19.24%CP)and reduced CP with“optimal”AA profile(OPT;14.00%CP).Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1,14,18,and 21 of lactation.Between d 14 and 18,a subset of 9 sows(CON=4,OPT=5)was infused with a mixed solution of 3-[methyl-2H3]histidine(bolus injection)and[13C]bicarbonate(priming dose)first,then a constant 2-h[13C]bicarbonate infusion followed by a 6-h primed constant[1-13C]lysine infusion.Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment,Lys oxidation rate,whole body protein turnover,and muscle protein breakdown.Results Over the 21-d lactation period,compared to CON,sows fed OPT had greater litter growth rate(P<0.05).Compared to CON,sows fed OPT had greater efficiency of Lys(P<0.05),Lys mammary flux(P<0.01)and whole-body protein turnover efficiency(P<0.05).Compared to CON,sows fed OPT tended to have lower whole body protein breakdown rate(P=0.069).Muscle protein breakdown rate did not differ between OPT and CON(P=0.197).Conclusion Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown.These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.

Low crude protein formulation with supplemental amino acids for its impacts on intestinal health and growth performance of growing-finishing pigs

Background Low crude protein(CP)formulations with supplemental amino acids(AA)are used to enhance intestinal health,reduce costs,minimize environmental impact,and maintain growth performance of pigs.However,extensive reduction of dietary CP can compromise growth performance due to limited synthesis of non-essential AA and limited availability of bioactive compounds from protein supplements even when AA requirements are met.Moreover,implementing a low CP formulation can increase the net energy(NE)content in feeds causing excessive fat deposition.Additional supplementation of functional AA,coupled with low CP formulation could further enhance intestinal health and glucose metabolism,improving nitrogen utilization,and growth performance.Three experiments were conducted to evaluate the effects of low CP formulations with supplemental AA on the intestinal health and growth performance of growing-finishing pigs.Methods In Exp.1,90 pigs(19.7±1.1 kg,45 barrows and 45 gilts)were assigned to 3 treatments:CON(18.0%CP,supplementing Lys,Met,and Thr),LCP(16.0%CP,supplementing Lys,Met,Thr,Trp,and Val),and LCPT(16.1%CP,LCP+0.05%SID Trp).In Exp.2,72 pigs(34.2±4.2 kg BW)were assigned to 3 treatments:CON(17.7%CP,meeting the requirements of Lys,Met,Thr,and Trp);LCP(15.0%CP,meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and VLCP(12.8%CP,meeting Lys,Thr,Trp,Met,Val,Ile,Phe,His,and Leu).In Exp.3,72 pigs(54.1±5.9 kg BW)were assigned to 3 treatments and fed experimental diets for 3 phases(grower 2,finishing 1,and finishing 2).Treatments were CON(18.0%,13.8%,12.7%CP for 3 phases;meeting Lys,Met,Thr,and Trp);LCP(13.5%,11.4%,10.4%CP for 3 phases;meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and LCPG(14.1%,12.8%,11.1%CP for 3 phases;LCP+Glu to match SID Glu with CON).All diets had 2.6 Mcal/kg NE.Results In Exp.1,overall,the growth performance did not differ among treatments.The LCPT increased(P<0.05)Claudin-1 expression in the duodenum and jejunum.The LCP and LCPT increased(P<0.05)CAT-1,4F2hc,and B0AT expressions in the jejunum.In Exp.2,overall,the VLCP reduced(P<0.05)G:F and BUN.The LCP and VLCP increased(P<0.05)the backfat thickness(BFT).In Exp.3,overall,growth performance and BFT did not differ among treatments.The LCPG reduced(P<0.05)BUN,whereas increased the insulin in plasma.The LCP and LCPG reduced(P<0.05)the abundance of Streptococcaceae,whereas the LCP reduced(P<0.05)Erysipelotrichaceae,and the alpha diversity.Conclusions When implementing low CP formulation,CP can be reduced by supplementation of Lys,Thr,Met,Trp,Val,and Ile without affecting the growth performance of growing-finishing pigs when NE is adjusted to avoid increased fat deposition.Supplementation of Trp above the requirement or supplementation of Glu in low CP formulation seems to benefit intestinal health as well as improved nitrogen utilization and glucose metabolism.

Stabilizing perovskite precursors with the reductive natural amino acid for printable mesoscopic perovskite solar cells

Solution processability significantly advances the development of highly-efficient perovskite solar cells.However,the precursor solution tends to undergo irreversible degradation reactions,impairing the device performance and reproducibility.Here,we utilize a reductive natural amino acid,Nacetylcysteine(NALC),to stabilize the precursor solution for printable carbon-based hole-conductorfree mesoscopic perovskite solar cells.We find that I_(2) can be generated in the aged solution containing methylammonium iodide(MI) in an inert atmosphere and speed up the MA-FA^(+)(formamidinium) reaction which produces large-size cations and hinders the formation of perovskite phase.NALC effectively stabilizes the precursor via its sulfhydryl group which reduces I_(2) back to I^(-)and provides H^(+).The NALC-stabilized precursor which is aged for 1440 h leads to devices with a power conversion efficiency equivalent to 98% of that for devices prepared with the fresh precursor.Furthermore,NALC improves the device power conversion efficiency from 16.16% to 18.41% along with enhanced stability under atmospheric conditions by modifying grain boundaries in perovskite films and reducing associated defects.

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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.

Standardized ileal digestibility of amino acids in soybean meal fed to non-pregnant and pregnant sows

Background Two studies were designed to determine standard ileal crude protein(CP)and amino acid(AA)digestibility of soybean meal(SBM)from different origins fed to non-pregnant and pregnant sows.Seven solvent-extracted SBMs from soybeans produced in the USA,Brazil,and China were selected.In Exp.1,eight different diets were created:a nitrogen(N)-free diet and 7 experimental diets containing SBM from different origins as the only N source.Eight non-pregnant,multiparous sows were arranged in an 8×8 Latin square design(8 periods and 8 diets).In Exp.2,the diet formula was the same as in Exp.1.Eight gestating sows(parity 3)were assigned to 4 different diets in a replicated 4×3 Youden square design(three periods and four diets)in mid-gestation and again in late-gestation stages.Results When fed to non-pregnant and late-gestating sows,the standardized ileal digestibility(SID)of CP and most AAs from different SBM were not significantly different(P>0.05).When fed to mid-gestating sows,the SID values for Arg,His,Lys,Phe,Cys,Gly,Ser,and Tyr in SBM 1 were lower than in SBM 4 and 5(P<0.05),whereas SID for Leu from SBM 5 was higher than in SBM 1 and 4(P<0.05).SID values for Ile,Ala,and Asp from SBM 4 were lower than in SBM 1 and 5(P<0.05).Sows had significantly greater SID values for Lys,Ala,and Asp during mid-gestation when compared with late-gestation stages(P<0.05).Mid-gestating sows had greater SID value for Val and lower SID value for Tyr when compared with non-pregnant and late-gestating sows(P<0.01),whereas non-pregnant sows had significantly greater SID value for Met when compared with gestating sows(P<0.01).Conclusions When fed to mid-gestating sows,the SID values for most AAs varied among SBM samples.The SID values for Lys,Met,Val,Ala,Asp,and Tyr in SBM were affected by sow gestation stages.Our findings provide a cornerstone for accurate SBM use in sow diets.

Abomasal infusion of branched-chain amino acids or branched-chain keto-acids alter lactation performance and liver triglycerides in fresh cows

Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)concentra-tions whereas cows with high circulating BCAA levels have low liver triglyceride(TG).Our objective was to determine the impact of BCAA and their corresponding ketoacids(branched-chain ketoacids,BCKA)on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum.Methods Thirty-six multiparous Holstein cows were used in a randomized block design experiment.Cows were abomasally infused for the first 21 d postpartum with solutions of 1)saline(CON,n=12);2)BCA(67 g valine,50 g leu-cine,and 34 g isoleucine,n=12);and 3)BCK(77 g 2-ketovaline calcium salt,57 g 2-ketoleucine calcium salt,and 39 g 2-ketoisoleucine calcium salt,n=12).All cows received the same diet.Treatment effects were determined using PROC GLIMMIX in SAS.Results No differences were detected for body weight,body condition score,or dry matter intake averaged over the first 21 d postpartum.Cows receiving BCK had significantly lower liver TG concentrations compared to CON(6.60%vs.4.77%,standard error of the mean(SEM)0.49)during the first 3 weeks of lactation.Infusion of BCA increased milk yield(39.5 vs.35.3 kg/d,SEM 1.8),milk fat yield(2.10 vs.1.69 kg/d,SEM 0.08),and lactose yield(2.11 vs.1.67 kg/d,SEM 0.07)compared with CON.Compared to CON,cows receiving BCA had lower plasma glucose(55.0 vs.59.2 mg/dL,SEM 0.86)but higherβ-hydroxybutyrate(9.17 vs.6.00 mg/dL,SEM 0.80).Conclusions Overall,BCAA supplementation in this study improved milk production,whereas BCKA supplementa-tion reduced TG accumulation in the liver of fresh cows.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Six Amino Acids among Natural Moisturizing Factors Responsible for Skin Hydration: Improvement and Anti-Aging of Skin by Galactomyces Ferment Filtrate-PiteraTM Containing Skin Moisturizer

Background: Natural moisturizing factors (NMFs) are filaggrin-derived components in the cornified layer that are critical for maintaining healthy skin moisturization and barrier function. However, studies have reported conflicting findings on the relationship between NMF levels and aging, while few studies have investigated this relationship clinically. To fill this research gap, we determined the levels of major NMF components such as free amino acids, pyrrolidone carboxylic acid, and urocanic acids, and individually verified their relationships with skin hydration, barrier function, age, and skin aging. Purpose: The objective of this study was to clinically investigate the relationship between NMF components levels and skin aging in facial skin. The main NMF components were obtained from facial skin and quantified. We then selected NMF components showing strong relationships to skin hydration, and analyzed the relationships of the levels of these selected NMF components with signs of skin aging, namely, texture, pores, wrinkles, and dullness (L-value). We also examined the efficacy of treatment with a skin care formula (SK-II Facial Treatment Essence, called SK-II FTE hereafter) including Galactomyces ferment filtrate (GFF, PiteraTM) on the selected NMF component levels associated with skin hydration and barrier function, and the signs of skin aging of texture, pores, wrinkles, and dullness (L-value). Method: We conducted two clinical trials in this research. In Study 1, we measured 23 NMF components using tape-stripped cornified layer to quantify them via an HPLC method in 196 Asian females aged 20 to 59 (mean S.D., 38.6 9.4). Facial visual aging parameters [texture, pores, wrinkles, and dullness (L-value)], as well as elasticity (R7), skin hydration, and TEWL, were quantified using facial skin imaging and skin physical property measurement devices. Study 2 was performed to evaluate whether the facial application of SK-II FTE affects the NMF levels and skin aging parameters in 63 Asian female volunteers aged 20 to 55 (38.4 9.03). During the course of Study 2, 0.6 mL of SK-II FTE was applied to the face twice daily in the morning and afternoon. Skin measurements were performed at the start of the day (baseline) and at week 8. Results: In Study 1, we examined the stratum corneum levels of 23 NMF components comparing to the skin hydration status in 196 female subjects. The subjects were divided into two groups using the median of each measured NMF component. Skin hydration values were compared between the two groups defined for each NMF component. The results showed that subjects with higher levels of six amino acids, alanine, arginine, asparagine, glutamine, glycine, and histidine, exhibited significantly higher skin hydration than those with lower amino acid levels. No significant differences in skin hydration values were found for the other 17 NMF components. We then analyzed whether the sum of these six amino acid NMF components (called 6-AA-NMFs, hereafter) is affected by aging. The 6-AA-NMF level peaked in the subjects aged 25-29, and then gradually and significantly decreased with age. Interestingly, the 6-AA-NMF level was significantly correlated with the skin hydration value, but not with TEWL. In addition, the 6-AA-NMF level demonstrated significant correlations with the signs of skin aging of texture, pores, wrinkles, and dullness (L-value). Then, in Study 2, we examined whether the daily application of SK-II FTE affects the 6-AA-NMF level and visual aging parameters in 63 females. SK-II FTE demonstrated significant increases of the levels of 6-AA-NMFs and each of its components associated with hydration and barrier function, and improvements of skin texture, pores, wrinkles, and dullness (L-value) during the 8 weeks of treatment of facial skin. Conclusion: These clinical studies with large numbers of subjects across a wide age range revealed that six amino acids as NMF components were highly correlated with facial skin hydration in the stratum corneum. The levels of these six NMF components were also found to decrease at ages after the 30 s and were significantly correlated with major signs of skin aging. Notably, these six NMF components (6-AA-NMFs) were increased by SK-II FTE treatment associated with improvements of skin hydration and signs of skin aging, namely, texture, pores, wrinkles, and dullness (L-value). These studies were limited by the lack of investigation of why some NMF components were not associated with skin hydration. More clinical trials examining various NMF components and their relationship with aging are anticipated.