Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: A systematic review and meta-analysis.

N-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in Major Depressive Disorder (MDD) pathophysiology. To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a pre-registered meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (n = 1308) and first episode of depression (n = 242) patients to healthy controls (HC, n = 1242). Sixty-two studies were meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in chronic MDD compared to HC within the frontal lobe (Hedges' g = -0.330; p = 0.018), the occipital lobe (Hedges' g = -0.677; p = 0.007), thalamus (Hedges' g = -0.673; p = 0.016), and frontal (Hedges' g = -0.471; p = 0.034) and periventricular white matter (Hedges' g = -0.478; p = 0.047). We highlighted a gap of knowledge regarding NAA levels in first episode of depression patients. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. We highlighted field strength and correction for voxel grey matter as moderators of NAA levels detection. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression.

Formation of Three-Dimensional Polysuccinimide Electrospun Fiber Meshes Induced by the Combination of CaCl2 and Humidity.

Even though electrospinning is getting more and more attention, the preparation of 3D nanofibrous meshes is still a big challenge that limits the application of electrospun materials, especially in tissue engineering. To overcome this problem, several solutions are introduced but most of them focus on the postprocessing of the electrospun meshes. This paper presents a straightforward novel method that utilizes the joint effect of the addition of CaCl2 and the relative environmental humidity (RH), which can induce the random 3D formation of polysuccinimide (PSI) electrospun fibers with different such as wrinkled or ribbon-like structures. Although the effect of humidity and inorganic salt additives on the micro and macrostructure of electrospun fibers is known, the connection between the two in this manner has never been presented. To investigate the effect, fibers with different PSI and CaCl2 concentrations at different humidity RH levels are prepared, and their microstructure is visualized with high-resolution scanning electron microscopy (SEM). To reveal the nature of the interaction between the polymer and the CaCl2, Fourier-transformed infrared (FTIR), X-ray diffraction (XRD), and thermogravimetry (TGA) measurements are carried out and 3D nanofibrous structures are obtained.

Glutamatergic and N-Acetylaspartate Metabolites in Bipolar Disorder: A Systematic Review and Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.

The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine (Gln), Glx, and N-acetylaspartate (NAA). Proton Magnetic Resonance Spectroscopy (1H-MRS) allows one to quantify these metabolites in the human brain. Thus, we conducted a systematic review and meta-analysis of the literature to compare their levels between BD patients and healthy controls (HC). The main inclusion criteria for inclusion were 1H-MRS studies comparing levels of Glu, Gln, Glx, and NAA in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampi between patients with BD in clinical remission or a major depressive episode and HC. Thirty-three studies were included. NAA levels were significantly lower in the left white matter PFC (wmPFC) of depressive and remitted BD patients compared to controls and were also significantly higher in the left dorsolateral PFC (dlPFC) of depressive BD patients compared to HC. Gln levels were significantly higher in the ACC of remitted BD patients compared to in HC. The decreased levels of NAA of BD patients may be related to the alterations in neuroplasticity and synaptic plasticity found in BD patients and may explain the deep white matter hyperintensities frequently observed via magnetic resonance imagery.

Circulating N-Acetylaspartate does not track brain NAA concentrations, cognitive function or features of small vessel disease in humans.

N-acetylaspartate (NAA) is the second most abundant metabolite in the human brain; although it is assumed to be a proxy for a neuronal marker, its function is not fully elucidated. NAA is also detectable in plasma, but its relation to cerebral NAA levels, cognitive performance, or features of cerebral disease has not been investigated. To study whether circulating NAA tracks cerebral NAA levels, and whether circulating NAA correlates with cognitive function and features of cerebral small vessel disease (SVD). Two datasets were analyzed. In dataset 1, structural MRI was acquired in 533 subjects to assess four features of cerebral SVD. Cognitive function was evaluated with standardized test scores (N = 824). In dataset 2, brain 1H-MRS from the occipital region was acquired (N = 49). In all subjects, fasting circulating NAA was measured with mass spectrometry. Dataset 1: in univariate and adjusted for confounders models, we found no correlation between circulating NAA and the examined features of cerebral SVD. In univariate analysis, circulating NAA levels were associated inversely with the speed in information processing and the executive function score, however these associations were lost after accounting for confounders. In line with the negative findings of dataset 1, in dataset 2 there was no correlation between circulating and central NAA or total NAA levels. This study indicates that circulating NAA levels do not reflect central (occipital) NAA levels, cognitive function, or cerebral small vessel disease in man.

Multiscale Engineering of Nanofiber-Aerogel Composite Nanogenerator with Tunable Triboelectric Performance Based on Multifunctional Polysuccinimide.

Multiscale polymer engineering, involving chemical modification to control their triboelectric polarities as well as physicomechanical modification to maximize charge transfer and structural durability, is paramount to developing a high-performance triboelectric nanogenerator (TENG). This report introduces a highly efficient and comprehensive strategy to engineer high-performance TENG based on multifunctional polysuccinimide (PSI). With the ability of PSI to undergo facile nucleophilic addition with amines, sodium sulfate and quaternary ammonium chlorides having opposite charged groups are conjugated to PSI in varying densities. The resulting Sulfo-PSI and TMAC-PSI, respectively, processed into nanofibrous films, demonstrate highly enhanced and variable triboelectric properties based on the charge type and density. To further enhance the mechanical toughness and biocompatibility necessary for wearable applications, these PSI nanofibers are processed into alginate aerogel (AG). The sustained triboelectric performance of this nanofiber-AG TENG as a wearable energy harvester and biosensor is examined and validated in detail.

Ionic mitigation of CD4+ T cell metabolic fitness, Th1 central nervous system autoimmunity and Th2 asthmatic airway inflammation by therapeutic zinc.

T helper (Th) cells provide immunity to pathogens but also contribute to detrimental immune responses during allergy and autoimmunity. Th2 cells mediate asthmatic airway inflammation and Th1 cells are involved in the pathogenesis of multiple sclerosis. T cell activation involves complex transcriptional networks and metabolic reprogramming, which enable proliferation and differentiation into Th1 and Th2 cells. The essential trace element zinc has reported immunomodulatory capacity and high zinc concentrations interfere with T cell function. However, how high doses of zinc affect T cell gene networks and metabolism remained so far elusive. Herein, we demonstrate by means of transcriptomic analysis that zinc aspartate (UNIZINK), a registered pharmaceutical infusion solution with high bioavailability, negatively regulates gene networks controlling DNA replication and the energy metabolism of murine CD3/CD28-activated CD4+ T cells. Specifically, in the presence of zinc, CD4+ T cells show impaired expression of cell cycle, glycolytic and tricarboxylic acid cycle genes, which functionally cumulates in reduced glycolysis, oxidative phosphorylation, metabolic fitness and viability. Moreover, high zinc concentrations impaired nuclear expression of the metabolic transcription factor MYC, prevented Th1 and Th2 differentiation in vitro and reduced Th1 autoimmune central nervous system (CNS) inflammation and Th2 asthmatic airway inflammation induced by house dust mites in vivo. Together, we find that higher zinc doses impair the metabolic fitness of CD4+ T cells and prevent Th1 CNS autoimmunity and Th2 allergy.

Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate.

Uncoupling proteins (UCPs) form a distinct subfamily of the mitochondrial carrier family (MCF) SLC25. Four UCPs, DmUCP4A-C and DmUCP5, have been identified in Drosophila melanogaster on the basis of their sequence homology with mammalian UCP4 and UCP5. In a Parkinson's disease model, DmUCP4A showed a protective role against mitochondrial dysfunction, by increasing mitochondrial membrane potential and ATP synthesis. To date, DmUCP4A is still an orphan of a biochemical function, although its possible involvement in mitochondrial uncoupling has been ruled out. Here, we show that DmUCP4A expressed in bacteria and reconstituted in phospholipid vesicles catalyzes a unidirectional transport of aspartate, which is saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. Swelling experiments carried out in yeast mitochondria have demonstrated that the unidirectional transport of aspartate catalyzed by DmUCP4 is not proton-coupled. The biochemical function of DmUCP4A has been further confirmed in a yeast cell model, in which growth has required an efflux of aspartate from mitochondria. Notably, DmUCP4A is the first UCP4 homolog from any species to be biochemically characterized. In Drosophila melanogaster, DmUCP4A could be involved in the transport of aspartate from mitochondria to the cytosol, in which it could be used for protein and nucleotide synthesis, as well as in the biosynthesis of ß-alanine and N-acetylaspartate, which play key roles in signal transmission in the central nervous system.

Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.

BACKGROUND: In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition's underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population. METHODS: A sample of 20 adolescents with JIA and 20 controls aged 13-17 years were recruited to complete surveys, provide medical histories and biospecimens, and undergo assessments. Fasting morning plasma samples were processed with liquid chromatography-mass spectrometry. Data were centered, scaled, and analyzed using generalized linear models accounting for age, sex, and medications (p-values adjusted for multiple comparisons using the Holm method). Spearman's correlations were used to evaluate relationships among metabolites, time since diagnosis, and disease severity. RESULTS: Of 72 metabolites identified in the samples, 55 were common to both groups. After adjustments, 6 metabolites remained significantly different between groups. Alpha-glucose, alpha-ketoglutarate, serine, and N-acetylaspartate were significantly lower in the JIA group than in controls; glycine and cystine were higher. Seven additional metabolites were detected only in the JIA group; 10 additional metabolites were detected only in the control group. Metabolites were unrelated to disease severity or time since diagnosis. CONCLUSIONS: The metabolic signature of adolescents with JIA relative to controls reflects a disruption in oxidative stress; neurological health; and amino acid, caffeine, and energy metabolism pathways. Serine and N-acetylaspartate were promising potential biomarkers, and their metabolic pathways are linked to both JIA and cardiovascular disease risk. The pathways may be a source of new diagnostic, treatment, or prevention options. This study's findings contribute new knowledge for systems biology and precision health approaches to JIA research. Further research is warranted to confirm these findings in a larger sample.

Glutamate and N-Acetylaspartate Alterations Observed in Early Phase Psychosis: A Systematic Review of Proton Magnetic Resonance Spectroscopy Studies.

Glutamate and N-acetylaspartate have been investigated in the neuropathology of chronic schizophrenia, with fewer studies focusing on early phase psychosis. Additionally, there has been little review and synthesis of the literature focused on multiple brain regions. This systematic review aims to provide a clear report of the current state of research on glutamate and n-acetylaspartate concentrations in early phase psychosis (defined as the first five years following psychosis onset) in multiple brain regions. Existing literature was searched systematically to compile reports of glutamate/glutamate+glutamine (Glx) and n-acetylaspartate absolute levels and ratios in both male and female individuals with early phase psychosis. Reports on glutamate/Glx concentrations in the medial prefrontal region and thalamus were varied, but the majority of reports suggested no alterations in EPP. No studies reported glutamate alterations in the hippocampus or cerebellum. There was no evidence for n-acetylaspartate alterations in the caudate, basal ganglia, and medial prefrontal cortex, and minimal evidence for NAA reductions in the thalamus, anterior cingulate cortex, and hippocampus. Future research should focus on the regions that are less commonly reported, and should aim to explore possible confounds, such as medication status and substance use.

MAFLD progression contributes to altered thalamus metabolism and brain structure.

Metabolic associated fatty liver disease (MAFLD), commonly known as non-alcoholic fatty liver disease, represents a continuum of events characterized by excessive hepatic fat accumulation which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and in some severe cases hepatocellular carcinoma. MAFLD might be considered as a multisystem disease that affects not only the liver but involves wider implications, relating to several organs and systems, the brain included. The present study aims to investigate changes associated with MAFLD-induced alteration of thalamic metabolism in vivo. DIAMOND (Diet-induced animal model of non-alcoholic fatty liver disease) mice were fed a chow diet and tap water (NC NW) or fat Western Diet (WD SW) for up to 28 weeks. At the baseline and weeks 4, 8, 20, 28 the thalamic neurochemical profile and total cerebral brain volume were evaluated longitudinally in both diet groups using 1H-MRS. To confirm the disease progression, at each time point, a subgroup of animals was sacrificed, the livers excised and placed in formalin. Liver histology was assessed and reviewed by an expert liver pathologist. MAFLD development significantly increases the thalamic levels of total N-acetylaspartate, total creatine, total choline, and taurine. Furthermore, in the WD SW group a reduction in total cerebral brain volume has been observed (p < 0.05 vs NC NW). Our results suggest that thalamic energy metabolism is affected by MAFLD progression. This metabolic imbalance, that is quantifiable by 1H-MRS in vivo, might cause structural damage to brain cells and dysfunctions of neurotransmitter release.

Inverse Association Between Hypothalamic N-Acetyl Aspartate/Creatine Ratio and Indices of Body Mass in Adolescents with Obesity.

BACKGROUND: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. OBJECTIVES: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. METHODS: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). RESULTS: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). CONCLUSIONS: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.

The Auditory Afferent Pathway as a Clinical Marker of Alzheimer's Disease.

Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer's disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG.

Targeted delivery of emamectin benzoate by functionalized polysuccinimide nanoparticles for the flowering cabbage and controlling Plutella xylostella.

BACKGROUND: Plutella xylostella, one of the most destructive and cosmopolitan pests of cruciferous crops, is especially harmful to the young tissues of the flowering cabbage (Brassica campestris L.). Although emamectin benzoate (EB) has high insecticidal activity against P. xylostella, one major reason of low utilization for EB is the lack of internal transport in the young plants. RESULTS: In this study, four kinds of functional EB/polysuccinimide (PSI) with glycine methylester nanoparticles (EB@PGA NPs) were prepared. The obtained EB@PGA NPs could effectively protect EB from photolysis, and the degradation rate of EB@PGA NPs was <30% in 24 h. Simulating the intestinal pH = 9 of P. xylostella, the highest cumulative release rate of EB@PGA NPs could reach 89.61% in 24 h. Furthermore, EB@PGA NPs could delivery EB into the young tissues of the flowering cabbage through the nanocarrier, and the highest transport efficiency of EB@PGA25 reached 1.437%. The bioactivity of EB@PGA25 against P. xylostella larvae (LC50  = 0.34 µg mL-1 ) was 1.6-fold higher than that of EB (LC50  = 0.53 µg mL-1 ). EB@PGA could easily become 'internalized' into the intestinal wall of P. xylostella, thus increasing the penetration of the drug and enhancing the insecticidal activity. CONCLUSION: The accurate delivery of insecticides by PGA nanocarriers into young tissues of plants could be a promising new method for the efficient management of field pests and diseases. © 2021 Society of Chemical Industry.

Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes.

There is an urgent need for a better understanding of the pathophysiology of cognitive impairment in syndromes associated with frontotemporal lobar degeneration. Here, we used magnetic resonance spectroscopy to quantify metabolite deficits in sixty patients with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n = 11, progressive supranuclear palsy n = 26, corticobasal syndrome n = 11, primary progressive aphasias n = 12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex. Metabolite concentrations were corrected for age, sex, and partial volume then compared with cognitive and behavioral measures using canonical correlation analysis. Metabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64) = 1.73, p < 0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R = 0.85, p < 0.001).

Neurometabolite correlates with personality and stress in healthy emerging adults: A focus on sex differences.

Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p<0.05) negative correlates of stress with the NAA/Cr ratio in the pCC, and of extraversion with WM metabolite ratios. In regards of sex differences, a significantly higher NAA/Cho ratio in the pCC (p<0.05), the dACC (p<0.01), and in the left and right posterior WM matter (p<0.05), and a lower Cho/Cr ratio in the dACC (p<0.01) was detected in women. Moreover, the two sexes differed in regards of metabolite correlates of openness, conscientiousness, extraversion, agreeableness, neuroticism, stress, hopelessness, and self-esteem, and in multiple regression model predictions. Our results point to a role of the ACC in conscientiousness through its involvement in higher-order cognitive control as part of the salience network and internally directed thoughts as part of the default mode network (DMN). Furthermore, the two sexes differ in terms of metabolite correlates of openness and conscientiousness in the pCC, suggesting mental process involvement through the DMN, and of agreeableness in the dACC, possibly through involvement in social cognitive processes, particularly in women. Additionally, our results suggest that the ACC is linked to the so-called Alpha-factor of personality. Our findings on stress correlates contribute to the existing literature of the involvement of the ACC as part of the limbic system. In addition, our results suggest a possible role of the pCC in stress-regulatory processes through a possible co-involvement of stress, hopelessness, and self-esteem in the pCC in men, where higher self-esteem may help to cope with stress.

Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults.

Elevated expression of ß-amyloid (Aß1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aß1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

Effects of repeated manganese treatment on proton magnetic resonance spectra of the globus pallidus in rat brain.

Excessive manganese is neurotoxic, which means that it can affect the concentrations of metabolite in 1 H MRS. In addition, manganese is paramagnetic and it may influence the relaxation times of the metabolite. The aim of this study is to assess the sensitivity of the metabolite relaxation properties and concentrations to exogenous manganese deposition in the globus pallidus (GP) of rat brain after repeated manganese injection. Proton magnetic resonance spectroscopy (1 H MRS) experiments in vivo and ex vivo were carried out to evaluate the changes in the metabolite concentration and the major metabolite relaxation times, and histological experiments were also performed after repeated manganese administration. Only the T1 value for N-acetylaspartate (NAA) of the GP was significantly reduced after 1 day of manganese injection compared with that of the control group (p < 0.025). The T1 and T2 values for NAA and total creatine (tCr) (p < 0.025), along with the amounts of NAA, tCr, myo-inositol, choline, and glutamate (p < 0.0086) in the GP, were all significantly decreased after 5 days of manganese administration compared with that of the control group. The changes in the concentration and relaxation properties of NAA and tCr in the GP of rat brain indicated that manganese represented paramagnetism and neurotoxicity after repeated administration. Accurate knowledge of relaxation properties and concentrations of NAA and tCr in this study could help appropriate selection of sequence parameters to improve the ability to distinguish the brain regions affected in cases of manganese poisoning.

Efficacy of Zn-Aspartate in comparison with ZnSO4 and L-Aspartate in amelioration of drought stress in maize by modulating antioxidant defence; osmolyte accumulation and photosynthetic attributes.

Human population is exceeding beyond the carrying capacity of earth resources and stresses like water shortage faced by the plants is jeopardizing the food security. Current research study was aimed to investigate the potentials of Zn-Aspartate (Zn-Asp), Zn-Sulphate (ZnSO4) and L-Aspartate (L-Asp) to be used as osmolytes and role of various levels of these chemicals in combating drought stress in maize plants in Punjab, Pakistan. Study was performed on two plots corresponding to drought and controlled environments. The lamina of maize plants was sprinkled row wise with various treatments including No spray (NS), water sprinkle (WS), sprinkle with ZnSO4 0.25% and 0.50%, sprinkle with Zn-Asp 0.25% and 0.50% and Foliar sprinkle of L-Asp 0.5% and 1%, respectively. Role of major osmoprotectants and secondary metabolites was analyzed and positive changes were found in total soluble sugars (41.16), flavonoids (5387.74), tocopherol content (9089.18), ascorbic acid (645.27) and anthocyanin (14.84) conc. which assists in mitigating drought menace on maize. Shoot mineral ions (Ca, K, Zn, P, Mg and N) status of water stressed maize plants was also analyzed and it was found that application experimental dose enhanced their availability to crop. Physio-biochemical studies were performed on antioxidants enzymes like superoxide dismutase (SOD), peroxidase (POD), carotenoid content (CC), malondialdehyde, hydrogen peroxide, aspartate and free amino acid contents. The activity of SOD was increased by 28.5% and activity of POD was increased by 33.33% due to foliar applied 0.5% Zn-Asp under drought stress. Photosynthetic pigments (chlorophyll A, B and total chlorophyll content) analysis was also carried out in this study. It was found that conc. of different chlorophylls pigments increased (chl-A: 2.24, chl-B: 25.12, total chl: 24.30) which enhanced photosynthetic activity culminating into better growth and yield). The level of malondialdehyde and hydrogen peroxide decreased by 43.9% and 32.8% respectively on treatment with 0.5% Zn-Asp proving the efficacy of the treatment in drought amelioration. Study reveals that Zn-Asp induced modulations are far better than conventional sulphate salts in mitigating water scarce environment. Current study recommends the use of the Zn-Asp to meet the global food and agricultural challenges as compared to ZnSO4 and L-Asp due to its better drought amelioration properties. This research provides valuable informations which can used for future research and practical use in agriculture fields by indigenous and other people to enhance yield of maize to meet the food necessities of country.

N-acetyl l-aspartate and Triacetin modulate tumor suppressor MicroRNA and class I and II HDAC gene expression induce apoptosis in Glioblastoma cancer cells in vitro.

Glioblastoma multiforme (GBM), grade IV glioma and is aggressive, malignant primary brain cancer. Altered expression and activity of epigenetic proteins such as histone deacetylases (HDACs) are involved in GBM metastasis. Also, acetates are important to brain metabolites that regulate cell proliferation and apoptosis. Here, we have examined the effect of the acetates on the cell-cycle. U87MG cancer cells treated with N-acetyl l-aspartate (NAA) and sodium acetate have exhibited G1 phase cell-cycle arrest whereas U87MG cells treated with Triacetin (TA), and potassium acetate has induced G2/M cell cycle arrest. We have observed inhibition of histone deacetylase (HDAC) mRNA levels in acetate treated U87MG cells. Interestingly, acetates-treated U87MG cells have shown a significant reduction in the mRNA level of class II HDACs than class I HDACs. Acetate treated cells have exhibited an enhanced expression of various microRNAs such as miR-15b, miR-92, miR-101, miR-155, miR-199, miR-200, miR-223, miR-16, and miR-17 that are involved in the inhibition of cancer cell proliferation, invasion, migration, and angiogenesis. Further, these acetate molecules regulate genes involved in mammalian target of rapamycin complex 2 (mTORC2) such as mammalian stress-activated protein kinase-interacting protein (mSIN1), protein observed with Rictor 2 (Protor 2), and protein kinase C α (PKCα). The present study reveals the possible involvement of the mTORC2 complex during acetate-mediated HDAC inhibition, as well as microRNA modulation. Furthermore, molecular modeling studies were employed to understand the binding mode of these acetate molecules to mTOR, Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor), and HDAC-8 proteins. Thus in this study, we have identified the pivotal role of acetates in the modulation of mTOR complex, epigenetic genes and provide structural as well as functional insights that will help in future drug discovery against GBM cancer therapy.

Expression, purification, and biochemical characterization of an NAD+-dependent homoserine dehydrogenase from the symbiotic Polynucleobacter necessarius subsp. necessarius.

Homoserine dehydrogenase (HSD), encoded by the hom gene, is a key enzyme in the aspartate pathway, which reversibly catalyzes the conversion of l-aspartate ß-semialdehyde to l-homoserine (l-Hse), using either NAD(H) or NADP(H) as a coenzyme. In this work, we presented the first characterization of the HSD from the symbiotic Polynucleobacter necessaries subsp. necessarius (PnHSD) produced in Escherichia coli. Sequence analysis showed that PnHSD is an ACT domain-containing monofunctional HSD with 436 amnio acid residues. SDS-PAGE and Western blot demonstrated that PnHSD could be overexpressed in E. coli BL21(DE3) cell as a soluble form by using SUMO fusion technique. It could be purified to apparent homogeneity for biochemical characterization. Size-exclusion chromatography revealed that the purified PnHSD has a native molecular mass of ∼160 kDa, indicating a homotetrameric structure. The oxidation activity of PnHSD was studied in this work. Kinetic analysis revealed that PnHSD displayed an up to 1460-fold preference for NAD+ over NADP+, in contrast to its homologs. The purified PnHSD displayed maximal activity at 35 °C and pH 11. Similar to its NAD+-dependent homolog, neither NaCl and KCl activation nor L-Thr inhibition on the enzymatic activity of PnHSD was observed. These results will contribute to a better understanding of the coenzyme specificity of the HSD family and the aspartate pathway of P. necessarius.