Background: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition that may be related to an imbalance of neural transmitters. The gut microbiota is the largest ecosystem in the human body, and the brain-gut axis theory proposes that the gut microbiome can affect brain function in multiple ways. The purpose of this study was to explore the gut microbiota in children with ADHD and assess the possible role of the gut microbiota in disease pathogenesis to open new avenues for ADHD treatment.Methods: A case-control design was used. We enrolled 17 children aged 6-12 years with ADHD who were treated in the Pediatric Outpatient Department of the First Medical Center of the Chinese PLA General Hospital from January to June, 2019. Seventeen children aged 6-12 years were selected as the healthy control (HC) group. Fecal samples of cases and controls were analyzed by shotgun metagenomics sequencing. Alpha diversity and the differences in the relative abundances of bacteria were compared between the two groups. Functional annotations were performed for the microbiota genes and metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results:There was no significant difference in the alpha diversity of gut microbiota between the ADHD and HC groups. Compared with HCs, Faecalibacterium and Veillonellaceae were significantly reduced in children with ADHD (P < 0.05), Odoribacter and Enterococcus were significantly increased [linear discriminant analysis (LDA) > 2]. At the species level, Faecalibacterium prausnitzii, Lachnospiraceae bacterium, and Ruminococcus gnavus were significantly reduced in the ADHD group (P < 0.05), while Bacteroides caccae, Odoribacter splanchnicus, Paraprevotella xylaniphila, and Veillonella parvula were increased (P < 0.05). Metabolic pathway analysis revealed significant between-group differences in the metabolic pathways of neurotransmitters (e.g., serotonin and dopamine) (P < 0.05). Frontiers in Neuroscience | www.frontiersin.org 1 February 2020 | Volume 14 | Article 127 Wan et al. Gut Microbiota Role in ADHDConclusion: Composition differences of gut microbiota in subjects with ADHD may contribute to brain-gut axis alterations and affect neurotransmitter levels, which could contribute to ADHD symptoms.
enzyme substitution therapy ͉ hyperphenylalaninemia ͉ long-term efficacy ͉ PKU mouse model ͉ injectable nonmammalian protein
Rapeseed (Brassica napus L.) is a very important edible oil crop in the world, and the production is inhibited by abiotic stresses, such as salinity. Plant hormones can alleviate the stress by regulating the physiological processes and gene expression. To study the plant responses to salinity in combination with GR24, a synthesized strigolactone, the oilseed rape variety (Zhongshuang 11) replications were grown in the pots in a controlled growth chamber under three levels of salinity (0, 100, and 200 mM NaCl) and 0.18 μM GR24 treatments at the seedling stage for 7 days. The results showed that salinity depressed the shoots and roots growth, whereas GR24 improved the growth under salt stress. Leaf chlorophyll contents and gas exchange parameters (net photosynthetic rates, stomatal conductance, intercellular CO2 concentration, and transpiration rate) were also reduced significantly with increasing salinity, and these effects could be partially reversed by GR24 application. Additionally, GR24 treatment significantly increased and decreased the photosystem II quantum yield and non-photochemical quenching, respectively, under salinity stress conditions. The activities of peroxidase and superoxide dismutase increased, and lipid peroxidation measured by the level of malondialdehyde reduced due to GR24 application. The transcriptome analysis of root and shoot was conducted. Three hundred and forty-two common differentially expressed genes (DEGs) after GR24 treatment and 166 special DEGs after GR24 treatment under salinity stress were identified in root and shoot. The DEGs in root were significantly more than that in shoot. Quantitative PCR validated that the stress alleviation was mainly related to the gene expression of tryptophan metabolism, plant hormone signal transduction, and photosynthesis.
Phenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of Phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; second, we used silica sol-gel material as a matrix to demonstrate that a silica matrix can provide protection to entrapped PAL proteins against intestinal proteases, as well as a low pH of 3.5; finally, we demonstrated that PEGylation of AvPAL surface lysines can reduce the inactivation of the enzyme by trypsin.
BACKGROUND: Bee pollen has been regarded as a complete nutritional human dietary supplement but its nutrient absorption and biological effects may be restricted by the complex pollen wall. The aim of this study was to explore the effects of ultrasonic and ball-milling treatment on the release of nutritional components and on in vitro and in vivo antioxidant effects of rose (Rosa rugosa) bee pollen. RESULTS: Bee pollen walls were broken to varying degrees, nutrients were released, and in vitro and in vivo antioxidant effects of bee pollen were improved. The scavenging effects of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 ′ -azinobis(3-ethylbenzothiazolone-6-sulfonic acid) (ABTS) radicals, and oxygen radical absorbance capacity (ORAC) were improved. In aging mice, wall-breaking treatment led to better organ recovery, enhanced superoxide dismutase (SOD) and catalase (CAT) effects, and malondialdehyde (MDA) reduction. Eight compounds of rose bee pollen ethanol extract, including isorhamnetin 3-O-diglucoside and N ′ , N ′′ , N ′′′ -dicaffeoyl p-coumaroyl spermidine were identified by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) assay.CONCLUSION: This study showed that ultrasonic treatment had greater wall-disruption effects of bee pollen on nutrient release and antioxidant effect promotion. In conclusion, rose bee pollen, with wall-breaking treatments, may have potential value as an ingredient in functional food processing.
Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous for its blue flowers. To understand the chemical basis of the rich blue colors in this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as one pink and one white cultivar were determined using high-performance liquid chromatography and mass spectrometry. Along with two known compounds, eight putative anthocyanins were identified in the tepals of grape hyacinth for the first time. The accumulation and distribution of anthocyanins in the plant showed significant cultivar and flower development specificity. Violet-blue flowers mainly contained simple delphinidin-type anthocyanins bearing one or two methyl-groups but no acyl groups, whereas white and pink flowers synthesised more complex pelargonidin/cyanidin-derivatives with acyl-moieties but no methyl-groups. The results partially reveal why solid blue, orange or red flowers are rare in this plant in nature. In addition, pelargonidin-type anthocyanins were found for the first time in the genus, bringing more opportunities in terms of breeding of flower color in grape hyacinth.
Background: Infantile spasm (IS) is one of the most common catastrophic epilepsy syndromes in infancy characterized by epileptic spasm. While adrenocorticotropic hormone (ACTH) is the first-line treatment for IS, it is evident that the seizures associated with IS exhibit a clear circadian rhythm; however, the precise mechanisms underlying such seizures remain unclear. Melatonin is an important amine hormone and is regulated by circadian rhythm. Circadian proteins, especially Aryl Hydrocarbon Receptor Nuclear Trasnslocator-like Protein (ARNTL or BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and their target proteins Period Circadian Regulator 1 (PER1), Period Circadian Regulator 2 (PER2), Cryptochrome 1 (CRY1), and Cryptochrome 2 (CRY2), play key roles in circadian rhythm. This study explored the relationships between melatonin, genes associated with circadian rhythm, and epileptic spasm. Materials and Methods: Eighteen female rats were mated with nine male rats and 16 became pregnant. Twelve pregnant rats were subjected to prenatal stress by forced swimming in cold water from the day of conception. Rat pups produced by stressed mothers received an intraperitoneal injection of N-methyl-D-aspartate (NMDA) on the 13th day after birth and were divided into four groups: NMDA (15 mg/kg), NMDA+ACTH (20 IU/kg), NMDA+melatonin (55 mg/kg), and NMDA+ACTH+melatonin (n = 36/group). Offspring from four dams that were not subjected to prenatal stress were used as controls. We then recorded latency and the frequency of flexion seizures. All offspring were sacrificed on the 14th day after birth and CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was analyzed by western blotting, immunohistochemistry, and immunofluorescence. Results: NMDA induced spasm-like symptoms in rats. ACTH and melatonin significantly increased seizure latency and significantly reduced the frequency of seizures (P < 0.05). CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was significantly lower in the NMDA group than the controls (P < 0.05). ACTH significantly increased the expression of CLOCK, BAML1, PER1, and CRY1 (P < 0.05) and melatonin significantly increased the expression of CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 (P < 0.05) compared with those of the NMDA group. There were no significant differences in the expression of BMAL1, CRY2, PER1, and PER2 when compared between the NMDA+ACTH+melatonin and control groups (P > 0.05). Wan et al. Circadian and Infantile Spasm Conclusion: ACTH and melatonin significantly increased the expression of circadian genes and improved NMDA-induced seizures. The anticonvulsant effects of ACTH and melatonin are likely to involve regulation of the expression of these genes.
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