Project description:Pleiotrophin (PTN) is a cytokine involved in nerve tissue repair processes, neuroinflammation and neuronal survival. PTN expression levels are upregulated in the nigrostriatal pathway of Parkinson's Disease (PD) patients. We aimed to characterize the dopaminergic injury and glial responses in the nigrostriatal pathway of mice with transgenic Ptn overexpression in the brain (Ptn-Tg) after intrastriatal injection of the catecholaminergic toxic 6-hydroxydopamine (6-OHDA) at a low dose (5 µg). Ten days after surgery, the injection of 6-OHDA induced a significant decrease of the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and of the striatal TH contents in Wild type (Wt) mice. In contrast, these effects of 6-OHDA were absent in Ptn-Tg mice. When the striatal Iba1 and GFAP immunoreactivity was studied, no statistical differences were found between vehicle-injected Wt and Ptn-Tg mice. Furthermore, 6-OHDA did not cause robust glial responses neither on Wt or Ptn-Tg mice 10 days after injections. In metabolomics studies, we detected interesting metabolites that significantly discriminate the more injured 6-OHDA-injected Wt striatum and the more protected 6-OHDA-injected Ptn-Tg striatum. Particularly, we detected groups of metabolites, mostly corresponding to phospholipids, whose trends were opposite in both groups. In summary, the data confirm lower 6-OHDA-induced decreases of TH contents in the nigrostriatal pathway of Ptn-Tg mice, suggesting a neuroprotective effect of brain PTN overexpression in this mouse model of PD. New lipid-related PD drug candidates emerge from this study and the data presented here support the increasingly recognized "lipid cascade" in PD.
Project description:We performed a large-scale, site-specific N-glycoproteome profiling study of human Alzheimer’s disease (AD) and control brains using mass spectrometry–based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomic data-driven network analysis showed 13 modules of co-regulated N-glycopeptides/glycoproteins, 6 of which are associated with AD phenotypes.
Project description:Cognitive dysfunction is a central nervous system (CNS) complication of diabetes mellitus (DM) that is characterized by impaired memory and cognitive ability. An in-depth understanding of metabolic alterations in the brain associated with DM will facilitate our understanding of the pathogenesis of cognitive dysfunction. The present study used an in vitro culture of primary neurons in a high-glucose (HG) environment to investigate characteristic alterations in neuron metabolism using nuclear magnetic resonance (NMR)-based metabonomics. High performance liquid chromatography (HPLC) was also used to measure changes in the adenosine phosphate levels in the hippocampal regions of streptozotocin (STZ)-induced diabetic rats. Our results revealed significant elevations in phosphocholine and ATP production in neurons and decreased formate, nicotinamide adenine dinucleotide (NAD+), tyrosine, methionine, acetate and phenylalanine levels after HG treatment. However, the significant changes in lactate, glutamate, taurine and myo-inositol levels in astrocytes we defined previously in astrocytes, were not found in neurons, suggested cell-specific metabolic alterations. We also confirmed an astrocyte-neuron lactate shuttle between different compartments in the brain under HG conditions, which was accompanied by abnormal acetate transport. These alterations reveal specific information on the metabolite levels and transport processes related to neurons under diabetic conditions. Our findings contribute to the understanding of the metabolic alterations and underlying pathogenesis of cognitive decline in diabetic patients.
Project description:The posttranslational N-glycosylation of food proteins is important to their structure and function. However, the N-glycoproteomics of yellow preserved egg white were rarely reported. This study explored the changes of N-glycoproteome in yellow preserved eggs white after salt and alkali treatment. A total of 213 N-glycosites were identified on 102 glycoproteins, revealing prevalent glycosylation motifs and multiple N-glycosites within proteins. Salt and alkali treatment significantly altered the glycosylation patterns, impacting major proteins differently. GO analysis indicated the roles of differentially expressed glycoproteins in responding to stimuli and biological regulation. KEGG analysis emphasized the importance of salivary secretion pathway in enzyme secretion and peptide generation. Protein domain analysis highlighted the downregulation of Serpin. Protein-protein interaction networks revealed Apolipoprotein B as central players. This study provides essential structural information on the glycosylation modifications of egg white proteins, contributing to our understanding of the mechanisms behind the functional properties of preserved eggs.
Project description:BackgroundCastor is an important industrial raw material. Drought-induced oxidative stress leads to slow growth and decreased yields in castor. However, the mechanisms of drought-induced oxidative stress in castor remain unclear. Therefore, in this study, physiological, biochemical, and RNA-seq analyses were conducted on the roots of castor plants under PEG-6000 stress for 3 d and 7 d followed by 4 d of hydration.ResultsThe photosynthetic rate of castor leaves was inhibited under PEG-6000 stress for 3 and 7 d. Biochemical analysis of castor roots stressed for 3 d and 7 d, and rehydrated for 4 d revealed that the activities of APX and CAT were highest after only 3 d of stress, whereas the activities of POD, GR, and SOD peaked after 7 d of stress. RNA-seq analysis revealed 2926, 1507, and 111 differentially expressed genes (DEGs) in the roots of castor plants under PEG-6000 stress for 3 d and 7 d and after 4 d of rehydration, respectively. GO analysis of the DEGs indicated significant enrichment in antioxidant activity. Furthermore, KEGG enrichment analysis of the DEGs revealed significantly enriched metabolic pathways, including glutathione metabolism, fatty acid metabolism, and plant hormone signal transduction. WGCNA identified the core genes PP2C39 and GA2ox4 in the navajowhite1 module, which was upregulated under PEG-6000 stress. On the basis of these results, we propose a model for the response to drought-induced oxidative stress in castor.ConclusionsThis study provides valuable antioxidant gene resources, deepening our understanding of antioxidant regulation and paving the way for further molecular breeding of castor plants.
Project description:Astrocytes, the most abundant glial cell population in the central nervous system, have important functional roles in the brain as blood brain barrier maintenance, synaptic transmission or intercellular communications [1], [2]. Numerous studies suggested that astrocytes exhibit a functional and morphological high degree of plasticity. For example, following any brain injury, astrocytes become reactive and hypertrophic. This phenomenon, also called reactive gliosis, is characterized by a set of progressive gene expression and cellular changes [3]. Interestingly, in this context, astrocytes can re-acquire neurogenic properties. It has been shown that astrocytes can undergo dedifferentiation upon injury and inflammation, and may re-acquire the potentiality of neural progenitors [4], [5], [6], [7]. To assess the effect of inflammation on astrocytes, primary mouse astrocytes were treated with tumor necrosis factor α (TNFα), one of the main pro-inflammatory cytokines. The strength of this study is that pure primary astrocytes were used. As microglia are highly reactive immune cells, we used a magnetic cell sorting separation (MACS) method to further obtain highly pure astrocyte cultures devoid of microglia. Here, we provide details of the microarray data, which have been deposited in the Gene Expression Omnibus (GEO) under the series accession number GSE73022. The analysis and interpretation of these data are included in Gabel et al. (2015). Analysis of gene expression indicated that the NFκB pathway-associated genes were induced after a TNFα treatment. We have shown that primary astrocytes devoid of microglia can respond to a TNFα treatment with the re-expression of genes implicated in the glial cell development.
Project description:Schizophrenia is a psychiatric disorder that affects more than 21 million people worldwide. It is an incurable disorder and the primary means of managing symptoms is through administration of pharmacological treatments, which consist heavily of antipsychotics. First-generation antipsychotics have the properties of D2 receptor antagonists. Second-generation antipsychotic are antagonists of both D2 and 5HT2 receptors. Recently, there has been increasing interest in the effects of antipsychotics beyond their neuronal targets and oligodendrocytes are one of the main candidates. Thus, our aim was to evaluate the molecular effects of typical and atypical drugs across the proteome of the human oligodendrocyte cell line, MO3.13. For this, we performed a mass spectrometry-based, bottom-up shotgun proteomic analysis to identify differences triggered by typical (chlorpromazine and haloperidol) and atypical (quetiapine and risperidone) antipsychotics. Proteins which showed changes in their expression levels were analyzed in silico using Ingenuity® Pathway Analysis, which implicated dysregulation of canonical pathways for each treatment. Our results shed light on the biochemical pathways involved in the mechanisms of action of these drugs, which may guide the identification of novel biomarkers and the development of new and improved treatments.
Project description:Morchella sextelata, one of the true morels, has recently been artificially cultivated with stable production in China. Analysis of the variations in primary metabolites during the vegetative stages of M. sextelata is critical for understanding the metabolic process. In this study, three developmental stages were categorized based on morphological and developmental changes, including the young mushroom period, marketable mature period, and physiological maturity period. Untargeted metabolomics-based mass spectrometry was used to analyze the change of metabolites during the growth stages of M. sextelata. The result showed that the metabolites' content at the different growth stages were significantly different. The relative contents of linoleic acid, mannitol, oleamide, and betaine were higher at each growth stage. Flavor substances were significantly metabolizable during commodity maturity, while amino acids, organic acids, and lipids were significantly metabolizing at physiological maturity. Pathway analysis of the most significant changes involved Pyrimidine metabolism, Vitamin B6 metabolism, Arginine biosynthesis, Lysine biosynthesis, and Lysine degradation. The results can provide a theoretical basis for further clarifying the metabolic regulation mechanism and lay the foundation for optimizing the cultivation process of M. sextelata.
Project description:BackgroundDespite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.MethodsThe metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.ResultsFour out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.ConclusionsOur preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.
Project description:BackgroundAnalyze possible relationships between HAdV and markers for inflammation, specifically the C-reactive protein (CRP) and procalcitonin (PCT) tests, along with other haematological markers.MethodsRetrospective study of 487 children presenting with fever and/or acute respiratory symptoms in the Paediatric Emergency Department. Analyses included viral presence/absence (both HAdV and other respiratory viruses) in respiratory exudates, CRP and PCT alterations in plasma, and haematological markers in whole blood.ResultsViral load was >500 copies/103 cells of HAdV in 127 cases (26.1%), of which 66 (52%, P<0.0001) had alterations in PCT, and 112 (88.1%, P<0.0001) in CRP. Haematological markers were similar either HAdV was present or not, although many HAdV positive patients demonstrated leukocytosis (66%). Bacterial cultures from 141 samples showed altered PCT in 27 (60%) with HAdV infection, in 3 (18.7%) with bacterial infection, and 13 (26.5%) without either viral or bacterial infection (P<0.05). CRP was altered in 88.9% of HAdV infected children and in 87% infected with bacteria, although the percentage was greater than in cases where other respiratory viruses were present (61.3% P<0.05).ConclusionsResults demonstrate a clear relationship between HAdV infection and alterations in PCT and CRP which should be taken into account in paediatric patient management.