Peripheral tissues metabolites and biological functions in Post-stroke Depression

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral tissues metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral tissues of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was “phenylalanine metabolism” and the pathway containing the most associated molecules was “aminoacyl-tRNA biosynthesis”, which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral tissues are associated with PSD, especially the disruption of “phenylalanine metabolism” and “aminoacyl-tRNA biosynthesis” pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD.

Untargeted metabolomics and transcriptomics identified glutathione metabolism disturbance and PCS and TMAO as potential biomarkers for ER stress in lung

Endoplasmic reticulum (ER) stress is a cellular state that results from the overload of unfolded/misfolded protein in the ER that, if not resolved properly, can lead to cell death. Both acute lung infections and chronic lung diseases have been found related to ER stress. Yet no study has been presented integrating metabolomic and transcriptomic data from total lung in interpreting the pathogenic state of ER stress. Total mouse lungs were used to perform LC–MS and RNA sequencing in relevance to ER stress. Untargeted metabolomics revealed 16 metabolites of aberrant levels with statistical significance while transcriptomics revealed 1593 genes abnormally expressed. Enrichment results demonstrated the injury ER stress inflicted upon lung through the alteration of multiple critical pathways involving energy expenditure, signal transduction, and redox homeostasis. Ultimately, we have presented p-cresol sulfate (PCS) and trimethylamine N-oxide (TMAO) as two potential ER stress biomarkers. Glutathione metabolism stood out in both omics as a notably altered pathway that believed to take important roles in maintaining the redox homeostasis in the cells critical for the development and relief of ER stress, in consistence with the existing reports.

Deprivation of Food Increasing Activation of Gene

Through food we eat DNA every day. The raw material for new DNA comes from food only. The DNA replication is a complex process and many signalling molecules, many enzymes and replication controlling factors ultimately comes from food metabolism only. In this brief review we have described that during fasting metabolic process does not stop and adopted altered pathway while metabolising stored glycogen in liver and muscle. Consuming old stored glycogen from liver and muscles to feed glucose to the brain and synthesizing fresh glycogen benefits other body organs too.

Aberrant sphingomyelin 31P-NMR signatures in giant cell tumour of bone

An understanding of the biochemistry of the giant cell tumour of bone (GCTB) provides an opportunity for the development of prognostic markers and identification of therapeutic targets. Based on metabolomic analysis, we proposed glycerophospholipid metabolism as the altered pathway in GCTB and the objective of this study was to identify these altered metabolites. Using phosphorus-31 nuclear magnetic resonance spectroscopy (³¹P-NMR), sphingomyelin was determined as the most dysregulated phospholipid in tissue samples from six patients with GCTB; subsequently, enzymes related to its biosynthesis and hydrolysis were examined using immunodetection techniques. High expression of sphingomyelin synthases 1 and 2, but low expression of neutral sphingomyelinase 2 (nSMase2), was found in GCTB tissues compared to non-neoplastic bone tissues. Sphingomyelin/ ceramide biosynthesis is dysregulated in GCTB due to alterations in the expression of SMS1, SMS2, and nSMase2.

Obturation Techniques in Primary Teeth using Endoflas as Obturation Material – A Systematic Review

A pulpectomy is the treatment of choice for pulpally involved primary teeth. Pulp therapy prevents the premature loss of primary teeth which could result in loss of arch length, an altered pathway of the eruption of primary teeth, development of aberrant habits. It also restores the dentition to a functional state. Endoflas is a newer obturation material which has a proven clinical success rate. There are various obturation techniques available in the literature. The systematic review aimed to extract and systematically identify the existing literature, which compares different obturation techniques used in the root canal treatment of primary teeth using endoflas as obturation material. The search was done using the MeSH terms and keyword search in the electronic databases, including PubMed, Cochrane, LILAC, Sigle, Science Direct and Google scholar. A total of 13 articles were chosen after the initial screening of the title. Then based on the inclusion and exclusion criteria and the availability of the full texts, a total of 3 articles were included. This systematic review concludes that there is a need to update the existing literature to find out the beat ideal obturation technique which can provide void-free and ideal obturation of the root canal of the primary teeth using Endoflas.

Rapid detection of hydrazine in a naphthol-fused chromenyl loop and its effectiveness in human lung cancer cells: tuning remarkable selectivity via the reaction altered pathway supported by theoretical studies

A new chemosensor (NAC) is reported for fast and selective detection of N2H4 in a novel way.

Altered Pathway Routing in a Class ofSalmonella enterica Serovar Typhimurium Mutants Defective in Aminoimidazole Ribonucleotide Synthetase

ABSTRACT In Salmonella enterica serovar Typhimurium, purine nucleotides and thiamine are synthesized by a branched pathway. The last known common intermediate, aminoimidazole ribonucleotide (AIR), is formed from formylglycinamidine ribonucleotide (FGAM) and ATP by AIR synthetase, encoded by the purI gene in S. enterica. Reduced flux through the first five steps of de novo purine synthesis results in a requirement for purines but not necessarily thiamine. To examine the relationship between the purine and thiamine biosynthetic pathways, purI mutants were made (J. L. Zilles and D. M. Downs, Genetics 143:37–44, 1996). Unexpectedly, some mutantpurI alleles (R35C/E57G and K31N/A50G/L218R) allowed growth on minimal medium but resulted in thiamine auxotrophy when exogenous purines were supplied. To explain the biochemical basis for this phenotype, the R35C/E57G mutant PurI protein was purified and characterized kinetically. The Km of the mutant enzyme for FGAM was unchanged relative to the wild-type enzyme, but theV max was decreased 2.5-fold. TheKm for ATP of the mutant enzyme was 13-fold increased. Genetic analysis determined that reduced flux through the purine pathway prevented PurI activity in the mutant strain, andpurR null mutations suppressed this defect. The data are consistent with the hypothesis that an increased FGAM concentration has the ability to compensate for the lower affinity of the mutant PurI protein for ATP.