Differences In Amino Acid Metabolism Research Articles

Serum metabolomics analyses reveal biomarkers of osteoporosis and the mechanism of Quanduzhong capsules

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.

Long-term thermal stress induces hepatic injury and alters the thermotolerance response in Hong Kong catfish (Clarias fuscus)

Global climate change has a significant impact on fish survival and the aquaculture industry. Even highly adaptable organisms like Siluriformes fish are susceptible to these effects. This study investigates the consequences of extreme high temperature on Hong Kong catfish (Clarias fuscus), a species known for its long-term habitation in tropical and subtropical regions. In this study, C. fuscus were cultivated for 90 days at high temperature (HT, 34 °C) and normal temperature (NT, 26 °C), followed by subjecting the two groups to high temperature stress (34 °C) and temperature recovery (26 °C). The hepatic histology, biochemical, and transcriptomic characteristics of the species were examined before acute high temperature stress (NT-C, HT-C), after acute high temperature stress (NT-T, HT-T), and after temperature recovery (NT-R, HT-R). The histological analysis revealed that long-term heat stress damaged the liver tissue of C. fuscus. Furthermore, significant damage was observed in the liver tissues of the NT group under acute high temperature stress, while no further damage was observed in the HT group. The biochemical analysis showed that 90 days of heat stress altered the body's immune and oxidative balance, resulting in an increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and a decrease in malondialdehyde (MDA) content. Upon acute heat stress, the liver function of the NT group was disordered and unable to produce enough total-bilirubin (T-BIL), while the aspartate aminotransferase (AST) activity of the HT group was more susceptible to being affected. Long-term heat stress led to significant changes in gene expression, with the NT group showing three times more differentially expressed genes (DEGs) identified in the liver compared to the HT group under acute heat stress conditions. Analysis of DEG enrichment during the same treatment period in both groups revealed significant differences in amino acid metabolism and lipid metabolism pathways. These results suggest that long-term heat stress caused liver tissue damage in C. fuscus, altering immune and oxidative balance, enzyme activity sensitivity, as well as the body's response to acute heat stress pathways and intensity. This study lays the groundwork for future investigations into fish adaptability to sudden temperature changes and aquaculture strategies to mitigate heat stress in fish facing extreme temperatures.

Different metabolic adaptation strategies after overwintering in Eutrema sp. and Arabidopsis accessions under field conditions in Germany.

Successful overwintering is a prerequisite for high fitness in temperate perennials and winter annuals and is highly dependent on increased freezing tolerance and timely balancing of deacclimation with growth resumption in spring. To assess fitness costs associated with overwintering and elucidate metabolic mechanisms underlying winter survival and the switch from acclimated freezing tolerance to growth resumption, we performed a comparative field study using 14 Eutrema salsugineum accessions, E. halophilum, E. botschantzevii and 11 Arabidopsis thaliana accessions differing in freezing tolerance. Winter survival and reproductive fitness parameters were recorded and correlated with phenological stage and metabolite status during growth resumption in spring. The results revealed considerable intraspecific variation in winter survival, but survival rates of the extremophyte Eutrema were not inherently better. In both Eutrema and A. thaliana, improved winter survival was associated with reduced reproductive fitness. Metabolic analysis by GC-MS revealed intrinsic differences in the primary metabolism of the two genera during deacclimation. Eutrema contained higher levels of several amino and chlorogenic acids, while Arabidopsis had higher levels of several sugars and sugar conjugates. In both genera, increased levels of several soluble sugars were associated with increased winter survival, whereas myo-inositol has different roles in overwintering of Eutrema and A. thaliana. In addition, differences in amino acid metabolism and polyhydroxy acids levels after winter survival were found. The results provide strong evidence for a trade-off between increased winter survival and reproductive fitness in both Eutrema and Arabidopsis and document inherent differences in their metabolic strategies to survive winter.

Dynamics of lipoperoxidation and amino acid spectrum in patients with delirium after intramedullary osteosynthesis with ropivocaine epidural anesthesia

Introduction The pathogenesis of postoperative delirium, its causes, and factors contributing to its development remain a subject of debate. We consider it promising to study the dynamics of lipoperoxidation, cortisol levels and amino acid metabolism in patients with postoperative delirium. Such studies will reveal diagnostic and prognostic markers.The aim was to identify differences in the dynamics of lipoperoxidation, amino acid balance and cortisol levels in patients with and without delirium.Materials and methods A total of 41 patients who underwent surgery for a femoral fracture under epidural anaesthesia were included in the study. All patients underwent a daily test, the Confused Consciousness Assessment Method. If it was positive, delirium was diagnosed; thus, two groups were identified: with postoperative delirium (n = 12) and without delirium (n = 29).Results In the preoperative delirium group, there was a relative lack of glucocorticosteroids as measured by reduced cortisol levels (pU < 0.01) and inhibition of lipid peroxidation as reduced Schiff bases (pU = 0.01). There were no significant differences in amino acid metabolism of the major amino acid pools. The intraoperative period in both groups had similar characteristics and no significant differences. In the postoperative period inhibition of lipoperoxidation in the delirium group changed into its greater activation, which was revealed by increased levels of ketodienes and conjugated trienes in isopropanol phase (pU < 0.01). There was also an increase in the aromatic pool (pU < 0.01) due to an increase in large neutral amino acids (phenialanine, pU = 0.0, tryptophan, pU = 0.02, tyrosine, pU < 0.01) and a decrease in the aliphatic pool (pU < 0.01). Cortisol levels remained significantly lower in the delirium group (pU < 0.01).Discussion The preoperative decrease in the studied indices in the delirium group may indicate initial reductive stress. In the postoperative period, patients with and without delirium differ in their metabolic activity with respect to lipoperoxidation and amino acid metabolism, and cortisol levels remain significantly lower in the delirium group.Conclusion The development of delirium is facilitated by initial reductive stress and a tolerant adaptation strategy.

The amino acid metabolomics signature of differentiating myocardial infarction from strangulation death in mice models

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC–MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI.

Integrated Human Skin Bacteria Genome Catalog Reveals Extensive Unexplored Habitat-Specific Microbiome Diversity and Function.

The skin is the largest organ in the human body. Various skin environments on its surface constitutes a complex ecosystem. One of the characteristics of the skin micro-ecosystem is low biomass, which greatly limits a comprehensive identification of the microbial species through sequencing. In this study, deep-shotgun sequencing (average 21.5Gigabyte (Gb)) from 450 facial samples and publicly available skin metagenomic datasets of 2069 samples to assemble a Unified Human Skin Genome (UHSG) catalog is integrated. The UHSG encompasses 813 prokaryotic species derived from 5779 metagenome-assembled genomes, among which 470 are novel species covering 20 phyla with 1385 novel assembled genomes. Based on the UHSG, the core functions of the skin microbiome are described and the differences in amino acid metabolism, carbohydrate metabolism, and drug resistance functions among different phyla are identified. Furthermore, analysis of secondary metabolites of the near-complete genomes further find 1220 putative novel secondary metabolites, several of which are found in previously unknown genomes. Single nucleotide variant (SNV) reveals a possible skin protection mechanism: the negative selection process of the skin environment to conditional pathogens. UHSG offers a convenient reference database that will facilitate a more in-depth understanding of the role of skin microorganisms in the skin.

Sex Related Differences In Amino Acid Metabolism In Chronic Obstructive Pulmonary Disease

Sex Related Differences In Amino Acid Metabolism In Chronic Obstructive Pulmonary Disease

Alanine-specific appetite in slow growing chickens is associated with impaired glucose transport and TCA cycle

BackgroundThe rate of protein accretion and growth affect amino acid requirements in young animals. Differences in amino acid metabolism contribute to individual variations in growth rate. This study aimed at determining how amino acid needs may change with growth rates in broiler chickens. Experiment 1 consisted of testing amino acid choices in two chicken groups with extreme growth rates (the slowest –SG- or fastest –FG- growing birds in a flock). Essential (EAA) (methionine, lysine and threonine) or non-essential (NEAA) (alanine, aspartic acid and asparagine) amino acids were added to a standard control feed (13.2 MJ/kg; 21.6% crude protein). The chickens were offered simultaneous access to the control feed and a feed supplemented with one of the two amino acid mixes added at 73% above standard dietary levels. Experiment 2 consisted of the selection of the bottom 5 SG and top 5 FG chickens from a flock of 580 to study differences in amino acid metabolism using the proventriculus representing gut sensing mechanism. In this experiment, transcriptomic, proteomic, and genomic analyses were used to compare the two groups of chickens.ResultsSG preferred NEAA, while they rejected EAA supplemented feeds (P < 0.05). However, FG rejected NEAA (P < 0.05), and they were indifferent to EAA supplemented feed (P > 0.05). Transcriptomic and proteomic analyses identified 909 differentially expressed genes and 146 differentially abundant proteins associated with differences in growth rate (P < 0.05). The integration of gene expression and protein abundance patterns showed the downregulation of sensing and transport of alanine and glucose associated with increased alanine catabolism to pyruvate in SG chickens.ConclusionDietary preferences for NEAA in the SG group are associated with a potential cytosolic depletion of alanine following an upregulation of the catabolism into TCA cycle intermediates.

Alterations of the gut microbial community structure and function with aging in the spontaneously hypertensive stroke prone rat

Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood–brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same age range. We hypothesized that we could identify key microbes involved in the development of HT by comparing WKY and SHRSP microbiota during the pre-hypertensive state and longitudinally. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and fecal microbiota analyzed by16S rRNA gene sequencing. SHRSP showed significant elevations in SBP, as compared to WKY, beginning at 8 weeks of age (p < 0.05 at each time point). Bacterial community structure was significantly different between WKY and SHRSP as early as 4 weeks of age, and remained different throughout the study (p = 0.001–0.01). At the phylum level we observed significantly reduced Firmicutes and Deferribacterota, and elevated Bacteroidota, Verrucomicrobiota, and Proteobacteria, in pre-hypertensive SHRSP, as compared to WKY. At the genus level we identified 18 bacteria whose relative abundance was significantly different in SHRSP versus WKY at the pre-hypertensive ages of 4 or 6 weeks. In an attempt to further refine bacterial candidates that might contribute to the SHRSP phenotype, we compared the functional capacity of WKY versus SHRSP microbial communities. We identified significant differences in amino acid metabolism. Using untargeted metabolomics we found significant reductions in metabolites of the tryptophan-kynurenine pathway and increased indole metabolites in SHRSP versus WKY plasma. Overall, we provide further evidence that gut dysbiosis contributes to hypertension in the SHRSP model, and suggest for the first time the potential involvement of tryptophan metabolizing microbes.

Comparative transcriptome and metabolome analyses reveal the methanol dissimilation pathway of Pichia pastoris

BackgroundPichia pastoris (Komagataella phaffii) is a model organism widely used for the recombinant expression of eukaryotic proteins, and it can metabolize methanol as its sole carbon and energy source. Methanol is oxidized to formaldehyde by alcohol oxidase (AOX). In the dissimilation pathway, formaldehyde is oxidized to CO2 by formaldehyde dehydrogenase (FLD), S-hydroxymethyl glutathione hydrolase (FGH) and formate dehydrogenase (FDH).ResultsThe transcriptome and metabolome of P. pastoris were determined under methanol cultivation when its dissimilation pathway cut off. Firstly, Δfld and Δfgh were significantly different compared to the wild type (GS115), with a 60.98% and 23.66% reduction in biomass, respectively. The differential metabolites between GS115 and Δfld were mainly enriched in ABC transporters, amino acid biosynthesis, and protein digestion and absorption. Secondly, comparative transcriptome between knockout and wild type strains showed that oxidative phosphorylation, glycolysis and the TCA cycle were downregulated, while alcohol metabolism, proteasomes, autophagy and peroxisomes were upregulated. Interestingly, the down-regulation of the oxidative phosphorylation pathway was positively correlated with the gene order of dissimilation pathway knockdown. In addition, there were significant differences in amino acid metabolism and glutathione redox cycling that raised our concerns about formaldehyde sorption in cells.ConclusionsThis is the first time that integrity of dissimilation pathway analysis based on transcriptomics and metabolomics was carried out in Pichia pastoris. The blockage of dissimilation pathway significantly down-regulates the level of oxidative phosphorylation and weakens the methanol assimilation pathway to the point where deficiencies in energy supply and carbon fixation result in inefficient biomass accumulation and genetic replication. In addition, transcriptional upregulation of the proteasome and autophagy may be a stress response to resolve formaldehyde-induced DNA–protein crosslinking.

Alterations of amino acid metabolism and intestinal microbiota in Chinese mitten crab (Eriocheir sinensis) fed on formulated diet and iced trash fish

Formulated diet (FD) and iced trash fish (ITF) are common diets during E. sinensis farming. However, whether FD can completely replace ITF during long-term E. sinensis farming is still unclear. Thus this study was conducted to compare the differences in amino acid metabolism and intestinal microbiota of the E. sinensis fed on different diets. The crabs were randomly divided into three groups fed on FD, ITF and mixed diet (MD, FD: ITF = 1:1), respectively. The results showed that there were no significant differences in amino acid composition among FD, MD and ITF groups. The activities of AST and ALT, and the mRNA levels of amino acid metabolism-related genes were significantly up-regulated in FD or/and MD groups compared with ITF group. The diversity of intestinal bacterial community was similar between the FD and ITF groups, but the relative abundance of dominant taxa showed marked differences between the two groups. At the phylum level, the relative abundance of Firmicutes was significantly higher, but the relative abundance of Proteobacteria was significantly lower in the FD group than that in ITF group. Meanwhile, at genus level, the relative abundance of Candidatus_Hepatoplasma in FD was higher than that in ITF group. Data related to functional prediction demonstrated that the significantly differenced pathways between the two groups were observed in metabolism (Pyrimidine metabolism, Glycolysis/Gluconeogenesis and Citrate cycle) and environmental information processing (transporters). The overall results indicated that replacement of ITF by FD did not affect amino acid composition, but altered amino acid metabolism and the relative abundance of intestinal microbiota. Our data provided a valuable reference for FD application replacing ITF during long-term E. sinensis farming.

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion.

Access to liver transplantation continues to be hindered by the severe organ shortage. Extended-criteria donor livers could be used to expand the donor pool but are prone to ischemia-reperfusion injury (IRI) and post-transplant graft dysfunction. Ex situ machine perfusion may be used as a platform to rehabilitate discarded or extended-criteria livers prior to transplantation, though there is a lack of data guiding the utilization of different perfusion modalities and therapeutics. Since amino acid derivatives involved in inflammatory and antioxidant pathways are critical in IRI, we analyzed differences in amino acid metabolism in seven discarded non-steatotic human livers during normothermic- (NMP) and subnormothermic-machine perfusion (SNMP) using data from untargeted metabolomic profiling. We found notable differences in tryptophan, histamine, and glutathione metabolism. Greater tryptophan metabolism via the kynurenine pathway during NMP was indicated by significantly higher kynurenine and kynurenate tissue concentrations compared to pre-perfusion levels. Livers undergoing SNMP demonstrated impaired glutathione synthesis indicated by depletion of reduced and oxidized glutathione tissue concentrations. Notably, ATP and energy charge ratios were greater in livers during SNMP compared to NMP. Given these findings, several targeted therapeutic interventions are proposed to mitigate IRI during liver machine perfusion and optimize marginal liver grafts during SNMP and NMP.

1H-NMR analysis of amino acid metabolism in aqueous humor of patients with cataract, according to diabetes status.

ObjectiveTo investigate the differences in amino acid metabolism in aqueous humor of patients with cataract, according to diabetes status, using a 1H-nuclear magnetic resonance approach.MethodsAqueous humor samples from patients with age-related cataract, with or without diabetes, were collected during cataract surgery. All samples underwent nuclear magnetic resonance spectra analysis to characterize their metabolic function. Potential metabolic pathways were analyzed via MetaboAnalyst 3.0.ResultsThis study included eight aqueous humor samples from patients with cataract and diabetes and eight aqueous humor samples from age- and sex-matched patients with cataract alone. Four metabolites were found to significantly differ in the aqueous humor of patients with cataract and diabetes, relative to patients with cataract alone; these metabolites were glucose (higher in patients with diabetes), valine, lysine, and tyrosine (all lower in patients with diabetes). Aminoacyl-tRNA biosynthesis was presumed to be involved in the metabolic differences observed in patients with cataract, according to diabetes status.ConclusionsThe amino acid metabolic profile in the aqueous humor differed among patients with cataract, according to diabetes status. Disturbance of amino acid metabolism in the aqueous humor may be related to cataract formation in patients with diabetes.

Comparative metatranscriptomic profiling and microRNA sequencing to reveal active metabolic pathways associated with a dinoflagellate bloom

Harmful algal blooms (HABs) have increased as a result of global climate and environmental changes, exerting increasing impacts on the aquatic ecosystem, coastal economy, and human health. Despite great research efforts, our understanding on the drivers of HABs is still limited in part because HAB species' physiology is difficult to probe in situ. Here, we used molecular ecological analyses to characterize a dinoflagellate bloom at Xiamen Harbor, China. Prorocentrum donghaiense was identified as the culprit, which nutrient bioassays showed were not nutrient-limited. Metatranscriptome profiling revealed that P. donghaiense highly expressed genes related to N- and P-nutrient uptake, phagotrophy, energy metabolism (photosynthesis, oxidative phophorylation, and rhodopsin) and carbohydrate metabolism (glycolysis/gluconeogenesis, TCA cycle and pentose phosphate) during the bloom. Many genes in P. donghaiense were up-regulated at night, including phagotrophy and environmental communication genes, and showed active expression in mitosis. Eight microbial defense genes were up-regulated in the bloom compared with previously analyzed laboratory cultures. Furthermore, 76 P. donghaiense microRNA were identified from the bloom, and their target genes exhibited marked differences in amino acid metabolism between the bloom and cultures and the potential of up-regulated antibiotic and cell communication capabilities. These findings, consistent with and complementary to recent reports, reveal major metabolic processes in P. donghaiense potentially important for bloom formation and provide a gene repertoire for developing bloom markers in future research.

Transcriptomic analysis reveals differences in the regulation of amino acid metabolism in asexual and sexual planarians

Many flatworms can alternate between asexual and sexual reproduction. This is a powerful reproductive strategy enabling them to benefit from the features of the two reproductive modes, namely, rapid multiplication and genetic shuffling. The two reproductive modes are enabled by the presence of pluripotent adult stem cells (neoblasts), by generating any type of tissue in the asexual mode, and producing and maintaining germ cells in the sexual mode. In the current study, RNA sequencing (RNA-seq) was used to compare the transcriptomes of two phenotypes of the planarian Dugesia ryukyuensis: an asexual OH strain and an experimentally sexualized OH strain. Pathway enrichment analysis revealed striking differences in amino acid metabolism in the two worm types. Further, the analysis identified serotonin as a new bioactive substance that induced the planarian ovary de novo in a postembryonic manner. These findings suggest that different metabolic states and physiological conditions evoked by sex-inducing substances likely modulate stem cell behavior, depending on their different function in the asexual and sexual reproductive modes. The combination of RNA-seq and a feeding assay in D. ryukyuensis is a powerful tool for studying the alternation of reproductive modes, disentangling the relationship between gene expression and chemical signaling molecules.

Evolutionary expression differences of creatine synthesis-related genes: Implications for skeletal muscle metabolism in fish

The creatine/phosphocreatine system is the principal energy buffer in mammals, but is scarcely documented in fish. We measured the gene expression of major enzymes of this system, glycine amidinotransferase (GATM), guanidinoacetate N-methyltransferase (GAMT) and muscle-type creatine kinase (CKM) in kidney, liver, and muscle tissues of fish and mammals. CKM was expressed strongly in the muscles of all examined species. In contrast, GATM and GAMT were strongly expressed in the muscle tissue of fish, but not of mammals. This indicates that creatine synthesis and usage are spatially separated in mammals, but not in fish, which is supported by RNA-Seq data of 25 species. Differences in amino acid metabolism along with methionine adenosyltransferase gene expression in muscle from fishes but not mammals further support a central metabolic role of muscle in fish, and hence different organization of the creatine/phosphocreatine biosynthesis system in higher and lower vertebrates.

Changes in Free Amino Acid Content in the Flesh and Peel of ‘Cavendish’ Banana Fruit as Related to Branched-chain Ester Production, Ripening, and Senescence

The concentrations of free amino acids in the peel and pulp of banana (Musa sp., AAA group, Cavendish subgroup, cv. Valery) fruit during ripening at 22 °C were measured. All 20 amino acids were quantified at seven distinct ripening stages as defined by measures of internal ethylene, O2, and CO2 concentrations, aroma volatile emissions, and peel color. Volatile production commenced 2 days after the peak in ethylene production and 1 day following the climacteric peak in internal CO2. The maximum rate of branched-chain ester synthesis occurred 2 to 3 days after its onset. Production of 2-methylpropyl and 3-methylbutyl esters was much higher in the pulp compared with the peel, confirming that the pulp, rather than the peel, is the primary site of banana aroma synthesis. Of the amino acids measured, only leucine, valine, and cysteine increased concomitantly with ester formation. This was observed in the pulp, but not in the peel. The data suggest the metabolic pathways for valine and leucine formation also support, respectively, the synthesis of 2-methylpropyl and 3-methylbutyl esters. It is not clear how leucine and valine can accumulate despite the fact that they act as feedback inhibitors of their respective synthetic pathways. There was a slight peak in the formation of several other amino acids in the pulp (e.g., alanine, arginine, asparagine, glutamine, and methionine) coinciding with the climacteric respiratory peak in CO2, but a similar pattern was not seen for the peel. These data are the first to demonstrate distinct differences in amino acid metabolism in the peel and pulp of banana related to their role in ripening and aroma biosynthesis.

Rapid discrimination of human oesophageal squamous cell carcinoma by mass spectrometry based on differences in amino acid metabolism

Oesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132.13, and m/z 175.13 were higher in cancer tissue while the relative abundances of m/z 82.99, m/z 133.11, m/z 147.08, m/z 154.06, and m/z 188.05 were higher in normal tissue. Using partial least squares analysis, the mass spectra of cancer samples was discriminated from those of normal tissues, and the discriminatory ions were obtained from loading plots. Dimethylglycine(m/z 104), proline(m/z 116), isoleucine(m/z 132), asparagine(m/z 133), glutamine(m/z 147), and arginine(m/z 175) were identified by collision-induced dissociation experiments. Using the ROC curve analysis, we verified the validity of six amino acids for the identification of tumour tissue. Further investigations of tissue amino acids may allow us to better understand the underlying mechanisms involved in OC and develop novel means to identify tumour tissue during operation.

Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131-4. ©2017 AACR.

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in Blastomyces.