Argininosuccinate Research Articles

Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus.

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC-MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury.

Fatal hyperammonemia in the setting of late-onset argininosuccinic acid lyase enzyme deficiency (ASLD): a case report

Fatal hyperammonemia in the setting of late-onset argininosuccinic acid lyase enzyme deficiency (ASLD): a case report

Unveiling the roles of dietary Tryptophan and Arginine metabolism in Lactobacillus rhamnosus GG-mediated barrier protection

Inflammatory bowel disease (IBD) is often characterized by increased intestinal paracellular permeability and abnormalities in tight junctions (TJ). IBD patients commonly exhibit reduced serum tryptophan (TRP) levels. Furthermore, animal models on low-TRP diets are more susceptible to chemically induced intestinal inflammation, while those on high-TRP diets show reduced inflammation. The interaction between TRP and gut microbiota in reinforcing the intestinal barrier warrants further investigation. To address this, we introduced Lactobacillus rhamnosus GG (LGG), known for enhancing the gut barrier, and PBS as a control into germ-free mice fed TRP-suffcient or -deficient diets. Our analysis of the mouse ileal transcriptome revealed dramatic upregulation of key genes in arginine metabolism only in LGG-TRP mice, particularly of argininosuccinate lyase ( Asl) that catabolizes argininosuccinate (ASA). Interestingly, our in-silico analysis of human IBD data GEO 179285 transcriptome showed marked dysregulation of similar genes, including inappropriate increases in ASA synthetase ( Ass1). Moreover, this unique expression pattern in the mouse ileum was TRP-dependent and specific to LGG, and not observed in mice monocolonized with pathobiont Ruminococcus gnavus or specific pathogen-free mice. LC-MS analysis of fecal and serum metabolites in LGG-TRP mice revealed elevated levels of fecal arginine, glutamine, and aspartate, suggesting their involvement in host arginine biosynthesis, along with significant reductions in serum ASA levels. ASA was highly negatively correlated with numerous TJ genes, suggesting its potential to compromise barrier function. Indeed, treating mouse enteroids with ASA enhanced dextran permeability, exacerbated LPS disruption of the gut barrier, and decreased expression of TJ genes Ocln and Tjp1. Furthermore, elevated serum ASA and decreased colonic ASL levels were observed in colitis-afflicted mice, perturbing gut homeostasis, as indicated by increased fecal lipocalin-2 and delayed colitis recovery after intraperitoneal ASA administration. We propose that LGG-TRP stimulates gut-mediated ASA turnover as evidenced by substantial increases in Asl levels. Interestingly, LGG alone reduced ASA concentration in the culture medium under anaerobic and aerobic conditions. Collectively, our study identifies ASA as a potential biomarker of gut inflammation and enhanced permeability. Moreover, we highlight the potential of LGG-TRP therapy for IBD-associated leaky gut conditions, offering novel insights for gut health interventions. NIHR01-AT010243 (NG,RF), R01DK119198 (NG), NSF 1754783 (RF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Amino Acids Profile in Children with Acute Brucellosis.

Many new cases of brucella infections are seen in Turkey every year, especially in March, April, and May, due to the consumption of local unpasteurized cheese. Amino acids profiles have not been studied in brucellosis so far. The amino acid profiles may be affected by infectious diseases. Our study aims to evaluate the plasma amino acid profile in the progression of acute brucellosis. Plasma amino acid profile was performed by an 8045 LC-MS / MS device (Shimadzu 8045, Japan) using JASEM amino acid kit. Analysis of 45 amino acid profiles was made and results profiles showed significant differences in concentrations and types of amino acids in brucella patients. We observed a significant difference in terms of alanine, arginine, aspartic acid, glutamine, glutamic acid, glycine, isoleucine, ornithine, phenylalanine, proline, tyrosine, valine, alpha-aminoadipic acid, alpha-amino-pimelic acid, argininosuccinic acid, gamma-aminobutyric acid, thiaproline, 1-methylhistidine, 3-methylhistidine, hydroxylysine, hydroxyproline, cystine, serotonin, ethanolamine, and taurine (p-value < 0.05 for each). No significant differences were determined regarding asparagine, citrulline, histidine, leucine, alloisoleucine, lysine, methionine, serine, threonine, tryptophan, anserine, alpha aminobutyric acid, beta aminoisobutyric acid, beta-alanine, cystathionine, histamine, and 5-oh-trp (p-value > 0.05 for all). Patients with brucellosis have a specific profile of amino acids which may reflect sequelae of pathological and metabolic biochemical changes in the disease process due to the growth of Brucella spp. in the human body leading to an imbalance of amino acid levels.

Adaptation of high performance liquid chromatography (HPLC) for detection of argininosuccinic acid

Adaptation of high performance liquid chromatography (HPLC) for detection of argininosuccinic acid

Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors

Argininosuccinate lyase deficiency (ASLD) is a recessive metabolic disorder caused by variants in ASL. In an essential step in urea synthesis, ASL breaks down argininosuccinate (ASA), a pathognomonic ASLD biomarker. The severe disease forms lead to hyperammonemia, neurological injury, and even early death. The current treatments are unsatisfactory, involving a strict low-protein diet, arginine supplementation, nitrogen scavenging, and in some cases, liver transplantation. An unmet need exists for improved, efficient therapies. Here, we show the potential of a lipid nanoparticle-mediated CRISPR approach using adenine base editors (ABEs) for ASLD treatment. To model ASLD, we first generated human-induced pluripotent stem cells (hiPSCs) from biopsies of individuals homozygous for the Finnish founder variant (c.1153C>T [p.Arg385Cys]) and edited this variant using the ABE. We then differentiated the hiPSCs into hepatocyte-like cells that showed a 1,000-fold decrease in ASA levels compared to those of isogenic non-edited cells. Lastly, we tested three different FDA-approved lipid nanoparticle formulations to deliver the ABE-encoding RNA and the sgRNA targeting the ASL variant. This approach efficiently edited the ASL variant in fibroblasts with no apparent cell toxicity and minimal off-target effects. Further, the treatment resulted in a significant decrease in ASA, to levels of healthy donors, indicating restoration of the urea cycle. Our work describes a highly efficient approach to editing the disease-causing ASL variant and restoring the function of the urea cycle. This method relies on RNA delivered by lipid nanoparticles, which is compatible with clinical applications, improves its safety profile, and allows for scalable production.

Analysis of Relationships between Metabolic Changes and Selected Nutrient Intake in Women Environmentally Exposed to Arsenic.

Nutrients involved in the metabolism of inorganic arsenic (iAs) may play a crucial role in mitigating the adverse health effects associated with such exposure. Consequently, the objective of this study was to analyze the association between the intake levels of nutrients involved in iAs metabolism and alterations in the metabolic profile during arsenic exposure. The study cohort comprised environmentally exposed women: WL (lower total urinary arsenic (As), n = 73) and WH (higher As, n = 73). The analysis included urinary untargeted metabolomics (conducted via liquid chromatography-mass spectrometry) and the assessment of nutrient intake involved in iAs metabolism, specifically methionine, vitamins B2, B6, and B12, folate, and zinc (based on 3-day dietary records of food and beverages). In the WL group, the intake of all analyzed nutrients exhibited a negative correlation with 5 metabolites (argininosuccinic acid, 5-hydroxy-L-tryptophan, 11-trans-LTE4, mevalonic acid, aminoadipic acid), while in the WH group, it correlated with 10 metabolites (5-hydroxy-L-tryptophan, dihyroxy-1H-indole glucuronide I, 11-trans-LTE4, isovalerylglucuronide, 18-oxocortisol, 3-hydroxydecanedioic acid, S-3-oxodecanoyl cysteamine, L-arginine, p-cresol glucuronide, thromboxane B2). Furthermore, nutrient intake demonstrated a positive association with 3 metabolites in the WL group (inosine, deoxyuridine, glutamine) and the WH group (inosine, N-acetyl-L-aspartic acid, tetrahydrodeoxycorticosterone). Altering the intake of nutrients involved in iAs metabolism could be a pivotal factor in reducing the negative impact of arsenic exposure on the human body. This study underscores the significance of maintaining adequate nutrient intake, particularly in populations exposed to arsenic.

Abnormal arginine synthesis confers worse prognosis in patients with middle third gastric cancer

BackgroundGastric cancer at different locations has distinct prognoses and biological behaviors, but the specific mechanism is unclear.MethodsNon-targeted metabolomics was performed to examine the differential metabolite phenotypes that may be associated with the effects of tumor location on the prognosis of gastric cancer. And silencing of the rate-limiting enzyme to evaluate the effect of abnormal changes in metabolic pathway on the functional biological assays of gastric cancer cells HGC-27 and MKN28.ResultsIn a retrospective study of 94 gastric cancer patients, the average survival time of patients with gastric cancer in the middle third of the stomach was significantly lower than that of patients with gastric cancer in other locations (p < 0.05). The middle third location was also found to be an independent risk factor for poor prognosis (HR = 2.723, 95%CI 1.334–5.520), which was closely associated with larger tumors in this location. Non-targeted metabolomic analysis showed that the differential metabolites affected 16 signaling pathways including arginine synthesis, retrograde endocannabinoid signaling, arginine biosynthesis, and alanine and aspartate and glutamate metabolism between gastric cancer and normal tissue, as well as between tumors located in the middle third of the stomach and other locations. Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of the arginine biosynthesis pathway, catalyzes the production of argininosuccinic acid. Here, knockdown of ASS1 significantly inhibited the proliferation, colony formation, and migration/invasion of gastric cancer cells, and promoted apoptosis.ConclusionsOur study suggests that abnormal arginine synthesis may lead to larger tumor size and worse prognosis in gastric cancer located in the middle third position of the stomach. These findings may provide the basis for the stratification and targeted treatment of gastric cancer in different locations.

Multinomial machine learning identifies independent biomarkers by integrated metabolic analysis of acute coronary syndrome

A multi-class classification model for acute coronary syndrome (ACS) remains to be constructed based on multi-fluid metabolomics. Major confounders may exert spurious effects on the relationship between metabolism and ACS. The study aims to identify an independent biomarker panel for the multiclassification of HC, UA, and AMI by integrating serum and urinary metabolomics. We performed a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based metabolomics study on 300 serum and urine samples from 44 patients with unstable angina (UA), 77 with acute myocardial infarction (AMI), and 29 healthy controls (HC). Multinomial machine learning approaches, including multinomial adaptive least absolute shrinkage and selection operator (LASSO) regression and random forest (RF), and assessment of the confounders were applied to integrate a multi-class classification biomarker panel for HC, UA and AMI. Different metabolic landscapes were portrayed during the transition from HC to UA and then to AMI. Glycerophospholipid metabolism and arginine biosynthesis were predominant during the progression from HC to UA and then to AMI. The multiclass metabolic diagnostic model (MDM) dependent on ACS, including 2-ketobutyric acid, LysoPC(18:2(9Z,12Z)), argininosuccinic acid, and cyclic GMP, demarcated HC, UA, and AMI, providing a C-index of 0.84 (HC vs. UA), 0.98 (HC vs. AMI), and 0.89 (UA vs. AMI). The diagnostic value of MDM largely derives from the contribution of 2-ketobutyric acid, and LysoPC(18:2(9Z,12Z)) in serum. Higher 2-ketobutyric acid and cyclic GMP levels were positively correlated with ACS risk and atherosclerosis plaque burden, while LysoPC(18:2(9Z,12Z)) and argininosuccinic acid showed the reverse relationship. An independent multiclass biomarker panel for HC, UA, and AMI was constructed using the multinomial machine learning methods based on serum and urinary metabolite signatures.

To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening.

Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.4(ASL):c.283C>T (p.Arg95Cys) and a likely benign variant NM_000048.4(ASL): c.1319T>C (p.Leu440Pro). Functional characterisation of the likely benign genetic variant in ASL was performed. Genomic sequencing was performed on the index patient presenting with non-specific symptoms of poor feeding and lethargy and shown to have increased serum and urine argininosuccinic acid. Functional assay using HEK293T cell model was performed. ASL enzymatic activity was reduced for Leu440Pro. This study highlights the role of functional testing of a variant that may appear benign in a patient with a phenotype consistent with ASL deficiency, and reclassifies NM_000048.4(ASL): c.1319T>C (p.Leu440Pro) variant as likely pathogenic.

A-326 Argininosuccinic Acid - is it Routinely Detectable in the Urine of Healthy Individuals?

Abstract Background Argininosuccinic aciduria is a genetic disorder that results in elevated levels of argininosuccinic acid (ASA) in urine and blood. While there is seemingly a consensus within the clinical literature that any detectable amount of ASA in blood/plasma is diagnostic for argininosuccinic aciduria, yet there is conflict as to whether ASA in urine can be found in unaffected individuals. Some literature states that ASA should not be found in the urine of a healthy individual, while other literature reports low levels of ASA in the urine of healthy individuals. Additionally, many laboratories do not have a normal range for ASA within urine, which implies that any level of ASA found within urine is indicative of argininosuccinic aciduria. This conflict may in part be due to differences in the methods used to determine ASA levels. Newer liquid chromatography tandem mass spectrometry (LCMSMS) methods have been shown to be more sensitive than ion-exchange chromatography (IEC) based amino acid methods for detection of ASA. Additionally, the detection of ASA via IEC requires the heating and acidification of the sample to convert ASA into a single peak for quantitation. Heating and acidification is not routinely done for urine amino acid analysis with IEC; with routine IEC urine amino acid analysis, ASA migrates as three small peaks that may go unnoticed. In our clinical laboratory, which utilizes the less sensitive IEC method, our procedure describes the presence of any ASA in urine as diagnostic for argininosuccinic aciduria. Given the conflicting literature, we set forth to determine whether low levels can be detected in unaffected individuals with an IEC method, and if so, establish a normal range of ASA levels in urine with IEC. Methods Twenty waste urine samples from patients with no prior diagnoses of argininosuccinic aciduria were evaluated. ASA levels within the samples were determined via high performance ion exchange chromatography for separation of compounds followed by derivatization with ninhydrin for spectrophotometric detection with a Hitachi Amino Acid analyzer. The samples were acidified and heated, which converts ASA into a single anhydride peak for accurate quantitation, and the results were normalized to urine creatinine. Results ASA was detected in all twenty urine samples, with an average ASA concentration of 27.2 μmol/g Cr and a range of 11.3–47.7 μmol/g Cr. Conclusion Given these findings, our clinical laboratory procedure has been updated to include the information that ASA can be present in the urine of healthy individuals up to a concentration of 50 μmol/g Cr. Other clinical laboratories that analyze urine to identify argininosuccinic aciduria should be aware of the misinformation in the literature that claims that ASA is not present in the urine of healthy individuals.

Urine and serum metabolomics study of wild ginseng in rats with spleen-qi deficiency using rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Patients with a spleen-qi deficiency often exhibit dysfunction in the metabolic system. Metabolites are considered the most direct reflection of individual physiological and pathological conditions and represent attractive candidates to provide deep insights into disease phenotypes. This study examines the potential therapeutic mechanism of wild ginseng on spleen-qi deficiency through the analysis of serum and urine metabolomics using rapid-resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. The reasons for the superiority of wild ginseng treatment over cultivated ginseng were also analyzed in depth. After wild ginseng intervention, anandamide, urobilinogen, aldosterone, and testosterone glucuronide were significantly reduced in serum. Meanwhile, argininosuccinic acid, L-cysteine, and seven other metabolites were significantly elevated in serum. Nine metabolites, including L-acetylcarnitine, and citrulline were elevated in the urine, and trimethylamine N-oxide, adrenic acid, and 10 other metabolites were reduced. Arginine biosynthesis, pantothenate and CoA biosynthesis, thiamin metabolism, taurine, and tryptophan metabolism pathways were mainly improved. Further analysis was conducted on the relationship between Lactobacillus and Akkermansia bacteria with metabolites, and it was found that they are mainly related to amino acid metabolites. This study provides strong theoretical support and direction for further explanation of the immune mechanism of wild ginseng and lays the foundation for future studies.

ASL mRNA-LNP Therapeutic for the Treatment of Argininosuccinic Aciduria Enables Survival Benefit in a Mouse Model.

Argininosuccinic aciduria (ASA) is a metabolic disorder caused by a deficiency in argininosuccinate lyase (ASL), which cleaves argininosuccinic acid to arginine and fumarate in the urea cycle. ASL deficiency (ASLD) leads to hepatocyte dysfunction, hyperammonemia, encephalopathy, and respiratory alkalosis. Here we describe a novel therapeutic approach for treating ASA, based on nucleoside-modified messenger RNA (modRNA) formulated in lipid nanoparticles (LNP). To optimize ASL-encoding mRNA, we modified its cap, 5' and 3' untranslated regions, coding sequence, and the poly(A) tail. We tested multiple optimizations of the formulated mRNA in human cells and wild-type C57BL/6 mice. The ASL protein showed robust expression in vitro and in vivo and a favorable safety profile, with low cytokine and chemokine secretion even upon administration of increasing doses of ASL mRNA-LNP. In the ASLNeo/Neo mouse model of ASLD, intravenous administration of the lead therapeutic candidate LNP-ASL CDS2 drastically improved the survival of the mice. When administered twice a week lower doses partially protected and 3 mg/kg LNP-ASL CDS2 fully protected the mice. These results demonstrate the considerable potential of LNP-formulated, modified ASL-encoding mRNA as an effective alternative to AAV-based approaches for the treatment of ASA.

Targeted Amino Acids Profiling of Human Seminal Plasma from Teratozoospermia Patients Using LC-MS/MS.

Identifying the metabolome of human seminal plasma (HSP) is a new research area to screen putative biomarkers of infertility. This case-control study was performed on HSP specimens of 15 infertile patients with teratozoospermia (defined as normal sperm morphology < 4%) and 12 confirmed fertile normozoospermic men as the control group to investigate the seminal metabolic signature and whether there are differences in the metabolome between two groups. HSPs were subjected to LC-MS-MS analysis. MetaboAnalyst5.0 software was utilized for statistical analysis. Different univariate and multivariate analyses were used, including T-tests, fold change analysis, random forest (RF), and metabolite set enrichment analysis (MSEA). Teratozoospermic samples contained seventeen significantly different amino acids. Upregulated metabolites include glutamine, asparagine, and glycylproline, whereas downregulated metabolites include cysteine, γ-aminobutyric acid, histidine, hydroxylysine, hydroxyproline, glycine, proline, methionine, ornithine, tryptophan, aspartic acid, argininosuccinic acid, α-aminoadipic acid, and β-aminoisobutyric acid. RF algorithm defined a set of 15 metabolites that constitute the significant features of teratozoospermia. In particular, increased glutamine, asparagine, and decreased cysteine, tryptophan, glycine, and valine were strong predictors of teratozoospemia. The most affected metabolic pathways in teratozoospermic men are the aminoacyl-tRNA, arginine, valine-leucine, and isoleucine biosynthesis. Altered metabolites detected in teratozoospermia were responsible for various roles in sperm functions that classified into four subgroups as follows: related metabolites to antioxidant function, energy production, sperm function, and spermatogenesis. The altered amino acid metabolome identified in this study may be related to the etiology of teratozoospermia, and may provide novel insight into potential biomarkers of male infertility for therapeutic targets.

Pistachio, Pomegranate and Olive Byproducts Added to Sheep Rations Change the Biofunctional Properties of Milk through the Milk Amino Acid Profile.

This study was carried out to determine the effects of adding pistachio shell (PIS), pomegranate hull (POM), and olive pulp (OP) to the diet on milk amino acid and fatty acid parameters in Awassi sheep. In the study, 40 head of Awassi sheep, which gave birth at least twice, were used as animal material. Sheep were fed a control diet without added byproducts (CON), rations containing PIS, POM, and OP. Milk amino acid profile was determined by liquid chromatography-tandem mass spectrometry, milk fatty acid gas chromatography-flame ionization detection device. There was a dramatic reduction in alanine, citrulline, glutamine, glutamic acid, glycine, leucine, ornithine and alphaaminoadipic acid in the research groups. In the PIS group, argininosuccinic acid, gammaminobutyric acid, beta-alanine and sarcosine; In the POM group, asparagine, gammaminobutyric acid, beta-alanine, and taurine; In the OP group, a significant positive increase was found in terms of alanine, histidine, gammaminobutyric acid, and taurine amino acids. The applications in the study did not have a statistically significant effect on the ratio of short, medium and long chain fatty acids in milk (p>0.05). In the presented study, it was determined that PIS, POM, and OP, which were added to the sheep rations at a rate of 5%, caused significant changes in the milk amino acid profiles. In this change in milk amino acid profiles, the benefit-harm relationship should be considered.

Metabolomics study of ribavirin in the treatment of orthotopic lung cancer based on UPLC-Q-TOF/MS

Ribavirin is a common antiviral drug, especially for patients with hepatitis C. Our recent studies demonstrated that ribavirin showed anti-tumor activity in colorectal cancer and hepatocellular carcinoma, but its effects on lung cancer remains unclear. This study aimed to evaluate the anti-tumor activity of ribavirin against lung cancer and elucidate the underlying mechanism. We established orthotopic mouse model of lung cancer (LLC and GLC-82) and employed an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach. We found that ribavirin significantly inhibited the proliferation and colony formation of lung cancer cells. Tumor sizes of orthotopic lung cancer in ribavirin-treated groups were also significantly lower than those in control groups. Metabolomics analysis revealed that ribavirin mainly affected 5 metabolic pathways in orthotopic lung tumor models, taurine and hypotaurine metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism, arginine biosynthesis and arachidonic acid metabolism. Furthermore, we identified 5 upregulated metabolites including β-nicotinamide adenine dinucleotide (NAD+), nicotinamide (NAM), taurine, ornithine and citrulline, and 7 downregulated metabolites including 1-methylnicotinamide (MNAM), S-adenosyl-l-homocysteine (SAH), N1-Methyl-2-pyridone-5-carboxamide (2PY), homocysteine (Hcy), linoleic acid, arachidonic acid (AA) and argininosuccinic acid in ribavirin-treated groups. These results provide new insight into the anti-tumor mechanism of ribavirin for lung cancer.

Effects of dietary cellulose supplementation on the intestinal health and ammonia tolerance in juvenile yellow catfish Pelteobagrus fulvidraco

Cellulose can reduce endogenous ammonia production of non-ruminant animals by altering intestinal microbiota structure. Although the utilization of cellulose in fish is limited, we speculate that cellulose has a potential role in regulating fish ammonia tolerance. Four experiment diets with different cellulose levels (Ctrl, 4.00%, 6.00% and 8.00%) were formulated and fed to yellow catfish for 84 days. This study found that dietary supplemented with 6.00% cellulose can improve growth performance (final body weight and weight gain rate), blood health (total protein, albumin and globulin), intestinal digestive enzyme activity (protease, lipase and cellulase), and ensure intestinal structure integrity (villi length), and maintain intestinal microbiota stability (Shannon and Chao1 indexes). After 96 h ammonia stress, serum ammonia content and cumulative mortality were negative correlated with Cetobacterium abundance. The activities of ammonia metabolism enzyme (glutamine synthetase, carbamyl phosphate synthetase, argininosuccinic acid synthase and arginase) and antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) in 4.00% and 6.00% cellulose groups were higher than those in Ctrl and 8.00% cellulose groups. The highest mRNA expression levels of antioxidant-related genes (Cu/Zn-SOD, CAT, GPX and GR) and inflammation-related genes (IL1, IL 8 and TNFɑ) were found in 8.00% cellulose group. This study indicates dietary supplemented with cellulose can increase the Cetobacterium abundance in intestinal tract, which is closely related to ammonia tolerance of yellow catfish. The levels of 4.00–6.00% cellulose in dietary is recommended in juvenile yellow catfish.

Investigation of the effect of vitamin K1 prophylaxis on newborn screenings tests in newborns.

Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements. Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma.

Nowadays,the mechanical ventilation (MV) aims to rest the respiratory muscles while providing adequate gas exchange, and it has been a part of basic life support during general anesthesia as well as in critically ill patients with and without respiratory failure. However, MV itself has the potential to cause or worsen lung injury, which is also known as ventilator-induced lung injury (VILI). Thus, the early diagnosis of VILI is of great importance for the prevention and treatment of VILI. This study aimed to investigate the metabolomes in the lung and plasma of mice receiving mechanical ventilation (MV). Healthy mice were randomly assigned into control group; (2) high volume tidal (HV) group (30 ml/kg); (3) low volume tidal (LV) group (6 ml/kg). After ventilation for 4h, mice were sacrificed and the lung tissue and plasma were collected. The lung and plasma were processed for the metabolomics analysis. We also performed histopathological examination on the lung tissue. We detected moderate inflammatory damage with alveolar septal thickening in the HV group compared with the normal and LV groups.The metabolomics analysis results showed MV altered the metabolism which was characterized by the dysregulation of γ-amino butyric acid (GABA) system and urea cycle (desregulations in plasma and lung guanidinosuccinic acid, argininosuccinic acid, succinic acid semialdehyde and lung GABA ), Disturbance of citric acid cycle (CAC) (increased plasma glutamine and lung phosphoenol pyruvate) and redox imbalance (desregulations in plasma and/or lung ascorbic acid, chenodeoxycholic acid, uric acid, oleic acid, stearidonic acid, palmitoleic acid and docosahexaenoic acid). Moreover, the lung and plasma metabolomes were also significantly different between LV and HV groups. Some lung and plasma metabolites related to the GABA system and urea cycle, citric acid cycle and redox balance were significantly altered, and they may be employed for the evaluation of VILI and serve as targets in the treatment of VILI.

Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery.

Acute ischemic stroke (AIS) is characterized by a sudden blockage of one of the main arteries supplying blood to the brain, leading to insufficient oxygen and nutrients for brain cells to function properly. Unfortunately, metabolic alterations in the biofluids with AIS are still not well understood. In this study, we performed high-throughput target metabolic analysis on 44 serum samples, including 22 from AIS patients and 22 from healthy controls. Multiple-reaction monitoring analysis of 180 common metabolites revealed a total of 29 metabolites that changed significantly (VIP > 1, p < 0.05). Multivariate statistical analysis unraveled a striking separation between AIS patients and healthy controls. Comparing the AIS group with the control group, the contents of argininosuccinic acid, beta-D-glucosamine, glycerophosphocholine, L-abrine, and L-pipecolic acid were remarkably downregulated in AIS patients. Twenty-nine out of 112 detected metabolites enriched in disturbed metabolic pathways, including aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, lysine degradation, phenylalanine, tyrosine, and tryptophan biosynthesis metabolic pathways. Collectively, these results will provide a sensitive, feasible diagnostic prospect for AIS patients.