Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis

BACKGROUND Helicobacter pylori(H.pylori)infection is a major risk factor for chronic gastritis,affecting approximately half of the global population.H.pylori eradication is a popular treatment method for H.pylori-positive chronic gastritis,but its mecha-nism remains unclear.Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment.However,no clinical study has been conducted on urinary metabolomics of chronic gastritis.AIM To elucidate the urinary metabolic profiles during H.pylori eradication in patients with chronic gastritis.METHODS We applied LC–MS-based metabolomics and network pharmacology to in-vestigate the relationships between urinary metabolites and H.pylori-positive chronic gastritis via a clinical follow-up study.RESULTS Our study revealed the different urinary metabolic profiles of H.pylori-positive chronic gastritis before and after H.pylori eradication.The metabolites regulated by H.pylori eradication therapy include cis-aconitic acid,isocitric acid,citric acid,L-tyrosine,L-phenylalanine,L-tryptophan,and hippuric acid,which were involved in four metabolic pathways:(1)Phenylalanine metabolism;(2)phenylalanine,tyrosine,and tryptophan biosynthesis;(3)citrate cycle;and(4)glyoxylate and dicarboxylate metabolism.Integrated metabolomics and network pharmacology revealed that MPO,COMT,TPO,TH,EPX,CMA1,DDC,TPH1,and LPO were the key proteins involved in the biological progress of H.pylori eradication in chronic gastritis.CONCLUSION Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H.pylori-positive chronic gastritis patients.

Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Examination of Urinary Chlorpyrifos Biomarker Concentrations and Heart Rate in a Sample of US Children and Adolescents

Objective: The purpose of the investigation is to determine if a relationship exists between heart rate and urinary biomarkers of chronic, subacute chlorpyrifos pesticide exposure in youth. Methods: Using 2001-2002 NHANES data, a sample of 1233 children ages 6 - 18 was grouped based on detection status of 3,5,6-trichloropyridinol (TCPy) in urine. Radial pulse and brachial pulse were recorded as measures of heart rate by physicians. T-tests and linear regression analyses were performed to test for associations between TCPy concentrations and heart rate. Results: None of the associations between TCPy levels and heart rate outcomes were found to be significant. Nonsignificant effects in the TCPy-detected groups included a slightly reduced heart rate in girls, as well as a slightly elevated heart rate in boys when compared to the undetected controls. Neither was there any significant observable difference in heart rate due to detection status in the sample overall. Conclusions: At this time, an effect on heart rate attributable to chronic, low-level chlorpyrifos exposure in youth cannot be determined. Children and adolescents detected did not demonstrate a substantial change in pulse measures when compared to controls. It is recommended that subsequent studies examine chlorpyrifos biomarkers as they may relate to other indicators of cardiovascular health.

Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.