Perturbations in Amino Acid Metabolism in Children with Kaschin-Beck Disease: A Study of Urinary Target Metabolomics

Kaschin-Beck disease (KBD) is an endemic and chronic osteoarthropathy characterized by pathological aspects including chondrocyte degeneration, necrosis, progressive loss of articular cartilage, and secondary degenerative osteoarthrosis of epiphyseal cartilage, epiphyseal plate cartilage, and articular cartilage, during puberty[1]. The main clinical symptoms are limb joint pain, thickening, deformation, limited movement, muscle atrophy, and in case of more severely affected patients, short fingers (toes), short limbs, and even short stature[1].

Screening of Genes with Unique Mutations of Microcus

Yersinia pestis is the causative agent of bubonic and pneumonic plagues.Strains of Y.pestis are classified into four biovars:antiqua,mediaevalis,orientalis,and microtus[1].There are two microtus-related plague foci in China:the Microtus brandti plague focus in the Xilin Gol Grassland(focus L)and the Microtus fuscus plague focus in the Qinghai-Tibet Plateau(focus M).Microtus strains are avirulent to humans,and experiments have shown that strains isolated from Microtus brandti in Inner Mongolia are virulent

Serum Metabolomic Indicates Potential Biomarkers and Metabolic Pathways of Pediatric Kashin-Beck Disease

Objective To explore potential serum biomarkers of children with Kashin-Beck Disease(KBD)and the metabolic pathways to which the biomarkers belong.Methods A two-stage metabolomic study was employed.The discovery cohort included 56 patients,51 internal controls,and 50 external controls.The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases(HMDB)and Metlin databases.MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes(KEGG)database were used to analyze the metabolic pathways of the candidate metabolites.The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients,41 internal controls,and 50 external controls.Results Eight candidate metabolites were identified out in the discovery study,namely kynurenic acid,N-α-acetylarginine,6-hydroxymelatonin,sphinganine,ceramide,sphingosine-1 P,spermidine,and glycine.These metabolites exist in sphingolipid,glutathione,and tryptophan metabolic pathways.In the second-stage study,five candidate metabolites were validated,including kynurenic acid,N-α-acetylarginine,sphinganine,spermidine,and sphingosine-1 P.Except for spermidine,all substances exhibited low expression in the case group compared with the external control group,and the difference in levels of sphinganine,spermidine,and sphingosine-1 P was statistically significant.Conclusion The direction of change of levels of sphinganine,spermidine,and sphingosine-1 P in the two-stage study cohorts was completely consistent,and the differences were statistically significant.Therefore,these substances can be used as potential biomarkers of KBD.Furthermore,these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.