An untargeted metabolomics study of cardiac pathology damage in rats caused by low selenium diet alone or in combination with T-2 toxin.

T-2 toxin is a highly cardiotoxic environmental contaminant. Selenium can uphold the cardiovascular system's functionality. Selenium insufficiency is common. The aim of this study was to elucidate the effects of low selenium diet alone or in combination with T-2 toxin on myocardial tissue damage. Thirty-two Sprague-Dawley rats of 3 weeks of age were randomized into control, low selenium diet, low selenium diet combined with T-2 toxin groups (at doses of 10 ng/g and 100 ng/g body weight) for 12-weeks intervention. Pathohistology and ultrastructural changes in cardiac tissue were observed. Changes in cardiac metabolites were analyzed using untargeted metabolomics. The findings demonstrated that cardiac tissue abnormalities, interstitial bleeding, inflammatory cell infiltration, and mitochondrial damage can be brought on by low selenium diet alone or in combination with the T-2 toxin. A low selenium diet alone or in combination with the T-2 toxin affected cardiac metabolic profiles and resulted in aberrant modifications in many metabolic pathways, including the metabolism of amino acids, cholesterol, and thiamine. Accordingly, low selenium diet and T-2 toxin may have a synergistic effect. Our findings provide fresh insights into the processes of cardiac injury by revealing the effects of low selenium diet and T-2 toxin on cardiac metabolism.

Identification of N-Glycoproteins of Knee Cartilage from Adult Osteoarthritis and Kashin-Beck Disease Based on Quantitative Glycoproteomics, Compared with Normal Control Cartilage.

Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell-cell or cell-ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.

Alterations of IL-1beta and TNF-alpha expression in RAW264.7 cell damage induced by two samples of PM2.5 with different compositions.

Fine particulate matter 2.5 (PM2.5) has been demonstrated by previous studies to be associated with cell damage. To explore the impact of the composition of PM2.5 on PM2.5-mediated inflammation, this study investigated the composition of PM2.5 collected during the wintertime indoor heating season and observed its inflammatory effect. Samples were collected during the heating season from December 5, 2017, to January 8, 2018, in Xi'an. Compositions of organic carbon (OC), elemental carbon (EC), and water-soluble ions were analysed. Two representative samples (sample 1 and 2) were selected with significant differences in compositions. They were configured into four concentrations (0.1 µg/mL, 1 µg/mL, 10 µg/mL, 20 µg/mL) and used as interventions on RAW264.7 cells for 4 h and 24 h separately. Cell viability was detected by CCK-8. Tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) gene and protein expression levels were detected by real-time quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. The results showed that the cell viability of sample 1 intervened cells at 4 h and 24 h was lower than that of sample 2. IL-1ß gene in most PM2.5 intervention groups was lower than in the control group. Protein expression was higher at 4 h than at 24 h. In conclusion, PM2.5 components influence cell viability and expression of IL-1ß and TNF-α, while high concentrations of NO3-, Cl-, Na+, K+, Mg2+, Ca2+, and others in the PM2.5 composition have a significant harmful effect.

Identification of proteins and N-glycosylation sites of knee cartilage in Kashin-Beck disease compared with osteoarthritis.

The aim of this study was to identify crucial proteins and N-glycosylated sites in the pathological mechanism of Kashin-Beck disease (KBD) compared with osteoarthritis (OA). Nine KBD knee subjects and nine OA knee subjects were selected for the study. Quantitative proteomics and N-glycoproteomics data of KBD and OA were obtained by protein and N-glycoprotein enrichment and LC-MS/MS analysis. Differentially expressed proteins or N-glycosylation sites were examined with a comparative analysis between KBD and OA. Total 2205 proteins were identified in proteomic analysis, of which 375 were significantly different. Among these, 121 proteins were up-regulated and 254 were down-regulated. In N-glycoproteomic analysis, 278 different N-glycosylated sites that were related to 187 N-glycoproteins were identified. Proteins and their N-glycosylated sites are associated with KBD pathological process including ITGB1, LRP1, ANO6, COL1A1, MXRA5, DPP4, and CSPG4. CRLF1 and GLG1 are proposed to associate with both KBD and OA pathological processes. Key pathways in KBD vs. OA proteomic and N-glycoproteomic analysis contained extracellular matrix receptor interaction, focal adhesion, phagosome, protein digestion, and absorption. N-glycosylation may influence the pathological process by affecting the integrity of chondrocytes or cartilage. It regulated the intercellular signal transduction pathway, which contributes to cartilage destruction in KBD.