ABSTRACT
BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P＜0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.
ABSTRACT
BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.
ABSTRACT
Objective:To explore the molecular mechanism of paraquat (PQ)-induced lung injuries.Methods:Male C57BL/6 mice aged 6 to 8 weeks were randomly divided into four groups. Mice in the experimental groups (three groups, nine rats in each group) were intraperitoneally injected with 40 mg/kg PQ to establish an infection model, and mice in the control group ( n=9) were intraperitoneally injected with the same dose of saline. Mice were sacrificed at day 2, 7 and 14 after PQ administration. Pathological changes of lung tissues from mice model were observed by Hematoxylin-eosin staining. The expression of different proteins in the lung tissues at different time points were detected and identified by tandem mass spectrometry tag technology (TMT), and the functional analysis was performed. Results:Compared with the control group, there were 91 (69 up and 22 down), 160 (103 up and 57 down) and 78 (45 up and 33 down) proteins in the PQ-2 d, 7 d, and 14 d groups, respectively, and there was significant difference of protein expression . The subcellular localization analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and -7 d groups were mainly distributed in the extracellular space, while in the PQ-14 d group were mainly distributed in the nuclear. GO analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and PQ-7 d groups were mainly involved in humoral immunity and coagulation-related reactions, while in the PQ-14 d group were mainly involved in chemotactic and regulatory responses such as neutrophil aggregation. The KEGG signaling pathway analysis showed that the complement and coagulation cascades was the most important pathway in the PQ-2d and PQ-7 d groups, while metabolism of xenobiotics by cytochrome P450 was the most important pathway in the PQ-14 d group.Conclusions:It is the first time that TMT was used to analyze PQ-induced lung injuries in mice model at different time points. This study demonstrates the molecular mechanism of PQ-induced lung injuries at protein levels, and elucidates that humoral immunity and complement-coagulation pathways charge the main role of PQ-induced lung injuries. This study may provide an important theoretical basis for further research and clinical treatment.