NOD-like Pathway Research Articles

Expression and metabolism profiles of CVT associated with inflammatory responses and oxygen carrier ability in the brain.

As the main type of stroke, the incidence of cerebral venous thrombosis (CVT) has been rising. However, the comprehensive mechanisms behind it remain unclear. Thus, the multi-omics study is required to investigate the mechanism after CVT and elucidate the characteristic pathology of venous stroke and arterial stroke. Adult rats were subjected to CVT and MCAO models. Whole-transcriptome sequencing (RNA-seq) and untargeted metabolomics analysis were performed to construct the transcriptome and metabolism profiles of rat brains after CVT and also MCAO. The difference analysis, functional annotation, and enrichment analysis were also performed. Through RNA-seq analysis, differentially expressed genes (DEGs) were screened. 174 CVT specific genes including Il1a, Ccl9, Cxxl6, Tnfrsf14, etc., were detected. The hemoglobin genes, including both Hba and Hbb, were significantly downregulated after CVT, compared both to the MCAO and Sham groups. Metabolism analysis showed that CVT had higher heterogeneity of metabolism compared to MCAO. Metabolites including N-stearoyltyrosine, 5-methoxy-3-indoleaceate, Afegostat, pipecolic acid, etc. were specially regulated in CVT. Through the immune infiltration analysis, it was found that CVT had a higher immune response, with the abundance of certain types of immune cells increased, especially T helper cells. It was important to find the prevalence of the activation of inflammatory chemokine, cytokine, NOD-like pathway, and neutrophil extracellular trap. We explored and analyzed the gene expression and metabolomic characteristics of CVT, revealed the specific inflammatory reaction mechanism of CVT and found the markers in transcriptome and metabolism levels. It points out the direction for CVT early diagnosis and treatment.

Reaction of a nitrosyl complex of Mn(II)-porphyrinate with superoxide: NOD activity is favoured over SOD activity.

A five-coordinated {Mn(NO)}6 complex of Mn(II)-porphyrinate, [Mn(TMPP2-)(NO)], 1 {TMPPH2 = 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin}, upon reaction with two equivalents of superoxide (O2-) in THF at -40 °C results in the corresponding MnIII-OH complex [MnIII(TMPP2-)(OH)], 2, via the formation of a putative MnIII-peroxynitrite intermediate. Spectral studies and chemical analysis suggest that one equivalent of superoxide ion is consumed to oxidize the metal center of complex 1 leading to [MnIII(TMPP2-)(NO)]+, while the subsequent equivalent reacts with [MnIII(TMPP2-)(NO)]+ to form the corresponding peroxynitrite intermediate. UV-visible and X-band EPR spectroscopic studies suggest the involvement of a MnIV-oxo species in the reaction, which forms through the O-O bond cleavage of the peroxynitrite moiety with concomitant release of NO2. The formation of MnIII-peroxynitrite is further supported by the well-established phenol ring nitration experiment. The released NO2 has been trapped using TEMPO. It should be noted that in cases of MnII-porphyrin complexes, the reaction with superoxide generally proceeds through a SOD-like pathway where the first equivalent of superoxide ion oxidizes the MnII center and itself is reduced to peroxide (O22-), while the subsequent equivalent of superoxide reduces the MnIII center with the release of O2. In contrast, here the second equivalent of superoxide reacts with the MnIII-nitrosyl complex and follows a NOD-like pathway.

Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring

BackgroundPsoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.MethodsThe study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography–mass spectrometry (LC–MS)/MS.ResultsA total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV.ConclusionsThese findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.