AIM: To investigate the role of nuclear factor- κB (NF- κB) in the expression of monocyte chemoatractant protein- 1 (MCP- 1) in human mesangial cells (HMCs) induced by oxidized low- density lipoprotein (Ox- LDL).METHODS: HMCs were used as target cells. Inhibitory κBα (IκBα) and MCP- 1 protein level was measured by cell ELISA.Activities of transcriptional factors NF- κB were determined by electrophoresis mobility shift assay (EMSA). Immunohistochemistry was used to detect the translocation of Rel p65. RESULTS: NF - κB DNA - binding activation in MCs was observed when 10-100 mg/L Ox - LDL was added to the medium, and 50 mg/L Ox - LDL caused the strongest effect (8.50 ± 1.14, P ＜ 0.01vs control; P ＜ 0.05 vs 10, 25 and 100 mg/L Ox - LDL). The most optimal stimulation time was 60 min ( 11.0 ± 2.11, P ＜0.01 vs control; P ＜ 0.05 vs 30 min or 240 min). IκBα protein level in MC dropped down most obviously after 60 min incubation with 50 mg/L Ox - LDL (0.050 ± 0.006, n = 5, P ＜ 0.01 vs control), while MCP- 1 expression level was the highest (0.331± 0.016, n = 5, P ＜ 0.01 vs control). The translocation of Rel p65 from cytoplasm to nucleus was detected too. NF - κB inhibitor pyrroledithiocarbomate (PDTC) could inhibit these effects induced by Ox- DL. CONCLUSION: Activation of NF- κB regulate the expression of MCP- 1 in HMCs induced by Ox - LDL.

AIM: To investigate the role of nuclear factor-?B (NF-?B) in the expression of monocyte chemoatractant protein-1 (MCP-1) in human mesangial cells (HMCs) induced by oxidized low-density lipoprotein (Ox-LDL). METHODS: HMCs were used as target cells. Inhibitory ?B? (I?B?) and MCP-1 protein level was measured by cell ELISA. Activities of transcriptional factors NF-?B were determined by electrophoresis mobility shift assay (EMSA). Immunohistochemistry was used to detect the translocation of Rel p65. RESULTS: NF-?B DNA-binding activation in MCs was observed when 10-100 mg/L Ox-LDL was added to the medium, and 50 mg/L Ox-LDL caused the strongest effect (8.50?1.14, P

Glioma, the most common intrinsic tumor of the central nervous system, is characterized by its high incidence and poor prognosis. The aim of this study was to identify differentially expressed genes (DEGs) between glioblastoma multiforme (GBM) and low-grade glioma (LGG) to explore prognostic factors of different grades of gliomas. Single-cell transcriptome sequencing data of gliomas were collected from the NCBI Gene Expression Omnibus (GEO), which included a total of 29 097 cell samples from three datasets. For the analysis of human gliomas of different grades, 21 071 cells were obtained by filtering, and 70 genes were screened from differentially expressed genes by gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, from which the gene DLL3 was focused by reviewing the literature. The TCGA-based gene expression profiling interactive analysis (GEPIA) database was used to explore the survival curves of genes in LGG and GBM, and the gene expression profiling interactive analysis and tumor immune estimation resource (TIMER) database was used to study the expression of key genes in gliomas of different grades, predicting biomarkers that were closely related to immunotherapy. The cBioPortal database was used to explore the relationship between DLL3 expression and 25 immune checkpoints. Gene set enrichment analysis (GSEA) further identified pathways associated with central genes. Finally, the efficacy of biomarkers in prognosis and prediction was validated in the Chinese glioma genome atlas (CGGA). These results demonstrated that prognostic genes are associated with tumor proliferation and progression. Analysis of biological information and survival suggested that these genes might serve as a promising prognostic biomarker and as new targets for selecting therapeutic strategies.
Humans ; Biomarkers ; Brain Neoplasms/pathology* ; Gene Expression Profiling/methods* ; Glioblastoma/pathology* ; Glioma/pathology* ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Biomarkers, Tumor

Retinoblastoma (RB) is the most common intraocular malignant tumor in infants and young children. The key causative factors in the progression of RB remain unclear. Therefore, identifying genes closely associated with RB progression may provide important clues for disease diagnosis and gene therapy. However, tumor tissues have strong cellular heterogeneity. There may be significant differences in cell function and gene expression among cells in different pathological states. In this study, we downloaded single-cell transcriptome sequencing data of RB tumors and adjacent tissues from the GEO public database. Subsequently, we analyzed RB tumor transcriptional profiles with different disease duration at the single-cell level and identified cell groups and gene sets potentially associated with RB progression. The results showed that the tumor tissue and the adjacent tissues had overall consistency in the single-cell transcriptional map, but there were obvious differences in the distribution proportions of G1 phase cells, G2 phase cells, and microglia cells of cone precursors in RB tumor and the adjacent tissues. Furthermore, the role of three cell populations in the progression of RB tumors was emphatically analyzed. We found that in the early stage of RB tumors, cone precursor cells proliferated abnormally in G1 phase. With the progression of RB tumors, the proportion of cone precursor cells in G2 phase increased significantly. Meanwhile, the results of differential analysis of microglial populations during RB progression showed that the key genes mainly involved in immune response include RPL23, B2M, and HLA superfamily genes. This study provides new perspectives and data resources for the research of RB pathogenesis and progress.
Child ; Infant ; Humans ; Child, Preschool ; Retinoblastoma/pathology* ; Transcriptome ; Retinal Neoplasms/pathology*

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.