High mobility group box-1 protein promotes astrocytic CCL5 production through the MAPK/NF-κB pathway following spinal cord injury.

Astrocytes act as immune cells that can produce a series of chemokines to attract large numbers of leucocytes to the lesion site, where they contribute to excessive inflammation following spinal cord injury (SCI). However, the relevant regulatory mechanism involved in chemokine production by astrocytes has not been fully elucidated. In the present study, we examined the correlation between C-C motif chemokine ligand 5 (CCL5) and high mobility group box-1 protein (HMGB1) in a T8-T10 spinal cord contusion model. Our results revealed that SCI-induced CCL5 protein levels increased synchronously with the increase in HMGB1. Administration of an HMGB1-neutralizing antibody significantly reduced the protein expression of CCL5 in the context of SCI. An in vitro study revealed that HMGB1 binding with TLR2/4 receptors potently facilitates the production of CCL5 by astrocytes by activating the intracellular ERK/JNK-mediated NF-κB pathway. Furthermore, the HMGB1-induced release of CCL5 from astrocytes is involved in promoting microglia/macrophage accumulation and M1 polarization. The inhibition of HMGB1 activity reduces microglia/macrophage infiltration by decreasing the expression of CCL5 and improves motor functional recovery following SCI. Our results provide insights into the new functions of HMGB1-mediated astrocytic CCL5 production, which elicits inflammatory cell recruitment to the site of injury; this recruitment is associated with excessive inflammation activation. These data may provide a new therapeutic strategy for central nervous system (CNS) inflammation.

Exploring the effects of matrix metalloproteinase-13 on the malignant biological behavior of tongue squamous cell carcinoma via the TNF signaling pathway based on bioinformatics methods.

Background: Identification of the etiology, molecular mechanisms, and carcinogenic pathways of tongue squamous cell carcinoma (TSCC) is crucial for developing new diagnostic and therapeutic strategies. This study used bioinformatics methods to identify key genes in TSCC and explored the potential functions and pathway mechanisms related to the malignant biological behavior of TSCC. Methods: Gene chip data sets (i.e., GSE13601 and GSE34106) containing the data of both TSCC patients and normal control subjects were selected from the Gene Expression Omnibus (GEO) database. Using a gene expression analysis tool (GEO2R) of the GEO database, the differentially expressed genes (DEGs) were identified using the following criteria: |log fold change| >1, and P<0.05. The GEO2R tool was also used to select the upregulated DEGs in the chip candidates based on a P value <0.05. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) function analysis, and a protein-protein interaction (PPI) network analysis were then conducted. The results were displayed using R language packages, including volcano plots, Venn diagrams, heatmaps, and enriched pathway bubble charts. Genes from the MalaCards database were compared with the candidate genes, and a thorough review of the literature was conducted to determine the clinical significance of these genes. Finally, feature gene-directed chemical drugs or targeted drugs were predicted using the Comparative Toxicogenomics Database (CTD). Results: In total, 767 upregulated DEGs were identified from GSE13601 and 695 from GSE34106. By intersecting the upregulated DEGs from both data sets using a Venn diagram, 100 DEGs related to TSCC were identified. The enrichment analysis of the KEGG signaling pathways identified the majority of the pathways associated with the upregulated DEGs, including the Toll-like receptor signaling pathway, the extracellular matrix-receptor interaction, the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction, the chemokine signaling pathway, the interlukin-17 signaling pathway, and natural killer cell-mediated cytotoxicity. The PPI network and module analyses of the shared DEGs ultimately resulted in five clusters and 55 candidate genes. A further intersection analysis of the TSCC-related genes in the MalaCards database via a Venn diagram identified three important shared DEGs; that is, matrix metalloproteinase-1 (MMP1), MMP9, and MMP13. In the CTD, seven drugs related to MMP13 were identified for treating tongue tumors. Conclusions: This study identified key genes and signaling pathways involved in TSCC and thus extended understandings of the molecular mechanisms that underlie the development and progression of TSCC. Additionally, this study showed that MMP13 may influence the malignant biological behavior of TSCC through the TNF signaling pathway. This finding could provide a theoretical basis for research into early differential diagnosis and targeted treatment.

CD3D, GZMK, and KLRB1 Are Potential Markers for Early Diagnosis of Rheumatoid Arthritis, Especially in Anti-Citrullinated Protein Antibody-Negative Patients.

Early diagnosis and monitoring of rheumatoid arthritis (RA) progress are critical for effective treatment. In clinic, the detection of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are usually combined to diagnose early RA. However, the poor specificity of RF and high heterogeneity of ACPA make the early diagnosis of RA still challenging. Bioinformatics analysis based on high-throughput omics is an emerging method to identify novel and effective biomarkers, which has been widely used in many diseases. Herein, utilizing an integrated strategy based on expression correlation analysis and weighted gene coexpression network analysis (WGCNA), we identified 76 RA-trait different expression genes (DEGs). Combined with protein-protein interaction (PPI) network construction and clustering, new hub genes associated in RA synovia, CD3D, GZMK, and KLRB1, were identified. We verified the specificity of these genes in the synovium of RA patients through three external datasets. We also observed high sensitivity and specificity of them for ACPA-negative patients. CD3D, GZMK, and KLRB1 are potentially key mediators of RA pathogenesis and markers for RA diagnosis.

Modification of the anterior-posterior tongue rotation flap for oral tongue reconstruction.

The aim of this study is to evaluate the efficacy and long-term outcome of a modification of the anterior-posterior tongue rotation flap used for reconstruction of tongue following cancer ablation. From April 2016 to September 2017, 21 consecutive patients with tumor classification (T2), lymph node classification (N0) tongue cancer on the anterior and middle one-third portion were selected for this study. A modification of the anterior-posterior tongue rotation flap was selected for tongue reconstruction after the cancer resection. Patient's scorings of swallowing, chewing, speech and taste were recorded. Patient after tongue flap reconstruction acquired satisfied tongue movement that allows normal functional outcomes for swallowing, chewing, speech and taste. Local tumor recurrence was not observed during the follow-up examination (range, 12-24 months). The modification of the anterior-posterior tongue rotation flap was a safe and reliable treatment for medium-size tongue cancer (T2N0), especially suitable to patients who cannot endure prolonged surgery.