Dendritic cells (DCs) are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses against cancer. Tumor cells can escape from immune attack by secreting suppressive cytokines that solely or cooperatively impair the immune function of DCs. However, the underlying mechanisms are not fully defined. Vascular endothelial growth factor (VEGF) has been identified as a major cytokine in the tumor microenvironment. To elucidate the effects of VEGF on the motility and immune function of mature DCs (mDCs), the cells were treated with 50 ng/mL VEGF and investigated by proteomics and molecular biological technologies. The results showed that VEGF can impair the migration capacity and immune function of mDCs through the RhoA‐cofilin1 pathway mediated by the VEGF receptor 2, suggesting impaired motility of mDCs by VEGF is one of the aspects of immune escape mechanisms of tumors. It is clinically important to understand the biological behavior of DCs and the immune escape mechanisms of tumor as well as how to improve the efficiency of antitumor therapy based on DCs.
Hematoporphyrin (HP) and protoporphyrin IX (PPIX) are useful porphyrin photosensitizers with significant application values in photodynamic therapy. Currently, many strategies have been developed to improve their clinical performance, such as incorporating them with nanoparticle (NP) carriers. In this work, we studied the possibility of using β-lactoglobulin (BLG) as a potential NP carrier due to their hydrophobic affinity, pH sensitivity, and low cost of extraction and preservation. The interaction mechanisms of BLG with HP and PPIX were investigated using spectroscopic techniques and molecular docking methods. The molecular docking results agree well with the experimental results, which demonstrate that the formations of HP-BLG and PPIX-BLG complexes are endothermic processes and the main acting force is hydrophobic force. Furthermore, the opening–closure states of EF loop have a great influence on the HP-BLG complex formation, where the central hydrophobic cavity of β-barrel is available for HP binding at pH 7.4 but not available at pH 6.2. However, the formation of the PPIX-BLG complex is less dependent on the states of the EF loop, and the binding sites of PPIX are both located on the external surface of BLG under both pH 7.4 and 6.2 conditions. All of our results would provide new insight into the mechanisms of noncovalent interactions between BLG and HP/PPIX. It is believed that this work indicated the potential application values of BLG in designing pH-sensitive carriers for the delivery of HP and PPIX, as well as other poorly soluble drugs.
Genome-scale metabolic models (GSMMs) constitute a platform that combines genome sequences and detailed biochemical information to quantify microbial physiology at the system level. To improve the unity, integrity, correctness, and format of data in published GSMMs, a consensus IMGMD database was built in the LAMP (Linux + Apache + MySQL + PHP) system by integrating and standardizing 328 GSMMs constructed for 139 microorganisms. The IMGMD database can help microbial researchers download manually curated GSMMs, rapidly reconstruct standard GSMMs, design pathways, and identify metabolic targets for strategies on strain improvement. Moreover, the IMGMD database facilitates the integration of wet-lab and in silico data to gain an additional insight into microbial physiology. The IMGMD database is freely available, without any registration requirements, at http://imgmd.jiangnan.edu.cn/database.
Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cancer by incidence worldwide, with approximately 700,000 new cases in 2018 (accounting for 11% of all cancers). The occurrence and development of tumors are closely related to the immunological function of the body and sensitivity to treatment schemes as well as prognosis. It is urgent for clinicians to systematically study patients’ immune gene maps to help select a treatment plan and analyze the potential to cure HNSCC. Here, the transcriptomic data of HNSCC samples were downloaded from The Cancer Genome Atlas (TCGA), and 4,793 genes differentially expressed in normal and cancer tissues of HNSCC were identified, including 1,182 downregulated and 3,611 upregulated genes. From these genes, 400 differentially expressed immune-related genes (IRGs) were extracted, including 95 downregulated genes and 305 upregulated genes. The prognostic values of IRGs were evaluated by univariate Cox analysis, and 236 genes that were significantly related to the overall survival (OS) of patients were identified. The signaling pathways that play roles in the prognosis of IRGs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the expression profiles of IRGs and OS in 499 HNSCC patients based on TCGA dataset were integrated. Potential molecular mechanisms and characteristics of these HNSCC-specific IRGs were further explored with the help of a new prognostic index based on IRGs developed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A total of 64 hub genes (IRGs associated with prognosis) were markedly associated with the clinical outcome of HNSCC patients. KEGG functional enrichment analysis revealed that these genes were actively involved in several pathways, e.g., cytokine–cytokine receptor interaction, T-cell receptor signaling, and natural killer cell-mediated cytotoxicity. IRG-based prognostic signatures performed moderately in prognostic predictions. Interestingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. These data screened several IRGs of clinical significance and revealed drivers of the immune repertoire, demonstrating the importance of a personalized IRG-based immune signature in the recognition, surveillance, and prognosis of HNSCC.
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