RESUMO
Background: We performed a differential analysis, enrichment analysis, and immune-infiltration analysis of the thyroid-associated ophthalmopathy (TAO) gene using data from the Gene Expression Omnibus (GEO) database to provide a theoretical basis for understanding the immune-related mechanisms of TAO. Methods: We searched the GEO database for "Graves disease" and selected the genes expressed in the lacrimal gland of thyroid-related eye disease patients as the test group and the genes expressed in the lacrimal gland of normal subjects as the control group. Immune-related differentially expressed genes (irDEGs), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction, gene-gene interaction (GGI) network, pivotal gene identification, and immune-infiltration analyses were carried out, and finally, risk-prediction models were constructed. Results: The GSE105149 and GSE58331 data sets contained 200 DEGs, of which 15 were immune-related. In relation to the GO biological processes (BPs), the main pathways included the interleukin (IL)-27-mediated signaling pathway, the IL-35-mediated signaling pathway, cytokine activity, T helper 17 cell differentiation, the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, cytokine-cytokine receptor interaction, the Janus kinase and signal transducer and activator of transcription signaling pathway, and other KEGG pathways. Cluster of differentiation (CD)4+ T cells, monocytes, M0 macrophages, and Mast cells were significantly elevated in TAO, while M2 macrophages were significantly reduced. In the immune cell correlation analysis, CD4+ T cells and naïve B cells were significantly positively correlated with activated natural killer (NK) cells, and Mast cells were positively correlated with plasma cells and negatively correlated with M2 macrophages. Risk models for a total of 6 genes (i.e., Janus kinase 1, heat shock protein 90-α, phospholipase A 2 group IIA, fibroblast growth factor 3, glucose-6-phosphate isomerase, and protein disulfide isomerase family A, member 2), were constructed, and over 100 potential targeted therapeutic agents were obtained. Conclusions: In TAO, various types of immune cells infiltrate to different degrees, and the immune response and inflammatory response are throughout the disease. Our constructed risk-prediction models provide a reference for predicting TAO.
RESUMO
GLOBOCAN estimates 36 types of cancers in 185 countries based on the incidence, mortality, and prevalence in the year 2019. Nowadays, chemotherapy is the most widely used cancer treatment among immune, radio, hormone, and gene therapies. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nano-assembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic Gemcitabine (GEM) drug. The GEM prodrugs were gifted to impulsively self-assemble into excellent steady nanoparticles size on covalent conjugation of linoleic acid hydrophobic through amide group with â¼100 nm. Newly synthesized GEM-NPs morphology was confirmed by various electron microscopic techniques. After successful synthesis, we have evaluated the anticancer property of GEM and GEM-NPs against B-CPAP (papillary thyroid carcinoma) and FTC-133 (human follicular thyroid carcinoma) cancer cell lines. Further studies such as AO-EB (acridine orange-ethidium bromide), nuclear staining and flow cytometry analyses on cell death mechanism signified that the cytotoxicity was associated with apoptosis in thyroid cancer cells. GEM-NPs show excellent biocompatibility compared to GEM. The present study explained that GEM-NPs as a safe and hopeful strategy for chemotherapeutics of thyroid cancer therapy and deserve for further clinical evaluations.
