Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. ESCC has a generally poor prognosis and there is a lack of available biomarkers for diagnosis and prognosis. The aim of the study was to identify novel biomarkers for ESCC. We screened the overlapping differentially expressed genes (DEGs) acquired from six Gene Expression Omnibus (GEO) ESCC datasets and The Cancer Genome Atlas (TCGA) ESCC datasets. Subsequently, protein-protein interaction network analysis was performed to identify the key hub genes. Then, Kaplan Meier survival and receiver operating curve (ROC) analysis were utilized to clarify the diagnostic and prognostic role of these hub genes. The UALCAN database, single cell RNA sequencing (scRNA-seq) and real-time quantitative PCR (qPCR) were performed to confirm the expression levels of identified hub genes. Finally, immune infiltration analysis was conducted to investigate the role of these genes in the pathogenesis of ESCC. The results showed that PBK, KIF2C, NUF2, KIF20A, RAD51AP1, and DEPDC1 effectively distinguish ESCC tissues from normal samples, and all of them were significantly correlated with overall survival. The results of scRNA-seq and qPCR indicated that the expression levels of hub genes in ESCC were significantly higher than in normal cells or tissues. Further immune infiltration analysis showed that infiltration of dendritic cells was significantly negatively correlated with PBK, KIF2C, NUF2, RAD51AP1, and DEPDC1 expression levels. In conclusion, our results suggest that PBK, KIF2C, NUF2, KIF20A, RAD51AP1 and DEPDC1 are all potential biomarkers for ESCC diagnosis and prognosis may also be potential therapeutic targets for ESCC.

Acquired Immunodeficiency Syndrome is caused by the Human Immunodeficiency Virus (HIV), and a significant number of fatalities occur annually. There is a dire need to develop an effective vaccine against HIV-1. Understanding the structural proteins of viruses helps in designing a vaccine based on immunogenic peptides. In the current experiment, we identified gp120 epitopes using bioinformatic epitope prediction tools, molecular docking, and MD simulations. The Gb-1 peptide was considered an adjuvant. Consecutive sequences of GTG, GSG, GGTGG, and GGGGS linkers were used to bind the B cell, Cytotoxic T Lymphocytes (CTL), and Helper T Lymphocytes (HTL) epitopes. The final vaccine construct consisted of 315 amino acids and is expected to be a recombinant protein of approximately 35.49 kDa. Based on docking experiments, molecular dynamics simulations, and tertiary structure validation, the analysis of the modeled protein indicates that it possesses a stable structure and can interact with Toll-like receptors. The analysis demonstrates that the proposed vaccine can provoke an immunological response by activating T and B cells, as well as stimulating the release of IgA and IgG antibodies. This vaccine shows potential for HIV-1 prophylaxis. The in-silico design suggests that multiple-epitope constructs can be used as potentially effective immunogens for HIV-1 vaccine development.

Human Immunodeficiency Virus (HIV-1) is known to establish a persistent latent infection. The use of combination antiretroviral therapy (cART) can effectively reduce the viral load, but the treatment can be costly and may lead to the development of drug resistance and life-shortening side effects. It is important to develop an ideal and safer in vivo target therapy that will effectively block viral replication and expression in the body. Exosomes have recently emerged as a promising drug delivery vehicle due to their low immunogenicity, nanoscale size (30-150nm), high biocompatibility, and stability in the targeted area. Exosomes, which are genetically produced by different types of cells such as dendritic cells, neurons, T and B cells, epithelial cells, tumor cells, and mast cells, are designed for efficient delivery to targeted cells. In this article, we review and highlight recent developments in the strategy and application of exosome-based HIV-1 vaccines. We also discuss the use of exosome-based antigen delivery systems in vaccine development. HIV-1 antigen can be loaded into exosomes, and this modified cargo can be delivered to target cells or tissues through different loading approaches. This review also discusses the immunological prospects of exosomes and their role as biomarkers in disease progression. However, there are significant administrative and technological obstacles that need to be overcome to fully harness the potential of exosome drug delivery systems.

DNA methylation of promoter regions is often associated with epigenetic silencing of gene expression, and DNA methyltransferase (DNMTs) has been used to suppress gene expression. In order to explore the synergistic roles of two methyltransferase members Dnmt3a and Dnmt1, we constructed expression plasmid that could express a recombinant DNMTs consisting of the C‐terminal domains of both Dnmt3a and Dnmt1 fused to a zinc finger domain which binds to the PD‐L1 promoter of human prostate cancer cells (DU145). Programmed death ligand 1 (PD‐L1, B7‐H1, CD‐274) is a transmembrane protein widely expressed on antigen‐presenting and other immune cells. The interaction of PD‐L1 with its receptor PD‐1 is considered an ‘immune checkpoint' for possible cancer therapy. DU145 cells treated with the Dnmt3aC‐1C plasmid showed significantly reduced expression of PD‐L1 as compared to Dnmt3aC or Dnmt1C alone. Our results show that the fusion of Dnmt1 improves the methylation activity of Dnmt3a and enhances its biological functions. This combinatorial strategy can be used to better control PD‐L1 expression to support cytotoxic T lymphocytes (CTL) response against tumors.

Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants.