Toll‑like receptor 3 ligands for breast cancer therapies (Review).

Breast cancer is the most common cause of cancer worldwide and is the leading cause of mortality for women across most of the world. Immunotherapy is a burgeoning area of cancer treatment, including for breast cancer; these are therapies that harness the power of the immune system to clear cancerous cells. Toll-like receptor 3 (TLR3) is an RNA receptor found in the endosome, and ligands that bind to TLR3 are currently being tested for their efficacy as breast cancer immunotherapeutics.

TAK-242 treatment and its effect on mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

Purpose: Intervertebral disc (IVD) degeneration is accompanied by mechanical and gene expression changes to IVDs. SPARC-null mice display accelerated IVD degeneration, and treatment with (toll-like receptor 4 (TLR4) inhibitor) TAK-242 decreases proinflammatory cytokines and pain. This study examined if chronic TAK-242 treatment impacts mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

Two DExD/H-box helicases, DDX3 and DHX9, identified in rainbow trout are able to bind dsRNA.

In mammals, the multifunctional DExH/D-box helicases, DDX3 and DHX9, are nucleic acid sensors with a role in antiviral immunity; their role in innate immunity in fish is not yet understood. In the present study, full-length DDX3 and DHX9 coding sequences were identified in rainbow trout (Oncorhynchus mykiss). Bioinformatic analysis demonstrated both deduced proteins were similar to those of other species, with ~80% identity to other fish species and ~70-75% identity to mammals, and both protein sequences had conserved domains found amongst all species.

In vitro transcribed dsRNA limits viral hemorrhagic septicemia virus (VHSV)-IVb infection in a novel fathead minnow (Pimephales promelas) skin cell line.

The farming of baitfish, fish used by anglers to catch predatory species, is of economic and ecological importance in North America. Baitfish, including the fathead minnow (Pimephales promelas), are susceptible to infection from aquatic viruses, such as viral hemorrhagic septicemia virus (VHSV). VHSV infections can cause mass mortality events and have the potential to be spread to novel water bodies through baitfish as a vector.

Understanding Viral dsRNA-Mediated Innate Immune Responses at the Cellular Level Using a Rainbow Trout Model.

Viruses across genome types produce long dsRNA molecules during replication [viral (v-) dsRNA]. dsRNA is a potent signaling molecule and inducer of type I interferon (IFN), leading to the production of interferon-stimulated genes (ISGs), and a protective antiviral state within the cell. Research on dsRNA-induced immune responses has relied heavily on a commercially available, and biologically irrelevant dsRNA, polyinosinic:polycytidylic acid (poly I:C).

Visualizing Virus-Derived dsRNA Using Antibody-Independent and -Dependent Methods.

Long double-stranded (ds) RNA molecules are produced as a byproduct of viral replication. Studying virus-derived dsRNA is important for understanding virus replication, understanding host responses to virus infections, and as a diagnostic tool for virus presence and replication. Here, we describe four different techniques for visualizing dsRNA; two antibody-dependent methods (immunoblotting and immunocytochemistry), as well as two antibody-independent methods (differential digestion and acridine orange staining).

Scavengers for bacteria: Rainbow trout have two functional variants of MARCO that bind to gram-negative and -positive bacteria.

Class A scavenger receptors (SR-As) are a family of surface-expressed receptors who bind a wide range of polyanionic ligands including bacterial components and nucleic acids and play a role in innate immunity. Macrophage receptor with collagenous structure (MARCO) is a SR-A family member that has been studied in mammals largely for its role in binding bacteria. To date there is little information about SR-As in general and MARCO specifically in fish, particularly what ligands individual SR-A family members bind remains largely unknown.

Identifying connexin expression and determining gap junction intercellular communication in rainbow trout cells.

Gap junctions are groups of membrane-bound channels that allow the passage of small molecules and ions between cells, permitting cell-cell communication. Because of their importance in cell homeostasis, gap junction presence and function were characterized in three commonly studied rainbow trout cell lines, namely RTgill-W1, RTgutGC, and RTG-2. Firstly, gap junction presence was determined by screening for gap junction protein alpha 7 and alpha 1 (GJA7 and GJA1) presence at the transcript level and GJA7 at the protein level.

Fish interferon-stimulated genes: The antiviral effectors.

Type I interferons (IFN) are the cornerstone cytokine of innate antiviral immunity. In response to a viral infection, IFN signaling results in the expression of a diverse group of genes known as interferon-stimulated genes (ISGs). These ISGs are responsible for interfering with viral replication and infectivity, helping to limit viral infection within a cell.

Length-dependent innate antiviral effects of double-stranded RNA in the rainbow trout (Oncorhynchus mykiss) cell line, RTG-2.

Effectively all viruses produce long dsRNA during their replicative cycle. In mammals long dsRNA molecules induce a robust response through the production of type 1 interferon, interferon-stimulated genes (ISGs) and an antiviral state. This response is less well understood in fish.

Class-A scavenger receptor function and expression in the rainbow trout (Oncorhynchus mykiss) epithelial cell lines RTgutGC and RTgill-W1.

Class A scavenger receptors (SR-As) are cell surface receptors that bind a range of ligands, including modified low-density lipoproteins (mLDLs) and nucleic acids. Due to their ability to bind extracellular dsRNA, SR-As play an important role in the viral dsRNA initiated immune pathway. Most research on SR-As has focused on mammalian models, and there has been limited research on SR-As in fish.