Magnetotactic bacteria AMB-1 with active deep tumor penetrability for magnetic hyperthermia of hypoxic tumors.

Tumor hypoxia is a great physiological barrier for tumor treatment. The development of efficient detection and treatment methods for tumor hypoxia has great scientific and clinical significance. In this work, we investigated the potential of magnetotactic bacteria AMB-1 for magnetic resonance imaging (MRI)-guided magnetic hyperthermia treatment of hypoxic tumors. Our investigations reveal that AMB-1 bacteria can selectively migrate to the hypoxic regions of solid tumors due to their anaerobic characteristics, showing active deep tumor penetrability. Moreover, AMB-1 bacteria exhibit high MRI contrast and magnetic heating performances because of the excellent magnetic performance of their magnetosomes. In vivo studies demonstrate that AMB-1 can not only generate T2-weighted contrast signals in tumor tissue, but also efficiently ablate hypoxic solid tumors through the magnetic hyperthermia effect. We believe that this novel microbial therapy can be a potential weapon for hypoxic tumor treatment.

Engineering manganese ferrite shell on iron oxide nanoparticles for enhanced T1 magnetic resonance imaging.

Doping Mn (II) ions into iron oxide (IO) as manganese ferrite (MnIO) has been proved to be an effective strategy to improve T1 relaxivity of IO nanoparticle in recent years; however, the high T2 relaxivity of MnIO nanoparticle hampers its T1 contrast efficiency and remains a hurdle when developing contrast agent for early and accurate diagnosis. Herein, we engineered the interfacial structure of IO nanoparticle coated with manganese ferrite shell (IO@MnIO) with tunable thicknesses. The Mn-doped shell significantly improve the T1 contrast of IO nanoparticle, especially with the thickness of ∼0.8 nm. Compared to pristine IO nanoparticle, IO@MnIO nanoparticle with thickness of ∼0.8 nm exhibits nearly 2 times higher T1 relaxivity of 9.1 mM-1s-1 at 3 T magnetic field. Moreover, exclusive engineering the interfacial structure significantly lower the T2 enhancing effect caused by doped Mn (II) ions, which further limits the impairing of increased T2 relaxivity to T1 contrast imaging. IO@MnIO nanoparticles with different shell thicknesses reveal comparable T1 relaxation rates but obvious lower T2 relaxivities and r2/r1 ratios to MnIO nanoparticles with similar sizes. The desirable T1 contrast endows IO@MnIO nanoparticle to provide sufficient signal difference between normal and tumor tissue in vivo. This work provides a detailed instance of interfacial engineering to improve IO-based T1 contrast and a new guidance for designing effective high-performance T1 contrast agent for early cancer diagnosis.

Molecular and functional characterization of ovis aries IFN-epsilon.

Interferon-epsilon (IFN-ε) is a type I IFN playing an essential role in innate and adaptive immunity against viral infection. Ovis aries IFN-ε (OvIFN-ε), consisting of 582 bp and which encodes a protein of 193 amino acids containing a signal peptide of 21 amino acids, was cloned and characterized. OvIFN-ε shares 51.6∼ 86.5% similarity to other species of IFN-ε, and evolves from the IFN-ε branch but not the other types of IFN. Additionally, OvIFN-ε gene is well conserved during evolution, and is highly transcribed in the liver, lung, brain, skin, ovary and uterus. Recombinant protein of OvIFN-ε was expressed in Escherichia coli and purified with nickel chelated column, which exhibited broad antiviral activity in vitro, sensitivity of trypsin, and stability of pH and temperature to some extent. Furthermore, OvIFN-ε could induce the transcription of ISG15, Mx1 and OAS in a time-dependent manner, as well as inhibit the VSV and BVDV replication in Ovis aries peripheral blood lymphocyte cells and MDBK cells. This study revealed OvIFN-ε has the typical characterization of type I IFNs and exerts antiviral activity against VSV and BVDV, and induces the expression of ISGs, which not only enriches the understanding of IFN-ε, but also facilitates further research on the antiviral defense responses of Ovis aries.

Characterization and signaling pathway analysis of interferon-kappa in bovine.

A bovine interferon-kappa (BoIFN-κ) gene was amplified, which encodes a protein of 215 amino acids sharing 63% identity with human IFN-κ. BoIFN-κ was demonstrated to have antiviral and antiproliferative activities. Moreover, BoIFN-κ was shown to be highly sensitive to trypsin, however, it remained stable despite changes in pH and temperature. Result showed that BoIFN-κ can bind with bovine type I IFN receptors, and the antiviral activity can be blocked by antibodies against type I IFN receptors or BoIFN-κ. Additionally, BoIFN-κ can induce the transcription of Mx1, ISG15 and ISG56 gene, as well as the expression of Mx1 protein. The NF-κB, ISRE, and BoIFN-ß promoter can all be activated by BoIFN-κ. This study revealed that BoIFN-κ exhibits the typical characteristics of type I IFNs and exerts antiviral activity via activation of the JAK-STAT signaling pathway. Overall, these findings will enrich the current knowledge about IFN-κ and facilitate further research on the role of type I IFN in antiviral defense responses in bovine.