Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1.

Background: Influenza A (H1N1) virus is an acute respiratory infectious disease that causes massive morbidity and mortality worldwide. As an essential trace element, selenium is widely applied in the treatment of various diseases because of its functions of enhancing immune response, antioxidant and antiviral mutation. In this study, we constructed the selenium-containing metal complex drug delivery system Ru(biim)(PhenSe)2 (RuSe), and investigated the anti-influenza virus efficacy and the potential antiviral mechanism for RuSe. Methods: The inhibitory effect of RuSe on influenza-mediated apoptosis was examined by cell count assay, cell cycle assay, Annenxin-V assay, TUNEL-DAPI assay and reactive oxygen species level determination. Virulence assay, PCR and neuraminidase inhibition assay revealed the inhibition of RuSe on influenza virus. At the level of animal experiments, two animal models were used to clarify the role of RuSe through HE staining, immunohistochemical staining, cytokine determination, selenium metabolism determination and selenium protein expression level determination. Results: The results of this study confirm that RuSe enhances the expression levels of selenium proteins GPx1 and TrxR1 by regulating selenium metabolism, thereby inhibiting viral replication and assembly and regulating virus-mediated mitochondria-related apoptosis. On the other hand, animal experiments show that RuSe can reduce lung tissue inflammation and inhibit lung tissue cell apoptosis in mice, and improve the survival state of mice. In addition, RuSe significantly improves the low immune response of Se-deficient mice by regulating selenium metabolism, and effectively alleviated lung fibrosis and lung tissue apoptosis in Se-deficient mice. Conclusions: This study suggests that RuSe provides a promising new approach for the clinical treatment of influenza virus.

Selenium Atom-Polarization Effect Determines TrxR-Specific Recognition of Metallodrugs.

Thioredoxin reductase (TrxR) is highly overexpressed in cancer cells to promote malignant tumor survival. Designing drugs that inhibit TrxR activity is a promising approach to achieve highly effective cancer chemotherapy. However, the selectivity of TrxR inhibitors continue to be a challenge for scientists. In this work, we demonstrate a new strategy to selectively inhibit TrxR through constructing electrophilic center -N-Se(δ+)-N- by using the polarization effect of the selenium atom. The constructed electrophilic center interacts noncovalently with the active motif of TrxR to avoid the interference of other residues in human tissues, thereby selectively inhibiting intracellular TrxR activity. Computational and experimental analysis confirms that the formed electrophilic selenium center preferred to attack the SeC residues in the redox active center of TrxR at the 498 site through strong noncovalent interactions. Both in vitro and in vivo experimental results confirmed that this strategy can significantly improve the anticancer effect. This study may provide a novel route to design highly effective and selective chemotherapeutic drugs.

Recombinant human thyroid-stimulating hormone as an alternative for thyroid hormone withdrawal in thyroid cancer management.

PURPOSE OF REVIEW: The purpose of the review is to summarize the current findings of using recombinant human thyroid-stimulating hormone (rhTSH, also known as Thyrogen) as adjuvant stimulation for diagnostic monitoring, thyroid remnant ablation, and treatment of metastatic thyroid cancer. RECENT FINDINGS: A negative Thyrogen-stimulated thyroglobulin level has a negative predictive value of up to 98.5%. Therefore, it is unnecessary to repeat a Thyrogen-stimulated thyroglobulin level in the surveillance of patients with a negative result. There are no significant differences found in the rate of recurrence or persistent disease between Thyrogen-assisted and thyroid hormone withdrawal-ablated patient groups. Studies have shown that rapid clearance of excess radioiodine from the body in the euthyroid state with Thyrogen stimulation has significantly reduced whole body radiation exposure as compared with the hypothyroid state in withdrawal patients. SUMMARY: Thyrogen-assisted diagnosis and radioiodine ablation of thyroid remnant provide a reliable tool in the management of thyroid cancer without sacrificing patient quality of life. We believe that the use of Thyrogen for radioiodine treatment of metastatic thyroid cancer may also provide a better option due to its rapid preparation time and safety. Further prospective studies are required for the assessment of long-term outcomes.