BACKGROUND: Human Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells.
METHODS: The experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential.
RESULTS: In the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways.
CONCLUSIONS: SeC might provide an effective selenium species with antiviral properties for the therapies against HAdV-14.

Overproduction of reactive oxygen species (ROS) and cumulative oxidative stress induce the degeneration of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) of PD patients. Due to its redox property, melanin-like polydopamine (PDA) has been studied for its ability to remove ROS with a series of antioxidant enzyme mimetic activities including superoxide dismutase (SOD) and catalase (CAT). Glutathione peroxidase (GPx) is important for maintaining ROS metabolic homeostasis, but only a few GPx-like nanozymes have been studied for in vivo therapy. As we know, selenocysteine is essential for the antioxidant activity of GPx. Hence, we co-synthesized PDA with selenocystine (SeCys) to prepare a nanocomposite (PDASeCys) with GPx-like activity. The results showed that the PDASeCys nanocomposite has the same CAT and SOD enzymatic activities as PDA but better free radical scavenging efficiency and additional GPx enzymatic activity than PDA. In the 1-methyl-4-phenyl-pyridine ion (MPP+)-induced PD cell model, PDASeCys could increase intracellular GPx levels effectively and protect SH-SY5Y neuronal cells from oxidative stress caused by MPP+. In vivo, the PDASeCys nanocomposite effectively inhibited 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPTP)-induced Parkinson-related symptoms of mice when it was injected into the substantia nigra (SN). This polydopamine-based nanocomposite containing selenocystine with a variety of enzymatic activities including GPx-like activity synthesized by a one-pot method provides convenience and safety in the neuromelanin-like nanozyme-based therapeutic strategy for oxidative stress-induced PD.

Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs\' local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic BCL-xl/w genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

UNASSIGNED: Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids - selenocysteine and selenocystine - on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD.
UNASSIGNED: C57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis.
UNASSIGNED: Selenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids.
UNASSIGNED: We found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.

BACKGROUND: The unique hypervariable C-terminal region (HVR) of K-Ras4B, one of the most frequently mutated proteins in many powerful cancers, contains a C-terminal farnesylated and methylated Cys and a poly-lysine motif, which decides the association of K-Ras4B to the inner leaflet of plasma membrane for activating the downstream signaling activity. In our previous work, we inserted an additional Cys in K-Ras4B HVR peptide synthesis for NCL in the semi-synthesis of K-Ras4b protein, but it is not suitable for application in protein dimerization research. The recently developed selenocysteine (Sec, U) mediated native chemical ligation reaction followed by selective deselenization, which can help to broaden the scope of protein synthesis, requires the generation of the peptide fragment with an N-terminal Sec.
OBJECTIVE: To synthesize K-Ras4B HVR peptide containing both N-terminal Sec and C-terminal farnesylated and methylated Cys to achieve traceless protein semi-synthesis.
RESULTS: We have developed a facile synthesis approach for producing Boc-Sec)2-OH using economic Se powder, which can facilitate scaling up preparation of peptides containing Sec at the N-terminus. Furthermore, we synthesized K-Ras4B HVR peptide containing selenocystine by utilization of Boc-Sec)2-OH. Finally, we took K-Ras4B HVR peptide as an example to test the compatibility of farnesylation reaction at Cys with the N-terminal Sec)2, and the farnesyl group was successfully added to the thiol group of Cys.

UNASSIGNED: Selenocystine (SeC) is a nutritionally available selenoamino acid presenting novel anticancer potential against human cancers. However, neither the effects nor mechanism of SeC against choriocarcinoma growth has been clarified yet. This study investigated the anticancer effects and mechanism of SeC against JEG-3 human choriocarcinoma growth in vitro and in vivo.
UNASSIGNED: The in vitro anticancer efficiency was evaluated with cell viability, apoptosis, and oxidative stress. JEG-3 cell viability was determined with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell cycle distribution and apoptosis were examined by flow cytometric analysis. Oxidative damage was detected with immunofluorescence and western blotting. The in vivo anticancer efficiency was evaluated in immunodeficient mouse model of choriocarcinoma. The mechanism was also investigated.
UNASSIGNED: SeC dose and time dependently inhibited the viability of JEG-3 cells in vitro. The result of flow cytometry (FCM) analysis showed that obvious S-phase arrest and cell apoptosis were initiated by SeC in JEG-3 cells, which was further convinced by the decreased levels of cyclin A, poly-ADP-ribose polymerase cleavage, and activation of caspase-3,-7, and-9. In addition, SeC resulted in significant generation of reactive oxygen species (ROS) and superoxide anion, followed by the activation of DNA damage. However, SeC-induced oxidative damage and apoptosis were effectively blocked after ROS inhibition. Further investigation indicated that SeC effectively suppressed JEG-3 choriocarcinoma tumor xenograft growth in vivo. The mechanism may be the induction of cell apoptosis and oxidative damage through inhibiting cell proliferation (Ki-67) and angiogenesis (CD-31).
UNASSIGNED: Our findings supported that human choriocarcinoma growth could be inhibited by SeC in vitro and in vivo through triggering oxidative damage-mediated S-phase arrest and apoptosis. Thus, SeC may be promising in the treatment of human choriocarcinoma.

We present a highly selective and sensitive colorimetric method for the detection of selenocystine (SeCys) coexisting with other amino acids, especially cysteine (Cys) using the gold nanoparticles (AuNPs). Firstly, Cys was oxidized to cystine (Cys-Cys) by dissolved oxygen under Cu2+ catalysis in the pre-reaction, which eliminated the interference of Cys in the SeCys sensing process. Then SeCys induced the rapid aggregation of AuNPs through Au-Se bond and complex formation of Cu2+-SeCys in the colorimetric reaction, in which the color change of AuNPs from red to blue or purple with the naked eye detection or with a UV-vis spectrophotometric determination. The concentration of SeCys was quantified by the value at 670 nm from the second-derivative SPR absorbance spectrum. The linear range was from 2 μM to 14 μM with correlation coefficient of 0.999 and a detection limit (LOD) was 0.14 μM. Moreover, the colorimetric response of AuNPs exhibited remarkable specificity to SeCys coexisting with 18 amino acids in a simulation sample, in which the total concentration of Cys and Cys-Cys was less than 15 μM and the each concentration of other 16 common amino acids was 10 μM.

As nitric oxide (NO) plays vital roles in the cardiovascular system, incorporating this molecule into cardiovascular stents is considered as an effective method. In the present study, selenocystine with different chirality (i.e., l- and d-selenocystine) was used as the catalytic molecule immobilized on TiO2 films for decomposing endogenous NO donor. The influences of surface chirality on NO release and platelet behavior were evaluated. Results show that although the amount of immobilized l-selenocystine on the surface was nearly the same as that of immobilized d-selenocystine, in vitro catalytic NO release tests showed that l-selenocystine immobilized surfaces were more capable of catalyzing the decomposition of S-nitrosoglutathione and thus generating more NO. Accordingly, l-selenocystine immobilized surfaces demonstrated significantly increased inhibiting effects on the platelet adhesion and activation, when compared to d-selenocystine immobilized ones. Measurement of the cGMP concentration of platelets further confirmed that surface chirality played an important role in regulating NO generation and platelet behaviors. Additionally, using bovine serum albumin and fibrinogen as model proteins, the protein adsorption determined with quartz crystal microbalance showed that the l-selenocystine immobilized surface enhanced protein adsorption. In conclusion, surface chirality significantly influences protein adsorption and NO release, which may have significant implications in the design of NO-generating cardiovascular stents.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective treatment options. New therapeutic approaches are urgently needed to improve the prognosis of TNBC. Here we demonstrated that a redox modulator, selenocystine (SeC), significantly inhibits TNBC cell proliferation in a dose- and time-dependent manner. Through cell apoptosis assays and cell cycle distribution analyses, we have shown that the in vitro inhibitory effect of SeC on TNBC cells can be attributed to the induction of apoptosis and the S-phase arrest in a dose-dependent manner. Therefore, this finding implies that SeC potentially is a novel therapeutic agent for TNBC.