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.

BACKGROUND: Selenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure.
METHODS: We retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium.
RESULTS: Selenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 μg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine.
CONCLUSIONS: Selenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.

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.

Bacteria are increasingly relying on biofilms to develop resistance to antibiotics thereby resulting in their failure in treating many infections. In spite of continuous research on many synthetic and natural compounds, ideal anti-biofilm molecule is still not found thereby warranting search for new class of molecules. The current study focuses on exploring anti-biofilm potential of selenocystine against respiratory tract infection (RTI)-causing bacteria. Anti-bacterial and anti-biofilm assays demonstrated that selenocystine inhibits the growth of bacteria in their planktonic state, and formation of biofilms while eradicating preformed-biofilm effectively. Selenocystine at a MIC50 as low as 42 and 28 μg/mL effectively inhibited the growth of Klebsiella pneumonia and Pseudomonas aeruginosa. The antibacterial effect is further reconfirmed by agar cup diffusion assay and growth-kill assay. Selenocystine showed 30-60% inhibition of biofilm formation in K. pneumonia, and 44-70% in P. aeruginosa respectively. It also distorted the preformed-biofilms by degrading the eDNA component of the Extracellular Polymeric Substance matrix. Molecular docking studies of selenocystine with quorum sensing specific proteins clearly showed that through the carboxylic acid moiety it interacts and inhibits the protein function, thereby confirming its anti-biofilm potential. With further validation selenocystine can be explored as a potential candidate for the treatment of RTIs.

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.

Organoselenium drugs like selenourea (SeU) and selenocystine (SeC) are found to exhibit several medicinal properties and have reported roles in the field of cancer prevention. However, studies related to their interactions with the major erythroid protein, haemoglobin (HbA) are still in dearth despite being of prime importance. In view of this, it was considered essential to investigate the interaction of these two anticancer drugs with Hb. Both the drugs showed significant changes in absorption spectra of Hb at wavelength of maximum absorption (λmax) 630 nm. SeU itself had no effect on the absorbance value at 630 nm with respect to time even with 400 µM concentration. However, it was rapidly converted to nanoselenium in presence of nitrite and there was an increase in the absorbance rate at 630 nm from 3.39 × 10-3 min-1 (without nitrite) to 8.94 × 10-3 min-1 in presence of nitrite (200 µM) owing to the generation of reactive oxygen species in the medium. Although the generation and increase in peak intensity at 630 nm in Hb generally indicates the formation and rise in the levels of methaemoglobin (metHb), nanoselenium was observed to follow a different path. Instead of causing oxidation of Fe2+ to Fe3+ responsible for metHb formation, nanoselenium was found to interact with the protein part, thereby causing changes in its secondary structure which is reflected in the increasing absorbance at 630 nm. SeC, however, showed a different effect. It was shown to act as a novel agent to reduce nitrite-induced metHb formation in a dose-dependent manner. The efficiency of SeC was again found to be less in diabetic blood samples as compared to the non-diabetic ones. For similar ratio of metHb to SeC (1:8), % reduction of metHb was found to be 27.46 ± 0.82 and 16.1 ± 2.4 for non-diabetic and diabetic samples, respectively, with a two tailed P-value much <0.05 which implies that the data are highly significant.

Selenium containing drugs like selenomethionine, selenocystine, selenourea and methylseleninic acid are reported to exhibit potential anticancer effect. However, these anticancer drugs may exert adverse effects when used over a prolonged period. Little is known about the interaction of these selenium containing drugs with the vital erythroid protein hemoglobin. In this work a comparative study of the interaction of organo-selenium drugs with hemoglobin and heme moiety has been performed using different spectroscopic techniques to find out their role on drug induced methemoglobinemia. We found that though these selenium containing drugs have similar binding affinity towards hemoglobin, they have differential interactions with the heme group. Isothermal calorimetric titration study showed that selenourea has the lowest binding affinity (Kd 19.28 μM) towards HbA as compared to other drugs, selenomethionine, selenocystine and methylseleninic acid (Kd 7.69 μM, 4.88 μM and 10.5 μM at 37 °C respectively). This result is also supported by the molecular docking study. Methylseleninic acid was found to have detrimental effects on nitrite induced methemoglobinemia, a hematological disorder caused due to excessive conversion of Fe2+ to Fe3+ in hemoglobin. Hence the results of the study would help to develop a better insight on the mechanism of action and anticipate the toxicity of these drugs which require further optimization before their actual use in the treatment of cancer.

Plant biofortification with selenium in interaction with the application of an arbuscular mycorrhizal fungi (AMF)-based formulate,with the goal of enhancing Se bioavailability, is beneficial for the development of the environmentally friendly production of functional food with a high content of this microelement. Research was carried out in order to assess the effects of an AMF-based formulate and a non-inoculated control in factorial combination with two selenium treatments with an organic (selenocystine) or inorganic form (sodium selenate) and a non-treated control on the yield, quality, antioxidant properties, and elemental composition of shallot (Allium cepa L. Aggregatum group). Selenocystine showed the best effect on the growth and yield of mycorrhized plants, whereas sodium selenate was the most effective on the non-inoculated plants. The soluble solids, total sugars, monosaccharides, titratable acidity, and proteins attained higher values upon AMF inoculation. Sodium selenate resulted in higher soluble solids, total sugars and monosaccharide content, and titratable acidity than the non-treated control, and it also resulted in higher monosaccharides when compared to selenocystine; the latter showed higher protein content than the control. Calcium, Na, S, and Cl bulb concentrations were higher in the plants inoculated with the beneficial microorganisms. Calcium and sodium concentrations were higher in the bulbs of plants treated with both the selenium forms than in the control. Selenocystine-treated plants showed enhanced accumulation of sulfur and chlorine compared to the untreated plants. The AMF inoculation increased the bulb selenium content by 530%, and the Se biofortification with selenocystine and sodium selenate increased this value by 36% and 21%, respectively, compared to control plants. The AMF-based formulate led to increases in ascorbic acid and antioxidant activity when compared to the non-inoculated control. The bulb ascorbic acid was increased by fortification with both selenium forms when compared to the non-treated control. The results of our investigation showed that both AMF and selenium application represent environmentally friendly strategies to enhance the overall yield and quality performances of shallot bulbs, as well as their selenium content.

Selenocysteine (Sec) residue cannot be directly attached to a peptide sequence unless the selenol form is protected beforehand and several problems have been reported in the preparation of Sec building blocks. In this article a series of selenocystine, the oxidized form of Sec, containing peptides has been synthesized using a new methodology, where Boc-NH-chloroalanine is coupled with methyl ester protected residues (Ala, Met, Phe) using DCC/HOBt as the coupling reagents providing di- and tripeptides. Further, the treatment of disodium diselenide with chloroalanine peptides (Boc-ClAla-Ala-OMe, Boc-ClAla-Met-OMe and Boc-ClAla-Ala-Phe-OMe) afforded the respective selenocystine-containing peptides (Boc-Sec-Ala-OMe, Boc-Sec-Met-OMe and Boc-Sec-Ala-Phe-OMe).

A novel selenium based screen-printed electrode was developed based on the immobilization of selenocystine on aryl diazonium salt monolayers anchored to a carbon-nanofiber screen-printed electrode support (SeCyst-SPCNFE). SeCyst-SPCNFE was analytically compared to a screen-printed carbon nanofiber electrode modified with L-Cystine (Cyst-SPCNFE) for the determination of Pb(II) and Cd(II) by stripping voltammetric techniques. Their analytical performance suggests that SeCyst-SPCNFE could be a much better alternative for metal ion determination at trace levels than Cyst-SPCNFE. The proposed electrode was successfully applied for the simultaneous voltammetric determination of trace Pb(II) and Cd(II) in a wastewater reference material with a very high reproducibility (3.2%) and good trueness (2.6%).