Calcium silicate biocomposites: effects of selenium oxide on the physico-mechanical features and theirin-vitrobiological assessments.

Bone tissue regenerative material serves as a prospective recovery candidate with self-adaptable biological properties of bio-activation, degradability, compatibility, and antimicrobial efficacy instead of metallic implants. Such materials are highly expensive due to chemical reagents and complex synthesis procedures, making them unaffordable for patients with financial constraints. This research produced an efficient bone tissue regenerative material using inexpensive naturally occurring source materials, including silica sand and limestone. The extracted SiO2and CaO particles (75:25 wt%) were subjected to hydrothermal synthesis (water treatment instead of chemical solvents) to produce the CaSiO3biomaterial (code: S). Selenium oxide was doped with calcium silicate at 3, 5, and 10 wt.% to enhance its properties, yielding biocomposite materials (i.e. S3, S5, and S10). The physico-mechanical properties of these materials were investigated with x-ray diffraction, Fourier transform infrared, FESEM-EDS, and micro-universal testing machine. The results revealed that the synthesized biocomposites have a crystalline wollastonite phase with a porously fused rough surface. From structural parametric calculations, we found that the biocomposites have reduced particle size and enhanced surface area due to the influence of selenium oxide. The biocomposite S10, having high SeO2content, attained the maximum compressive strength of 75.2 MPa.In-vitrostudies of bioactivity, biodegradability, biocompatibility, and antibacterial activity were performed. At 7 and 14 d of bioactivity, the synthesized biocomposites are capable of dissolving their ions into simulated body fluid (SBF) solution to precipitate hydroxyapatite and a required Ca/P ratio of 1.69 was achieved by S3. A comparative analysis has been performed on the degradation activity in Tris-HCl and the consequent pH changes during SBF treatment. The bio-analysis revealed that the biocomposite S3 shows enhanced bioactivity through a controlled degradation rate and secured cell viability of 88% at a concentration of 100 µg ml-1. It also offers significant bacterial inhibition potency againstE.coliandS.aureusbacteria.

Sensitive voltammetric quantification of carminic acid in candies using selenium dioxide nanoparticles based electrode.

Carminic acid is a food colorant which concentration has to be controlled due to the possible negative health effects. Sensitive voltammetric method is developed for carminic acid determination using electrode modified with SeO2 nanoparticles (SeO2 NPs) and hexadecyltriphenylphosphonium bromide (HDTPPB) acting as dispersive agent for nanoparticles and electrode surface co-modifier. SeO2 NPs of 37-45 nm are uniformly distributed at the electrode increasing its electroactive area (41 ± 2 vs. 8.9 ± 0.2 mm2 for bare glassy carbon electrode (GCE)). Electrochemical impedance spectroscopy data confirm an 18.3-fold decrease of charge transfer resistance compared to GCE (12.7 ± 0.3 vs. 232 ± 7 kΩ, respectively). In differential pulse mode, the linear dynamic ranges of carminic acid are 0.010-2.5 and 2.5-10 µmol L-1 with a detection limit of 3.4 nmol L-1. The method is successfully employed in candies and lozenges for sore throat treatment. The approach is simple, reliable, and can be used as an alternative to chromatography in routine analysis.

Sub-Flap Use of Nano-Selenium Oxide Solution Enhances Skin Flap Viability in Rats: Study the Novel Role of mTOR and p-mTOR Expression.

BACKGROUND: Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markers in rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. MATERIALS AND METHODS: Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. RESULTS: Treatment with NSeO significantly reduced necrosis (P<0.05). It also resulted in a decrease in MDA level (P<0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P<0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. CONCLUSION: NSeO can reduce flap necrosis and enhance tissue healing in rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Side-Chain Selenium-Grafted Polymers Combining Antiangiogenesis Treatment with Photodynamic Therapy and Chemotherapy.

The abnormal tumor vasculature in solid tumors creates hypoxia and leads to compromising the delivery and anticancer efficiency of nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability might normalize tumor vessels and improve the therapeutic effect of O2-related treatment like PDT. Herein, we designed and prepared ROS-responsive side-chain selenium-grafted polymers, which had potential antiangiogenic activity, as vehicles to load photodynamic therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR irradiation, the C-Se bonds on the side chain of polymers could be cleaved in the presence of 1O2 produced by Ce6 and further formed organic selenic acid through selenoxide elimination reaction. The generated seleninic acid could downregulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released oridonin could significantly increase the intracellular ROS concentration. Both could modulate cancer cells' microenvironment to reinforce PDT. Therefore, these nanomedicines could be a good candidate for synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.

Redox-Mediated Reversible Supramolecular Assemblies Driven by Switch and Interplay of Peptide Secondary Structures.

The construction of reversible supramolecular self-assembly in vivo remains a significant challenge. Here, we demonstrate the redox-triggered reversible supramolecular self-assembly governed by the "check and balance" of two secondary conformations within a brushlike peptide-selenopolypeptide conjugate. The conjugate constitutes a polypeptide backbone whose side chain contains selenoether functional moieties and double bonds to be readily grafted with ß-sheet-prone short-peptide NapFFC. The backbone of the conjugate initially assumes a robust and rigid α-helical conformation, which inhibits the supramolecular assembly of the short peptide in the side chain and yields an overall irregular aggregate morphology under native/reduced conditions. Upon oxidation of the selenoether to more hydrophilic selenoxide, the backbone helix switches to a flexible and disordered conformation, which unleashes the side-chain NapFFC self-assembly into nanofibrils via the adoption of ß-sheet conformation. The reversible switch of the supramolecular morphology enables efficient loading and tumor-microenvironment-triggered release of anticancer drugs for in vivo cancer treatment with satisfactory efficacy and biocompatibility. The interplay and interaction between two well-defined secondary structures within one scaffold offer tremendous opportunity for the design and construction of functional supramolecular biomaterials.

Expanding the Toolbox for Peptide Disulfide Bond Formation via l-Methionine Selenoxide Oxidation.

In this study, l-methionine selenoxide (MetSeO) was used as an oxidant for the construction of peptide disulfide bonds. Excellent yields for various disulfide-containing peptides were achieved via the MetSeO oxidation method in different solvents and on a resin. Most importantly, the construction of disulfide bonds can be performed in the trifluoroacetic acid cocktail used for the cleavage of peptides from the resin, which obviates the steps of peptide purification and lyophilization. This facilitates and simplifies the synthesis of disulfide-containing peptides. Kinetic and mechanistic studies of the reaction between MetSeO and dithiothreitol (DTT, a model compound of dicysteine-containing peptide) show that the reaction is first order in both [MetSeO] and [DTT], and a reaction mechanism is proposed that can help us gain insights into the reaction of the oxidative synthesis of disulfide bonds via MetSeO oxidation.

Organoselenium-based BOPHY as a sensor for detection of hypochlorous acid in mammalian cells.

Phenylselenide substituted BOPHY probes (BOPHY-SePh and PhSe-BOPHY-SePh) were synthesized and characterized by NMR spectroscopy and single-crystal XRD. Both the probes selectively detect HOCl in water with high sensitivity over other reactive oxygen species. A fluorescence "turn-on" event was attained due to cease of the PET process through transformation of selenide to selenoxide. Both the probes react with HOCl in less than 1 s. PhSe-BOPHY-SePh probe depicted low background fluorescence due to presence of two phenylselenide groups at BOPHY. PhSe-BOPHY-SePh probe has a low detection limit (0.63 µM) than BOPHY-SePh probe (1.08 µM). The bioimaging studies of both the probes were carried out in MCF 7 cells. Both the probes exhibited a good fluorescence response for HOCl in vitro and in mammalian cells. In addition, the probes showed reversibility with all bio-thiols, which was validated in MCF 7 cells using GSH.

Controllable Radical Polymerization of Selenide Functionalized Vinyl Monomers and Its Application in Redox Responsive Photonic Crystals.

Selenium-containing monomer (p-phenylseleno) styrene (p-PhSeSt) is polymerized by reversible addition-fragmentation chain transfer polymerization. Polymer, (P(p-PhSeSt)), with controlled molecular weight and narrow molecular weight is obtained. The selenide moiety in obtained P(p-PhSeSt) can be selectively oxidized to selenoxide or selenone groups by H2 O2 or NaClO, respectively. These oxidized groups can be further reduced to selenide by Na2 S2 O4 . The structure changing of polymers during such redox cycle is characterized by nuclear magnetic resonance, X-ray photoelectron spectroscopy, and size exclusion chromatography. Properties, such as thermal performance, glass transition temperature, water contact angles, and refractive indices, of the resulting polymers are systematically investigated before and after oxidation. In addition, SiO2 inverse opal photonic crystal (IOPC) is fabricated by sacrificial polymer colloidal template method. Owing to changes of the RIs of P(p-PhSeSt) after selective oxidation, the predictable change of PC bandgap as a redox-responsive PC sensor is successfully realized, which provides new perspectives for modulating photonic crystals.

Selenium-doped hydroxyapatite nanoparticles for potential application in bone tumor therapy.

In the present study we have studied the incorporation and release of selenite ions (SeO32-) in hydroxyapatite nanoparticles for the treatment of bone tumors. Two types of selenium-doped hydroxyapatite (HASe) nanoparticles (NPs) with a nominal Se/(P + Se) molar ratio ranging from 0.01 up to 0.40 have been synthesized by a new and mild wet method. The two series of samples were thoroughly characterized and resulted to be slightly different in chemical composition, but they had similar properties in terms of morphology and degree of crystallinity. Selenium release from HASe was investigated under neutral and acidic conditions to simulate both healthy tissues and the low-pH environment surrounding a tumor mass, respectively. The comparison of the release profiles at two pH values clearly showed the possibility of modulating the Se release by simply changing the amount of Se in the HASe particles. The correlation between the physicochemical properties of HASe and their dissolution as a function of pH has been also investigated to facilitate future application of the NPs as chemotherapeutic adjuvant agents. Finally, the cytotoxic activity of HASe was evaluated using prostate (PC3) and breast (MDA-MB-231) cancer cells as well as healthy human bone marrow stem cells (hBMSc). HASe NPs exerted a good cytocompatibility at low concentration of Se but, with high Se doping concentration, they displayed strong cytotoxicity.

Can Selenoenzymes Resist Electrophilic Modification? Evidence from Thioredoxin Reductase and a Mutant Containing α-Methylselenocysteine.

Selenocysteine (Sec) is the 21st proteogenic amino acid in the genetic code. Incorporation of Sec into proteins is a complex and bioenergetically costly process that evokes the following question: "Why did nature choose selenium?" An answer that has emerged over the past decade is that Sec confers resistance to irreversible oxidative inactivation by reactive oxygen species. Here, we explore the question of whether this concept can be broadened to include resistance to reactive electrophilic species (RES) because oxygen and related compounds are merely a subset of RES. To test this hypothesis, we inactivated mammalian thioredoxin reductase (Sec-TrxR), a mutant containing α-methylselenocysteine [(αMe)Sec-TrxR], and a cysteine ortholog TrxR (Cys-TrxR) with various electrophiles, including acrolein, 4-hydroxynonenal, and curcumin. Our results show that the acrolein-inactivated Sec-TrxR and the (αMe)Sec-TrxR mutant could regain 25% and 30% activity, respectively, when incubated with 2 mM H2O2 and 5 mM imidazole. In contrast, Cys-TrxR did not regain activity under the same conditions. We posit that Sec enzymes can undergo a repair process via ß-syn selenoxide elimination that ejects the electrophile, leaving the enzyme in the oxidized selenosulfide state. (αMe)Sec-TrxR was created by incorporating the non-natural amino acid (αMe)Sec into TrxR by semisynthesis and allowed for rigorous testing of our hypothesis. This Sec derivative enables higher resistance to both oxidative and electrophilic inactivation because it lacks a backbone Cα-H, which prevents loss of selenium through the formation of dehydroalanine. This is the first time this unique amino acid has been incorporated into an enzyme and is an example of state-of-the-art protein engineering.

Continuous Bioinspired Oxidation of Sulfides.

A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen peroxide as the final oxidant. The scope of the proposed methodology was investigated using aryl alkyl sulfides, aryl vinyl sulfides, and dialkyl sulfides as substrates, evidencing, in general, a good applicability. The scaled-up synthesis of (methylsulfonyl)benzene was also demonstrated, leading to its gram-scale preparation.

Sustainable approach to almond skin mediated synthesis of tunable selenium microstructures for coating cotton fabric to impart specific antibacterial activity.

Currently, the synthesis of nanostructured inorganic materials with tunable morphology is still a great challenge. In this study, almond skin extract was employed for the biogenic synthesis of selenium nanoparticles with tunable morphologies such as rods and brooms. The effects of various synthesis parameters on morphologies were investigated using UV-Visible spectroscopy and scanning electron microscopy (SEM) which indicated that selenium brooms (SeBrs) were best synthesized using almond skin extract and optimized conditions of SeO2, ascorbic acid, pH, incubation temperature and time. Based on these results, the mechanism of SeBrs synthesis is proposed as having involved four stages such as nucleation, self-assembly, Ostwald ripening, and decomposition. Further, the test of antibacterial activity together with minimum inhibitory concentrations and minimum bactericidal concentrations indicated the selective, specific and good activity against B. subtilis. In addition, in situ coating of SeBrs on cotton fabric and its investigation by SEM demonstrated successful coating. Evident from plate-based assay and study of growth kinetics, coated fabric exhibited excellent anti-B. subtilis activity which demonstrated that biogenic SeBrs can be employed to coat cotton fabrics that can be used in operation theatres to reduce the episodes of Bacillus related Bacteraemia.

[3,3]-Sigmatropic Rearrangement/Haller-Bauer Reaction of Aryl Sulfoxides and Selenoxides with Difluoroenoxysilanes: Access to CF2H-Containing Chalcogenides.

A mild and general procedure for the difluoromethylation of organochalcogen compounds has been accomplished via sulfoxide and selenoxide-directed [3,3]-sigmatropic rearrangement/Haller-Bauer reaction with difluoroenoxysilanes. The reactions showed good functional group compatibility, wide substrate applicability, and facile scalability. The synthetic utility is highlighted by the iterative use of this protocol to construct multi-CF2H-containing chalcogenides and the late-stage modification of pharmaceuticals.

Metal organic framework UiO-66 and activated carbon composite sorbent for the concurrent adsorption of cationic and anionic metals.

A composite sorbent for the simultaneous removal of both Hg2+ and SeO32- from aqueous media was produced from the solvothermal synthesis of a zirconium metal organic framework, UiO-66, in the presence of activated carbon. The composite sorbent has a large surface area of 1051 m2 g-1 with crystalized porous structures and has strong thermal stability up to 600 °C. The contaminant uptake of the sorbent follows a Langmuir adsorption isotherm with maximum sorption capacity of 205 mg g-1 and 168 mg g-1 for Hg2+ and SeO32-, respectively. Scanning electron microscopy-energy dispersive spectroscopy results show that the Se regions overlap exclusively with Zr-rich regions suggesting that SeO32- adsorption depends entirely on the exposed UiO-66 surface. In addition, X-ray photoelectron spectroscopy spectra of Se 3d and Hg 4f showed the association of SeO32- and Hg2+ on the UiO-66 and carbon surfaces, respectively. The sorbent could facilitate the development of a single process for the simultaneous removal of cationic Hg and anionic Se as well as other similar ionic metals with opposite charges from aqueous media.

A multi-omics approach reveals mechanisms of nanomaterial toxicity and structure-activity relationships in alveolar macrophages.

In respect to the high number of released nanomaterials and their highly variable properties, novel grouping approaches are required based on the effects of nanomaterials. Proper grouping calls for a combination of an experimental setup with a higher number of structurally similar nanomaterials and for employing integrated omics approaches to identify the mode of action. Here, we analyzed the effects of seven well-characterized NMs comprising different chemical compositions, sizes and chemical surface modifications on the rat alveolar macrophage cell line NR8383. The NMs were investigated at three doses ranging from 2.5 to 10 µg/cm2 after 24 h incubation using an integrated multi-omics approach involving untargeted proteomics, targeted metabolomics, and src homology 2 (SH2) profiling. By using Weighted Gene Correlation Network Analysis (WGCNA) for the integrative data, we identified correlations of molecular pathways with physico-chemical properties and toxicological endpoints. The three investigated SiO2 variants induced strong alterations in all three omics approaches and were, therefore, be classified as "active." Two organic phthalocyanines showed minor responses and Mn2O3 induced a different molecular response pattern than the other NMs. WGCNA revealed that agglomerate size and surface area as well as LDH release are among the most important parameters correlating with nanotoxicology. Moreover, we identified key drivers that can serve as representative biomarker candidates, supporting the value of multi-omics approaches to establish integrated approaches to testing and assessment (IATAs).

Selenoxide elimination manipulate the oxidative stress to improve the antitumor efficacy.

Selenoxide elimination reaction has been widely used in the field of organic synthesis. However, few studies have been conducted to apply this reaction in biodegradable nanomedicine. In this work, the selenoxide elimination reaction was used for cancer treatment via producing excess cellular reactive oxygen species (ROS) for the first time. The ß-seleno diesters and porphyrin derivates containing nanoparticle could be responsive to the intracellular ROS and produce acrylates through the elimination reaction. The acrylates would further deplete intracellular GSH in tumor cells and finally improved the anticancer activity in the mice tumor model. Different from traditional ROS-responsive nanomedicine, the elimination product of this reaction could regenerate cytotoxic ROS and specifically disturb the redox balance of tumor cells. This work would provide attractive avenues for the development of therapeutic strategies against cancer via synthesis of well-designed biodegradable polymers.

Intramolecular Büchner Reaction and Oxidative Aromatization with SeO2 or O2.

Intramolecular Büchner reaction of 1-diazo-5-phenylpentan-2-ones followed by oxidation with SeO2 or O2 in the presence of silica gel regioselectively gave 8-formyl-1-tetralones or one-carbon-lacking 1-tetralones, respectively.

Biological Antagonism Inspired Detoxification: Removal of Toxic Elements by Porous Polymer Networks.

Water contamination by toxic heavy elements is becoming an urgent problem in environmental science and separation technologies. However, the design of sophisticated absorbents with high stability and outstanding removal efficacy for ion coadsorption is still a technical challenge. Herein, inspired by biological Hg/Se antagonism detoxification, we have designed the first porous polymer network (PPN) for the concurrent removal of Hg/Se species in aqueous solutions. Remarkably, the MoS42- functionalized PPN-150-MoS4 exhibits a rapid and highly efficient simultaneous removal of toxic anions (SeO42- and SeO32-) and metals (Hg2+). The high thiophilicity of Hg2+ leads to 99.9% removal within minutes. More importantly, selenite and selenate, typically known for being difficult to remove from aqueous environments, can be removed by PPN-150-MoS4, exhibiting >99% removal within minutes when in the presence of Hg2+. At the same time, the removal efficiency for Se(IV) and Se(VI) oxoanions in the absence of Hg2+ is very low, reaching only 14% removal. Overall, PPN-150-MoS4 exhibits one of the highest adsorption capacities toward SeO32- (124 mg/g), making it a promising and cheap sorbent material for water remediation applications. This work provides a fresh route for detoxification and remediation strategies that aim to regulate the presence of toxic ions in nature. The material herein shall guide the state-of-the-art design of efficient water treatment techniques through a combination of biological antagonism and materials chemistry.

Synergistic combination of PEGylated selenium nanoparticles and X-ray-induced radiotherapy for enhanced anticancer effect in human lung carcinoma.

In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNP + X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.

Nanoparticles synthesis by Agaricus soil basidiomycetes.

We examined the effect of various concentrations of HAuCl4, AgNO3, Na2SeO3, Na2SiO3, and GeO2 on mycelial growth of the soil basidiomycetes Agaricus bisporus and A. arvensis in submerged and solid media. Fungal mycelial extracts and cell-free culture filtrates were able to reduce ions of Au, Ag, Se, Si, and Ge compounds, forming Au0, Ag0, Se0, Si0/SiO2 and Ge0/GeO2 nanoparticles. The physical characteristics of the mycogenic nanoparticles differed depending on the species of Agaricus and the type of extract. Au nanospheres obtained with cell-free culture filtrates were of 2-5 nm diameter in A. bisporus and of 2-10 nm in A. arvensis. Nanoparticles produced by extracts of mycelia were several times larger and highly heterogenous. Ag nanoparticles produced by cell-free culture filtrates were spherical or irregular-shaped and agglomerated, whereas with extracts of mycelia, small homogenous nanospheres of 1-10 nm were formed. Se nanospheres obtained with cell-free culture filtrates were of 100-250 nm diameter in A. bisporus and of 150-550 nm diameter in A. arvensis. The particles synthesized with extracts of mycelia were of 40-140 nm in A. bisporus and of 100-250 nm in A. arvensis. Incubation of Na2SiO3 with cell-free culture filtrates resulted in porous Si nanoparticles of 30-65 nm in A. bisporus and of 50-200 nm in A. arvensis. Ge nanoparticles synthesized by both Agaricus species were mostly spheres of 50-250 nm diameter.