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Background/objectives: Polymethoxyselenoflavone (PMSF) is a compound that substitutes the oxygen atom in a flavonoid with selenium. This study aimed to investigate the effects of PMSFs on lipid metabolism in adipocytes and their anti-obesity potential., Subjects/methods: To test lipolytic and thermogenic effects of the compounds in vitro, adipocytes differentiated from immortalized pre-brown adipocyte progenitors and pre-white adipocyte cell lines were treated with 19 PMSFs. The expression levels of brown adipocyte markers and genes related to mitochondrial metabolism were analyzed by qPCR and western blot. In vivo anti-obesity effect was investigated using diet-induced obesity mouse models and adipocyte-specific ATGL knockout mice., Results: The qPCR analysis identified 2-(3,4-dimethoxyphenyl)-4H-selenochromen-4-one (DMPSC) as the most potent brown adipogenic candidate among the 19 compounds tested in this study. DMPSC treatment significantly increased the mitochondrial content and oxidative metabolism in adipocytes in vitro. Mechanistically, DMPSC treatment increased lipolysis through activation of PKA downstream signaling. Consistently, the in vivo treatment of DMPSC increased energy consumption, reduced body weight, and improved glucose tolerance in mice fed with high-fat diets. Moreover, DMPSC treatment increased brown adipocyte marker expression and mitochondrial content in adipose tissue of mice. The anti-obesity effects were absent in adipocyte-specific ATGL knockout mice, indicating that the DMPSC effect is mediated by cytosolic lipase-dependent mechanisms., Conclusions: Collectively, our results indicated that DMPSC exerted anti-obesity effects partially through the PKA signaling-mediated activation of lipolysis and brown adipose tissue metabolism.

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations' health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications' experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs.

Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3 , 6 , 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.

Selenium deficiency is a common nutritional disorder in dairy cattle globally. However, selenium supplementation can lead to selenium toxicity. This study evaluated a novel, low-toxicity selenium supplement, selenitetriglycerides, to determine its efficacy and safety in dairy cows. The study was conducted on 12 Holstein Friesian cows divided in two equal groups (control group without supplementation of selenium and experimental group with supplementation of selenitetriglycerides). Experimental cows (n=6) were orally administered 300 mg/cow/day of selenitetriglycerides for 14 days (days 1-14) and then monitored for a further 14 days (days 15-28). Blood from both groups of cows was sampled for determination of selenium concentrations, activity of aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma- -glutamyl transferase, concentrations of triglycerides, cholesterol, non-esterified fatty acids, glucose, total protein, urea, creatinine and hematological parameters. Serum selenium concentrations in the experimental group increased significantly on day 2 (from 64.92±6.89 μg/L to 127.95±13.75 μg/L), peaked on day 7 (266.22±14.21 μg/L) and remained significantly above the initial baseline values (day 1) for 28 days. Serum selenium concentrations in the control group did not change significantly during the 28 day period (65.22 μg/L on 1st day and 64,35 μg/L on 28th day) and were significantly lower than those in the experimental group from day 2 to day 28. The results of clinical examinations, analyses of hematological parameters, and liver and kidney function tests showed that selenitetriglycerides had no adverse effect on the health or on the metabolic or haematological statuses of the cows. These findings indicate that selenitetriglycerides are safe and effective selenium supplements for cattle., (Copyright© by the Polish Academy of Sciences.)

Drought is an important environmental stress that has negative effects on plant growth leading to a reduction in yield. In this study, the positive role of nanoparticles of SiO 2 , Se, and Se/SiO 2 (SiO 2 -NPs, Se-NPs and Se/SiO 2 -NPs) has been investigated in modulating negative effects of drought on the growth and yield of strawberry plants. Spraying of solutions containing nanoparticles of SiO 2 , Se, and Se/SiO 2 (50 and 100 mg L -1 ) improved the growth and yield parameters of strawberry plants grown under normal and drought stress conditions (30, 60, and 100%FC). Plants treated with Se/SiO 2 (100 mg L -1 ) preserved more of their photosynthetic pigments compared with other treated plants and presented higher levels of key osmolytes such as carbohydrate and proline. This treatment also increased relative water content (RWC), membrane stability index (MSI) and water use efficiency (WUE). In addition, exogenous spraying of Se/SiO 2 increased drought tolerance through increasing the activity of antioxidant enzymes including catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and superoxide dismutase (SOD) as well as decreasing lipid peroxidation and hydrogen peroxide (H 2 O 2 ) content. Increase in biochemical parameters of fruits such as anthocyanin, total phenolic compounds (TPC), vitamin C and antioxidant activity (DPPH) in strawberry plants treated with Se/SiO 2 under drought stress revealed the positive effects of these nanoparticles in improving fruit quality and nutritional value. In general, our results supported the positive effect of the application of selenium and silicon nanoparticles, especially the absolute role of Se/SiO 2 (100 mg L -1 ), on the management of harmful effects of soil drought stress not only in strawberry plants, but also in other agricultural crops.

Selenium oxychloride (SOC) was employed as a highly reactive selenide reagent to synthesize selenized Artemisia sphaerocephala polysaccharides (SeASP). Se content of SeASP was significantly increased (∼22,400 μg/g) as compared to HNO 3 /H 2 SeO 3 selenylation method (1703 μg/g). Furthermore, selenized ASP was prepared by using microwave-assisted synthesis which obviously enhanced selenylation kinetics. FT-IR, Raman, XPS and NMR results exhibited seleno-group was substituted at C6 position in the form of selenite (Se 4+ ). SEC-MALLS suggested SOC system could effectively avoid the degradation of polysaccharide chain. Meanwhile, MALLS calculation, MB spectrophotometric method and AFM observation showed SeASP appeared spherical and rod-shaped conformation after selenylation. Seleno-groups were more likely to affect the conformational transformation of polysaccharide chains. Moreover, SeASP could significantly enhance antiproliferative activity against three tumor cells, of which the IC 50 value of HepG2 was calculated as 24.35 μg/mL. It was found that higher Se content could effectively improve the antitumor activities of Se-polysaccharides in vitro., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A series of thirty-one selenocompounds covering a wide chemical space was assessed for in vitro leishmanicidal activities against Leishmania infantum amastigotes. The cytotoxicity of those compounds was also evaluated on human THP-1 cells. Interestingly most tested derivatives were active in the low micromolar range and seven of them (A.I.3, A.I.7, B.I.1, B.I.2, C.I.7 C.I.8 and C.II.8) stood out for selectivity indexes higher than the ones exhibited by reference compounds mitelfosine and edelfosine. These leader compounds were evaluated against infected macrophages and their trypanothione reductase (TryR) inhibition potency was measured to further approach the mechanism by which they caused their action. Among them diselenide tested structures were pointed out for their ability to reduce infection rates. Three of the leader compounds inhibited TryR effectively, therefore this enzyme may be implicated in the mechanism of action by which these compounds cause their leishmanicidal effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic. Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno-bis(S-glutathionyl) arsinium ion [(GS) 2 AsSe] - . Consistent with this, human selenium deficiency in arsenic-endemic regions is associated with arsenic-induced disease, leading to the initiation of human selenium supplementation trials. In contrast to the protective effect observed in vivo, in vitro studies have suggested that selenite increases arsenite cellular retention and toxicity. This difference might be explained by the rapid conversion of selenite to selenide in vivo. In the current study, selenite did not protect the human hepatoma (HepG2) cell line against the toxicity of arsenite at equimolar concentrations, however selenide increased the IC 50 by 2.3-fold. Cytotoxicity assays of arsenite + selenite and arsenite + selenide at different molar ratios revealed higher overall mutual antagonism of arsenite + selenide toxicity than arsenite + selenite. Despite this protective effect, in comparison to 75 Se-selenite, HepG2 cells in suspension were at least 3-fold more efficient at accumulating selenium from reduced 75 Se-selenide, and its accumulation was further increased by arsenite. X-ray fluorescence imaging of HepG2 cells also showed that arsenic accumulation, in the presence of selenide, was higher than in the presence of selenite. These results are consistent with a greater intracellular availability of selenide relative to selenite for protection against arsenite, and the formation and retention of a less toxic product, possibly [(GS) 2 AsSe] - ., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acute graft-versus-host-disease (GVHD), limits the use of hematopoietic cell transplant (HCT) to treat a variety of malignancies. Any new therapeutic approach must satisfy three requirements: 1) Prevent GVHD, 2) Maintain anti-pathogen immunity, and 3) Maintain anti-tumor immunity. In prior studies we have shown that the selective photosensitizer 2-Se-Cl eliminates highly alloreactive lymphocytes from the graft prior to HCT preventing GVHD and that antiviral immune responses were preserved following incubation with 2-Se-Cl. In this report, we investigated whether 2-Se-Cl treatment preserves antitumor immunity, and then used high dimensional flow cytometry to identify the determinants of successful immune reconstitution. Donor C57BL/6 splenocytes were cocultured for 4 days with irradiated BALB/c splenocytes and then exposed to 2-Se-Cl. Photodepletion (PD)-treated splenocytes were then infused into lethally irradiated BALB/c mice inoculated with A20 leukemia/lymphoma cells. Recipient mice that received PD-treated splenocytes survived > 100 days without evidence of GVHD or leukemia. In contrast, mice that did not receive PD-treated cells at time of HCT died of leukemia progression. Multiparameter flow cytometry of cytokines and surface markers on peripheral blood samples 15 days after HCT demonstrated unique patterns of immune reconstitution. We found that before clinical disease onset GVHD was marked by functionally exhausted T cells, while tumor clearance and long-term survival were associated with an expansion of polyfunctional T cells, monocytes, and DCs early after transplantation. Taken together these results demonstrate that 2-Se-Cl photodepletion is a new treatment that can facilitate HCT by preventing GVHD while preserving antiviral and anti-tumor immunity., Competing Interests: The authors have declared that no competing interests exist.

Herein, we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H 2 O 2 ) in cultured mouse neurons. First, α -methylene- β -hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (3a-f). We next prepared cultures of neurons from 7-day-old mice ( n = 36). H 2 O 2 (10 -5  M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. (PhSe) 2 was used as a positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2'-nonenal, 8-isoprostane), DNA (8-hydroxy-2'-deoxyguanosine), and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, 3b, 3d, and 3f exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe) 2 . These novel aromatic selenocyanates could be promising to be tried in most sophisticated in vitro studies or even at the preclinical level., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Tiago E. A. Frizon et al.)

Kohlrabi (Brassica oleracea L. var. gongylodes L.) was biofortified with selenium (Se), as selenite and selenate, and iodine (I), as iodide and iodate, and their combinations through foliar spraying, to study absorption of these elements by the plants, separately and in combination. The effects on selected physiological and morphological traits and optical characteristics were monitored. Treatments with Se positively affected total chlorophylls and carotenoids, and leaf stomata dimensions. Addition of I decreased total chlorophylls and increased anthocyanins. In reflectance spectra of the leaves, specific colour regions differed significantly due to the different treatments. Reflectance in the UV correlated positively with Se and I contents of the leaves, which indicated lower demand for production of phenolic compounds. Differences in reflectance in UV part of the spectra could be a consequence of changes in the cuticle. The Se and I levels increased markedly in leaves and tubers, without loss of biomass or yield. Se had antagonistic effects on accumulation of I in leaves. The similar levels of Se and I in the leaves and tubers suggest that the transport of both elements in these plants occurs from the leaves to the tubers through the phloem. According to the Se and I contents in the kohlrabi tubers, biofortification with both elements simultaneously is feasible for human nutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.

In the present study, twenty-four selenocyanate and diselenide compounds were synthesized and characterized, and their anticancer activities against the human cancer cell lines Caco2, BGC-823, MCF-7 and PC-3 were determined. Interestingly, most of the new compounds were active in reducing the viability of different cancer cell lines. Two compounds exhibited higher promising activities than other derivatives. The most active compound showed the least IC 50 values against the four cancer cell lines, particularly to PC-3 with IC 50 values below 5 μm. Two compounds were selected to monitor the expression levels of Bcl-2, IL-2 and caspase-3 molecular biomarkers. Interestingly, the two compounds downregulated the Bcl-2 expression levels and upregulated the expression of IL-2 and caspase-3 in PC-3 cells compared to untreated cells. Moreover, most of the synthesized organoselenides exhibited good Gpx-like activities comparable to ebselen. These results appear that introduction of selenocyanate (-SeCN) or diselenides (-Se-Se-) moiety to some carboxy derivatives could serve as a promising launch point for the further design of this type of organic selenium anticancer agent., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

The photothermal/photodynamic synergistic therapy is a promising tumor treatment, but developing nanosystems that achieve synchronous photothermal/photodynamic functions is still quite challenging. Here, we use a simple method to synthesize molybdenum selenide nanoparticles (MoSe 2 NPs) with a photothermal effect as a carrier, and load a photosensitizer ICG to form a nanosystem (MoSe 2 @ICG-PDA-HA)with dual photothermal/photodynamic functions under near-infrared irradiation. In addition, the surface modification of the nanosystem with acid-responsive release polydopamine (PDA) and tumor-targeted hyaluronic acid (HA) enhanced the stability of the photosensitizer ICG and the accumulation of ICG at tumor sites. The multicellular sphere assay simulated solid tumors and demonstrated that MoSe 2 @ICG-PDA-HA could significantly inhibit the 4T1 cell growth. The anti-tumor experiments in tumor-bearing mice showed that MoSe 2 @ICG-PDA-HA not only significantly inhibited the growth of 4T1 subcutaneous tumors, but also inhibited their metastasis. This study presented a nanosystem that could improve the photostability of optical materials and enhance the photothermal/photodynamic synergy effect, providing a new idea for finding a way to effectively treat breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We studied changes in the transcription of genes encoding cytokines (TNF, IL-6, IL-10, and IL-32), cell activation markers (ICAM1, CD38, Fas, and FCGRIII), ROS production catalyst (NOX2), autophagy (Beclin 1, LC3B, and p62) and apoptosis (BAX, BCL2) regulators in peripheral blood mononuclear cells upon contact with quantum dots CdSe/ZnS-MPA and CdSe/CdSeZnS/ZnS-PTVP. Up-regulation of TNF, ICAM1, Fas, p62 mRNA and down-regulation of the FCGRIII and NOX2 mRNA in response to the presence of quantum dots were revealed. The formation of serum protein corona on the surface of quantum dots abolished this effect.

Carbonic anhydrases (CAs, E.C. 4.2.1.1) are metalloenzymes expressed on a variety of cell types. Their overexpression leads to serious pathologies, including cancer. The discovery of a series of selenolesters with high structural diversity as novel CA inhibitors is reported here. These compounds show remarkable in vitro inhibition against a panel of human CA isoforms such as hCA I, II, IX and XII. We observed that they undergo a CA mediated hydrolysis, releasing different active selenol fragments, which act as CA inhibitors. Notably, to the best of our knowledge, this is the first example of an enzyme with selenolesterase activity. In addition, X-ray crystallographic data support the proposed mechanism, proving selenolesters as novel pro-drug inhibitors with potential pharmacological applications.

ZnS quantum dots (QDs) and their core/shell (CdSe/ZnS) structures were studied for Zn based precursor reactivities. ZnS and CdSe/ZnS QDs were prepared selecting aqueous route and then characterized via XRD, TEM, EDX, PL, RAMAN and FTIR practices. Core/shell nanostructures were synthesized by taking dissimilar precursors for the shell formation. Photoluminescence spectra of prepared QDs corroborate the effectual luminescence. Prepared QDs have large surface area that make them useful alternative as organic antimicrobial agent which are highly irritant and unstable. Study of antimicrobial behavior of QD structures was carried out by disk diffusion method. Antimicrobial study of QDs and their core/shell structures was performed against gram negative and gram positive bacteria, E. coli, A. baumanni and Bacillus subtilis respectively. It is found that elemental composition and size of QDs plays important role in antimicrobial behavior. Prepared QDs are fluorescent and have a key role in complex microbial population studies and identification of bacteria., (Copyright © 2018. Published by Elsevier B.V.)

Herein, we disclose the first set of unique selenium-containing SnAP reagents for the direct synthesis of C-substituted selenomorpholines and 1,4-selenazepanes, including their amino acid derivatives from commercially available aldehydes under mild conditions. These elusive N-unprotected heterocycles are not accessible by classical routes. Biological evaluation of these compounds revealed promising activities against clinically relevant fungal strains.

Functionalised aliphatic selenols, straightforwardly obtained through ring-opening reaction of strained heterocycles, represent a new chemotype acting as carbonic anhydrase inhibitors (CAIs). These compounds showed pronounced selectivity towards the cytosolic human (h) isoforms such as the hCA I, II and VII rather than the membrane tumor associate hCA IX. In addition, we reported for the first time the X-ray crystal structure of an aliphatic selenol bound to the hCA I zinc ion, and that afforded the opportunity to decipher in detail the inhibition mechanism underpinning such a new class of CAIs. In this context selenols are interesting leads worth developing for the obtainment of novel and efficient selective CAIs potentially useful for the management of a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy and arthritis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The purpose of this study was to investigate the interactions between different selenium (Se) compounds including sodium selenite (SS), selenium-enriched yeast (SY), and nano-selenium (NS) and various essential trace elements involved in the antioxidant systems, and to evaluate the effects on laying performance and egg quality. A total of 288 21-week-old Hyline Sophie hens were allotted to four dietary treatments: (1) basal diet without Se supplementation; (2) basal diet supplemented with 0.3 mg/kg Se of SS; (3) basal diet supplemented with 0.3 mg/kg Se of SY; (4) basal diet supplemented with 0.3 mg/kg Se of NS. Each treatment had eight replicates with nine hens per replicate. The trial lasted for 35 days. Results demonstrated that NS supplementation decreased the egg production (EP) and increased the feed conversion rate (FCR) and eggshell thickness and that SY changed the egg shape index (p < 0.05). Supplementation with three Se compounds significantly increased serum Se concentration and glutathione peroxidase (GSH-Px) activity in all treatment groups, as well as total superoxide dismutase (T-SOD) activity in the SY and NS groups. Yolk iron (Fe) and copper (Cu) concentrations in the NS group were also increased with Se supplementation. While the serum zinc (Zn) concentration decreased in the NS and SY groups, as well as the yolk manganese (Mn) concentration in the SY group. And the total antioxidant capability (T-AOC) of yolk with 3 days of storage in the SY and NS groups, malondialdehyde (MDA) value in the NS group, and the T-SOD activity and MDA value of yolk with 10 days of storage in the SY group also decreased. Thus, the source of Se compounds may influence the balance between Se and other trace elements including Zn, Mn, Fe, and Cu, which is important for proper antioxidant defense in blood and egg yolk of laying hens.

Aim to study the molecular mechanisms of apoptotic death of mouse testicular teratocarcinoma cells (line F-9) under exposure to the widely used selenium-containing compounds with antitumor activity, sodium selenite and methylseleninic acid. Methods fluorescence microscopy, MTT assay, Western blotting. Results It was shown that sodium selenite at a concentration of 10 μM and methylseleninic acid at concentrations of 1 and 10 μM cause apoptosis-dependent death of F-9 cells, excluding necrotic death. Western blotting showed an increase in the expression of XBP1s when treating F-9 cells with 1 μM methylseleninic acid. Conclusions 10 μM methylseleninic acid leads to cell apoptosis, most likely by activation of the IRE1 signaling pathway under prolonged stress of the endoplasmic reticulum.

Dietary selenium deficiency is recognized as a global problem. Pork is the most widely consumed meat throughout the world and an important source of selenium for humans. In this study, a reliable approach was developed for analyzing selenium and its speciation in the muscles of pigs after different selenium treatments. The selenium source deposition efficiency was ranked as: selenomethionine > methylselenocysteine > selenite, and the muscle selenium content had a dose effect with selenomethionine supplementation. In total, four species of selenium were detected in the muscles of pigs and the distributions of these selenium species were greatly affected by the dietary selenium supplementation forms and levels. Selenomethionine (>70% of total selenium) and selenocystine (>11%) were the major selenium species, followed by methylselenocysteine and selenourea. Therefore, selenium-enriched pork produced from selenomethionine is a good source for improving human dietary selenium intake., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Gracilaria has been shown to be an important source of marine bioactive natural biomaterials and compounds. Although there are no enough patents used Gracilaria worldwide, the current study tries to put the Gracilaria on the spot for further important patents in the future., Objective: The current study investigates the pharmaceuticals and biochemical activity of Gracilaria because no previous studies have been carried out to examine the biochemical and pharmaceutical activates of Gracilaria from the Suez Canal of Egypt as an excellent source for bioactive compounds., Methods: Different advanced experimental models and analytical techniques, such as cytotoxicity, total antioxidant capacity, anticancer, and anti-inflammatory profiling were applied. The phytochemical analysis of different constituents was also carried out., Results: The mineral analysis revealed the presence of copper (188.3 ppm) and iron (10.07 ppm) in addition to a remarkable wealth of selenium and sulfur contents giving up to 36% of its dry mass. The elemental analysis showed high contents of sulfur and nitrogen compounds. The GCMS profiling showed varieties of different bioactive compounds, such as fatty acids, different types of carotenoids in addition to pigments, alkaloids, steroids. Many other compounds, such as carbohydrates and amino acids having antioxidant, anti-inflammatory, and antiviral activities, etc. were identified. The cytotoxicity activity of Gracilaria marine extract was very effective against cancerous cell lines and showed high ability as a potent antitumor due to their bioactive constituents. Specialized screening assays using two anticancer experimental models, i.e., PTK and SKH1 revealed 77.88% and 84.50% inhibition anticancer activity; respectively. The anti-inflammatory activities investigated using four different experimental models, i.e., COX1, COX2, IL6, and TNF resulted in 68%, 81.76%, 56.02% and 78.43% inhibition; respectively. Moreover, Gracilaria extracts showed potent anti-Alzheimer with all concentrations., Conclusion: Gracilaria proved to be a multi-product source of marine natural products for different biotechnological applications. Our recommendation is to investigate the Gracilaria bioactive secondary metabolites in order to create and innovate in more patents from current important seaweeds (Gracilaria)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The incidence of symptomatic radiation induced lung pneumonitis (RILP), a major dose limiting side effect of thoracic radiotherapy, is in the range of 15-40%. Therapeutic options for the prevention and treatment of RILP are limited. Hence there is a need for developing novel radioprotectors to prevent RILP which can be patient compliant. This study sought to evaluate the efficacy of oral 3,3'-diselenodipropionic acid (DSePA), a novel selenocystine derivative to prevent RILP. C3H/HeJ (pneumonitis responding) mice received a single dose of 18 Gy, whole thorax irradiation and a subset were treated with DSePA orally (2.5 mg/kg), three times per week beginning 2 h post irradiation and continued till 6 months. DSePA delayed onset of grade ≥ 2 RILP by 45 days compared to radiation control (~105 versus ~60 days). It also reversed the severity of pneumonitis in 3/10 radiation treated mice leading to significant improvement in asymptomatic survival compared to radiation control (~180 versus ~102 days). DSePA significantly (p < 0.05) reduced the radiation-mediated infiltration of polymorphonuclear neutrophils (PMN) and elevation in levels of cytokines such as IL1-β, ICAM-1, E-selectin, IL-17 and TGF-β in the bronchoalveolar lavage fluid. Moreover DSePA lowered PMN-induced oxidants, maintained glutathione peroxidase activity and suppressed NF-kB/IL-17/G-CSF/neutrophil axis in the lung of irradiated mice. Additionally, this compound did not protect A549 (lung cancer) derived xenograft tumor from radiation exposure in SCID mice. DSePA offers protection to normal lung against RILP without affecting radiation sensitivity of tumors. It has the potential to be developed as an oral agent for preventing RILP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications., Competing Interests: The authors declare no conflicts of interest, and the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone-dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. We compared the inhibitory effects of Re-diSe and of its diselenide ligand (di-Se) on MDA-MB231 and a normal HEK-293 human embryonic cell line, after 72 h and 120 h of exposure. The cytotoxicity was also studied by flow cytometry using ethidium bromide assays, as well as the effects on the ROS production by DFCA-test, while the levels of TGF-β1, VEGF-A, IGF-1 were addressed by ELISA tests. The dose required to inhibit 50% of the proliferation (IC 50 ) of MDA-MB231 breast cancer cells decreased with the time of exposure to 120 h, while the free ligand (di-Se) was found poorly active, demonstrating the important role of Re in this Re-diSe combination. The cytotoxic effects of Re-diSe were highly selective for cancer cells, with a significant increase of the number of dead cancer cells at 5 μM for an exposure time of 120 h, while normal cells were not affected. A remarkable and significant decrease of the production of ROS together with a decrease of VEGF-A, TGF-β1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.

Rationale and Objectives: Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress., Methods: Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min., Results: Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC., Conclusions: These preclinical results indicate that administration of selenium-containing compounds might help to treat depression associated with inflammation and oxidative stress. Graphical abstract ᅟ.

To investigate the immunomodulatory mechanism of low relative molecular mass seleno-aminopolysaccharide, a metabolomics method based on liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) was used to analyze the endogenous metabolites changes in the liver of Acanthopagrus schlegelii . The potential biomarkers were screened using non-targeted mass spectrometry with the XCMS plus software, and the related metabolic pathways were analyzed using MetaboAnalyst3.0 website. The results showed that the liver metabolites in the low relative molecular mass seleno-aminopolysaccharide-fed group were significantly different from those in the blank group. Also, 32 biomarkers were identified. Additionally, low relative molecular mass seleno-aminopolysaccharide could enhance the immune function of Acathopagrus schlegelii via amino acid, nucleotide, and nitrogen metabolism, aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis, and other metabolic pathways. This study therefore provides a scientific basis for elucidating the immunoenhancement mechanism of low relative molecular mass seleno-aminopolysaccharide.

Selenium sulfide is a well-known bioactive chemical whose biosynthesis as a nanoparticle (NP) is a controversial issue. In the present study, we employed Saccharomyces cerevisiae to generate a novel synthetic process of selenium sulfide NPs. The addition of selenium/sulfur precursors to S. cerevisiae culture produced NPs, which we isolated and characterized the physicochemical properties, toxicity, and antifungal activity. Transmission electron microscopy indicated the presence of the NPs inside the cells. Selenium sulfide NPs were successfully synthesized with average size of 6.0 and 153 nm with scanning electron micrographs and 360 and 289 nm in Zeta sizer using different precursors. The presence of sulfur/selenium in the particles was confirmed by energy-dispersive X-ray spectroscopy and elemental mapping. Fourier-transform infrared spectroscopy supported the production of selenium sulfide NPs. X-ray diffractograms showed the presence of characteristic peaks of selenium sulfide NPs which were further confirmed by mass spectrometry. The obtained NPs strongly inhibited the growth of pathogenic fungi that belonged to the genera Aspergillus, Candida, Alternaria and the dermatophytes, while no cytotoxicity was observed in MTT assay. In conclusion, efficient green synthesis of selenium sulfide NPs with appropriate physicochemical properties is possible in bio-systems like S. cerevisiae., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Based on the potent anti-HIV activity of L-2',3'-dideoxycytidine (L-ddC), L-2',3'-dideoxy-4'-selenonucleosides (L-4'-Se-ddNs) have been synthesized from natural chiral template, L-glutamic acid, using Pummerer-type condensation as a key step. All synthesized compounds were assayed for anti-HIV-1 activity, but none of them did show any significant antiviral activity up to 100 μM, probably due to conformational differences between L-ddC and L-4'-Se-ddC, induced by the bulky selenium atom, which might play an important role in phosphorylation by cellular kinase.

A series of variously functionalized selenium-containing compounds were purposely synthesized and evaluated against a panel of cancer cell lines. Most of the compounds showed an interesting cytotoxicity profile with compound 5 showing a potent activity on MCF7 cells. The ethyl amino derivative 5 acts synergistically with cis -platin and inhibits the GST enzyme with a potency that well correlates with the cytotoxicity observed in MCF7 cells. A computational analysis suggests a possible binding mode on the GST enzyme. As the main outcome of the present study, the ethyl amino derivative 5 emerged as a valid lead compound for further, future developments.

Major depression and anxiety are highly incapacitating psychiatric disorders often present simultaneously, and the causal relationship between these disorders and inflammation are under extensive investigation. The treatment for this comorbidity still relies on drugs acting on the serotonergic neurotransmission, but the modulation of immune-inflammatory pathways has attained an increasing interest in the drug discovery. We have previously demonstrated that the selenoorganic compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) possess antioxidant, anti-inflammatory, antinociceptive and antidepressant-like effect in mice. Considering these pharmacological properties and the structural similarities between tryptophan, serotonin and CMI, the aim of the present study was to investigate whether CMI ameliorates depression- and anxiogenic-like behavior induced by lipopolysaccharide (LPS) in Swiss male mice by modulating the serotonergic system and reducing neuroinflammation. The administration of CMI (1 mg/kg, i.g) reversed the behavioral deficits induced by LPS (0.83 mg/kg, i.p) in the tail suspension test, splash test and elevated plus maze. The pre-treatment of mice with WAY100635 (5-HT 1A receptor antagonist), ketanserin (5-HT 2A/2C receptor antagonist) and ondansetron (5-HT 3 receptor antagonist) prevented the antidepressant- and anxiolytic-like effect elicited by CMI treatment after the LPS challenge. The administration of CMI also counteracted the increased expression of pro-inflammatory cytokines and indoleamine 2,3-dioxygenase (IDO) in the prefrontal cortex and hippocampus of mice challenged with LPS. Additionally, a molecular docking analysis showed that CMI binds to the active site of the serotonin transporter and IDO. These findings suggest that CMI reversed behavioral and biochemical alterations in the depression-anxiety comorbidity induced by LPS, possibly by modulation of neuroinflammatory mediators and the serotonergic system., (Copyright © 2019. Published by Elsevier Ltd.)

Diselenide-containing paclitaxel nanoparticles (SePTX NPs) indicated selectivity of cytotoxicity between cancerous and normal cells in our previous work. Herein, the mechanism is revealed by molecular biology in detail. Cancer cells and normal cells were treated with the SePTX NPs and cell proliferation was measured using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell morphology. Measurement of reactive oxygen species (ROS) levels and biochemical parameters were employed to monitor oxidative stress of the cells. JC-1 assay was used to detect the mitochondrial dysfunction of the cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect apoptosis of the cells. Immunofluorescence analysis and western blotting were employed to monitor changes in signaling pathway-related proteins. Compared with PTX, SePTX NPs has a good selectivity to cancer cells and can obviously induce the proliferation damage of cancer cells, but has no significant toxicity to normal cells, indicating that SePTX NPs has a specific killing effect on cancer cells. The results of mechanism research show that SePTX NPs can successfully inhibit the depolymerization of microtubules and induce cell cycle arrest, which is related to the upregulation of p53 and CyclinB1. Simultaneously, SePTX NPs can successfully induce oxidative stress, cause mitochondrial dysfunction, resulting in mitochondrial pathway-mediated apoptosis, which is related to the upregulation of autophagy-related protein LC3-II. On the other hand, lewis lung cancer C57BL/6 mice were used to evaluate the anti-tumor effects of SePTX NPs in vivo . Our data show that SePTX NPs exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects. Collectively, these data indicate that the high antitumor effect and selective cytotoxicities of SePTX NPs is promising in future cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background/aim: Selenium-containing compounds are becoming new alternatives in experimental chemotherapy in order to overcome multidrug resistance in cancer. The main goal of this study was to determine whether combined treatment with new Se-compounds would increase the effect of conventional doxorubicin chemotherapy in breast cancer cell lines., Materials and Methods: Se-compounds were evaluated regarding their cytotoxic and apoptosis-inducing effect on MCF-7 and ATP-binding cassette subfamily B member 1 (ABCB1)-overexpressing KCR breast cancer cell lines. Moreover, the interaction of Se-compounds with doxorubicin was assessed using the MTT assay., Results: Selenoanhydride exerted a selective activity towards the doxorubicin-resistant KCR cell line overexpressing ABCB1. Among the selenoesters, only ketone-containing selenoesters exerted significant cytotoxic activity against MCF-7 and KCR cell lines and the Se-compounds acted synergistically with doxorubicin on the KCR cell line., Conclusion: The importance of the COSeCH 2 COCH 3 and COSeCH 2 CO(CH 3 ) 3 moieties for the cytotoxic and adjuvant role of Se-compounds was highlighted., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The effect of seleno-L-methionine (SeMet) on immunoglobulin (Ig) E-mediated allergic responses were investigated using rat basophilic leukemia RBL-2H3 cells. Cells were first treated with or without SeMet, sensitized with anti-dinitrophenyl IgE and stimulated with the antigen dinitrophenyl-human serum albumin, before the measurement of degranulation, calcium mobilization, mRNA expression and protein secretion of interleukin (IL)-4 and tumor necrosis factor (TNF)-α, and phosphorylation of spleen tyrosine kinase (Syk), Akt, and mitogen-activated protein kinases (MAPKs). The antigen-induced β-hexosaminidase release, a degranulation marker, was significantly inhibited by SeMet treatment. SeMet also significantly suppressed antigen-induced calcium mobilization. Antigen-induced increases in the mRNA expression and protein secretion of IL-4 and TNF-α were both significantly attenuated by SeMet treatment. In addition, SeMet significantly suppressed antigen-induced phosphorylation of Syk, Akt, and MAPKs. These results demonstrate that SeMet suppresses antigen-induced degranulation, and mRNA expression and protein secretion of IL-4 and TNF-α, and inhibits antigen-induced mobilization of calcium and activation of Syk, Akt, and MAPKs. Our study provides valuable information that may be useful in the prevention and treatment of allergic diseases.

Nanoscale copper chalcogenides have been widely used in nanomedicine, however, their pharmacokinetics, degradation, and biological effects of released copper ions are usually overlooked, which are crucial for their future clinical translation. Herein, we report the in vitro and in vivo release of copper ions from polyvinylpyrrolidone (PVP) functionalized ultrasmall copper selenide (Cu2-xSe) theranostic nanoparticles. We synthesized a Cu2+-specific fluorescent probe (NCM), which can quickly and specifically react with copper ions to exhibit very strong near infrared fluorescence. The in vitro study shows that copper ions can be slowly released from Cu2-xSe nanoparticles in aqueous solution with the progress of their oxidation. The release of copper ions from Cu2-xSe nanoparticles in RAW 264.7 murine macrophages is very fast, evidenced by the gradual increase of fluorescence intensity and the diffusion of fluorescence from cytoplasm into nuclei. We also demonstrate the distribution, degradation, and the metabolism of ultrasmall Cu2-xSe nanoparticles by the in vivo fluorescence imaging, the blood routine test, blood biochemistry and histology analysis, and the characterization of copper transport and binding proteins. The results show that ultrasmall Cu2-xSe nanoparticles were mainly eliminated through feces and urine from the body within 72 h after intravenous injection, and the released copper ions did not cause severe toxicity. Our research highlights the great potential of copper chalcogenide nanoparticles in nanomedicine.

Oxidative stress is a major risk factor for neurodegenerative disease. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the most potent defensive systems against oxidative stress. Selenepezil, a selenium-based compound, was previously found to exhibit excellent acetylcholinesterase (AChE) inhibition, to mimic endogenous glutathione peroxidase (GPx) activity, and to exhibit scavenging activity for hydrogen peroxide in vitro. However, none of these activities have been evaluated in a cellular model, and detailed molecular mechanisms are not elucidated. Moreover, whether selenepezil ameliorates memory deficits in vivo remains unknown. This study validated the cytoprotective effect of selenepezil against 6-hydroxydopamine (6-OHDA)- or H 2 O 2 -induced SH-SY5Y cell damage via alleviation or neutralization of intracellular microtubule disorder, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and cell apoptosis. Our study clearly demonstrated that selenepezil pretreatment exhibited remarkable cytoprotective effect in a Nrf2-dependent manner via activating the Keap1-Nrf2-ARE pathway and stimulating the transcription of Nrf2-ARE-regulated cytoprotective genes. Moreover, selenepezil·HCl exerts neuroprotective effect via attenuating Aβ-induced cognitive impairment in Alzheimer's disease (AD) rat and was more active than the reference drug donepezil. In summary, selenepezil deserves further consideration for AD therapy.

The antioxidant interactions between selenium species and tea polyphenols were investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals, cupric reducing antioxidant capacity (CUPRAC) and Folin-Ciocalteu (FC) assay. Se(IV) exhibited the lowest antioxidant properties in comparison to other selenium compounds in all assays. The highest reducing power was obtained for SeMet, while the highest ability to scavenging DPPH radicals for MeSeCys. The results obtained experimentally for the mixtures containing selenium species and green or black tea infusion were compared with theoretical values calculated by adding up the effects of both individual components analyzed separately. The results obtained from each assay clearly show that observed effect is not additive. In almost every case the theoretical value of antioxidant capacity was significantly higher from that obtained from the activity of the binary mixture of black tea infusion with selenium compound decreased in the order: SeMet > Se(IV) > Se(VI) > MeSeCys, while for similar mixtures with green tea infusion: MeSeCys > Se(VI) > SeMet ~ Se(IV).

Nanoparticles of cadmium selenide (CdSe) doped with europium, were synthesized as stabilizing agents using thioglycolic acid ligand. This method is based on the enhancing effect of CdSe quantum dots (QDs) doped with europium on chemiluminescence (CL) emission. This emission was generated by mixing CdSe QDs with manganese (II), iron (II) and chrome (II) sulfates as catalysts in the presence of hydrogen peroxide (H 2 O 2 ). The structural characteristics and morphology of these nanoparticles were investigated by scanning electron microscopy, Fourier transform infrared spectroscopy, ultraviolet-visible absorption spectroscopy, X-ray pattern and dynamic light scattering methods. The CdSe QDs doped with europium were used as the sensitizer in a luminol-hydrogen peroxide CL system. The sensitized CdSe QDs were analyzed for antibacterial activity against Gram-positive or Gram-negative bacteria. The results showed that the CdSe QDs are effective against all the studied bacteria, effectiveness was especially higher for Bacillus subtilis., (© 2019 John Wiley & Sons, Ltd.)

Organic selenium compounds have several pharmacological activities already described, as anti-inflammatory and antitumor activities, which have been attributed to their antioxidant effects. Because they are promising in pharmacology, the synthesis of these compounds has increased significantly. As many new molecules are synthesized the use of a simple model like Caenorhabditis elegans is highly advantageous for initial evaluation of the toxicity and therapeutic potential of these molecules. The objective of this study was to evaluate the toxicity and antioxidant capacity of a series of selenotriazoles compounds in C. elegans. The animals were exposed to the compounds in liquid medium for only 30 min at the first larval stage (L1). The compounds had no toxic effects at the concentrations tested. Treatment with selenotriazoles (10 μM) partially reversed the stress induced by the pesticide paraquat (1 mM). Se-Tz Ia compound partially increased the survival of worms treated with H 2 O 2 (0.5 mM). The compounds also increased the longevity of mev-1 mutants, which have a reduced life span by the production of excessive reactive oxygen species (ROS) in the mitochondria caused by a mutation in complex II of the electron transport chain. In addition, the compounds reduced the levels of ROS determined by the fluorescent probe DCF-DA as well as also reduced catalase enzyme activity in these animals. Based on the results found, it is possible to conclude that the compounds have antioxidant activity mainly in oxidative stress condition generated by a mitochondrial dysfunction in C. elegans., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Scope: Small selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo., Methods and Results: In the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data., Conclusion: Se species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus , methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli , and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogens.

Exposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L) could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

Selenium (Se) is an essential microelement for humans and a beneficial element for plants. Recently, biofortification with Se has emerged as a key strategy to increase crop Se content. Nonetheless, Se species matters a lot as inorganic Se species is mostly toxic to human health. In this study, we investigated the effects of different forms and mode of Se application on Se accumulation and speciation in rice. The results showed that root application of Se remarkably increased Se accumulation, photosynthetic rate, biomass accumulation and tolerance to cadmium stress in rice as compared to foliar application. However, the stimulatory effects of Se varied depending on the Se species used for root feeding. At vegetative stage, root application of Se-(Methyl) selenocysteine caused the highest water extractable Se content in leaves with major contribution from organic Se species such as Se-amino acid and non-amino acid organic Se. Further investigation at reproductive stage revealed that foliar application of sodium selenite (Na 2 SeO 3 ) resulted in the highest total Se content in rice seeds which was largely attributed to inorganic Se. In contrast, the root application of Na 2 SeO 3 led to the maximum accumulation of organic Se compounds which are advantageous to human health. Moreover, the root application of Se increased antioxidant capacity and selectively enhanced amino acids and essential element content in rice grain. This study deepens our understanding of the Se species in Se-enriched rice and suggests that root application of Se may ensure the safe intake of Se through rice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Selenium has been shown to have chemotherapeutic effects against cancer. However, the anti-cancer mechanism of selenium is not fully understood, and the role of hydrogen selenide (H 2 Se), which is a common metabolite of dietary selenium compounds, has not been elucidated due to the lack of detection methods. In this study, we revealed a new anti-cancer mechanism of selenite with the help of a H 2 Se fluorescent probe. Methods: HepG2 cells were cultured under a simulated tumor hypoxic microenvironment. The H 2 Se and H 2 O 2 levels were detected by fluorescent probes in living cells and in mice. Autophagic and apoptotic proteins were detected by Western blotting. The redox of HMGB1 protein were analyzed by non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis. Results: After pharmacological doses of Na 2 SeO 3 treatment of HepG2 cells under hypoxic conditions, high levels of H 2 Se were produced before cell death. The H 2 Se accumulation resulted in reductive stress instead of oxidative stress, which was induced by Na 2 SeO 3 treatment under normoxic conditions. Furthermore, H 2 Se targeted the HMGB1 protein and induced cell autophagy. H 2 Se could interrupt the disulfide bond in HMGB1 and promote its secretion. The reduced HMGB1 outside the cells stimulated cell autophagy by inhibiting the Akt/mTOR axis. Here, autophagy played a dual role, i.e., mild autophagy inhibited apoptosis, while excessive autophagy led to autophagy-associated cell death. Conclusions: These results show that H 2 Se plays a key role during HepG2 cell death induced by selenite. Our findings reveal a new anti-cancer mechanism of selenite and provide a new research area for selenium studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Selenium (Se) is an essential trace element with multiple functions that may help mitigate adverse health conditions. Cordyceps militaris is an edible mushroom with medicinal properties. The experiment was conducted under artificial cultivation, with five Se concentrations (0, 5, 10, 20, and 40 μg g -1 ) and three forms of Se (selenate, selenite, and selenomethionine). C. militaris can absorb inorganic from the substrate and convert it to organic Se compounds (selenocystine, selenomethionine, and an unknown species) in fruiting bodies. Compared with the control treatment, Se applications (40 μg g -1 selenate and selenite) significantly increased the Se concentration in fruiting bodies by 130.9 and 128.1 μg g -1 , respectively. The biofortification with selenate and selenite did not affect fruiting body production, in some case, but did enhance the biological efficiency. Moreover, the abundance of cordycepin and adenosine increased, while the amino acid contents remained relatively stable. Meanwhile, Se-biofortified C. militaris showed effective antioxidant activities. These results suggest that Se-biofortified C. militaris fruiting bodies may enhance human and animal health when it was included as part of a healthy diet or used as Se supplements.

Cadmium selenide nanoparticles (CdSe NPs) were synthesized by an easy and simple method and their properties were assessed by XRD, TEM and SEM techniques. The effects of CdSe NPs as well as Cd 2+ ions on Lemna minor plants were investigated. The absorption of CdSe NPs by the plants had some adverse consequences that were assessed by a range of biological analyses. The results revealed that both CdSe NPs and the ionic form of cadmium noticeably caused toxicity in L. minor. Morphological parameters as well as peroxidase (POD) activity were deteriorated. In contrast, the activities of some other antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) as well as the contents of total phenol and flavonoids went up. Taken all together, it could be implied that CdSe NPs as well as Cd 2+ were highly toxic to plants and stimulated the plant defense system in order to scavenge produced reactive oxygen species (ROS)., Competing Interests: The authors declare no conflict of interest.

Selol, an organic selenitetrigliceride formulation containing selenium at +4 oxidation level, has been suggested as anticancer drug. One of the causes of several diseases including cancer may be inflammation. This study aimed at determining the activity of Selol via measuring its effect on reactive oxygen species (ROS) generation, nuclear factor kappa B (NF-κB) activation, intercellular cell adhesion molecules-1 (ICAM-1), vascular cell adhesive molecule-1 (VCAM-1), and plateled-endothelial cell adhesive molecule-1 (PECAM-1) levels on control and on tumor necrosis factor-α (TNF-α)-stimulated human microvascular endothelial cells (HMEC-1). Cells were treated either with Selol 5% (4 or 8 μgSe/mL) or TNF-α (10 ng/mL) alone or with Selol concomitant with TNF-α. Selol treatment resulted in ROS generation, activation of NF-κB, downregulation of PECAM-1, VCAM-1 and slight upregulation ICAM-1 expression on the cell surface. TNF-α treatment reflected in sharp NF-κB activation, upregulation of both ICAM-1 and VCAM-1 in parallel with the downregulation of PECAM-1 expression on cell surface. Exposure to both compounds upregulated ICAM-1 and VCAM-1, downregulated PECAM-1 level on cell surface in parallel with no changes in level of NF-κB activation as compared with effects mediated by TNF-α alone. These results points to new look at Selol action since it shows a pro-inflammatory activity in parallel with effects on CAMs expression on the cell surface of human microvascular endothelial cells. However, since Selol enhances CAMs expression level when is present concomitantly with TNF-α this fact might suggest that selenium present in the condition of inflammation will make it worse., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The glutathione (GSH) S-transferase family of detoxification and signalling proteins represents a major hub for the metabolism of Selenium-derived compounds. At the same time, these compounds can be used to modulate the expression and multiple activities of GSTs and other glutathione-dependent genes, that are important aspects in both the chemoprevention and therapy of drug-resistant cancers. In this context, the isoform GSTP-1 (GSTP) appears to play a fundamental role. Besides promoting GSH-dependent detoxification of cellular electrophiles, GSTP physically interacts with a number of small molecules and cellular proteins producing regulatory effects across the main signal transduction and transcription pathways (identified as the "regulatory interactome of GSTP"). An emerging molecular mechanism behind such regulatory function is the activity of GSTP as a redox chaperonine responsible for the selective glutathionylation of protein Cys residues in the different subcellular compartments. The redox-sensitive transcription factor Nrf2 was recently identified as one of the regulatory nodes of this interactome at the interface between inflammation, adaptive stress response, and cell death pathways. The influence of Nrf2 in the stress response to cellular electrophiles and its regulatory interaction with GSTP are discussed in this review suggesting the hypothesis that this interaction may represent the actual pharmacological target of Se compounds with thiol peroxidase activity. These points are critically evaluated with a view to further development of these compounds in cancer prevention and the chemotherapy of drug-resistant tumours., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Fluorescent inorganic quantum dots are highly promising for biomedical applications as sensing and imaging agents. However, the low internalization of the quantum dots, as well as for most of the nanoparticles, by living cells is a critical issue which should be solved for success in translational research. In order to increase the internalization rate of inorganic CdSe/ZnS quantum dots, they were functionalized with a fluorinated organic ligand. The fluorinated quantum dots displayed an enhanced surface activity, leading to a significant cell uptake as demonstrated by in vitro experiments with HeLa cells. We combined the experimental and computational results of Langmuir monolayers of the DPPC phospholipid as a model cell membrane with in vitro experiments for analyzing the mechanism of internalization of the fluorinated CdSe/ZnS quantum dots. Surface pressure-molecular area isotherms suggested that the physical state of the DPPC molecules was greatly affected by the quantum dots. UV-vis reflection spectroscopy and Brewster Angle Microscopy as in situ experimental techniques further confirmed the significant surface concentration of quantum dots. The disruption of the ordering of the DPPC molecules was assessed. Computer simulations offered detailed insights in the interaction between the quantum dots and the phospholipid, pointing to a significant modification of the physical state of the hydrophobic region of the phospholipid molecules. This phenomenon appeared as the most relevant step in the internalization mechanism of the fluorinated quantum dots by cells. Thus, this work sheds light on the role of fluorine on the surface of inorganic nanoparticles for enhancing their cellular uptake., (Copyright © 2018 Elsevier B.V. All rights reserved.)