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Anticancer theranostic nanocarriers have the potential to enhance the efficacy of pharmaceutical evaluation of drugs. Semiconductor nanocrystals, also known as quantum dots (QDs), are particularly promising components of drug carrier systems due to their small sizes and robust photoluminescence properties. Herein, bright CdZnSeS quantum dots were synthesized in a single step via the hot injection method. The particles have a quasi-core/shell structure as evident from the high quantum yield (85 %), which decreased to 41 % after water solubilization. These water solubilized QDs were encapsulated into gallic acid / alginate (GA-Alg) matrices to fabricate imaging QDs@mod-PAA/GA-Alg particles with enhanced stability in aqueous media. Cell viability assessments demonstrated that these nanocarriers exhibited viability ranging from 63 % to 83 % across all tested cell lines. Furthermore, the QDs@mod-PAA/GA-Alg particles were loaded with betulinic acid (BA) and ceranib-2 (C2) for in vitro drug release studies against HL-60 leukemia and PC-3 prostate cancer cells. The BA loaded QDs@mod-PAA/GA-Alg had a half-maximal inhibitory concentration (IC 50 ) of 8.76 μg/mL against HL-60 leukemia cells, which is 3-fold lower than that of free BA (IC 50  = 26.55 μg/mL). Similar enhancements were observed with nanocarriers loaded with C2 and simultaneously with both BA and C2. Additionally, BA:C2 loaded QDs@mod-PAA/GA-Alg nanocarriers displayed a similar enhancement (IC50 = 3.37 μg/mL compared against IC50 = 11.68 μg/mL for free BA:C2). The C2 loaded QDs@mod-PAA/GA-Alg nanocarriers had an IC50 = 2.24 μg/mL against HL-60 cells. C2 and BA loaded QDs@mod-PAA/GA-Alg NCr had IC50 values of 7.37 μg/mL and 24.55 μg/mL against PC-3 cells, respectively., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Prostate cancer is the leading cause of cancer death in men. Some studies suggest that selenium Se (+4) may help prevent prostate cancer. Certain forms of Se (+4), such as Selol, have shown anticancer activity with demonstrated pro-oxidative effects, which can lead to cellular damage and cell death, making them potential candidates for cancer therapy. Our recent study in healthy mice found that Selol changes the oxidative-antioxidative status in blood and tissue. However, there are no data on the effect of Selol in mice with tumors, considering that the tumor itself influences this balance. This research investigated the impact of Selol on tumor morphology and oxidative-antioxidative status in blood and tumors, which may be crucial for the formulation's effectiveness. Our study was conducted on healthy and tumor-bearing animal models, which were either administered Selol or not. We determined antioxidant enzyme activities (Se-GPx, GPx, GST, and TrxR) spectrophotometrically in blood and the tumor. Furthermore, we measured plasma prostate-specific antigen (PSA) levels, plasma and tumor malondialdehyde (MDA) concentration as a biomarker of oxidative stress, selenium (Se) concentrations and the tumor ORAC value. Additionally, we assessed the impact of Selol on tumor morphology and the expression of p53, BCL2, and Ki-67. The results indicate that treatment with Selol influences the morphology of tumor cells, indicating a potential role in inducing cell death through necrosis. Long-term supplementation with Selol increased antioxidant enzyme activity in healthy animals and triggered oxidative stress in cancer cells, activating their antioxidant defense mechanisms. This research pathway shows promise in understanding the anticancer effects of Selol. Selol appears to increase the breakdown of cancer cells more effectively in small tumors than in larger ones. In advanced tumors, it may accelerate tumor growth if used as monotherapy. Therefore, further studies are necessary to evaluate its efficacy either in combination therapy or for the prevention of recurrence.

The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 10 9 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC 50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC 50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies., 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 © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Quantum dots are nanoparticles (2-10 nm) that emit strong and tunable fluorescence. Quantum dots have been heavily used in high-demand commercialized products, research, and for medical purposes. Emerging concerns have demonstrated the negative impact of quantum dots on living cells; however, the intracellular trafficking of QDs in yeast cells and the effect of this interaction remains unclear. The primary goal of our research is to investigate the trafficking path of red cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) in Saccharomyces cerevisiae and the impact QDs have on yeast cellular dynamics. Using cells with GFP-tagged reference organelle markers and confocal microscopy, we were able to track the internalization of QDs. We found that QDs initially aggregate at the exterior of yeast cells, enter the cell using clathrin-receptor-mediated endocytosis, and distribute at the late Golgi/trans-Golgi network. We also found that the treatment of red CdSe/ZnS QDs resulted in growth rate reduction and loss of polarized growth in yeast cells. Our RNA sequence analysis revealed many altered genes. Particularly, we found an upregulation of DID2 , which has previously been associated with cell cycle arrest when overexpressed, and a downregulation of APS2 , a gene that codes for a subunit of AP2 protein important for the recruitment of proteins to clathrin-mediated endocytosis vesicle. Furthermore, CdSe/ZnS QDs treatment resulted in a slightly delayed endocytosis and altered the actin dynamics in yeast cells. We found that QDs caused an increased level of F-actin and a significant reduction in profilin protein expression. In addition, there was a significant elevation in the amount of coronin protein expressed, while the level of cofilin was unchanged. Altogether, this suggests that QDs favor the assembly of actin filaments. Overall, this study provides a novel toxicity mechanism of red CdSe/ZnS QDs on yeast actin dynamics and cellular processes, including endocytosis.

The purpose of this study was to analyze the effects of cadmium toxicity on rat embryogenesis when exposed to other heavy metal citrates. Despite the variety of scientific publications discussing the influence of cadmium on mammalian postnatal development, the effect of this metal on embryogenesis has not yet been sufficiently studied. In this experimental study, cadmium chloride was administered to experimental pregnant female Wistar rats at a daily dose of 1.0 mg/kg. Rats were allocated at random into groups receiving either cadmium chloride alone or additional zinc citrate, cerium citrate, or nanocomposite (based on iodine, sulfur, and selenium citrate). The control group received distilled water at an equivalent volume. In each group, operational intervention occurred at the 13th and 20th day of gestation to assess numbers of live fetuses, corpora lutea, pre-implantation losses, post-implantation losses, and total implantation losses. When cadmium chloride alone was administered, a pronounced embryotoxic effect was observed, manifested as a significant decrease in the number of live fetuses. Experimental groups which received cadmium chloride with zinc citrate, cerium citrate, or nanocomposite had an increased number of live fetuses and corpora lutea, as well as a decreased number of implantation losses, compared to the group which only received cadmium chloride. Each combination of cerium, zinc, and selenium nanocomposite citrates demonstrated a compensatory effect on all measures of embryogenesis impacted by cadmium embryotoxicity. Thus, administration of the citrates of cerium, zinc, and selenium nanocomposite reduces cadmium embryotoxicity and its accumulation in the body.

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na 2 SeO 3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O 2 ), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O 2 ). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H 2 Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H 2 O 2 , leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/β-catenin, TGF-β, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

The study is aimed at elucidating the effect of selenium nanoparticles (SeNPs) on the death of cells in the primary culture of mouse cerebral cortex during oxygen and glucose deprivation (OGD). A primary cell culture of the cerebral cortex containing neurons and astrocytes was subjected to OGD and reoxygenation to simulate cerebral ischemia-like conditions in vitro. To evaluate the neuroprotective effect of SeNPs, cortical astrocytes and neurons were incubated for 24 h with SeNPs, and then subjected to 2-h OGD, followed by 24-h reoxygenation. Vitality tests, fluorescence microscopy, and real-time PCR have shown that incubation of primary cultured neurons and astrocytes with SeNPs at concentrations of 2.5-10 µg/ml under physiological conditions has its own characteristics depending on the type of cells (astrocytes or neurons) and leads to a dose-dependent increase in apoptosis. At low concentration SeNPs (0.5 µg/ml), on the contrary, almost completely suppressed the processes of basic necrosis and apoptosis. Both high (5 µg/ml) and low (0.5 µg/ml) concentrations of SeNPs, added for 24 h to the cells of cerebral cortex, led to an increase in the expression level of genes Bcl-2, Bcl-xL, Socs3, while the expression of Bax was suppressed. Incubation of the cells with 0.5 µg/ml SeNPs led to a decrease in the expression of SelK and SelT. On the contrary, 5 µg/ml SeNPs caused an increase in the expression of SelK, SelN, SelT, SelP. In the ischemic model, after OGD/R, there was a significant death of brain cells by the type of necrosis and apoptosis. OGD/R also led to an increase in mRNA expression of the Bax, SelK, SelN, and SelT genes and suppression of the Bcl-2, Bcl-xL, Socs3, SelP genes. Pre-incubation of cell cultures with 0.5 and 2.5 µg/ml SeNPs led to almost complete inhibition of OGD/R-induced necrosis and greatly reduced apoptosis. Simultaneously with these processes we observed suppression of caspase-3 activation. We hypothesize that the mechanisms of the protective action of SeNPs involve the activation of signaling cascades recruiting nuclear factors Nrf2 and SOCS3/STAT3, as well as the activation of adaptive pathways of ESR signaling of stress arising during OGD and involving selenoproteins SelK and SelT, proteins of the Bcl-2 family ultimately leading to inactivation of caspase-3 and inhibition of apoptosis. Thus, our results demonstrate that SeNPs can act as neuroprotective agents in the treatment of ischemic brain injuries., (© 2022. The Author(s).)

The reactivity of thiophene in Diels-Alder reactions is investigated with different maleimide derivatives. In this paper, we have synthesized for the first time the Diels-Alder adducts of thiophene at room temperature and atmospheric pressure. Maleimido-thiophene adducts were promoted by AlCl 3 . The effects of solvent, time, temperature and the use of different Lewis acids were studied, showing dramatic effects for solvent and Lewis acid. Furthermore, the catalysis with AlCl 3 is highly stereoselective, preferably providing the exo form of the adduct. Additionally, we also discovered the ability of AlCl 3 to catalyze the arylation of maleimides to yield 3-aryl succinimides in a straightforward manner following a Friedel-Crafts-type addition. The inclusion of a selenocyanate group contributes to the cytotoxic activity of the adduct. This derivatization (from compound 7 to compound 15 ) results in an average GI 50 value of 1.98 µM in the DTP (NCI-60) cell panel, resulting in being especially active in renal cancer cells.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Overexpression of pleomorphic adenoma gene like-2 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti-HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2-targeted drug candidates., Methods: The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti-proliferative and apoptosis-inducing effects of selenium sulfide (SeS 2 ), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor., Results: PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C-MET/STAT3 signaling axis. SeS 2 exerted significant anti-proliferative and apoptosis-inducing effects on HCC cells in a PLAGL2-dependent manner. Mechanistically, SeS 2 suppressed C-MET/STAT3, AKT/mTOR, and MAPK signaling and triggered Bcl-2/Cyto C/Caspase-mediated intrinsic mitochondrial apoptosis both in vitro and in vivo., Conclusions: Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS 2 as a PLAGL2 inhibitor in patients with HCC., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Fish oil (FO) and selenium (Se) possess antiangiogenic potential in malignant tumors. This study aimed to determine whether combination of FO and Se enhanced treatment efficacy of low-dose antiangiogenic agent Avastin (bevacizumab) in a dose-dependent manner and targeted multiple signaling pathways in triple-negative breast cancer (TNBC)-bearing mice. Randomized into five groups, mice received treatment with either physiological saline (control), Avastin alone, or Avastin in combination with low, medium, and high doses of FO/Se. The target signaling molecules for anticancer were determined either by measuring protein or mRNA expression. Avastin-treated mice receiving FO/Se showed lower tumor growth and metastasis than did mice treated with Avastin alone. Combination-treated mice exhibited lower expressions in multiple proangiogenic (growth) factors and their membrane receptors, and altered cytoplasmic signaling molecules (PI3K-PTEN-AKT-TSC-mTOR-p70S6K-4EBP1, Ras-Raf-MEK-ERK, c-Src-JAK2-STAT3-TMEPAI-Smad, LKB1-AMPK, and GSK3β/β-catenin). Dose-dependent inhibition of down-stream targets including epithelial-to-mesenchymal transition transcription factors, nuclear cyclin and cyclin-dependent kinases, cancer stem cell markers, heat shock protein (HSP-90), hypoxia-inducible factors (HIF-1α/-2α), matrix metalloprotease (MMP-9), and increased apoptosis were observed. These results suggest that combination treatment with FO and Se increases the therapeutic efficacy of Avastin against TNBC in a dose-dependent manner through multiple signaling pathways in membrane, cytoplasmic, and nucleic targets.

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe - /H 2 Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O 2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H 2 O 2 ), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.

Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs., (Copyright © 2021. Published by Elsevier Inc.)

Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of Na 2 SeO 3 , was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl 4 -induced method, followed by the administration of 0.2 mg kg -1 Na 2 SeO 3 via gavage three times per week for 4 weeks. Changes in H 2 Se, NADPH, and H 2 O 2 levels were monitored in real time by using NIR-H 2 Se, DCI-MQ-NADPH, and H 2 O 2 probes in vivo, respectively. H 2 Se continuously accumulated in the liver throughout the Na 2 SeO 3 treatment period, but the levels of NADPH and H 2 O 2 decreased. The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry. Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H 2 Se with the Na 2 SeO 3 treatment. Therefore, the therapeutic effect of Na 2 SeO 3 on liver fibrosis could be mainly attributed to H 2 Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na 2 SeO 3 and the prevention of liver fibrosis by administering inorganic selenium.

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.

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.

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.)

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.)

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.

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.

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.

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.

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.

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.

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.)

The effective insertion of intentional impurities in direct aqueous preparation of doped QDs still needs a chemical route with well-designed strategy. The present work reports a facile, one-pot, and aqueous-based method for green synthesis of Fe-doped ZnSe(S)/ZnSe(S) core/shell QDs with improved emission intensity. In the proposed strategy, by using a sulfur rich ZnSe(S) shell, we can provide a wider band gap shell with low structural defects in the interface between core and shell. Utilization of combined co-nucleation and growth doping strategies along with increasing the shell refluxing time all are the chemo-physical tactics which led to high intensity dopant-related emission. The antibacterial activity of the as-prepared doped core/shell QDs was investigated using agar disk diffusion method. The results show, these QDs have a significant antibacterial activity against different pathogenic bacteria comparing with the conventional antibiotics. The facility of suggested aqueous route for reaching a dopant emission, the bio-compatibility and considerable antibacterial characteristics of present QDs, nominate them as good candidates in further biological applications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Selenium (Se) incorporated into organic frameworks has demonstrated anticancer activity against several cancer types. One of the drawbacks of most of these constructs is their poor solubility and bioavailability, which can be overcome with the use of suitable nanocarriers. We have synthesized a series of 5-substituted amide selenodiazoles, based on the parent structure of ebselen, an organoselenium drug with proven cytoprotective activity, and solubilized them in polymeric micelles of poloxamines, poly(ethylene oxide)-poly(propylene oxide) X-shaped tetrablock-copolymers. Scattering methods (SANS and DLS) were employed to characterize the micellar nanocarriers. MTT biological evaluation highlights the selectivity of the Se-compounds towards cancer cells, with MCF-7 standing as the most responsive line. The alkylation of the heterocycle with a 12-carbon hydrophobic tail displays the highest activity, showing a 100-fold increase with respect to ebselen. This compound also exhibits the greatest increase in solubility in poloxamine micelles, overall resulting in a one-fold increase in activity with respect to the non-formulated form, making it a hit compound for further optimization., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Selenium nanoparticles have at present picked up a vital prospect in the field of medicine, due to their inquisitive properties when compared to other selenium compounds. They are comparatively better as anticancer, non- toxic, and biocompatible operators than selenite (SeO 3 -2 ) and selenate (SeO 4 -2 ) compounds. The mechanism behind the anticancerous property of SeNps is primarily due to the invasion of the apoptotic pathways and cell cycle arrest, which eventually lead to blockage of other pathways. Conjugation or surface modification of selenium nanoparticles enhances its anticancer adequacy by antibiotics, biomolecules or phytochemical compounds present in microbes or plants. Selenium, being an integral part of enzyme like glutathione peroxidase (GPx) and other seleno-chemical compounds, can enhance the chemotherapeutic activity by acting as a functional division of redox center and inhibiting the tissues from cellular damage by ROS. SeNps can open ways to new regular strategies for treating illnesses like malignancy, and this audit expresses the reasons why these nano measured medications can be the following huge achievement as chemotherapeutic operators., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chitosan-stabilized selenium nanoparticles (CTS-SeNPs) were prepared through the reduction of selenite acid with ascorbic acid. The optimal synthesis conditions of CTS-SeNPs were obtained by orthogonal experiments. Besides, the size, morphology and stability of CTS-SeNPs were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM) and dynamic light scattering (DLS). The results showed that, the CTS-SeNPs with diameter of about 54 nm could be obtained under the optimal conditions (temperature of 25 °C, reaction time of 2 h, Vc concentration of 0.04 M and the CTS concentration of 1.0 mg/mL). CTS-SeNPs were uniform spherical and could be stable for approximately 60 days at 4 °C. Further, the antidiabetic activities of CTS-SeNPs in streptozotocin (STZ)-induced diabetic mice were investigated as well. The results revealed that CTS-SeNPs at a dose of 2.0 mg Se/kg bw exhibited higher antidiabetic activity than other doses of CTS-SeNPs and other selenium compounds with the same selenium content., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Selenium nanoparticles (SeNPs) as a new replacement source of other Se forms applied in nutritional supplements have been associated with health-related issues. Pectin (PEC) as a well-known food-grade polysaccharide has been considered as a potential soft template for the preparation and stabilization of SeNPs in aqueous medium. In this study, therefore, PEC was used as a stabilizer and dispersing agent to form well-dispersed and stable SeNPs under a simple redox system of selenite and ascorbic acid. Se/PEC ratios significantly affected the color of the suspension, particle size, and surface morphology of the as-prepared SeNPs in the presence of PEC. PEC-SeNPs with a Se/PEC ratio of 1:2 appeared amorphous and exhibited a well-dispersed and stable spherical structure with an average size of ∼41 nm, which corresponds to the strong hydrogen bonding between the hydroxyl groups of PEC and SeNPs. The PEC-SeNPs (Se/PEC = 1:2) remained highly stable in different acidic solutions for at least 1 month. Small and highly stable PEC-SeNPs (Se/PEC = 1:2) possessed the strongest DPPH radical scavenging ability and antioxidant capacity among the evaluated PEC-SeNPs. They also possessed a low cytotoxic activity against cancer cells (SPCA-1 and HeLa) and normal cells (RWPE-1) in vitro. These findings suggested that pectin as a surface decorator could be effectively used to improve the stability and antioxidant capacity of SeNPs remarkably., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH₃SeH) being one of the key executors. In search of novel CH₃SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI 50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH₃SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds.

A series of selenides bearing benzenesulfonamide moieties was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the pathogenic bacteria Vibrio cholerae (VchCAα and VchCAβ) and Burkholderia pseudomallei (BpsCAβ) enzymes. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action showing excellent inhibitory action and selectivity for inhibiting VchCAα and BpsCAβ over the human (h) off-target isoforms hCA I and II. Identification of potent and possibly selective inhibitors of bacteria CAs over the human counterparts may lead to pharmacological tools useful for understanding the physiological role(s) of these under-investigated proteins., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The goal of this study was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. an 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially affect metabolic parameters and performance of growing steers grazing toxic endophyte-infected tall fescue mixed forage (E+) pasture. Predominately-Angus steers (BW = 183 ± 34 kg) were randomly selected from herds of fall-calving cows grazing E+ pasture and consuming VM mixes that contained 35 ppm Se as ISe, OSe, and MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of an E+ pasture (0.51 ppm total ergovaline per ergovalinine; 10.1 ha). Steers were assigned (n = 8 per treatment) to the same Se-form treatments upon which they were raised. Selenium treatments were administered by daily top-dressing 85 g of VM mix onto 0.23 kg soyhulls, using in-pasture Calan gates. The PROC MIXED procedure of SAS was used to assess effect of Se-form treatments on whole blood Se (ng/mL) and serum prolactin (ng/mL) at day 0, 22, 43, 64, and 86, and caudal arterial area (mm2) at day -7, 43, and 86. The effect of Se treatment on ADG (day 86), and liver glutamine synthetase (GS) mRNA, protein, and activity (nmol/mg wet tissue/min) were assessed using the PROC GLM procedure of SAS. Fisher's protected LSD procedure was used to separate treatment means. Whole blood Se increased (P < 0.01) for all treatments from day 0 to 22 and then did not change (P ≥ 0.17), and was greater (P ≤ 0.04) for MIX and OSe steers. Serum prolactin decreased (P < 0.01) over time and was greater (P < 0.05) for MIX and OSe steers. Liver GS mRNA content was 66% and 59% greater (P < 0.05) in MIX and OSe steers, respectively, than ISe steers. Liver GS protein content in MIX steers was 94% more (P < 0.01) than ISe steers. Moreover, MIX and OSe steers had 99% and 55% more (P ≤ 0.01) liver GS activity, respectively, than ISe steers. ADG was not affected (P = 0.36) by Se treatments. We conclude that consumption of 3 mg Se/d as OSe or MIX forms of Se in VM mixes increased 1) whole blood Se content, an indicator of greater whole-body Se assimilation; 2) serum prolactin, the reduction of which is a hallmark of fescue toxicosis; and 3) hepatic GS activity, indicating greater hepatic assimilation of acinar ammonia. However, 4) these positive effects on metabolic parameters were not accompanied by increased growth performance.

Objective: To compare the effectiveness of five kinds of selenium supplementation for the treatment of patients with Kashin-Beck disease, and rank these selenium supplementations based on their performance., Design: We searched for all publications between 1 January 1966 and 31 March 2017 using seven electronic databases. GRADE system to network meta-analyses (NMAs) was applied to rate the quality of the evidence. We conducted a random effects model NMA in STATA 12.1 to determine comparative effectiveness of each intervention. Rankings were obtained by using the surface under the cumulative ranking curve (SUCRA) values and mean ranks., Results: A total of 15 randomised controlled trials involving 2931 patients were included. After assessment of the overall quality of the evidence, we downgraded our primary outcomes from high to low or very low quality. NMAs showed that all five kinds of selenium supplementation had higher metaphysis X-ray improvement which were superior to placebo. Ranking on efficacy indicated that selenium salt was ranked the highest, followed by sodium selenite + vitamin E, selenium enriched yeast, sodium selenite and then sodium selenite + vitamin C., Conclusions: Based on the results of NMA, all five types of selenium supplements are more effective than placebo and so that selenium supplementation is of help in repairing metaphyseal lesions. Since the overall quality of the evidence was low or very low, the SUCRA values may be misleading and should be considered jointly with the The Grading of Recommendations Assessment, Development and Evaluation (GRADE) confidence in the estimates for each comparison. The quality of the evidence is insufficient to draw a conclusion about what method of selenium supplementation is most effective., Prospero Registration Number: CRD42016051874., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The protective effect of zinc selenium tea against metabolic syndrome (MetS) was tested by using a high-sucrose-high-fat diet (HSHFD)-induced MetS model. Fifty Sprague-Dawley rats were randomly divided into five groups: normal diet (C-group), HSHFD (CH-group), HSHFD + green tea (0.24 g/kg/day) (TH-group), HSHFD + low-dose zinc selenium organic tea (0.24 g/kg/day) (ZTHL-group), and HSHFD + high-dose zinc selenium organic tea (1.20 g/kg/day) (ZTHH-group). After 8 weeks, compared to both the C-group and CH-group, the hepatosomatic index (HI) was significantly reduced in the ZTHL-group (p < 0.05). Fasting blood glucose (FBG) levels were highest in the TH-group, followed by the CH-group, then the ZTHL-group, then the ZTHH-group, and finally the C-group. Compared with the CH-group, the serum total cholesterol (TC) and low density lipid-cholesterol (LDL-C) concentrations were significantly lower in the ZTHH-group (p < 0.05). Significant decreases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), alkaline phosphatase (ALP), and direct bilirubin (DBIL) levels were observed in ZTHL-group versus the CH-group (p < 0.05). Serum alpha-L-fucosidase (AFU) levels in the ZTHH-group were lower than in the CH-group (P < 0.01). Histopathological examination of the liver and fat biopsies illustrates that the liver cells showed a decrease in the extent of necrosis and dropsy in the ZTHL-group and ZTHH-group versus the CH-group. Zinc selenium tea showed a protection effect against hepatic damage.

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×10 9 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na 2 SeO 3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background/aim: To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells., Materials and Methods: Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells., Results: MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells., Conclusion: MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study. The exosomes were isolated from the GSC conditioned medium and the expression of IL13Rα2 in the GSC and exosomes was verified. The binding property of IL13QD to the tumor associated exosomes was initially confirmed by transmission electron microscopy. The force of attraction between the quantum dots and U251 glioma cells and the exosomes was investigated by atomic force microscopy, which indicated a higher force of binding interaction between the IL13QD and IL13Rα2 expressing glioma cells and exosomes secreted by glioma stem cells. Flow cytometry of the IL13QD and exosomes from the culture media and cerebrospinal fluid (CSF) of patients with glioma tumors indicated a distinctly populated complex pattern different from that of non-targeted quantum dots and bovine serum albumin (BSA) conjugated quantum dots confirming specific binding potential of the IL13QD to the tumor associated exosomes. The results of this study demonstrate that IL13QD can serve as an ex vivo marker for glioma stem cells and exosomes that can inform diagnosis and prognosis of patients harboring malignant disease., Statement of Significance: Functionalized quantum dots are flexible semiconductor nanomaterials which have an immense application in biomedical research. In particular, when they are functionalized with biomolecules like proteins or antibodies, they have the specialized ability to detect the expression of receptors and antigens in cells and tissues. In this study we designed a cytokine (interleukin-13) functionalized quantum dot to detect a cancer associated receptor expressed in cancer stem cells and the extracellular vesicles (exosomes) secreted by the cancer cells themselves. The binding pattern of these cytokine modified quantum dots to the cancer stem cells and exosomes alters the physical properties of the complex in the fixed and suspended form. This altered binding pattern can be monitored by a variety of techniques, including transmission electron microscopy, atomic force microscopy and flow cytometry, and subsequent characterization of this quantum dot binding profile provides useful data that can be utilized as a fingerprint to detect cancer disease progression. This type of functionalized quantum dot fingerprint is especially useful for invasive cancers including brain and other metastatic cancers and may allow for earlier detection of disease progression or recurrence, thus saving the lives of patients suffering from this devastating disease., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The present study aimed to evaluate the effect of organic and inorganic selenium (Se) supplementation on semen quality and blood serum profiles of buffalo bulls. Nine mature buffalo bulls were divided into three groups: control (non-supplemented); organic Se (10 mg Sel-Plex®/head twice weekly) and inorganic Se (10 mg sodium selenite/head twice weekly). Semen was collected twice a week for 3 months during Se supplementation. Semen properties were evaluated from fresh ejaculate. Moreover, fructose concentration, aspartate and alanine transaminase (AST and ALT) activities, total protein and total cholesterol were assayed in seminal plasma. Additionally AST, ALT, testosterone and Se levels were determined in the blood serum. Results showed that Se supplementation significantly (P < 0.05) influences the semen parameters during 3 months of treatment. Organic Se significantly (P < 0.05) increased the percentage of viable sperms compared to inorganic Se and the control group. Fructose concentration was significantly higher (P < 0.05) in the seminal plasma of organic Se-treated bulls. Serum testosterone and Se concentrations were significantly (P < 0.05) increased in the Se supplemented groups than the control group. In conclusion, Se supplementation improved the parameters of buffalo bull semen and more precisely, organic Se was more effective for the improvement of semen quality and some blood components than inorganic Se., (© 2016 Japanese Society of Animal Science.)

Selenophosphate synthetase (SPS) is essential for selenoprotein biosynthesis. In two SPS paralogues, SPS1 was only cloned from a cDNA library prepared from avian organ. However, the biological function of SPS1 in chicken central nervous system (CNS) remains largely unclear. To investigate the role of avian SPS1 in the development and selenium (Se) homeostasis of CNS, fertile eggs, chicken embryos, embryo neurons and chicks were employed in this study. The response of SPS1 transcription to the development and Se levels of CNS tissues was analyzed using qRT-PCR. SPS1 gene exists extensively in the development of chicken CNS. The wide expression of avian SPS1 can be controlled by the Se content levels, which suggests that SPS1 is important in the regulation of Se homeostasis. The fundamental mechanism of these effects is that Se alters the half-life and stability of SPS1 mRNA. Therefore, SPS1 exerts an irreplaceable biological function in chicken CNS and Se homeostasis is closely related to the expression of SPS1. These results suggested that SPS1 was required for the development and Se homeostasis of CNS in chicken.