Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice.

Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and Na2SeO3 might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and Na2SeO3 and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and Na2SeO3 (40 µg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and Na2SeO3 not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with Na2SeO3 but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.

Selenium nanoparticles inhibit the formation of atherosclerosis in apolipoprotein E deficient mice by alleviating hyperlipidemia and oxidative stress.

Atherosclerosis can cause severe cardiovascular diseases, which is the most common cause of death in the world. It's of great significance to study the prevention and treatment of atherosclerosis. Selenium nanoparticles (SeNPs) has drawn more and more attention due to high biological activity, high bioavailability, strong antioxidant capacity and low toxicity, exhibiting great potential in biomedical application. Thus, this study aimed at explore the anti-atherosclerotic effect of two kinds of SeNPs, bovine serum albumin (BSA) surface-decorated SeNPs and chitosan (CS) surface-decorated SeNPs (CS-SeNPs), in apolipoprotein E deficient (ApoE-/-) mice fed with a high-cholesterol and high-fat diet, and the possible mechanisms. The results demonstrated that both BSA-SeNPs (25, 50 and 100 µg Se/kg body weight/day) and CS-SeNPs (50 µg Se/kg body weight/day) could reduce atherosclerotic lesions in ApoE-/- mice after oral administration for 12 weeks. And these effects might mainly attributed to the ability of BSA-SeNPs and CS-SeNPs to inhibit hyperlipidemia by suppressing hepatic cholesterol and fatty acid metabolism, and alleviate oxidative stress by enhancing antioxidant activity. Moreover, the benefits of BSA-SeNPs were dose-dependent and the medium dose of BSA-SeNPs (50 µg Se/kg body weight/day) was optimal. Generally, BSA-SeNPs with mean size 38.5 nm and negative surface charge showed better anti-atherosclerotic effect than CS-SeNPs with mean size 65.8 nm and positive surface charge. These results suggested that SeNPs could significantly alleviate the formation of atherosclerosis in ApoE-/- mice, possibly by inhibiting hyperlipidemia and oxidative stress, exhibiting a potential to serve as an anti-atherosclerotic agent.

Long-term administration of low-dose selenium nanoparticles with different sizes aggravated atherosclerotic lesions and exhibited toxicity in apolipoprotein E-deficient mice.

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 µg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 µg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.

Selenium nanoparticles alleviate hyperlipidemia and vascular injury in ApoE-deficient mice by regulating cholesterol metabolism and reducing oxidative stress.

Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health worldwide. This study was designed to investigate the anti-atherosclerotic activity of selenium nanoparticles (SeNPs) in apolipoprotein E deficient (ApoE-/-) mice fed a high-cholesterol, high-fat diet. The results demonstrated that animals either treated with SeNPs (50 µg Se per kg per day) or with atorvastatin (10 mg per kg per day) alone showed significant relief of vascular injury after 8 weeks of treatment. SeNPs could obviously decrease the level of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, whereas increase serum high-density lipoprotein cholesterol. At the same time, SeNPs regulated the expression levels of key genes associated with cholesterol metabolism in the liver. Furthermore, SeNPs significantly reduced the lipid peroxidation level, but increased the NO level and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in the serum and liver. SeNPs also increased the expression levels of antioxidant selenoenzymes or selenoproteins in the liver. In addition, SeNPs could alleviate H2O2-induced cytotoxicity and oxidative stress by upregulating the activities of SOD and GPx in endothelial cells cultured in vitro. These results suggested that SeNPs could significantly alleviate hyperlipidemia and vascular injury in ApoE-/- mice, possibly by regulating cholesterol metabolism and reducing oxidative stress through antioxidant selenoenzymes/selenoproteins. SeNPs might be a potential candidate for the prevention of atherosclerosis.

Effects of kojic acid on boar sperm quality and anti-bacterial activity during liquid preservation at 17 C.

Bacteriospermia is a documented risk to sperm quality when boar semen is stored at 17 °C. The objective of this study was to evaluate the effects of kojic acid (KA) on sperm quality and anti-bacterial effect during liquid storage boar semen at 17 °C, as well as to explore sperm-oocyte binding and embryonic development in vitro. Boar semen was diluted with Beltsville thawing solution (BTS), and it contained KA at different concentrations (0, 0.02, 0.04, 0.06, 0.08, and 0.10 g/L). Bacterial concentrations and sperm quality parameters (motility, mitochondrial membrane potential, acrosome integrity, and plasma membrane integrity) were evaluated on each experimental day. Differences in microbial compositions were compared using 16S rDNA sequencing among the control group, 0.04 g/L KA, and 0.25 g/L gentamycin groups on experimental day 5, and the effects of KA on sperm capacitation, Western blot, total anti-oxidant capacity (T-AOC), reactive oxygen species (ROS) content, malondialdehyde (MDA) content, in vitro fertilization (IVF) parameters, sperm-oocyte binding, cleavage rates, and blastocyst rates were evaluated. The results showed that KA at the optimum concentration of 0.04 g/L significantly improved sperm quality parameters and sperm capacitation, increased T-AOC ability, enhanced IVF parameters and sperm-oocyte binding, increased cleavage and blastocyst rates, inhibited bacterial concentrations, reduced ROS and MDA content, and altered bacterial compositions (P < 0.05). Moreover, KA also increased the expression of anti-oxidant-related proteins, SOD1, SOD2 and CAT, and anti-apoptosis-related protein, Bcl 2, and decreased the expression of apoptosis-related proteins, caspase 3 and Bax in sperm (P < 0.05). These findings demonstrated that supplementation of antibiotic-free extenders for boar semen with 0.04 g/L KA has beneficial effects on liquid boar sperm preservation.

Effects of Isatis root polysaccharide on boar sperm quality during liquid storage and in vitro fertilization.

Liquid preservation of boar semen is a preferred method in pig husbandry, and antioxidants to protect against sperm oxidative stress during periods of storage have become the focus of recent research. Through its antioxidant activity, Isatis root polysaccharide (IRPS), a plant extract, can effectively reduce the cellular lipid peroxidation caused by the accumulation of reactive oxygen species inside mitochondria. In the present study, there was examination of the effects of no supplementation (Control) of a semen extender with or supplementation in different concentrations of IRPS (0.2, 0.4, 0.6, 0.8, and 1.2 mg/mL) on sperm quality variables and antioxidant capacity during liquid storage. The results indicate that after prolonged storage (≥ 3 days), the sperm motility was greater in the group supplemented with 0.6 mg/mL IRPS than in the other groups (P < 0.05). The use of this IRPS concentration also resulted in maintanence of acrosome integrity, plasma membrane integrity, mitochondrial membrane potential, and antioxidant capacity of the sperm (P < 0.05). Furthermore, the results of an in vitro fertilization study indicate IRPS at 0.6 mg/mL markedly increased the sperm fertilization capacity (P < 0.01) and embryonic development to the blastocyst stage (P < 0.05). The addition of 0.6 mg/mL IRPS enhanced the antioxidant capacity of boar sperm, resulting in greater preservation of sperm motility and fertilization capacity during liquid storage. These findings indicate that IRPS has the potential to be used as a component of a semen-preserving diluent to maintain sperm quality during storage.

A Novel lnc-RNA, Named lnc-ORA, Is Identified by RNA-Seq Analysis, and Its Knockdown Inhibits Adipogenesis by Regulating the PI3K/AKT/mTOR Signaling Pathway.

Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine-cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.