Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Potential anticancer activities of securinine and its molecular targets.

BACKGROUND: Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed. PURPOSE: This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug. METHODS: The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines. RESULTS: Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation. CONCLUSION: Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.

Pilot study of toxicological safety evaluation in acute and 28-day studies of selenium nanoparticles decorated by polysaccharides from Sargassum fusiforme in Kunming mice.

The monodisperse and nearly spherical selenium nanoparticles decorated by polysaccharides from Sargassum fusiforme (SFPS-SeNPs) were prepared, characterized, and evaluated in acute and 28-day toxicological safety studies. In the acute toxicity study, mice underwent oral administration of 26.94, 40.28, 60.21, 90.11, and 134.70 mg Se/kg of SFPS-SeNPs for 14 days. In the 28-day study, mice underwent a daily oral administration of 17.75, 8.87, and 4.43 mg Se/kg/day of SFPS-SeNPs, 4.43 mg Se/kg/day of Na2 SeO3 , and normal saline for 28 days. The animals' general behavior, body weight, biochemical and hematologic parameters, organ coefficients, pathological morphology, Se content, and accumulation rate of Se in vital organs were determined. Results showed that the median lethal dose was 88.76 Se mg/kg and no observed adverse effect level was 4.43 mg Se/kg/day for 28 days. Compared with Na2 SeO3 , SFPS-SeNPs may lead to slightly higher toxicological effects, and it probably accumulates in the liver in the oral dose of 4.43 mg Se/kg/day in Kunming mice. SFPS and nanotechnology can reduce the toxicity of selenium, and SFPS-SeNPs or SeNPs-polysaccharides can be potential candidates for drug delivery and food supplement. PRACTICAL APPLICATION: Selenium nanoparticles decorated by polysaccharides from Sargassum fusiforme can improve the stability and reduce the toxicity of selenium nanoparticles. These results of the toxicological safety evaluation can lay the foundation for the safe utilization of selenium nanoparticles decorated by polysaccharides and expand their application in the field of food and medicine.

Potential exploration of Fe3O4/biochar from sludge as the media of bioretention system and its comparison with conventional media.

The selection and configuration of soil media are a core issue of the bioretention system. A porous carbon material of Fe3O4/biochar (BSF) was prepared by adding pickling wastewater to modified sludge biochar, which could serve as a good adsorption performance and cheap media for bioretention system. Through the analytic hierarchy process (AHP), different media were evaluated according to their characteristics. By comparing the characteristics of BSF to bio-ceramic (BC), zeolite (ZE), and activated carbon (AC), it was found that BSF has a larger specific surface area and pore volume. The hydrological characteristics of the medium were also tested. The results show that BSF has better water-absorbing quality and hydraulic conductivity than the other three media, but the water-retention property of the medium seems to be inferior. BSF has stable adsorption performance for ammonia nitrogen (NH4+-N) and total phosphorus (TP) in rainwater. Its high adsorption capacity is maintained at 5-35°C, but it is very susceptible to pH factors. The adsorption process by BSF and other media conforms to pseudo-second-order kinetics and the Langmuir model in rainwater. In general, the performance of BSF is shown to be superior to BC, ZE, and AC, making it a potential medium for bioretention system.

Synthesis and evaluation of Grateloupia Livida polysaccharides-functionalized selenium nanoparticles.

Grateloupia Livida polysaccharides-functionalized selenium nanoparticles (GLP-SeNPs) have been successfully prepared in a simple redox system of sodium selenite and ascorbic acid. The size, morphology, structure, stability and thermal behavior were analyzed by various characterization methods. These results showed that, GLP-SeNPs (particle size of 115.54 nm) prepared in optimal synthesis conditions (temperature of 45 °C, reaction time of 3 h, GLP concentration of 1.0 mg/mL and ascorbic acid concentration of 0.04 M) obtained by orthogonal experiments were uniform spherical and could be stable for 30 days at 4 °C. GLP-SeNPs exhibited significant scavenging ability on DPPH, ABTS, hydroxyl radical and superoxide anion radical when compared to GLP and Na2SeO3. GLP-SeNPs showed selective cytotoxicity toward various human cancer cells, but not normal cells. Besides, GLP-SeNPs exhibited low oral acute toxicity. Taken together, GLP-SeNPs might be used as potential diet nutritional supplement or anticancer agent.

Preparation and antioxidant activity of selenium nanoparticles decorated by polysaccharides from Sargassum fusiforme.

In this study, the response surface method was employed to optimize the extraction conditions of the ultrasonic-assisted extraction of Sargassum fusiforme polysaccharides (SFPS). The effects of four independent variables (hot water extraction time, ultrasonic time, ultrasonic power, and material-to-liquid ratio) on the extraction rate of SFPS were tested. In addition, the SFPS functionalized nanoselenium (SFPS-SeNPs) was prepared by chemical reduction method, whose characterization and in vitro antioxidant activity were investigated. The results showed that the yield of the crude SFPS was 25.8% at the optimal conditions of material-to-liquid ratio 1:50 (w/v), ultrasonic power 200 W, ultrasonic time 15 min, and water bath time 130 min. A series of characterization experiments showed that the SFPS-SeNPs performed higher dispersion and stability than naked SeNPs. Furthermore, the in vitro antioxidant activity assay indicated that SFPS functioned as a modifier improved the free radical scavenging activity of SeNPs significantly. In conclusion, this study provided a method to extract SFPS as a carrier for SeNPs, and SFPS-SeNPs could not only improve the stability of SeNPs, but also exerted the biological activities of SFPS. PRACTICAL APPLICATION: This research provided new ideas for the application of SFPS and the development of nanoselenium preparation carriers.

MM-6mAPred: identifying DNA N6-methyladenine sites based on Markov model.

MOTIVATION: Recent studies have shown that DNA N6-methyladenine (6mA) plays an important role in epigenetic modification of eukaryotic organisms. It has been found that 6mA is closely related to embryonic development, stress response and so on. Developing a new algorithm to quickly and accurately identify 6mA sites in genomes is important for explore their biological functions. RESULTS: In this paper, we proposed a new classification method called MM-6mAPred based on a Markov model which makes use of the transition probability between adjacent nucleotides to identify 6mA site. The sensitivity and specificity of our method are 89.32% and 90.11%, respectively. The overall accuracy of our method is 89.72%, which is 6.59% higher than that of the previous method i6mA-Pred. It indicated that, compared with the 41 nucleotide chemical properties used by i6mA-Pred, the transition probability between adjacent nucleotides can capture more discriminant sequence information. AVAILABILITY AND IMPLEMENTATION: The web server of MM-6mAPred is freely accessible at http://www.insect-genome.com/MM-6mAPred/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Anti-obesity effects of Spirulina platensis protein hydrolysate by modulating brain-liver axis in high-fat diet fed mice.

Spirulina platensis is a blue-green algae with potential anti-obesity effects. In this study, the anti-obesity effects of whole Spirulina platensis (WSP), Spirulina platensis protein (SPP) and Spirulina platensis protein hydrolysate (SPPH) were compared in high-fat diet fed mice, and the potential acting mechanism of SPPH was also investigated. Totally, SPPH exhibited good anti-obesity effects (reducing 39.8%±9.7% of body weight), lowering 23.8%±1.6% of serum glucose, decreasing 20.8%±1.4% of total cholesterol, while positive drug Simvastatin had the corresponding values: 8.3%±4.6%, 24.8%±1.9% and -2.1%±0.2%, respectively. Subsequently, PCR array was used to conduct gene expression analysis in brain and liver tissues of SPPH-treated mice, which displayed distinctly different expression pattern. The most markedly changed genes included: Acadm (-34.7 fold), Gcg (2.5 fold), Adra2b (2 fold) and Ghsr (2 fold) in brain; Retn (39 fold), Fabp4 (15.5 fold), Ppard (6 fold) and Slc27a1 (5.4 fold) in liver. Further network analysis demonstrated that the significantly expressed genes in brain and liver tissues were mapped into an interacting network, suggesting a modulatory effect on brain-liver axis, major pathways were involved in the axis: PPAR, adipocytokine, AMPK, non-alcoholic fatty liver disease and MAPK. This study showed that Spirulina platensis protein hydrolysate possessed anti-obesity effect in mice.

Aqueous extract of danshen (Salvia miltiorrhiza Bunge) protects ovariectomized rats fed with high-fat diet from endothelial dysfunction.

OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in postmenopausal women. Danshen, the dried root of Salvia miltiorrhiza Bunge, has been used clinically in China to treat CVD and dyslipidemia in postmenopausal women, and its major active ingredients have been found to have an estrogenic effect. The aim of this study was to elucidate the underlying mechanism of danshen's protective effects on vascular function in an ovariectomized (OVX) hyperlipidemic rat model. METHODS: Thirty-five 6-month-old female Sprague-Dawley rats were randomly divided into five groups: sham-operated rats with low-fat control diet + vehicle, sham-operated rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle, OVX rats with HFD + 17ß-estradiol (1 mg kg d, PO), and OVX rats with HFD + danshen aqueous extract (600 mg kg d, PO). After 12 weeks of treatment, gains in body weight and serum lipid profile levels in rats were measured and histological examination of livers was carried out. Vascular function was evaluated by measuring relaxation responses. Molecular mechanisms were also analyzed in isolated aorta. RESULTS: Treatment with danshen aqueous extract reduced body weight gain, improved serum lipid profiles, and prevented formation of fatty liver induced by HFD and OVX. In addition, danshen could increase endothelial-dependent vasorelaxation and displayed vasoprotection in OVX rats fed with HFD, primarily by stimulating nitric oxide (NO) production, up-regulating the mRNA expression of endothelial NO synthase, and down-regulating the mRNA expression of tumor necrosis factor α, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 in the isolated aortas. CONCLUSIONS: We conclude for the first time that danshen aqueous extract could protect OVX rats fed with HFD from endothelial dysfunction. Its effect may be related to its abilities to normalize serum lipid profiles and enhance NO availability in the vascular system. Our findings indicate that danshen aqueous extract could be a promising natural supplement for postmenopausal women for preventing CVD.

[Comparison on extraction of volatile oils from Lithospermum erythrorhizon by different methods].

OBJECTIVE: To extract the volatile oils from Lithospermum erythrorhizon via ultrasound-enhanced sub-critical water extraction (USWE) and compare with ultrasound-enhanced solvent extraction (USE) and steam distillation extraction (SD). METHODS: The extraction yield of the volatile oils, the containing components of extract, the effect of scanvenging activities on free radical DPPH and reducing activities as well as the inhibitory on escherichia coli and staphylococcus aureus were investigated. RESULTS: The extraction yield of volatile oils by USWE, USE and SD were 2.39%, 1.93% and 0.62%, respectively, the extracts by three methods all contained six major components, but the extracts by SD and USE contained more impurities. The inhibitory effect on escherichia coli and staphylococcus aureus of the extract by SD and its reducing action were the best,but those by USWE were the worst. CONCLUSION: the extraction yield of volatile oils by USWE is the highest, and it contains less impurities based on the worst in reducing power and inhibitory effects.