Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress.

The enhancement of bioavailability of food bioactive compounds as dietary supplements can be achieved through the development of targeted delivery systems. This study aimed to develop a novel dual-targeted delivery system for hepatocytes and mitochondria using phacoemulsification self-assembly. The delivery systems were engineered by modifying whey protein isolate (WPI) with galactose oligosaccharide (GOS) and triphenylphosphonium (TPP) to improve AXT transport to the liver and promote hepatic well-being. The dual-targeted nanoparticles (AXT@TPP-WPI-GOS) significantly reduced reactive oxygen species in in vitro experiments, thereby slowing down apoptosis. The AXT@TPP-WPI-GOS exhibited a prominent mitochondrial targeting capacity with a Pearson correlation coefficient of 0.76 at 4 h. In vivo pharmacokinetic experiments revealed that AXT@TPP-WPI-GOS could enhance AXT utilization by 28.18 ± 11.69%. Fluorescence imaging in mice demonstrated significantly higher levels of AXT@TPP-WPI-GOS accumulation in the liver compared to that of free AXT. Therefore, these nanoparticles hold promising applications in nutrient fortification, improving the bioavailability of AXT and supporting hepatic well-being.

Tilianin improves lipid profile and alleviates atherosclerosis in ApoE-/- mice through up-regulation of SREBP2-mediated LDLR expression.

BACKGROUND: The huge global burden of atherosclerotic cardiovascular diseases (CVDs) represents an urgent unmet need for the development of novel therapeutics. Dracocephalum moldavica L. has been used as a traditional Uygur medicine to treat various CVDs for centuries. Tilianin is a major flavonoid component of D. moldavica L. and has potential for preventing atherosclerosis. However, the molecular mechanisms that tilianin attenuate atherosclerosis are far from fully understood. PURPOSES: The purpose of this study is to investigate the efficiency and underlying mechanisms of tilianin in controlling lipid profile and preventing atherogenesis. METHODS: The lipid-lowering effect of tilianin was evaluated in C57BL/6 and ApoE-/- mice by systematically determining serum biochemical parameters. The effects of tilianin on the atherosclerotic lesion were observed in aortic roots and whole aortas of ApoE-/- mice with oil red O staining. Caecal content from ApoE-/- mice were collected for 16S rRNA gene sequence analysis to assess the structure of the gut microbiota. The inhibition of hepatosteatosis was verified by histological examination, and a liver transcriptome analysis was performed to elucidate the tilianin-induced hepatic transcriptional alterations. Effects of tilianin on the expression and function of LDLR were examined in HepG2 cells and ApoE-/- mice. Further mechanisms underlying the efficacy of tilianin were investigated in HepG2 cells. RESULTS: Tilianin treatment improved lipid profiles in C57BL/6 and dyslipidemic ApoE-/- mice, especially reducing the serum LDL-cholesterol (LDL-C) level. Significant reductions of atherosclerotic lesion area and hepatosteatosis were observed in tilianin-treated ApoE-/- mice. The altered gut microbial composition in tilianin groups was associated with lipid metabolism and atherosclerosis. The liver transcriptome revealed that tilianin regulated the transcription of lipid metabolism-related genes. Then both in vitro and in vivo analyses revealed the potent effect of tilianin to enhance hepatic LDLR expression and its mediated LDL-C uptake. Further studies confirmed a critical role of SREBP2 in hepatic LDLR up-regulation by tilianin via increasing precursor and thus mature nuclear SREBP2 level. CONCLUSION: This study demonstrated the lipid-lowering effect of tilianin through SREBP2-mediated transcriptional activation of LDLR. Our findings reveal a novel anti-atherosclerotic mechanism of tilianin and underlie its potential clinical use in modulating CVDs with good availability and affordability.

Quantitative analysis of differentially expressed milk fat globule membrane proteins between donkey and bovine colostrum based on high-performance liquid chromatography with tandem mass spectrometry proteomics.

This study was designed to provide novel insights into milk fat globule membrane (MFGM) proteins in donkey colostrum (DC) and bovine colostrum (BC) using quantitative proteomics. In total, 179 (DC) and 195 (BC) MFGM proteins were characterized, including 71 shared, 108 DC-specific, and 124 BC-specific proteins. Fifty-one shared proteins were selected as differentially expressed MFGM proteins, including 21 upregulated and 30 downregulated proteins in DC. Gene ontology analysis showed that these proteins were mainly enriched in cellular components, including the extracellular exosome, extracellular space, and plasma membrane. Additionally, they were further involved in metabolic pathways, including cholesterol metabolism, the peroxisome proliferator-activated receptor signaling pathway, and purine metabolism. Furthermore, several key protein factors with high connectivity were identified via protein-protein interaction analysis. These results provide more comprehensive knowledge of differences in the biological properties of MFGM proteins in DC and BC as well as pave the way for future studies of the nutritional and functional requirements of these important ingredients toward the development of dairy products based on multiple milk sources.

Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

In Vitro and In Vivo Inhibition of Helicobacter pylori by Ethanolic Extracts of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

Natural products are sources for exploratory development of new agents to combat the gastric pathogen Helicobacter pylori. Some edible fungi, such as the lion's mane mushroom, have been used for several thousand years to treat digestive diseases. Ethanol-based extractions to prepare Hericium erinaceus extracts were tested for growth inhibition ability of six different H. pylori strains at an extract concentration that did not inhibit Escherichia coli growth, and further for dose-dependent antibactericidal capacity on H. pylori. H. erinaceus extract exhibited similar growth inhibitory effects on all H. pylori strains tested, with a minimum inhibitory concentration of about 2 mg/mL. H. pylori survival in phosphate-buffered saline (PBS) was decreased 3 logs by 2 mg/mL extract addition. H. erinaceus extract inhibited H. pylori adhesion capacity to human gastric epithelial cell line (ATCC CRL-1739) (AGS), even when H. erinaceus extract was added at a concentration that affected neither H. pylori nor AGS viability. Interleukin-8 (IL-8, representing an immune response factor) in supernatants from AGS and 8-oxo-guanine (8-oxoG, a marker for oxidative DNA damage among the total host cell DNA) were measured from AGS cells exposed to H. erinaceus extract before H. pylori addition. The subsequent H. pylori-mediated immune response (IL-8 production) was significantly (P < 0.01) decreased by H. erinaceus extract; at 1.0 mg/mL extract addition, IL-8 expression returned to nearly background level (no H. pylori added). H. pylori infection of AGS caused a 3-fold increase in host 8-oxoG, but this increase was abolished by including 2 mg/mL H. erinaceus extract. Mouse colonization assays of C57BL mice were performed on homogenized stomachs 3 weeks after inoculating H. pylori into the animals; mice receiving the H. erinaceus extract had a mean H. pylori load of 6 × 104 CFU/g of stomach, about 1 log lower than the control (no extract) animals.

Gynurincola endophyticus gen. nov., sp. nov., a novel bacterium of the family Chitinophagaceae.

A Gram-stain-negative, rod-shaped (0.2-0.4 µm×1.2-1.7 µm), endophytic bacterium, designated HBUM179779T, was isolated from the stem of a medicinal plant,Gynura bicolor, collected from Pixian county in Sichuan province, China. The strain did not produce endospores and its cells could secrete mucus. The predominant menaquinone was MK-7. The polar lipids were phosphatidylethanolamine, phosphatidylinositolmannosides, two unknown aminolipids, two unknown glycolipids and an unknown phospholipid. Branched fatty acids (iso-) and hydroxy fatty acids were the main fatty acids, which mainly included iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HBUM179779T fell within the family Chitinophagaceae, and its closest neighbour was Pseudoflavitalea rhizosphaerae T16R-265T (94.46 %). However, strain HBUM179779T did not make a coherent clade with members of the recognized organisms. The average nucleotide identity value between strain HBUM179779T and Pseudoflavitalea rhizosphaerae T16R-265T was 67.1 %. On the basis of the phylogenetic and phenotypic characteristics of this bacterium, a novel genus and species, Gynurincola endophyticus gen. nov., sp. nov., is proposed. The type strain is HBUM179779T (=CGMCC 1.15525T=NBRC 112424T).

Molecular hydrogen generated by elemental magnesium supplementation alters rumen fermentation and microbiota in goats.

We tested the hypotheses that supplementation of a diet with elemental Mg increases ruminal dissolved H2 (dH2) in rumen fluid, which in turn alters rumen fermentation and microbial community in goats. In a randomised block design, twenty growing goats were allocated to two treatments fed the same basal diet with 1·45 % Mg(OH)2 or 0·6 % elemental Mg. After 28 d of adaptation, we collected total faeces to measure total tract digestibility, rumen contents to analyse fermentation end products and microbial groups, and measured methane (CH4) emission using respiration chambers. Ruminal Mg2+ concentration was similar in both treatments. Elemental Mg supplementation increased dH2 at 2·5 h post morning feeding (+180 %, P<0·001). Elemental Mg supplementation decreased total volatile fatty acid concentration (-8·6 %, P<0·001), the acetate:propionate ratio (-11·8 %, P<0·03) and fungal copy numbers (-63·6 %, P=0·006), and increased propionate molar percentage (+11·6 %, P<0·001), methanogen copy numbers (+47·9 %, P<0·001), dissolved CH4 (+35·6 %, P<0·001) and CH4 emissions (+11·7 %, P=0·03), compared with Mg(OH)2 supplementation. The bacterial community composition in both treatments was overall similar. Ruminal dH2 was negatively correlated with acetate molar percentage and fungal copy numbers (P<0·05), and positively correlated with propionate molar percentage and methanogen copy numbers (P<0·05). In summary, elemental Mg supplementation increased ruminal dH2 concentration, which inhibited rumen fermentation, enhanced methanogenesis and seemed to shift fermentation pathways from acetate to propionate, and altered microbiota by decreasing fungi and increasing methanogens.

Glycomyces artemisiae sp. nov., an endophytic actinomycete isolated from the roots of Artemisia argyi.

An endophytic actinomycete strain, IXS4(T), was isolated from the root of Artemisia argyi, a medicinal plant collected from Yesanpo located in Laishui county, Hebei province, China. The 16S rRNA gene sequence of strain IXS(T) showed most similarity to Glycomyces mayteni YIM 61331(T) (98.23% 16S rRNA gene sequence similarity), Glycomyces scopariae YIM 56256(T) (98.00%), Glycomyces sambucus E71(T) (97.90%) and Glycomyces algeriensis NRRL B-16327(T) (97.10%). DNA-DNA hybridization values between strain IXS4(T) and the closely related type strains were well below 70%. The strain also showed a number of physiological and biochemical characteristics that were distinct from the closely related species. The strain contained MK-10(H2) and MK-11(H0) as the detected menaquinones. The peptidoglycan was mainly meso-diaminopimelic acid and the whole-cell sugars contained galactose, glucose, mannose, xylose and ribose. The major cellular fatty acids were iso-C14:0, iso-C15:0, iso-C16:0, anteiso-C15:0 and anteiso-C17:0. Based on the genetic and phenotypic properties, it is proposed that strain IXS4(T) represents a novel species of the genus Glycomyces, with the name http://dx.doi.org/10.1601/nm.7671Glycomyces artemisiae sp. nov. The type strain is IXS4(T) ( = HBUM178000(T) = CGMCC 4.7067(T) = NBRC 109773(T)).

Dynamic phosphorus budget for lake-watershed ecosystems.

Lake eutrophication caused by excess phosphorus (P) loading from point sources (PS) and nonpoint sources (NPS) is a persistent and serious ecological problem in China. A phosphorus budget, based on material flow analysis (MFA) and system dynamic (SD), is proposed and applied for the agriculture-dominated Qionghai Lake watershed located in southwestern China. The MFA-SD approach will not only cover the transporting process of P in the lake-watershed ecosystems, but also can deal with the changes of P budget due to the dynamics of watershed. P inflows include the fertilizer for agricultural croplands, soil losses, domestic sewage discharges, and the atmospheric disposition such as precipitation and dust sinking. Outflows are consisted of hydrologic export, water resources development, fishery and aquatic plants harvesting. The internal P recycling processes are also considered in this paper. From 1988 to 2015, the total P inflows for Lake Qionghai are in a rapid increase from 35.65 to 78.73 t/a, which results in the rising of P concentration in the lake. Among the total P load 2015, agricultural loss and domestic sewage account for 70.60% and 17.27% respectively, directly related to the rapid social-economic development and the swift urbanization. Future management programs designed to reduce P inputs must be put into practices in the coming years to ensure the ecosystem health in the watershed.