Design and characterization of protein-quercetin bioactive nanoparticles

<p>Abstract</p> <p>Background</p> <p>The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA), lysozyme (Lys), or myoglobin (Mb) used to load hydrophobic drugs such as quercetin (Q) and other flavonoids.</p> <p>Results</p> <p>Induced by dimethyl sulfoxide (DMSO), BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated.</p> <p>Conclusions</p> <p>BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology.</p

Pea albumin extracted from pea (Pisum sativum L.) seed protects mice from high fat diet-induced obesity by modulating lipid metabolism and gut microbiota

Plant protein has been reported to play a key role in the prevention of obesity and associated complications. It is unknown whether pea albumin may exert anit-obesity and obesity-associated metabolic disorders alleviation. Pea albumin was isolated from pea seed (Pisum sativum L.) and determined its functional role for anti-obesity and metabolic disorders alleviation in high fat diet (HFD)-fed mice. Pea albumin administration reduced body weight gain, improved glucose tolerance and insulin sensitivity, reduced inflammatory cytokines secretion, and alleviated hepatic steatosis in HFD-fed mice. Interestingly, pea albumin inhibited lipid accumulation in 3T3-L1 cells in vitro and modulated lipid metabolism by upregulating critical proteins implicated in lipolysis and fatty acid oxidation, and downregulating lipogenesis in vivo. Moreover, pea albumin restored gut microbial composition to normal fat diet condition and selectively promoted the growth of beneficial gut bacteria (Akkermansia, Parabacteroides etc.). Collectively, the data demonstrated that pea albumin protects mice from HFD-induced obesity and associated metabolic disorders

Dynamic Transformation of Nano-MoS2 in a Soil-Plant System Empowers Its Multifunctionality on Soybean Growth

Molybdenum disulfide (nano-MoS2) nanomaterials have shown great potential for biomedical and catalytic applications due to their unique enzyme-mimicking properties. However, their potential agricultural applications have been largely unexplored. A key factor prior to the application of nano-MoS2 in agriculture is understanding its behavior in a complex soil-plant system, particularly in terms of its transformation. Here, we investigate the distribution and transformation of two types of nano-MoS2 (MoS2 nanoparticles and MoS2 nanosheets) in a soil-soybean system through a combination of synchrotron radiation-based X-ray absorption near-edge spectroscopy (XANES) and single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS). We found that MoS2 nanoparticles (NPs) transform dynamically in soil and plant tissues, releasing molybdenum (Mo) and sulfur (S) that can be incorporated gradually into the key enzymes involved in nitrogen metabolism and the antioxidant system, while the rest remain intact and act as nanozymes. Notably, there is 247.9 mg/kg of organic Mo in the nodule, while there is only 49.9 mg/kg of MoS2 NPs. This study demonstrates that it is the transformation that leads to the multifunctionality of MoS2, which can improve the biological nitrogen fixation (BNF) and growth. Therefore, MoS2 NPs enable a 30% increase in yield compared to the traditional molybdenum fertilizer (Na2MoO4). Excessive transformation of MoS2 nanosheets (NS) leads to the overaccumulation of Mo and sulfate in the plant, which damages the nodule function and yield. The study highlights the importance of understanding the transformation of nanomaterials for agricultural applications in future studies.</p

Diversity in gut bacterial community of school-age children in Asia

10.1038/srep08397Scientific Reports

Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance

In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.Macrophage inflammation promotes insulin resistance during diet-induced obesity. Here the authors show that macrophage NOC4L is decreased in humans and mice with obesity, that macrophage NOC4L deficiency aggravated high-fat diet induced inflammation and insulin resistance, and that NOC4L interacts with toll-like receptor 4, to inhibit endocytosis, and thus blocks TLF4/TRIF inflammatory signaling

A Role of Exopolysaccharide Produced by <i>Streptococcus thermophilus</i> in the Intestinal Inflammation and Mucosal Barrier in Caco-2 Monolayer and Dextran Sulphate Sodium-Induced Experimental Murine Colitis

Exopolysaccharide (EPS) produced by probiotics may play an important role in gastrointestinal disease prevention, including ulcerative colitis. However, there is no literature reporting on the intervention effects of purified EPS. The aim of this study was to investigate the alleviating effect of the purified EPS produced by Streptococcus thermophilus MN-BM-A01 on murine model of colitis induced by dextran sulphate sodium (DSS). A water-soluble heteropolysaccharide (EPS-1) isolated from MN-BM-A01 was composed of rhamnose, glucose, galactose, and mannose in a molar ratio of 12.9:26.0:60.9:0.25, with molecular weight of 4.23 &#215; 105 Da. After EPS-1 administration, the disease severity of mouse colitis was significantly alleviated, mainly manifesting as the decrease of disease activity index and mitigated colonic epithelial cell injury. Meanwhile, pro-inflammatory cytokines levels (tumor necrosis factor-&#945;, interleukin-6, and interferon-&#947;) were significantly suppressed, the reduced expressions of tight junction protein (claudin-1, occludin, and E-canherin) were counteracted. In addition, the results in vitro showed that EPS-1 protected intestinal barrier integrity from the disruption by lipopolysaccharide in Caco-2 monolayer, increased expression of tight junction and alleviated pro-inflammatory response. Collectively, our study confirmed the protective effects of purified EPS produced by Streptococcus thermophilus on acute colitis via alleviating intestinal inflammation and improving mucosal barrier function

The Copper Homeostasis Transcription Factor CopR Is Involved in H2O2 Stress in Lactobacillus plantarum CAUH2

Transcriptional factors (TFs) play important roles in the responses to oxidative, acid, and other environmental stresses in Gram-positive bacteria, but the regulatory mechanism of TFs involved in oxidative stress remains unknown in lactic acid bacteria. In the present work, homologous overexpression strains with 43 TFs were constructed in the Lactobacillus plantarum CAUH2 parent strain. The strain overexpressing CopR displayed the highest sensitivity and a 110-fold decrease in survival rate under H2O2 challenge. The importance of CopR in the response to H2O2 stress was further confirmed by a 10.8-fold increase in the survival of a copR insertion mutant. In silico analysis of the genes flanking copR revealed putative CopR-binding “cop box” sequences in the promoter region of the adjacent gene copB encoding a Cu2+-exporting ATPase. Electrophoretic mobility shift assay (EMSA) analysis demonstrated the specific binding of CopR with copB in vitro, suggesting copB is a target gene of CopR in L. plantarum. The role of CopB involved in oxidative stress was verified by the significantly decreased survival in the copB mutant. Furthermore, a growth defect in copper-containing medium demonstrated that CopB functions as an export ATPase for copper ions. Furthermore, EMSAs revealed that CopR functions as a regulator that negatively regulates copB gene and Cu2+ serves as inducer of CopR to activate the expression of CopB in response to H2O2 stress in L. plantarum CAUH2. Our findings indicated that CopR plays an important role in enhancing oxidative resistance by regulating copB to modulate copper homeostasis

Lactobacillus paracasei N1115 attenuates obesity in high-fat diet-induced obese mice

Disruption of the microbial structure of intestinal bacteria due to a high-fat diet (HFD) is closely associated with metabolic disorders, such as obesity and type 2 diabetes. Probiotics are known to modulate the gut microbiota; therefore, we demonstrated the capability of Lactobacillus paracasei N1115 (LC-N1115) to attenuate obesity. Four-week-old male C57BL/6J mice were fed a HFD for 12 weeks to induce obesity and were then randomized to supplemented placebo or LC-N1115 treatment group for another 12 weeks. LC-N1115 treatment reduced weight gain and liver fat accumulation as well as triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The administration of LC-N1115 suppressed the expression of fatty acid synthase, interleukin-1 β, and toll-like receptor 4. Notably, the operational taxonomic units that negatively and positively correlated with the obesity phenotypes were enriched and reduced, respectively, in the LC-N1115 treatment group. These results indicate that LC-N1115 attenuates obesity by modulating the gut microbiota and the expression of lipid synthesis and proinflammatory cytokine genes

Quantitative Profiling of Bile Acids in Feces of Humans and Rodents by Ultra-High-Performance Liquid Chromatography&ndash;Quadrupole Time-of-Flight Mass Spectrometry

A simple, sensitive, and reliable quantification and identification method was developed and validated for simultaneous analysis of 58 bile acids (BAs) in human and rodent (mouse and rat) fecal samples. The method involves an extraction step with a 5% ammonium&ndash;ethanol aqueous solution; the BAs were quantified by high-resolution mass spectrometry (ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, UPLC&ndash;Q-TOF). The recoveries were 80.05&ndash;120.83%, with coefficient variations (CVs) of 0.01&ndash;9.82% for three biological species. The limits of detection (LODs) were in the range of 0.01&ndash;0.24 &mu;g/kg, and the limits of quantification (LOQs) ranged from 0.03 to 0.81 &mu;g/kg. In addition, the analytical method was used to identify and quantify BAs in end-stage renal disease (ESRD) patients, C57BL/6 mice, and Sprague-Dawley (SD) rats. The fecal BA profile and analysis of BA indices in these samples provide valuable information for further BA metabolic disorder research