Resveratrol-loaded selenium/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer's disease.

Resveratrol (Res) is a common natural polyphenol that inhibits inflammation and oxidative stress in Alzheimer's disease (AD). However, the absorption efficiency and in vivo bioactivity of Res are poor. High fat diet-induced metabolic disorders, including obesity and insulin resistance, can promote AD-related ß-amyloid (Aß) aggregation, Tau protein phosphorylation and neurotoxicity. Gut microbiota play a role in modulating metabolic syndrome and cognitive impairment. Herein, flower-like Res-loaded selenium nanoparticles/chitosan nanoparticles (Res@SeNPs@Res-CS-NPs) with higher loading capacity (64 %) were prepared to regulate gut microbiota in cases of AD with metabolic disorder. The nano-flowers could restore gut microbiota homeostasis to reduce lipopolysaccharide (LPS) formation and LPS-induced neuroinflammation. Additionally, Res@SeNPs@Res-CS-NPs can prevent lipid deposition and insulin resistance by decreasing Firmicutes levels and increasing Bacteroidetes levels in the gut, further inhibiting Aß aggregation and Tau protein phosphorylation through the JNK/AKT/GSK3ß signaling pathway. Moreover, Res@SeNPs@Res-CS-NPs treatment was able to regulate the relative levels of gut microbiota associated with oxidative stress, inflammation and lipid deposition, including Entercoccus, Colidextribacter, Rikenella, Ruminococcus, Candidatus_Saccharimonas, Alloprevotella and Lachnospiraceae_UCG-006. Overall, Res@SeNPs@Res-CS-NPs significantly enhances cognitive ability in AD mice with metabolic disorder, highlighting their potential for preventing cognitive impairments in AD.

A Flower-like Brain Targeted Selenium Nanocluster Lowers the Chlorogenic Acid Dose for Ameliorating Cognitive Impairment in APP/PS1 Mice.

Aß aggregation-related neuroinflammation and imbalance of brain glucose homeostasis play important roles in the pathological process of Alzheimer's disease (AD). Chlorogenic acid (CGA) is one of the most common dietary polyphenols with neuroprotective effects. However, due to the low bioavailability of CGA, its application dose is usually high in vivo. In our previous study, the spherical selenium nanoparticles act as drug carriers to improve the bioactivity of resveratrol. Here, the brain-targeting peptide (TGN peptide) and CGA were used to prepare a new flowerlike selenium nanocluster (TGN-CGA@SeNCs) for enhancing the bioavailability of CGA. After decoration on selenium nanoclusters, the solubility and stability of CGA was obviously increased. Oral administration of a low dose of CGA (80 mg/kg/body weight) only slightly inhibited Aß aggregate-related neuroinflammation and glucose homeostasis disorder in the brain. Moreover, CGA showed less effect on increasing the diversity and richness of gut microbiota. At the same concentration, the CGA-modified selenium nanocluster (CGA@SeNCs) and TGN-CGA@SeNCs showed better function in ameliorating the gut microbiota disorder. Especially, TGN-CGA@SeNCs significantly increased the relative abundance of Turicibacter, Colidextribacter, Ruminococcus, Alloprevotella, and Alistipes against oxidative stress, inflammation, and glucose homeostasis imbalance. Notably, only TGN-CGA@SeNCs can transport through the blood-brain barrier (BBB), and TGN-CGA@SeNCs showed better effects than CGA@SeNCs in regulating Aß aggregation and improving brain glucose homeostasis. These results broadened the application of TGN-CGA@SeNCs, effectively improving the bioactivity of CGA, which also lowers the CGA dose for preventing AD progression.

Multifunctional Selenium Nanoparticles with Different Surface Modifications Ameliorate Neuroinflammation through the Gut Microbiota-NLRP3 Inflammasome-Brain Axis in APP/PS1 Mice.

Neuroinflammation plays a critical role in Alzheimer's disease (AD). However, it is still unknown if neuroinflammation can be effectively treated using selenium nanoparticles (SeNPs) with different surface modifications. In this study, SeNPs were coated with dihydromyricetin (DMY), a natural polyphenol, to obtain DMY@SeNPs. Given that DMY@SeNPs are unstable under physiological conditions, they were decorated step-by-step with chitosan (CS/DMY@SeNPs) and with the blood brain barrier (BBB) targeting peptide Tg (TGNYKALHPHNG) to yield Tg-CS/DMY@SeNPs, which significantly reduced the aggregation of Aß and improved the anti-inflammatory effects of SeNPs in vitro. The mechanisms of CS/DMY@SeNPs and Tg-CS/DMY@SeNPs on regulating neuroinflammation are different. Only Tg-CS/DMY@SeNPs can cross the BBB; therefore, Tg-CS/DMY@SeNPs more successfully inhibited Aß aggregation and reduced inflammatory cytokine secretion via the NF-κB pathway in the brain of APP/PS1 mice compared to CS/DMY@SeNPs. Furthermore, both types of nanoparticles, however, were able to repair the gut barrier and regulate the population of inflammatory-related gut microbiota such as Bifidobacterium, Dubosiella, and Desulfovibrio. Of note, the relative abundance of Gordonibacter was only enhanced by Tg-CS/DMY@SeNPs, thereby downregulating the protein expression of the NLRP3 inflammasome and the concentrations of serum inflammatory factors. This demonstrates that Tg-CS/DMY@SeNPs ameliorate neuroinflammation through the gut microbiota-NLRP3 inflammasome-brain axis. Overall, our data suggest that Tg-CS/DMY@SeNPs are an ideal drug candidate for AD treatment.

Effect of dandelion root polysaccharide on the pasting, gelatinization, rheology, structural properties and in vitro digestibility of corn starch.

The influence of dandelion root polysaccharide (DRP) on the gelatinization properties and in vitro digestibility of corn starch was investigated. Pasting behaviors indicated that the addition of DRP led to an increase of the pasting temperature and a decrease of viscosity. Compared to native corn starch, the swelling power, solubility and content of amylose leaching were reduced as the DRP addition increased. Scanning electron microscopy (SEM) analysis showed that DRP was easily dispersed in the starchy matrix, and a more uniform structure was observed in corn starch/DRP pastes. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) analyses confirmed that the crystal shape of the corn starch gels was not changed and no new groups were produced with increasing DRP concentration. Moreover, DRP could improve the fluidity of the gelatinized corn starch and reduce its digestibility. These findings provided fundamental information about DRP's application in the whole processing of corn starch.

Using Cellulose Nanofibers and Its Palm Oil Pickering Emulsion as Fat Substitutes in Emulsified Sausage.

Nano cellulose is attracting great interest in food and nutraceutical fields and also provides a potential additive to develop functional meat products such as low fat sausage. Here, we compared 1 wt% aqueous dispersion of cellulose nanofiber (CNF) and its palm oil Pickering emulsion (CPOE) at the ratio of 1:1 (water: oil, v:v) for being fat alternatives replacing 30% and 50% of the original fat of the emulsified sausage. Replacing fat by CPOE and CNF resulted in lower fat content, lower cooking loss and higher moisture content and higher lightness values (P ≤ 0.05) at both fat levels. Textural analysis indicated that the products formulated with CPOE showed higher hardness, springiness, chewiness and the texture was enhanced by the addition of CNF, especially when 30% fat was substituted. Compared with the full-fat control, the sausages formulated with CPOE became more elastic and compact, especially by the incorporation of CNF according to the rheology and scanning electron microscope results. The reformulated products with CPOE and CNF at the 30% level showed higher sensory scores (P ≤ 0.05) while at the 50% level produced comparable quality to the control, but no significant differences were found in the overall acceptability. In summary, CNF and its Pickering emulsion provide the potential as potential fat alternatives for developing low fat meat products. PRACTICAL APPLICATIONS: Cellulose nanofibers present a variety of distinguishing properties, such as large surface area, great stability and high strength. The ability to stabilize emulsions and good biocompatibility enlarge its application in food. In this study, we attempted to use cellulose nanofibers and its palm oil Pickering emulsion as fat substitutes to partly replace the original fat of pork emulsified sausages, hoping to provide some basic information for using cellulose nanofibers and its Pickering emulsion as fat substitute to high fiber, low fat meat products.

Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts.

AIM: Extracellular superoxide dismutase (ecSOD) is a unique scavenger of superoxide anions and a promising target of gene therapy for ischemia/reperfusion injury (I/R). However, conventional gene therapies have limitation in effectiveness and efficiency. This study aimed to investigate the protective effects of ecSOD gene modified bone marrow mesenchymal stromal cells (BMSCs) on cardiac function improvement in mice infarcted heart. METHODS & RESULTS: BMSCs were isolated from Fluc(+) transgenic mice (Tg FVB[Fluc(+)]) and transfected by adenovirus combined with human ecSOD gene. ELISA was performed to determine ecSOD protein level. Female syngeneic FVB mice were randomized into 5 groups: (1) Sham group (sham); (2) MI group (MI); (3) MI+BMSCs group (BMSC); (4) MI+BMSCs-vector group (BMSC-vector); (5) MI+ BMSCs-ecSOD group (BMSC-ecSOD). MI was accomplished by ligation of the left anterior descending artery. BMSCs (2 x 10(6)) were injected into the border zone of infarction. In vivo bioluminescence imaging (BLI) was performed to monitor transplanted BMSCs viability. Echocardiography and histological staining revealed that BMSCs-ecSOD significantly reduced myocardial infarction size and improved cardiac function. Lucigenin chemiluminescence, DHE and TUNEL staining demonstrated that BMSCs-ecSOD delivery reduced ROS level and cell apoptosis both in vivo and in vitro. Western blot assay revealed that ecSOD supplementation increased FoxO3a phosphorylation in cardiomyocytes. Moreover, quantitative real-time PCR showed that pro-apoptotic factors (bim and bax) were decreased while the anti-apoptotic factor mir-21 expression was increased after ecSOD intervention. CONCLUSION: Intra-myocardial transplantation of adenovirus-ecSOD transfected BMSCs could exert potential cardiac protection against MI, which may be partly through reduction of oxidative stress and improvement of BMSCs survival.

Inhibitory effects of indigowoad root polysaccharides on porcine reproductive and respiratory syndrome virus replication in vitro.

BACKGROUND: Indigowoad root polysaccharide (IRPS) is a natural polysaccharide isolated from the traditional Chinese medicinal herb Radix Isatidis, and has many kinds of biological activities. However, the IRPS antiviral activity, especially the anti-porcine reproductive and respiratory syndrome virus (PRRSV) effect, has not been evaluated. METHODS: PRRSV was propagated in the MARC-145 cell line, and viral titre was determined by cytopathic effect and expressed as the 50% tissue culture infection dose (TCID(50)) in the current study. The cell cytotoxic effect of IRPS toward MARC-145 was evaluated by MTT assay firstly, then the inhibitory effects of IRPS on PRRSV replication in vitro were investigated by determining the effect of IRPS upon a single replicative cycle of PRRSV in MARC-145 cells. The effects of IRPS on viral RNA and protein synthesis in PRRSV-infected cells were investigated using real-time PCR and double-antibody (sandwich) ELISA. RESULTS: IRPS was able to effectively suppress the infectivity of the PRRSV in a dose-dependent manner, especially by adding IRPS during the PRRSV infection. IRPS could affect the attachment of PRRSV to MARC-145 cells, and also inhibit the viral RNA and protein synthesis. CONCLUSIONS: IRPS has an antiviral effect on PRRSV replication in MARC-145 cells and might be useful in medical development for antiviral research. However, the precise mechanism of the host and viral targets of IRPS are unknown, so further studies should be conducted to investigate the precise mechanism of IRPS inhibitory effect on PRRSV infection.