Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaoren Decoction (SZRD) is a classic traditional Chinese prescription, which has been commonly used for treating insomnia, depression and other nerve system diseases for a long time. AIM OF THIS STUDY: The present study aimed to explore the metabolic profiles in multi-biological samples and pharmacokinetic mechanism between healthy and depression model rats combined with a network pharmacology approach after administration of SZRD. MATERIALS AND METHODS: In our study, an ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap Mass Spectrometry method was firstly used to study the prototype components and metabolites of SZRD in plasma, brain, urine, and feces between healthy and depressed rats. The possible metabolic pathways were also speculated. Then a network pharmacological study was conducted on the components in the plasma of model rats. According to the above components screened by network pharmacology and the other reported representative active components, the comparative pharmacokinetic study was established for the simultaneous determination of mangiferin, spinosin, ferulic acid, liquiritin, formononetin. magnoflorine and isoliquiritin between healthy and depression model rats. Finally, molecular docking was used to validate the binding affinity between key potential targets and active components in pharmacokinetics. RESULTS: A total of 115 components were identified in healthy rats, and 101 components were identified in model rats. The prototype components and metabolites in plasma, brain, urine, and feces were also distinguished. The main metabolic pathways included phase I and phase II metabolic reactions, such as dehydrogenation, oxidation, hydroxylation, gluconaldehyde conjugation, glutathione conjugation and so on. These results provided a basis for the further study of antidepressive pharmacokinetic and pharmacological action in SZRD. Then, according to the degree value of network pharmacological study, it was predicted that 10 components and 10 core targets, which involved in the critical pathways such as neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, serotonergic synapse, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, etc. Finally, the established pharmacokinetic method was successfully applied to compare the pharmacokinetic behavior of these 7 active components in plasma of healthy and depressed rats after oral administration of SZRD. It showed that except magnoflorine, the pharmacokinetic parameters of each component were different between healthy and depressed rats. Molecular docking analysis also indicated that the active compounds in pharmacokinetics could bind tightly to the key targets of network pharmacological study. CONCLUSION: This study may provide important information for studying the action mechanism of SZRD in treating depression.

Maximizing TLR9 Activation in Cancer Immunotherapy with Dual-Adjuvanted Spherical Nucleic Acids.

Nucleic-acid-based immune adjuvants have been extensively investigated for the design of cancer vaccines. However, nucleic acids often require the assistance of a carrier system to improve cellular uptake. Yet, such systems are prone to carrier-associated adaptive immunity, leading to difficulties in a multidose treatment regimen. Here, we demonstrate that a spherical nucleic acid (SNA)-based self-adjuvanting system consisting of phosphodiester oligonucleotides and vitamin E can function as a potent anticancer vaccine without a carrier. The two functional modules work synergistically, serving as each other's delivery vector to enhance toll-like receptor 9 activation. The vaccine rapidly enters cells carrying OVA model antigens, which enables efficient activation of adaptive immunity in vitro and in vivo. In OVA-expressing tumor allograft models, both prophylactic and therapeutic vaccinations significantly retard tumor growth and prolong animal survival. Furthermore, the vaccinations were also able to reduce lung metastasis in a B16F10-OVA model.

Selenium deficiency induced apoptosis via mitochondrial pathway caused by Oxidative Stress in porcine gastric tissues.

Selenium (Se) is an essential nutrient for the body, which can ensure GSH-Px activity and has antioxidant effect. Se deficiency may lead to apoptosis in various tissues and organs in animals. Pigs as major livestock in the farming industry, Se deficiency can cause various types of diseases such as white muscle disease, and mulberry heart disease.The aim of this experiment was to investigate the effect and mechanism of Se deficiency on apoptosis in porcine gastric tissue. Forty weaned piglets were randomly divided into Se deficiency group and control group, and fed with low Se diet and normal diet for six weeks respectively. The histochemical characteristics, antioxidant indexes, apoptotic genes and apoptotic protein expression of gastric cells in Se-deficient piglets were detected. The results of antioxidant index, TUNEL, RT-PCR and Western blot showed that Se deficiency decreased the activities of CAT, SOD and GSH-Px, increased the apoptotic rate of porcine gastric tissue, increased the expression of Bax and Caspase-3, and decreased the expression of Bcl-2. The results demonstrated that Se deficiency could induce apoptosis in porcine gastric tissue cells through oxidative stress-induced mitochondrial pathway. The stomach was a key target of Se deficiency and may play a key role in the response to Se deficiency. Our study may provide new ideas for the prevention and treatment of swine gastric diseases caused by Se deficiency and is beneficial to the development of pig farming industry.

Comparison of bacterial nanocellulose produced by different strains under static and agitated culture conditions.

Bacterial nanocellulose (BNC) has many advantages over plant cellulose, which make it widely used in many fields, especially in the food industry. In this study, three strains including BCA263, BCC529, and P1 were selected for characteristics analysis of BNCs under static and agitated culture conditions. The BNCs produced under static culture condition were in the shape of uniform membrane, while BNCs produced under agitated culture were in form of small agglomerates and fragments. BCA263 and BCC529 strains were more suitable for static culture, while P1 strain was more suitable for agitated culture. BNCs produced under static culture condition exhibited higher crystallinity, stronger tensile strength, denser network structure, higher temperature resistance and good flame retardancy; while BNCs produced under agitated culture condition exhibited larger porous and lower crystallinity. Furthermore, BNCs produced under agitated culture condition were more suitable as a stabilizer of coffee milk beverage.

Synthetic Lift-off Polymer beneath Layer-by-Layer Films for Surface-Mediated Drug Delivery.

A broad range of biomaterials coatings and thin film drug delivery systems require a strategy for the immobilization, retention, and release of coatings from surfaces such as patches, inserts, and microneedles under physiological conditions. Here we report a polymer designed to provide a dynamic surface, one that first functions as a platform for electrostatic thin film assembly and releases the film once in an in vivo environment. Atom transfer radical polymerization (ATRP) was used to synthesize this polymer poly(o-nitrobenzyl-methacrylate-co-hydroxyethyl-methacrylate-co-poly(ethylene-glycol)-methacrylate) (PNHP), embedded beneath multilayered polyelectrolyte films. Such a base layer is designed to photochemically pattern negative charge onto a solid substrate, assist deposition of smooth layer-by-layer (LbL) polyelectrolyte in mildly acidic buffers and rapidly dissolve at physiological pH, thus lifting off the LbL films. To explore potential uses in the biomedical field, a lysozyme (Lys)/poly(acrylic acid) (PAA) multilayer film was developed on PNHP-coated silicon wafers to construct prototype antimicrobial shunts. Film thickness was shown to grow exponentially with increasing deposition cycles, and effective drug loading and in vitro release was confirmed by the dose-dependent inhibition of Escherichia coli (E. coli) growth. The efficacy of this approach is further demonstrated in LbL-coated microscale needle arrays ultimately of interest for vaccine applications. Using PNHP as a photoresist, LbL films were confined to the tips of the microneedles, which circumvented drug waste at the patch base. Subsequent confocal images confirmed rapid LbL film implantation of PNHP at microneedle penetration sites on mouse skin. Furthermore, in human skin biopsies, we achieved efficient immune activation demonstrated by a rapid uptake of vaccine adjuvant from microneedle-delivered PNHP LbL film in up to 37% of antigen-presenting cells (APC), providing an unprecedented LbL microneedle platform for human vaccination.