Elucidation of the anti-gastric cancer mechanism of Guiqi Baizhu Formula by integrative approach of chemical bioinformatics.

Gastric cancer (GC) has posed a great threat to the lives of people around the world. To date, safer and more cost-effective therapy for GC is lacking. Traditional Chinese medicine (TCM) may provide some new options for this. Guiqi Baizhu Formula (GQBZF), a classic TCM formula, has been extensively used to treat GC, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we evaluated the underlying mechanisms of GQBZF in treating GC by integrative approach of chemical bioinformatics. GQBZF lyophilized powder (0.0625 mg/mL, 0.125 mg/mL) significantly attenuated the expression of p-IGF1R, PI3K, p-PDK1, p-VEGFR2 to inhibit the proliferation, migration and induce apoptosis of gastric cancer cells, which was consistent with the network pharmacology. Additionally, atractylenolide Ⅰ, quercetin, glycyrol, physcione and aloe-emodin, emodin, kaempferol, licoflavone A were found to be the key compounds of GQBZF regulating IGF1R and VEGFR2, respectively. And among which, glycyrol and emodin were determined as key active compounds against GC by farther vitro experiments and LC/MS. Meanwhile, we also found that glycyrol inhibited MKN-45 cells proliferation and enhanced apoptosis, which might be related to the inhibition of IGF1R/PI3K/PDK1, and emodin could significantly attenuate the MKN-45 cells migration, which might be related to the inhibition of VEGFR2-related signaling pathway. These results were verified again by molecular dynamics simulation and binding interaction pattern. In summary, this study suggested that GQBZF and its key active components (glycyrol and emodin) can suppress IGF1R/PI3K/PDK1 and VEGFR2-related signaling pathway, thereby inhibiting tumor cell proliferation and migration and inducing apoptosis. These findings provided an important strategy for developing new agents and facilitated clinical use of GQBZF against GC.

Integrated transcriptomics and metabolomics reveal the toxic mechanisms of mercury exposure to an endangered species Tachypleus tridentatus.

Mercury (Hg) pollution is threatening the health of endangered Tachypleus tridentatus whereas the toxic mechanism is still unclear. This study combined transcriptomic and metabolomics technology to reveal the toxic mechanisms of mercury (Hg 2+, 0.025 mg/L) exposing to T. tridentatus larvae for 15 days. Mercury induced cellular toxicity and cardiovascular dysfunction by dysregulating the genes related to endocrine system, such as polyubiquitin-A, cathepsin B, atrial natriuretic peptide, etc. Mercury induced lipid metabolic disorder with the abnormal increase of lysoPC, leukotriene D4, and prostaglandin E2. Cytochrome P450 pathway was activated to produce anti-inflammatory substances to reconstruct the homeostasis. Mercury also inhibited arginine generation, which may affect the development of T. tridentatus by disrupting the crucial signaling pathway. The mercury methylation caused enhancement of S-adenosylmethionine to meet the need of methyl donor. The mechanisms described in present study provide new insight into the risk assessment of mercury exposure to T. tridentatus.

To study the protective effect of Huangqi Baihe Granules on Radiation brain injury based on network pharmacology and experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi baihe Granules (HQBHG), which is a key Chinese medical prescription, has a remarkable efficacy in oxidative stress and inflammation. Nevertheless, the therapeutic effect on Radiation brain injury (RBI) has rarely been studied. AIM OF THE STUDY: The study aimed to verify the effect of HQBHG against RBI and explore its potential mechanism. METHODS: The potential targets and mechanisms of HQBHG against RBI were predicted by network pharmacology and verified by established rat model of RBI Firstly, the therapeutic effect of HQBHG in RBI was confirmed by water maze test, HE staining and Enzyme-linked immunosorbent assay (ELISA). Secondly, the potential critical anti-RBI pathway of HQBHG was further explored by water maze, HE staining, immunofluorescence assays, ELISA and western blot. RESULTS: A total of 43 HQBHG anti-RBI targets were obtained. Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations showed that the treatment of HQBHG in RBI might be mainly related to oxidative stress, inflammation and PI3K/AKT pathway. Experimental studies have indicated that HQBHG can improve spatial learning and memory ability, alleviate pathological damage of brain tissue in RBI of rats. HQBHG also can down-regulate the levels of IL-1ß, TNF-α, ROS and MDA, meanwhile, GSH was significantly up-regulated. In addition, the HQBHG can increase the protein expression phosphorylations PI3K (p-PI3K), phosphorylations AKT(p-AKT) and Nrf2 in the brain tissue of RBI. CONCLUSION: HQBHG may alleviated RBI by regulated oxidative stress and inflammatory response through PI3K/AKT/Nrf2 pathway.

Microalgal-bacterial consortia for efficient wastewater treatment: Optimization using response surface methodology.

The performance of microalgal-bacterial consortia in wastewater treatment and biomass production needs to be further optimized to meet increasingly stringent effluent standards and operating costs. Besides, due to uncontrollability of ambient conditions, it is generally believed that operating conditions (e.g., aeration) respond to ambient conditions (e.g., illumination). Therefore, response surface methodology (RSM) based on Box-Behnken design was used in this study to analyze the removal of chemical oxygen demand (COD), NH3 -N and TP, and algal biomass of the microalgal-bacterial consortia within 48 h. The results showed that under medium illumination intensity (5000 lx), photoperiod (12:12) and aeration rate (0.55 L min -1 ), the removal efficiency of COD, NH3 -N and TP was the highest, and the maximal biomass growth rates were 95.43%, 95.49%, 89.42% and 99.63%, respectively. However, as the limited critical removal requirements of TP, the effluent standards can only be achieved within the small illumination intensity and photoperiod available range, even under medium aeration conditions, which means that under fixed operating conditions, the effective operation range will be very limited. In addition, based on RSM and differential equation analysis, the further study indicated that the effective treatment range can be greatly expanded within aeration responding, which meets the discharge standard of pollutants in China. PRACTITIONER POINTS: Illumination was responded by aeration for optimizing performance of microalgal-bacterial consortium for wastewater treatment and biomass productivity. The strategy of optimization was based on response surface methodology. The maximum effect on wastewater treatment and biomass productivity was based on partial differential equations and quadratic inhomogeneous equations. Limited to critical TP-removal requirements, effluent standards can meet only in the small-usable range of illumination, under medium aeration.

Layered Double Hydroxide Modified with Deoxycholic and Hyaluronic Acids for Efficient Oral Insulin Absorption.

INTRODUCTION: This study aimed to construct a layered double hydroxide (LDH) nanoparticle delivery system that was modified by deoxycholic acid (DCA) and hyaluronic acid (HA) to increase the bioavailability of oral insulin. METHODS: LDH-DCA-HA was synthesized by the hybridization of DCA and HA with LDH. Subsequently, insulin was loaded onto LDH-DCA-HA, resulting in the formation of INS@LDH-DCA-HA. The in vivo and in vitro mechanisms of insulin release, as well as the efficiency of insulin absorption, were analyzed before and after DCA-HA modification. RESULTS: MTT assay showed that there was satisfactory biocompatibility between LDH-DCA-HA and Caco-2 cells at a concentration below 1000 µg/mL. Flow cytometry analysis revealed that Caco-2 cells absorbed INS@LDH-DCA-HA more readily than insulin. Measurement of transepithelial electrical resistance indicated that INS@LDH-DCA-HA induced the reversible opening of tight cell junctions, thereby facilitating its absorption. This was confirmed via laser confocal microscopy analysis, revealing that a large amount of zonula occludens-1 tight junction (TJ) protein was utilized for the paracellular pathway of nanoparticles. We also measured the blood glucose levels of type I diabetic mice and found that oral INS@LDH-DCA-HA exerted a steady hypoglycemic effect lasting 12 h, with a small range of postprandial blood glucose fluctuation. Immunofluorescence analysis showed that the strong penetration ability of INS@LDH-DCA-HA allowed insulin to enter epithelial cells more readily than free insulin. Finally, immunohistochemical analysis of anti-SLC10A1 protein confirmed that the cholic acid transporter receptor protein played a key role in the functioning of INS@LDH-DCA-HA. CONCLUSION: LDH nanoparticles modified by DCA and HA improved the absorption efficiency of insulin by opening the TJs of cells and interacting with the cholic acid transporter receptor protein.

Convergent community structure of algal-bacterial consortia and its effects on advanced wastewater treatment and biomass production.

Microalgal-bacterial consortium is an effective way to meet increasingly stringent standards in wastewater treatment. However, the mechanism of wastewater removal effect has not been properly explained in community structure by phycosphere. And little is known about that the concept of macroecology was introduced into phycosphere to explain the phenomenon. In the study, the algal-bacterial consortia with different ratios of algae and sludge were cultured in same aerobic wastewater within 48 h in photobioreactors (PSBRs). Community structure at start and end was texted by metagenomic analysis. Bray-Curtis similarities analysis based on microbial community showed that there was obvious convergent succession in all consortia, which is well known as "convergence" in macroecology. The result showed that Bray-Curtis similarities at End (overall above 0.88) were higher than these at Start (almost less than 0.66). In terms of community structure, the consortium with 5:1 ratio at Start are the more similar with the consortia at End by which the maximum removal of total dissolved nitrogen (TDN, 73.69%), total dissolved phosphorus (TDP, 94.40%) and NH3-N (93.26%) in wastewater treatment process and biomass production (98.2%) higher than other consortia, according with climax community in macroecology with the highest resource utilization than other communities. Therefore, the macroecology can be introduced into phycosphere to explain the consortium for advanced wastewater treatment and optimization community structure. And the study revealed a novel insight into treatment effect and community structure of algal-bacterial consortia for advanced wastewater treatment, a new idea for to shortening the culture time of consortium and optimize predicting their ecological community structure and predicting ecological community.