CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ-δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

Quercetin Attenuates Oxidative Stress and Apoptosis in Brain Tissue of APP/PS1 Double Transgenic AD Mice by Regulating Keap1/Nrf2/HO-1 Pathway to Improve Cognitive Impairment.

Objective: The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)-like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. Methods: A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results: Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme-linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin-eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and Aß protein accumulation in AD mice. Western blot validated protein expression in the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO-1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO-1, caspase-3, Bcl-2, and Bax proteins in the Keap1/Nrf2/HO-1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Conclusion: Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.

Construct a novel anti-bacteria pool from hydrothermal liquefaction aqueous family.

Hydrothermal liquefaction aqueous phase (HTL-AP) is complex and toxic, which severely hinders the scale-up of HTL technology. Distinguished from degrading organics and extracting chemical energy or nutrients from HTL-AP via biological fermentation or algae cultivation, here, we propose an innovative strategy to valorize the HTL-AP as a powerful anti-bacterial pool. Six model ingredients, i.e. lipids, cellulose, xylan, lignin, protein and the mixture were employed, to obtain a thirty-HTL-AP pool for characteristics database construction. We found that the xylan group at 230 °C on Escherichia coli (E. coli) and at 200 °C on Staphylococcus aureus (S. aureus) exhibited the highest anti-bacterial activities via plate experiments, nearly equal to 100 µg/ml streptomycin which far exceeded the working concentration of streptomycin (10-50 µg/ml). The liquid cultivation studies further revealed HTL-APs from the mixture feedstock, protein, real biomass microalgae and cornstalk had more stable anti-bacterial activities as chemically stable substances. Interestingly, the Gram-positive strain S. aureus was more susceptible than the Gram-negative E. coli on the HTL-APs, probably owing to the outer selectively permeable membrane difference and the strong reducibility and acidity of HTL-APs. This study provides a new vision to seek the anti-bacterial potential of HTL aqueous, supporting further investigations on its molecular mechanism and new bactericide development.

Understand the antibacterial behavior and mechanism of hydrothermal wastewater.

Unlocking the antibacterial potential is an emerging strategy to valorizing the toxic wastewater from hydrothermal liquefaction (HTL). Here, we investigated the response and biological mechanism of antibacterial properties of HTL wastewater. Four different biowastes i.e. microalgae, cornstalk, cow manure and swine manure were used as the feedstock of HTL to create wastewater with diverse molecule spectrum, whereas ten strains i.e. five gram-positive strains and five gram-negative strains were employed to represent typical pathogenic microorganism. HTL wastewater exhibited antibacterial potential and obvious reduction on cell viability at high inclusion ratio, although the minimum inhibitory concentration (MIC) and cell response intensity varied depending on different HTL feedstocks and strain species. The decreased ATP generation and increased H2O2 accumulation in treated cells further confirmed the inhibition of HTL wastewater on the cell metabolism. The antibacterial mechanism of HTL wastewater was confirmed, including damage to biomolecules or membranes, depletion of crucial components, disruption of metabolic circuits and imbalance of creation of redox cofactor. The complex compounds in HTL wastewater were probably attributed to the multiple inhibition pathways and the relationship among those multiple pathways was speculated. The present study contributes to the mechanism analysis of complex compound mixture and bactericide characteristics of HTL wastewater.