Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis.

This study aims to investigate the mechanism of the anti-atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE-/- mice was observed using haematoxylin-eosin (HE) staining and oil red O (ORO) staining. The co-localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 µg/mL ox-LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK-8 assay. The co-localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p-mTOR/mTOR, p-4EBP1/4EBP1, p-P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT-PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q-Orbitrap high-resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE-/- mice. HYQT decreased the co-localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT-PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q-Orbitrap high-resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage-derived foam cell formation. It has been observed that HYQT and ox-LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis, while taurine plays a significant role in lipophagy.

A novel phosphorus-nitrogen-based hyperbranched polysiloxane for improving the fire safety of PA6 with suppressed melt droplets and good mechanical properties.

The combustible defects of polyamide 6 (PA6), especially the flammable melt-dripping behavior, have greatly limited its application in some particular fields. In this work, a halogen-free hyperbranched polysiloxane (PBDSi) containing DOPO and Schiff base was designed via Michael's addition reaction and dehydration-condensation reaction. Results showed that the char yield (Yc) of PBDSi attained 37.9 wt%, confirming the satisfactory charring behavior of PBDSi for preparing flame-retardant PA6. Just by adding 3 wt% of PBDSi, the serious melt droplets of PA6 were suppressed effectively. The prepared PA6/PBDSi-3 with 5 wt% of PBDSi could achieve the highest value of limited oxygen index (LOI) of 27.2 %, while that of PA6 is 21.0 %. Meanwhile, PA6/PBDSi-3 obtained an apparent reduction in the peak heat release rate (PHRR) value of 31.1 % compared with pure PA6. The cooperated effect of DOPO, Schiff base, and polysiloxane that contributed to generating a silicon-phosphorous-rich char layer and releasing incombustible volatiles that were determined to be the essential factor for the improved fire safety of PA6/PBDSi were explored intensively. Inspiringly, PA6/PBDSi composites exhibited a slight mechanical loss concerning PA6, overcoming the great challenge of developing additive flame-retardant materials to balance mechanical properties and fire safety.

DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: DiDang Decoction (DDD) is a traditional classical prescription that has been used to treat atherosclerosis (AS) and hyperlipidemia (HLP) in China. Nevertheless, the underlying mechanism of DDD remains unclear. AIM OF THE STUDY: To validate the mechanism of DDD in AS and HLP based on network pharmacology and in vitro experiments. MATERIALS AND METHODS: The chemical components of DDD were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database and literature mining, and the disease targets of AS and HLP were obtained from the Gencards, OMIM, and DisGeNET databases. The intersection genes were imported into the STRING database to construct protein-protein interaction (PPI) network, and the DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Combined with the results of KEGG pathway analysis, the HIF-1 signaling pathway was selected for further in vitro experiments. RESULTS: The results showed that network pharmacology predicted 112 targets related to DDD treatment of AS and HLP, and the top 10 related pathways are: Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, Chemical carcinogenesis - receptor activation, Pathways in cancer, Proteoglycans in cancer, Fluid shear stress and atherosclerosis, HIF-1 signaling pathway, Alcoholic liver disease, PPAR signaling pathway, and Coronavirus disease-COVID-19. In vitro experiments showed that DDD effectively reduced lipid accumulation in FFA-treated L02 cells; DDD attenuated mitochondrial damage and reduced ROS content; DDD inhibited ferroptosis and apoptosis; DDD up-regulated the expression of HIF-1α, Glutathione Peroxidase 4(GPX4), and Bcl2 proteins, and down-regulated expression of Bax protein. CONCLUSION: DDD exerts therapeutic effects on AS and HLP through multiple targets and pathways, and improves mitochondrial function, reduces ROS content, inhibits ferroptosis and apoptosis by activating the HIF-1 signaling pathway, which provides reliable theoretical and experimental support for DDD treatment of AS and HLP.

A review on application of molecular simulation technology in food molecules interaction.

Molecular simulation is a new technology to analyze the interaction between molecules. This review mainly summarizes the application of molecular simulation technology in the food industry. This technology has been employed to assess structural changes of biomolecules, the interaction between components, and the mechanism of physical and chemical property alterations. These conclusions provide a deeper understanding of the molecular interaction mechanism in foods, break through the limitations of scientific experiments and avoid blind and time-consuming scientific research. In this paper, the advantages and development trends of molecular simulation technology in the food research field are described. This methodology can be used to contribute to further studies of the mechanism of molecular interactions in food, confirm experimental results and provide new ideas for research in the field of food sciences.

Identification of potential target genes of breast cancer in response to Chidamide treatment.

Chidamide, a new chemically structured HDACi-like drug, has been shown to inhibit breast cancer, but its specific mechanism has not been fully elucidated. In this paper, we selected ER-positive breast cancer MCF-7 cells and used RNA-seq technique to analyze the gene expression differences of Chidamide-treated breast cancer cells to identify the drug targets of Chidamide's anti-breast cancer effect and to lay the foundation for the development of new drugs for breast cancer treatment. The results showed that the MCF-7 CHID group expressed 320 up-regulated genes and 222 down-regulated genes compared to the control group; Gene Ontology functional enrichment analysis showed that most genes were enriched to biological processes. Subsequently, 10 hub genes for Chidamide treatment of breast cancer were identified based on high scores using CytoHubba, a plug-in for Cytoscape: TP53, JUN, CAD, ACLY, IL-6, peroxisome proliferator-activated receptor gamma, THBS1, CXCL8, IMPDH2, and YARS. Finally, a combination of the Gene Expression Profiling Interactive Analysis database and Kaplan Meier mapper to compare the expression and survival analysis of these 10 hub genes, TP53, ACLY, PPARG, and JUN were found to be potential candidate genes significantly associated with Chidamide for breast cancer treatment. Among them, TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. Therefore, we identified four genes central to the treatment of breast cancer with Chidamide by bioinformatics analysis, and clarified that TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. This study lays a solid experimental and theoretical foundation for the treatment of breast cancer at the molecular level with Chidamide and for the combination of Chidamide.

Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils.

AIMS: To evaluate the impact of galangin treatment on cerebral ischemia-reperfusion (I/R) injury in gerbils and to identify potential mechanisms of the protective effect of galangin on hippocampal neurons after I/R injury. PRINCIPAL METHODS: A cerebral ischemia model using bilateral common carotid artery ligation in gerbils was established. The Morris water maze (MWM) test was used to evaluate the learning and memory ability of gerbils. The cell viability was evaluated with an MTT assay. The levels of lipid peroxide biomarkers were measured to estimate the injury due to lipid peroxide. The morphology was detected by electron micrography, immunofluorescence and Nissl staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to measure the molecular characteristics. KEY FINDINGS: In the MWM, gerbils treated with galangin after I/R injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4). Furthermore, the expression of the marker of ferroptosis was decreased in galangin-treated gerbils, and the effect of galangin was weakened when SLC7A11 was knocked down. These results show that galangin can inhibit ferroptosis by enhancing the expressions of SLC7A11 and GPX4 as well as reduce neuronal cell death. SIGNIFICANCE: Galangin inhibits ferroptosis through activation of the SLC7A11/GPX4 axis and has a protective effect on hippocampal neurons in gerbils after I/R.

Tanshinone IIA Combined With Cyclosporine A Alleviates Lung Apoptosis Induced by Renal Ischemia-Reperfusion in Obese Rats.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.