The application of Cortex Mori (CM) in the treatment of diabetes mellitus (DM) has been extensively documented in traditional medicine. In recent years, the chemical composition of CM has been gradually unraveled, and its therapeutic mechanism in treating DM, diabetic nephropathy, diabetic cardiomyopathy, and other related conditions has been highlighted in successive reports. However, there is no systematic study on the treatment of DM based on the chemical composition of CM. This study was conducted to systematically explore the hypoglycemic activity mechanism of CM based on its chemical composition. The material basis of Cortex Mori extract (CME) was investigated through qualitative analyses based on liquid chromatography-mass spectrometry (LC-MS). The possible acting mechanism was simulated using network pharmacology and validated in streptozotocin (STZ) + high fat diet (HFD)-induced diabetic rats and glucosamine-induced IR-HepG2 model with the assistance of molecular docking techniques. A total of 39 compounds were identified in CME by the LC-MS-based qualitative analysis. In diabetic rats, it was demonstrated that CME significantly ameliorated insulin resistance, blood lipid levels, and liver injury. The network pharmacology analysis predicted five major targets, including AKT1, PI3K, FoxO1, Gsk-3β, and PPARγ. Additionally, three key compounds (resveratrol, protocatechuic acid, and kaempferol) were selected based on their predicted contributions. The experimental results revealed that CME, resveratrol, protocatechuic acid, and kaempferol could promote the expression of AKT1, PI3K, and PPARγ, while inhibiting the expression of FoxO1 and Gsk-3β. The molecular docking results indicated a strong binding affinity between resveratrol/kaempferol and their respective targets. CME contains a substantial amount of prenylated flavonoids, which may be the focal point of research on the efficacy of CM in the treatment of DM. Besides, CME is effective in controlling blood glucose and insulin resistance, improving lipid levels, and mitigating liver injury in patients with DM. Relevant mechanisms may be associated with the activation of the PI3K/Akt pathway, the inhibition of the expression of FoxO1 and Gsk-3β, and the enhancement of PPARγ activity. This study represents the first report on the role of CME in the treatment of DM through regulating PPARγ, FoxO1, and Gsk-3β.

As one of the most common clinical cardiovascular diseases (CVDs), coronary heart disease (CHD) is the most common cause of death in the world. It has been confirmed that Zhishi Xiebai Guizhi decoction (ZXGD), a classical prescription of the traditional Chinese medicine (TCM), has achieved certain effects in the treatment of CHD; however, the mechanism still remains controversial. In this paper, an integrated approach, including UPLC-UESI-Q Exactive Focus, gene expression profiling, network pharmacology, and experimental validation, was introduced to systematically investigate the mechanism of ZXGD in the treatment of CHD. First, UPLC-UESI-Q Exactive Focus was applied to identify the chemical compounds of ZXGD. Then, the targets of the components for ZXGD were predicted by MedChem Studio software embed in the integrative pharmacology-based research platform of TCM, and the differentially expressed genes (DEGs) of CHD were obtained by gene expression profiling in gene expression omnibus database. The common genes of the above two genes were obtained by Venn analysis as the targets of GXGD in treatment with CHD. Third, the core targets were screened out by protein–protein interaction network analysis, and the kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed by the database for annotation, visualization, and integrated discovery bioinformatics resources. After that, the formula–herb–compound–target–pathway network was constructed to explore the mechanism of ZXGD in the treatment of CHD. Finally, molecular docking and the vitro experiment were carried out to validate some key targets. As a result, a total of 39 compounds, 12 core targets, and 4 pathways contributed to ZXGD for the treatment of CHD. This study preliminarily provided a foundation for the study on the mechanism against CHD for ZXGD and may be a reference for the compatibility mechanism and the extended application of TCM compound prescription.

Introduction: Previous studies have shown that in addition to having impairments in facial emotion recognition, patients with schizophrenia also show a lack of facial expression. Although negative symptoms such as decreased facial activity are common symptoms of schizophrenia, the related factors remain inconclusive. Therefore, this study compared healthy controls to explore the characteristics of facial muscle activity intensity in patients with schizophrenia and its relationship with negative symptoms.Methods: This observational and cross-sectional study conducted in a psychiatric hospital in China included a total of 135 patients with schizophrenia and 134 healthy controls. The negative symptoms of schizophrenia were evaluated using the Brief Negative Symptom Scale. The intensity of facial muscle activity under positive, neutral, and negative emotional stimuli conditions was automatically collected by a computer, including 17 values (F01-F17) that represent different facial muscle activities. Statistical tests were performed to analyze facial muscle activity indexes, to explore an objective and quantitative method to evaluate the negative symptoms of schizophrenia.Results: The facial muscle activity intensity of the schizophrenia group at F02 (outer eyebrow), F04 (upper eyelid), F07 (nose), F10 (dimple), F12 (lower jaw 1), F14 (lip 2), and F17 (blink) was lower than that of the healthy controls (p < 0.05). Under positive, neutral, and negative emotional stimuli conditions, the facial muscle activity intensity of F16 (lower jaw 2) was positively correlated with negative symptoms (p < 0.05).Conclusion: Our study indicated that patients with schizophrenia show defects in facial muscle activity and that is associated with negative symptoms.

The oncogenic role of ephrin type‐B receptor 4 (EPHB4) has been reported in many types of tumors, including chronic myeloid leukemia (CML). Here, we found that CML patients have a higher EPHB4 expression level than healthy subjects. EPHB4 knockdown inhibited growth of K562 cells (a human immortalized myelogenous leukemia cell line). In addition, transient transfection of EPHB4 siRNA led to sensitization to imatinib. These growth defects could be fully rescued by EPHB4 transfection. To identify an EPHB4‐specific inhibitor with the potential of rapid translation into the clinic, a pool of clinical compounds was screened and vandetanib was found to be most sensitive to K562 cells, which express a high level of EPHB4. Vandetanib mainly acts on the intracellular tyrosine kinase domain and interacts stably with a hydrophobic pocket. Furthermore, vandetanib downregulated EPHB4 protein via the ubiquitin‐proteasome pathway and inhibited PI3K/AKT and MAPK/ERK signaling pathways in K562 cells. Vandetanib alone significantly inhibited tumor growth in a K562 xenograft model. Furthermore, the combination of vandetanib and imatinib exhibited enhanced and synergistic growth inhibition against imatinib‐resistant K562 cells in vitro and in vivo. These findings suggest that vandetanib drives growth arrest and overcomes the resistance to imatinib in CML via targeting EPHB4.