Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

Oligosaccharides play important roles in many biological processes and have great medicinal potential. The structure-activity study of oligosaccharides is complicated by the diversity and complexity of their structures. This review summarizes the state of oligosaccharide structural analysis in recent years. The ionization methods and dissociation rule of acid oligosaccharides, neutral oligosaccharides and glycopeptides in mass spectrometry are discussed and the methods of extraction and purification of oligosaccharides, the suitable mass spectrometry models for different types of oligosaccharides, and the advantages and disadvantages of different mass spectrometry models are introduced. We believe that this review will be helpful for the further investigation of these important biological substances.

Phytoestrogens exhibit various pharmacological estrogen-like effects, such as in the prevention and treatment of osteoporosis, cardiovascular diseases, tumors, etc., but the specific mechanism is still unclear. In recent years, estrogen receptor alpha-mediated rapid non-genomic effects have been identified to play an important role in the pathogenesis of estrogen-related diseases. The research of phytoestrogens exerting pharmacological effects through non-genomic effects has also received increasing attention. This article summarizes the research progress in estrogen receptor alpha-mediated non-genomic effects and analyzes the possible involvement of rapid non-genomic effects in certain pharmacological effects of phytoestrogens. The future prospects of estrogen receptor-mediated non-genomic effects by phytoestrogens are also discussed.

The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.

We evaluate the therapeutic effects of baicalein on chemotherapy-induced intestinal mucositis (CIM) in mice. The role of gut microflora regulation in the therapeutic effects of baicalein was investigated meanwhile. Male Balb/c mice were randomly divided into three groups including normal control group, model group and experimental group. Except for normal control group, mice were injected with 5-fluorouracil and irinotecan to induce CIM. Animal welfare and experimental procedures comply follow the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Baicalein significantly reduced disease activity index (DAI) of CIM mice and decreased the content of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum. There were significant differences in the composition of the gut microbiota among groups according to the analysis of α diversity, β diversity, and the species differences. Compared with the normal control group, the Ruminococcaceae_UCG_014 and unclassified_f_Lachnospiraceae in mice of model group were significantly decreased while Bacteroides, Escherichia_Shigella, Enterococcus, Parabacteroides, Clostridium_sensu_stricto_1, and Lactococcus were significantly increased. Baicalein significantly decreased the abundance of Bacteroides, Escherichia_Shigella, Parabacteroides, Enterococcus, Clostridium_sensu_stricto_1, and Lactococcus. Meantime, norank_f_Muribaculaceae was notably increased by baicalein. The content of IL-6 and TNF-α in the serum of the three groups were positively correlated with the abundance of Clostridium_sensu_stricto_1, Lactococcus, Bacteroides, and Enterococcus according to correlation analysis. This study suggested the potential therapeutic effect of baicalein on CIM in mice. Regulation of gut microbiota probably plays a critical role in the therapeutic effects of baicalein.

This study investigated the effect of a novel adenosine derivative YZG-331 on the glutamate (Glu) content and its receptor N-methyl-D-aspartate receptor (NMDAR) in mouse frontal cortex. All procedures in this research were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. High performance liquid chromatography (HPLC) was used to detect the Glu contents in the mouse frontal cortex tissue homogenate and extracellular fluid which were collected by brain microdialysis method. Western blot and co-immunoprecipitation methods were used to detect the expressions of NMDAR in cell membranes and endosomes, as well as the expression levels of endocytosis-related proteins and their interaction. The results showed that there was no significant change in Glu content in the dialysates from mouse frontal cortex within 0-0.5 h period and 0.5-1 h period after intragastric administration of YZG-331 (40 mg·kg^-1). Compare to the control group, the Glu content in mouse frontal cortex homogenates has no significant statistical differences after 15 minutes of administration of compound YZG-331. YZG-331 significantly decreased the expressions of NMDAR subunits NR1 and NR2B in the mouse frontal cortex cell membrane, meanwhile significantly increased the expressions of NR1 and NR2B proteins in the frontal cortex endosomes. It also increased the phosphorylation levels of NMDAR subunit NR2B in the frontal cortex. In addition, the result of co-immunoprecipitation which used NR2B as bait protein showed that the expression of postsynaptic density-95 (PSD95) in NR2B and PSD95 immunoprecipitation complexes in mouse frontal cortex tissues was significantly reduced. These results indicate that YZG-331 does not affect the Glu content in mouse frontal cortex, but it weakens the interaction between NR2B and PSD95 by increasing the phosphorylation level of NR2B in the mouse frontal cortex. Therefore, it reduces the membrane stability of NMDAR and promotes NMDAR's endocytosis, which leading to the decrease of excitotary transmission. It may be one of the mechanisms of YZG-331 to exert sedative and hypnotic effects.

To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrap^TM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L^-1 FITC-TCF4 and 100 nmol·L^-1 β-catenin. Under these optimized conditions, a high Zxfactor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.

Idiopathic pulmonary fibrosis (IPF) is usually accompanied with inflammatory response, especially the macrophages. The co-culture model of macrophages and fibroblast, and IPF mice model induced by bleomycin were used here to explore the role of macrophages and interleukin-6 (IL-6) in IPF. All animals welfare and experiments were performed following the regulations of the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine. The results showed that the content of IL-6 in IPF mice induced by bleomycin was significantly increased, and there was a large amount of inflammatory cell infiltration in the lungs. The results of wound-healing and immunofluorescence showed that alternative activated (M2) macrophages could induce the migration and activation of fibroblasts at 36 h, and the expression of IL-6 was increased in the co-culture system. The results of wound-healing and sirius red assay proved that IL-6 could induce the migration and activation of fibroblast. The results showed that M2 macrophages induced fibroblasts to secrete IL-6, thereby inducing the activation and migration of fibroblast, which affect the development of IPF.

Stroke has been harmful to human health for a long time, and there is no satisfactory treatment strategy because of its complex pathogenesis. Taohechengqi decoction has been effective in the treatment of stroke. In this study, the components were collected by TCMSP, TCMIP, BATMAN-TCM and TCMID databases, the targets were predicted and screened by PharmMapper and BATMAN-TCM databases, and the functional enrichment analysis of the targets was carried out by using R language package clusterProfiler. Finally, the key targets are verified by GEO database and molecular docking. The results showed that 51 active components of Taohechengqi decoction may regulate 15 key targets such as nitric oxide synthase, endothelial (NOS3), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase-9 (MMP9), affecting vascular endothelial growth factor signaling pathway and other pathways to play a role in the prevention of stroke, affecting tumor necrosis factor signaling pathway and other pathways to play a role in the treatment of stroke. GEO data analysis showed that androgen receptor (AR), caspase-8 (CASP8), intercellular adhesion molecule 1 (ICAM1), interleukin-1 beta (IL1B), mitogen-activated protein kinase 14 (MAPK14), MMP9, myeloperoxidase (MPO), peroxisome proliferator-activated receptor gamma (PPARG), PTGS2 and cellular tumor antigen p53 (TP53) were up-regulated genes, while serum albumin (ALB), estrogen receptor 1 (ESR1), NOS3, transcription factor p65 (RELA) and proto-oncogene tyrosine-protein kinase Src (SRC) were down-regulated genes. GEO analysis explained that Taohechengqi decoction may prevent stroke by down-regulating ESR1, NOS3, and treat stroke by up-regulating ICAM1, IL1B, MAPK14, MMP9, PPARG, PTGS2, TP53, and down-regulating RELA and SRC. The study found that in the process of prevention and treatment of stroke, Taohechengqi decoction played a two-way regulation role through multi-genes and multiple ways, which provided a new strategy for the treatment of stroke.

To study the osteoprotective effect of 1, 2, 3, 4, 6-pentyl-O-galloyl-beta-D-glucose (PGG) its anti-osteoblast apoptosis related mechanism was investigated. A model of zebrafish osteoporosis induced by prednisolone (Pred, 25 μmol·L^-1) was established in vivo, and calcein staining was used to detect the effect of PGG on the bone area of zebrafish. Bone marrow mesenchymal stem cells were cultured in vitro, and the number of calcified nodules was observed by alizarin red staining, and the relevant indexes of osteoblast differentiation runt-related transcription factor 2 (Runx 2), osteocalcin (OCN) mRNA level were detected by qRT-PCR. The osteoblast cell line MC3T3-E1 cells was cultured in vitro, and 400 μmol·L^-1 hydrogen peroxide (H₂O₂) was used to intervene the injury to detect the effect of PGG on osteoblasts under oxidative stress. The effect of PGG on osteoblast activity was detected by MTT assay. The effect of PGG on apoptosis was observed by Hoechst 33342 staining. Western blot was used to detect the expression of Bcl-2, Bax, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). DCFH-DA fluorescence staining for detection of reactive oxygen species (ROS) levels. JC-1 staining was used to detect mitochondrial membrane potential levels. The results showed that PGG could significantly increase the vertebral area of the zebrafish model when compared with the model group. On the 14 th day of osteoblast differentiation, the number of calcified nodules in the PGG group was significantly increased when compared with the control group and the mRNA levels of Runx 2 and OCN were also significantly increased. In addition, under oxidative stress, PGG could increase osteoblast viability, significantly reduce the number of apoptotic cells, and increase the ratio of Bcl-2/Bax. Fluorescence staining results show that PGG decreased intracellular ROS fluorescence density and increased mitochondrial membrane potential. Western blot data showed that PGG could promote the expression of Nrf2 in the nuclear and enhance the expression of downstream protein HO-1. In conclusion, PGG could improve osteoporosis in zebrafish, and this effect may be related to the regulation of Nrf2/HO-1 signaling pathway to improve mitochondrial dysfunction, anti-oxidative stress in osteoblast apoptosis and promote bone formation. This study provides new ideas and clues for the discovery of anti-osteoporosis drugs.