We obtained 332 coding sequences from the Polyporus umbellatus transcriptome based on the BLASTx and ESTScan analyses. The codon usage patterns of P. umbellatus were calculated and statistically analyzed using CodonW. The results showed that the average GC content of genes was 53.57% and the average GC3 content was 57.98%, suggesting that genes favored codons ending with G or C. The effective number of codons (ENC) value range from 38.46 to 61, which indicates that these genes have low codon usage bias. The neutrality plot and ENC-plot analysis revealed that many factors such as mutation and selective pressure play an important role in shaping codon usage bias in P. umbellatus genes. Twenty-two optimal codons were identified as being biased toward codons ending with G or C using the high expression superior codon analysis method. This study will lay a foundation for future research on genetic engineering and molecular evolution in P. umbellatus.

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.

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.

The aim of this study was to analyze the anti-cancer effect and mechanism of action of the flavonoids of Astragalus membranaceus (TFA) when combined with cisplatin on Lewis lung carcinoma-bearing mice. This animal experiment was approved by the Committee of the Ethics of Animal Experiment of Shanxi University (SXULL2018012). Pharmacological indices such as tumor weight, tumor volume growth curves, inhibition rate and organ indices showed that the TFA could reduce toxicity and enhance the efficacy of cisplatin. The target of TFA was predicted by network pharmacology analysis and the result showed that calycosin-7-O-β-D-glucoside might be the main active compound responsible for the anticancer effect of TFA. TRP53 (cellular tumor antigen p53), RAC1 (Ras-related C3 botulinum toxin substrate 1), ERBB2 (receptor tyrosine-protein kinase erbB-2), VEGFA (vascular endothelial growth factor A) and STAT3 (signal transducer and activator of transcription 3) may be associated with TFA in enhancing efficacy and reducing the toxicity of cisplatin. The IL-6 content in serum and expression levels of STAT3 and p53 in tumor tissues suggested that TFA may inhibit tumor growth through the IL-6/STAT3 pathway; UPLC-MS-based serum metabolomic analysis suggested that the metabolic pathways related to lung cancer include sphingolipid metabolism, retinol metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, and the TFA-regulated corresponding pathway of bile acid biosynthesis. In this study, the anti-cancer effect and mechanism of action of TFA combined with cisplatin on Lewis lung carcinoma-bearing mice was analyzed by the combination of various techniques, which lay a foundation for further development of anticancer drugs.

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.

This study analyzed the effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair on endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression by using LC-MS liver metabolomics. Rats were randomly divided into 5 groups:a normal control group, a CUMS model group, a venlafaxine-positive group, and a high-low dose group for the Radix Bupleuri-Radix Paeoniae Alba herb pair, with continuous modeling and administration over 28 days. The efficacy of Radix Bupleuri-Radix Paeoniae Alba herb pair was evaluated by measuring traditional pharmacodynamic indicators of depression (body weight, open field test, sucrose preference test and forced swimming test). Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036). Liver metabolic profiles were obtained by the UHPLC-Q Exactive Orbitrap-MS metabolomics technique. The results show that the Radix Bupleuri-Radix Paeoniae Alba herb pair can significantly decrease depression-like behavior of rats in the CUMS model group. Increases in 25 depression-related metabolites were identified by LC-MS metabonomics, and the Radix Bupleuri-Radix Paeoniae Alba herb pair could significantly decrease 16 of them. Metabolic pathway analysis showed that D-glutamine and D-glutamate metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism were the main metabolic pathways altered by this herb pair in CUMS model rats.

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.

To study the reversal effect of docetaxel (DTX) and verapamil (VRP) liposome (DTX-VRP LP) on multidrug resistance of human breast cancer chemotherapy, DTX-VRP LP was prepared by thin film dispersion method. The particle size and zeta potential were measured by laser particle sizer. The drug loading, entrapment efficiency and the cumulative release rate of liposomes in phosphate buffer saline solution (PBS) with pH 7.4 and 6.8 were determined by ultrafiltration and dynamic dialysis, respectively. With DTX resistant human breast cancer cells (MCF-7/DTX) to study on the pharmacodynamics of liposomes in vitro and in vivo. The animal experiments were approved by the Animal Research Ethics Committee of School of Medicine of Shanghai Jiao Tong University (No. 2019-06-172). The average particle size and zeta potential of DTX-VRP LP were about 140.9 nm and -28.7 mV, respectively. The entrapment efficiency and drug loading of DTX and VRP in DTX-VRP LP were (81.7±3.9)%, (2.9±0.3)% and (59.6±0.6)%, (1.6±0.5)%, respectively. The cumulative release rate of the group of DTX-VRP LP was about 40% and 70% within 0-4 h in pH 7.4 and 6.8 PBS, respectively. It was slightly slower compared with other experimental groups. In vitro pharmacodynamics experiments, the value of IC₅₀ of DTX solution, DTX LP and DTX-VRP LP were 3.19±0.6, 1.46±0.48 and 1.12±0.33 μmol·L^-1 on human breast cancer cells (MCF-7), respectively. The results showed the data was not much difference between the other groups and all experimental groups had strong cytotoxicity on MCF-7. However, on the MCF-7/DTX, the IC₅₀ values of the other groups were greater than 10 μmol·L^-1 while DTX-VRP LP group 7.4±2.86 μmol·L^-1. The results showed DTX-VRP LP had obvious cytotoxicity with the concentration dependent reversal of multidrug resistance (MDR) of breast cancer MCF-7/DTX cells (P < 0.05), the other experimental groups had no effect on MCF-7/DTX cells. The inhibitory effect of MCF-7/DTX in vivo is consistent with that in vitro. In conclusion, DTX-VRP LP could reverse the MDR of MCF-7/DTX cells.

Qualitative and relatively quantitative methods were used to study the quality of cultivated Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium myrianthum Stearn, and Epimedium pubescens Maxim by ultra high-performance liquid chromatography coupled with photo-diode array and quadrupole time-of-flight mass spectrometry (UHPLC-PDA-Q-TOF/MS^E). Thirty-two compounds in cultivated and wild samples of E. sagittatum, E. myrianthum and E. pubescens were identified using UHPLC-Q-TOF/MS^E combined with the UNIFI data analysis platform. Principal component analysis (PCA) was used to compare the cultivated and wild samples of these three species. The results show that the chemical compositions of cultivated samples were consistent with the corresponding wild samples. UHPLC-PDA was used to determine the relative content of 12 flavonoids as well as total flavonoids in all samples. The results show that the relative chemical content of these flavonoids in cultivated and wild samples is similar and the quality of cultivated Epimedium is more stable. These qualitative and relatively quantitative methods using UHPLC-PDA-Q-TOF/MS^E combined with the UNIFI data analysis platform and PCA can be used to study the quality of cultivated Herba Epimedii. This research provides a scientific basis for the cultivation and rational development and utilization of Epimedium medicinal materials.

A collaborative inter-laboratory validation was carried out using a reporter gene assay to measure the bioactivity of anti-PD-1 monoclonal antibody, in order to study the applicability and transferability of the method. In this study, two collaborative schemes were designed to measure the precision, linearity and accuracy of the method. The results showed that the 95% confidence interval (CI) of the intra-assay precision was (1.72-16.89)%, inter-assay precision was (2.63-17.67)%, inter-laboratory precision was (9.00-14.26)%, all linear correlation coefficients were greater than 0.99, and the 95% CI for the accuracy at different potency levels was (91.83-104.40)% at 50%, (90.40-101.40)% at 75%, (94.71-105.60)% at 100%, (94.00-102.00)% at 125%, and (96.73-104.30)% at 150%. The collaborative validation results proved that the reporter gene assay for the bioactivity determination of anti-PD-1 monoclonal antibody has good precision, linearity and accuracy, and could be applied to the release and stability analysis of anti-PD-1 monoclonal antibodies in different laboratories.