The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

This study aimed to prepare silk fibroin nanoparticles (SF-NPs) and assess the physicochemical properties and biocompatibility of the formulation. An optimized and simplified solvent displacement method was employed to obtain SF-NPs. Single-factor prescription screening, such as silk fibroin (SF) solution concentration, the ratio of SF solution to organic solvent, ultrasonication power and time, and different types of organic phases, was used to optimize the formulation. The characterization of the optimal formulation included particle size, polydispersity index (PDI), zeta potential, morphology, and stability. The in vitro cell compatibility of the nanoparticles was evaluated using CCK-8 and Calcein-AM/PI cell viability staining. The results showed that when SF concentration was 20 mg·mL^-1, volume ratio of aqueous phase to acetone was 1∶6, ultrasonic power was 80 W and ultrasonic time was 3 min, the best SF-NPs was obtained. The nanoparticles prepared in this study exhibit a near-spherical shape, with a uniform size distribution, having an average size of 144.8 nm, a PDI of 0.174, and a zeta potential of -27.35 mV. Results from in vitro cell experiments demonstrate excellent cell compatibility of SF-NPs, showing the ability to promote cell proliferation. The SF-NPs which were successfully prepared in this study exhibit uniform particle size and excellent biocompatibility.

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg^-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg^-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg^-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg^-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

The AP2/ERF gene family is one of the largest transcription factor families in the plant kingdom, and plays an important role in response to biological and abiotic stresses, plant hormone responses, and plant growth and development. In this study, the AP2/ERF family of Panax notoginseng was identified by bioinformatics methods, and the physicochemical properties, structure, phylogenetic relationship, expression pattern and function of PnDREB4 gene of the family were analyzed. The results showed that 140 AP2/ERF family members were identified in P. notoginseng, which were divided into DREB, ERF, AP2, RAV and Sololit subgroups. The physicochemical properties and motifs of proteins were similar among the subgroups. There were 34 differentially expressed genes in the AP2/ERF family of Fusarium oxysporum infected P. notoginseng plants, and 19 genes were up-regulated. The expression level of PnDREB84 was up-regulated with the extension of Fusarium oxysporum infection time in the range of 0-96 h. The content of ABA and SA in P. notoginseng plants overexpressing PnDREB84 gene increased after 4 ℃ stress. The results showed that PnDREB84 gene plays a dual regulatory role in the process of biological stress and abiotic stress. PnDREB84 gene can be used as a potential molecular marker for the breeding of new varieties of P. notoginseng. The identification of AP2/ERF transcription factor and function analysis of PnDREB84 gene of P. notoginseng provided data support for the analysis of stress resistance mechanism of P. notoginseng and the breeding of new varieties.

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Anthocyanidin reductase (ANR) is one of the key enzyme in the flavonoid biosynthetic pathway, and its catalytic activity is important for the synthesis of plant anthocyanin. In this study, specific primers were designed according to the transcriptome data of Lonicera japonica Thunb., and the CDS, gDNA and promoter sequences of ANR genes from Lonicera japonica Thunb. and Lonicera japonica Thunb. var. chinensis (Wats.) Bak. were cloned. The results showed that the CDS sequences of LjANR and rLjANR were 1 002 bp, the gDNA sequences were 2 017 and 2 026 bp respectively, and the promoter sequences were 1 170 and 1 164 bp respectively. LjANR and rLjANR both contain 6 exons and 5 introns, which have the same length of exons and large differences in introns. The promoter sequences both contain a large number of light response, hormone response and abiotic stress response elements. Bioinformatics analysis showed that both LjANR and rLjANR encoded 333 amino acids and were predicted to be stable hydrophobic proteins without transmembrane segments and signal peptides. The secondary structures of LjANR and rLjANR were predicted to be mainly consisted of α-helix and random coil. Sequence alignment and phylogenetic analysis showed that LjANR and rLjANR had high homology with Actinidia chinensis var. chinensis, Camellia sinensis and Camellia oleifera, and were closely related to them. The expression levels of LjANR and rLjANR were the highest in flower buds and the lowest in roots. The expression patterns at different flowering stages were similar, with higher expression levels in S1 and S2 stages and then gradually decreased until reaching the lowest level in S4 stage, after a slow increase in S5 stage, the expression levels decreased again. The expression levels of ANR genes in the two varieties showed significant differences in roots, S2 and S5 stages, while the differences in stems, flower buds, S1, S3 and S6 stages were extremely significant. The prokaryotic expression vector pET-32a-LjANR was constructed for protein expression. The target protein was successfully expressed of about 59 kD. This study lays a foundation for further study on the function of ANR gene and provides theoretical guidance for breeding new varieties of Lonicera japonica Thunb.

Chloral hydrate is a commonly used central sedative drug before pediatric clinical examination, but its clinical safety and medication adherence are needed to focus on normally because of its poor stability and palatability. Under the premise of investigating the stability of different formulations, their palatability were also screened by using both human sensory and electronic tongue evaluation techniques. Human sensory evaluation has been conducted with the informed consent of all participants in accordance with the ethical requirements of the Good Clinical Practice for Drug Trials. The results showed that the addition of sorbitol and sucralose could effectively ensure the stability of the oral solution. Sorbitol is the main taste-masking component, and the ratio of 40% sorbitol and 0.5% sucralose can effectively mask the bitterness, astringency and spicy taste of 10% chloral hydrate oral solution. The results detected by human sensory and electronic tongue have good correlation and complementarity, and the combination of these two methods is more conducive to getting objective and reasonable conclusions.

Polygonatum franchetii Hua is a medicinal plant endemic to China from Polygonatum Mill. The chloroplast genomes of two P. franchetii individuals sampled from two different habitats were sequenced by using the DNBSEQ-T7 high-throughput sequencing platform. After assembly and annotation, the two complete chloroplast genomes were characterized, and then comparative and phylogenetic analyses were performed with other published chloroplast genome sequences from Polygonatum. The whole chloroplast genomes of the two P. franchetii individuals were 155 942 and 155 962 bp in length, with a large single copy region (LSC, 84 670 and 84 722 bp), a small single copy region (SSC, 18 564 and 18 566 bp) and a pair of reverse repeats (IRa/IRb, 26 354 and 26 337 bp), respectively. Both of them contained 113 genes, including 79 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Comparative analyses showed that the genome length, the guanine and cytosine (GC) content, genes content and order were highly conserved between the two P. franchetii individuals and among different Polygonatum species. The detected repeat sequences, including dispersed repeats, tandem repeats and simple sequence repeats (SSRs), were also relatively similar in types and positions, though showing a slightly difference in number. No significant expansion or contraction of the inverted repeat regions was found. Sequences variation between the two P. franchetii individuals was lower than that among different Polygonatum species. Besides, coding sequences (CDS) showed less divergence than noncoding sequences, and sequence divergence of IRs regions was lower than that of the LSC and SSC regions, both intraspecifically and interspecifically. Eight sequences with high nucleotide diversity among different species were screened, all of which were found located in the LSC and SSC regions. Phylogenetic inference showed that all Polygonatum species clustered into a monophyletic clade with a 100% bootstrap value, within which, species in section Verticillata formed a distinct group, section Sibirica and section Polygonatum were sister groups. The two P. franchetii individuals grouped together and showed the closest phylogenetic affinity to P. stenophyllum Maxim., belonging to the section Verticillata. The chloroplast genome of P. franchetii and its phylogenetic position in Polygonatum were comprehensively investigated and clearly elucidated in this study, the results may lay a foundation for the resource development and utilization of P. franchetii, as well as further molecular identification and phylogenetic studies of medicinal Polygonatum species.

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

Quantitative systems pharmacology (QSP) modeling is an emerging computational medicine approach with growing applications and significance in modern drug development. QSP models are generally formulated based on multiscale disease mechanisms and drug-target interactions, which makes them capable of integrating multimodal data from the preclinical and clinical space. This also enables them to generate quantitative characterization of the dynamic disease progression as well as high-throughput predictions of drug-induced efficacy and toxicity signals. Therefore, QSP modeling and model-based virtual clinical trials have been widely implemented to guide drug development, in scenarios such as target identification and assessment, clinical trial design, evaluation of combination therapy and biomarkers, and personalized medicine. In US and Europe, QSP modeling has been developing rapidly in the past 10 years and is now an integral part of the model-informed drug development paradigm; however, in China it is still a nascent field. Here we will present a comprehensive review of the recent advancements of QSP and its impact in modern drug development through a number of case studies. This review will provide guidance for the future drug development efforts and the growth of QSP practice in China.