To study the anti-tumor activities and the related mechanisms of dicumarol, the CCK-8 method was used to identify anti-tumor activities of dicumarol. HepG2 cells were used to explore the anti-tumor mechanisms by measuring several physiological and biochemical indexes. The results show that dicumarol can significantly inhibit the growth of HepG2, Hccc-9810 and MDA-MB-231 cell lines in a dose-dependent and time-dependent manner, with HepG2 cells showing the greatest sensitivity to dicumarol (with an IC₅₀ value of 3.19±0.68 µmol·L^-1 at 48 h). Dicumarol arrested the cell cycle at S phase and down-regulated the expression of anti-apoptotic protein Bcl-2 while promoting the expression of the pro-apoptotic proteins Bax and cleaved caspase-9. Dicumarol significantly decreased the levels of glutathione (GSH) and superoxide dismutase (SOD) in HepG2 cells, and increased the levels of malonaldehyde (MDA) and reactive oxygen species (ROS). Dicumarol also down-regulated the protein levels of NAD(P)H quinone oxidoreductase 1, 3-phosphoinositide-dependent protein kinase 1, and hypoxia inducible factor-1α under hypoxic conditions. The above results show that dicumarol can inhibit the proliferation of HepG2 cells and induce cycle arrest and apoptosis. Dicumarol may down-regulate the expression of HIF-1α by inhibiting the activity of NQO1 and PDK1, which leads to the accumulation of ROS, thereby generating oxidative stress and inducing apoptosis in HepG2 cells.

This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL^-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm² for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm², which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.

The solubility/dissolution, hygroscopicity and mechanical properties of drug candidates have a profound effect on oral bioavailability, processability and stability. The physicochemical properties of crystalline drug are closely related to inner crystal structure. Crystal engineering technologies, as strategies of altering the crystal structure and tailoring physicochemical properties at molecular level, possess the potential of enhancing the pharmaceutical performance of product. The current article reviewed the modification of drug solubility/dissolution, hygroscopicity and mechanical properties by crystal engineering technologies through polymorphic selection, amorphization/co-amorphization, as well as co-crystallization, which provided a reference for the applications of pharmaceutical crystallography in improving physicochemical properties and druggability.

Salvia miltiorrhiza Bge. is one of the most important traditional Chinese medicinal plants and is used for a variety of diseases and disorders, including cardiovascular diseases, hepatocirrhosis, chronic renal failure, Alzheimer's disease, angina pectoris, myocardial ischemia, liver diseases, and diabetic nephropathy. In recent years, with the shortage of uncultivated resources and uneven product quality of cultivated germplasm, the biosynthesis and regulation of its main active ingredient has become a topic of interest. The use of a multi-omics approach with Salvia miltiorrhiza may provide genetic information as well as insights into the synthesis and regulation of the active ingredient at the molecular level. The paper presented a systematic review of the genomics, transcriptomics, proteomics and metabolomics associated with Salvia miltiorrhiza, summarized the advances in biosynthesis, regulation and related functional genes, and also put forward some scientific problems of Salvia miltiorrhiza that need to be further studied in the future.

Zika virus (ZIKV) is an emerging mosquito-borne virus that is associated with severe congenital brain malformations in the fetus and Guillain-Barré syndrome in adults. However, there are currently no drugs or preventive vaccines approved for ZIKV infection. Here, ciclesonide has been found significantly against ZIKV activity by plaque and cytotoxicity assays in vitro, and its 50% effective concentration (EC₅₀) to ZIKV SZ01 and MR766 are (0.40±0.22) and (1.59±1.08) μmol·L^-1, respectively. Its 50% cytotoxic concentration (CC₅₀) to Vero cells are (64.70±7.33) μmol·L^-1; Virus yield reduction and Western blot assays showed that ciclesonide can inhibit replication of ZIKV. In addition, ciclesonide can also inhibit the replication of ZIKV in A549 cells; the results of time of drug addition analysis indicated that ciclesonide mainly acts on the ZIKV RNA synthesis stage. Ciclesonide can also inhibit the internalization of ZIKV. These results indicated that ciclesonide is a potential drug against ZIKV.

It is now widely accepted that platelet aggregation plays an important role in physiological hemostasis and pathological thrombosis associated with cardiovascular and cerebrovascular diseases. Anti-platelet aggregation drug research is also a hot spot of current research. The biggest challenge of antiplatelet therapy has been the molecular overlap of the hemostasis and thrombosis, leading to a serious risk of bleeding. Recent studies have emphasized the importance of shear stress generated from blood flow, which will primarily drive platelet activation and aggregation in thrombosis. So if we can take advantage of the differences between the physiological and pathological vascular blood flow environment, the development of selective anti-platelet therapy may be a safer treatment for cardiovascular and cerebrovascular diseases. In this review, we discuss the underlying mechanisms of shear-induced platelet activation. Later, we summarize the effects and mechanisms of compounds and traditional Chinese medicine on shear-induced platelet activation. The aim is to provide a reference for the study of biological pharmacology of traditional Chinese medicine for promoting blood circulation and removing blood stasis.

Based on Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7^th edition), the metabolism and pharmacokinetics of drugs used in clinical treatment of COVID-19 were reviewed. The antiviral drugs include remdesivir, chloroquine/hydroxychloroquine, lopinavir/ritonavir, favipiravir, arbidol, baicalin, baicalein and forsythin. Among them, the metabolism and pharmacokinetics of arbidol, baicalin and forsythin are the research results of the author's laboratory. This article aims to provide reference for the efficacy evaluation and rational drug use of COVID-19.

Coronaviruses (CoVs) are associated with some mammalian infectious diseases, which have caused several outbreaks of respiratory system infectious diseases in recent years. There is no effective vaccine or approved drug treatment against coronaviruses, and the development of anti-coronavirus agents is an urgent priority. Phenothiazines are a class of antipsychotic drugs, which were found that they have some other biological activities, like promising antibacterial, antifungal, anticancer, antiviral, etc. They can be used for drug repurposing. This review summarizes current researches on the potential anti-coronavirus activity of phenothiazine, discusses the mechanisms and some research difficulties, and provides a foundation for developing anti-coronavirus drugs which use phenothiazine as the lead compound.

Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.

Bulbophyllum orchids are popular for its ornamental appearance and great medicinal values. However, there is still a lack of research on phylogenetic relationship and species identification for this genus. In this study, the plastome sequences of three medicinal Bulbophyllum orchids (Bulbophyllum affine, Bulbophyllum pectinatum, Bulbophyllum funingense) were sequenced and analyzed. After assembly and annotation, it was found that the plastomes of Bulbophyllum plants encoded a total of 108 genes, including 74 protein-coding genes, 30 tRNA genes and 4 rRNA genes. Based on the analysis of mVISTA and comparison between junctions, it was found that the plastome structure of Bulbophyllum orchids was relatively conserved, and the variation mainly existed in the non-coding regions. Phylogenetic analysis showed that Bulbophyllum orchids were closely related to Dendrobium orchids. SSR analysis of Bulbophyllum showed that most SSRs were located in the intergenic spacer and had the most single nucleotide repeats. In addition, based on the comparative analysis of non-coding sequences, a total of 10 high-variability sequences were screened out, among which the combination of five non-coding region sequences, including psbI-trnS, psbC-trnS, clpP-ex1-psbB, psaJ-rpl33, rpl33-rps18, had the highest sequence variability and could be used in the species identification study of medicinal plants of Bulbophyllum. In conclusion, this study provides a theoretical basis for phylogenetic relationship and species identification of Bulbophyllum orchids through the comparative analysis of plastome sequences of three medicinal plants of the genus Bulbophyllum.