The chemical constituents from ethyl acetate extract of Gleditsiae spina were isolated and purified by various chromatographic methods such as MCI gel CHP-20, ODS, Sephadex LH-20, silica gel and semi-preparative HPLC. Seven lignans were isolated and identified by spectroscopic data analyses as (7R, 8S, 7'E, 7''S, 8''R)-buddlenol P (1), (+)-syringaresinol (2), (+)-isolariciresinol (3), (7S, 8R)-cedrusin (4), (7S, 8R)-4, 9, 9'-trihydroxy-3, 3'-dimethoxy-7, 8-dihydrobenzofuran-1'-propylneolignan (5), 3', 4-O-dimethylcedrusin (6), balanophonin (7). Among them, compound 1 is a new lignan, compounds 2-7 are isolated from the Gleditsia L. for the first time. MTT method was used to investigate the effect of compounds 2-7 on LPS-induced injury of NRK-52e cells. As a result, compounds 2, 3 and 7 exhibit protective effects against LPS-induced damage to NRK-52e 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.

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.

The goal of the present study was to determine the effectiveness and safety of hemoperfusion (HP) in beagle dogs with chronic kidney disease (CKD). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research New Drug Evaluation Research (IACUC2019071501). Twelve CKD model beagles were randomly divided into two groups: a low-frequency treatment group (n=6) and a high-frequency treatment group (n=6). The dogs in the high- and low-frequency groups received HP treatment every 3 days and once per week, respectively, for two treatments, with each session lasting 2 h. The test results showed that high-frequency HP treatment significantly decreased the accumulation of toxins in the CKD beagles. Hematology, coagulation function, electrolytes and liver function indicated that the HP treatment was safe. The body index effects were consistent between the low- and high-frequency treatment groups. Therefore, HP treatment once every 3 days was safe at the animal level. Multiple HP treatments every 3 days were more conducive than weekly treatments to the removal of uremic toxins with better prognosis and had no associated safety hazards.

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.

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.

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.

To identify the composition of iridoids from Hedyotis diffusa Willd and explore the mechanism on its anti-renal fibrosis effect based on network pharmacology, LC-Q/TOF-MS (liquid chromatograpy-quadrupole/time of flight mass spectrometry) was used to analyze the iridoid ingredients and the related targets of renal fibrosis were obtained by DisGeNET database and MalaCards database. The potential targets were screened by SYBYL-X7.3 software. We then imported the identified ingredients and potential target genes into Cytoscape3.7.1 to construct the compound-target network and the protein-protein interaction (PPI) network. Finally, the gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis of the selected core genes were made to explore the mechanism of iridoids against renal fibrosis. There were 10 active iridoid compounds and 111 corresponding targets including dimethylarginine dimethylaminohydrolase 1 (DDAH1), heparanase (HPSE), human kirsten rat sarcoma viral oncogene (KRAS), moesin (MSN), etc. in compound-target network. The GO functional enrichment analysis obtained 211 GO entries. Twenty related signal pathways including Toll-like receptor signaling pathway, transforming growth factor-beta (TGF-β) signaling pathway, renal cell carcinoma signaling pathway, and the Janus kinase/signal transducer and activator of tran-ions (Jak-STAT) signaling pathway were selected by KEGG enrichment analysis. We preliminarily investigated the mechanism of the iridoid compounds on renal fibrosis to provide guide information for the subsequent experimental research and clinical application.

High expression of Bcl-2 is associated with the development of pancreatic cancer, and downregulation of Bcl-2 is an effective approach for the treatment of pancreatic malignancy. In the present study exosomes were isolated from the cultured medium of human embryonic kidney cells (HEK293) by ultracentrifugation and exosome-coated Bcl-2 siRNA (exosiBcl-2) was synthesized using electroporation. The results showed that the particle size of exosiBcl-2 was 67.3±9.7 nm and the morphology of exosomes displayed a concave ring structure as determined by transmission electron microscopy (TEM). Western blot analysis indicated that exosomal proteins including CD9, CD81, CD63 and TSG101 were highly expressed. Confocal microscopy revealed that exosiBcl-2 was widely distributed in Miapaca-2 cells, and the transfection efficiency of exosiBcl-2 in Miapaca-2 was 77.2% as determined by flow cytometry. Treatment with exosiBcl-2 at a concentration of 100 nmol·L^-1 resulted in an inhibitory effect on the growth of Miapaca-2 cells with an inhibition rate of 63%. ExosiBcl-2 treatment can downregulate Bcl-2 and upregulate Bax protein. This study provides evidence that exosiBcl-2 is able to inhibit the growth of pancreatic cancer cells and the nanoparticles have potential to be developed as a novel anticancer agent.

Four cadinane-type sesquiterpenes were obtained from the petroleum ether of 95% ethanol extract of Eupatorium adenophorum Spreng by using an HP-20 macroporous resin column, silica gel, and semi-preparative HPLC. Their structures were determined by physical, chemical and spectroscopic methods and identified as eupatorinol (1), (+)-(5R, 7S, 9R, 10S)-2-oxocadinan-3, 6(11)-dien-12, 7-olide (2), (1S, 4R)-7-hydroxycalamenen-3-one(3) and (-)-(5R, 6R, 7S, 9R, 10S)-cadinan-3-ene-6, 7-diol (4). Among them, compound 1 is a new cadinane-type sesquiterpene, and compound 3 was isolated from this genus for the first time. In bioassay, none of these compounds displayed obvious cytotoxicity.