In order to enrich the types of Panax notoginseng saponins (PNS) sustained-release preparations and provide a new research idea for the research and development of traditional Chinese medicine sustained-release formulations, a series of Panax notoginseng saponins microspheres was prepared by a double emulsion method using a series of degradable amphiphilic macromolecule materials polyethylene glycol monomethyl ether-polymandelic acid (mPEG-PMA) as carrier. The structure and molecular weight of the series of mPEG-PMA were determined by nuclear magnetic resonance spectroscopy (1 HNMR) and gel chromatography (GPC). The results of the appearance, particle size, drug loading and encapsulation efficiency of the drug-loaded microspheres show that the mPEG10000-PMA (1:9) material is more suitable as a carrier for loading the total saponins of Panax notoginseng. The particle size was 2.51 ± 0.21 μm, the drug loading and encapsulation efficiency were 8.54 ± 0.16% and 47.25 ± 1.64%, respectively. The drug-loaded microspheres were used for in vitro release and degradation experiments to investigate the degradation and sustained release behaviour of the drug-loaded microspheres. The biocompatibility of the microspheres was studied by haemolytic, anticoagulant and cytotoxicity experiments. The pharmacological activity of the microspheres was studied by anti-inflammatory and anti-tumour experiments. The results showed that the drug-loaded microspheres could be released stably for about 12 days and degraded within 60 days. At the same time, the microspheres had good biocompatibility, anti-inflammatory and anti-tumour activities.

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a-8i and 9a-9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously affects the life quality of patients. Because of the damage caused by DR, there is an urgent need to develop effective drugs. Folic acid, a water-soluble vitamin, is one of the vitamin B complexes. Folic acid is widely found in the meat and vegetables. In the clinic, low folic acid levels in the body may have a certain correlation with DR. However, there is no relevant basic research proving a relationship between folic acid levels and DR. The purpose of this study was therefore to investigate whether folic acid has a protective effect on the retinal vascular endothelial cells against high glucose levels. Moreover, the molecular mechanism of action of folic acid was further explored. The results showed that folic acid significantly suppressed the cell viability, tube length, migrated cells and the percentage of BrdU⁺ cells compared with the high glucose group. Moreover, folic acid decreased the mRNA expression of TEAD1 and the protein expression of TEAD1 and YAP1. These findings indicate that folic acid can protect retinal vascular endothelial cells from high glucose-induced injury by regulating the proteins in the Hippo signaling pathway.

Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB) technology is a universal technology to detect DNA/RNA expression in living cells. As a natural polymers, chitosan (CS) nanoparticles could be used as a carrier for safe delivery of nucleic acid. In this study, we developed a probe using nanoparticles of miR-155 MB self assembled with CS (CS-miR-155 MB) to image the expression of miR-155 in cancer cells. Hybridization assay showed that the locked nucleic acid (LAN) modified miR-155 MB could target miR-155 effectively and sensitively. The miR-155 MB self-assembly with CS nanoparticles formed stable complexes at the proper weight ratio. The CS nanoparticles showed higher fluorescence intensity and transfection efficiency than the lipid-based formulation transfection agent by confocal microscopy and flow cytometry analysis. The CS-MB complexes were found to be easily synthesized and exhibited strong enzymatic stability, efficient cellular uptake, high target selectivity and biocompatibility. The CS-MB complexes can also be applied in other cancers just by simply changing for a targeted miRNA highly expressed in those cancer cells. Therefore, it is a promising vehicle used for detecting miRNA expression in living cells.

BF-30 is a single chain polypeptide of an N-segment with an α-helix from cathelicidin gene encoding, and it contains 30 amino acid residues, with a relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively. Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene glycol-b-dl-lactic acid-co-glycolic acid) block copolymers (4-arm-PEG-PLGA) by a double-emulsion solvent-evaporation method. Three release phases of cathelicidin-BF-30loaded 4-arm-PEG-PLGA microspheres were observed, including an initial burst-release phase, followed by a lag phase with minimal drug release and finally a secondary zero-order release phase. The delivery system released BF-30 over more than 15 days in vitro. Furthermore, the material for preparing the microspheres has good biocompatibility and biodegradability. Additionally, based on the drug resistance of food pathogenic bacteria, the antibacterial effects of BF-30 on Shigella dysenteriae CMCC 51105 (Sh. dysenteriae CMCC 51105), Salmonella typhi (S. typhi) and Staphylococcus aureus (S. aureus) as well as the stability of the in vitro release of the BF-30-loded microspheres were studied. The α-helix secondary structure and antibacterial activity of released BF-30 were retained and compared with native peptide. These BF-30 loaded microspheres presented <10% hemolysis and no toxicity for HEK293T cells even at the highest tested concentration (150 μg/mL), indicating that they are hemocompatible and a promising delivery and protection system for BF-30 peptide.

ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), often reduce drug efficacy and are the major cause of drug resistance. Astragaloside IV (ASIV), one of the bioactive saponins isolated from Astragalus membranaceus, has been demonstrated to alleviate the progression of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model for multiple sclerosis (MS). In the present study, we found for the first time that ASIV induced the upregulation of P-gp and BCRP in the central nervous system (CNS) microvascular endothelial cells of EAE mice. Further study disclosed that tariquidar, a P-gp inhibitor, could facilitate the penetration of ASIV into CNS. On bEnd.3 cells, a mouse brain microvascular endothelial cell line, tariquidar benefited the net uptake and transport of ASIV. Additional molecular docking experiment suggested that ASIV might be a potential substrate of P-gp. In EAE mice, tariquidar was demonstrated to enhance the efficacy of ASIV, as shown by attenuated clinical symptom and reduced incidence rate as well as mitigated inflammatory infiltration and decreased demyelination in the CNS. Collectively, our findings implicate that P-gp inhibitor can promote the therapeutic efficacy of ASIV on EAE mice, which may boost its clinical usage together with ASIV in the therapy of MS.

Microtubule-targeted drugs are the most effective drugs for adult patients with certain solid tumors. Taccalonolide AJ (AJ) can stabilize tubulin polymerization by covalently binding to β-tubulin, which enables it to play a role in the treatment of tumors. However, its clinical applications are largely limited by low water solubility, chemical instability in water, and a narrow therapeutic window. Clear-cell renal-cell carcinoma (cc RCC) accounts for approximately 70% of RCC cases and is prone to resistance to particularly targeted therapy drugs.

Apigenin is a natural flavonoid with significant biological activity, but poor solubility in water and low bioavailability limits its use in the food and pharmaceutical industries. In this paper, apigenin-7-O-β-(6″-O)-d-glucoside (AG) and apigenin-7-O-β-(6″-O-succinyl)-d-glucoside (SAG), rare apigenin glycosyl and succinyl derivatives formed by the organic solvent-tolerant bacteria Bacillus licheniformis WNJ02 were used in a 10.0% DMSO (v/v) system. The water solubility of SAG was 174 times that of apigenin, which solved the application problem. In the biotransformation reaction, the conversion rate of apigenin (1.0 g/L) was 100% at 24 h, and the yield of SAG was 94.2%. Molecular docking showed that the hypoglycemic activity of apigenin, apigenin-7-glucosides (AG), and SAG was mediated by binding with amino acids of α-glucosidase. The molecular docking results were verified by an in vitro anti-α-glucosidase assay and glucose consumption assay of active compounds. SAG had significant anti-α-glucosidase activity, with an IC50 of 0.485 mM and enhanced glucose consumption in HepG2 cells, which make it an excellent α-glucosidase inhibitor.