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Licorice is a remarkable traditional Chinese medicine obtained from the dried root and rhizomes of the Glycyrrhiza genus, and t has been utilized in China for many centuries. It consists of more than 300 compounds that are mainly divided into triterpene saponins, flavonoids, polysaccharides, and phenolic components. The active compounds of licorice have been found to possess multiple biological activities, including antitumor, anti-inflammatory, antiviral, antimicrobial, immunoregulatory, cardioprotective, and neuroprotective functions. In addition to providing a brief overview of licorice’s adjuvant properties, this review describes and analyzes the pharmacological mechanisms by which licorice components function to treat gastric cancer. Furthermore, licorice compounds are also found to be potent adjuvant chemotherapy agents, as they can improve the quality of life of cancer patients and alleviate chemotherapy-induced adverse effects.

Valnemulin (VML) is a semi-synthetic pleuromutilin derivative widely used to treat animal bacterial diseases. However, no study has comprehensively evaluated VML metabolism in aquatic animals, including crucian carp. This study aimed to investigate VML metabolism in crucian carp. VML metabolites in crucian carp were quantified via intraperitoneal injection and analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Three VML metabolites were detected in crucian carp via ultra-performance liquid chromatography-tandem quadrupole and time-of-flight mass spectrometry (UPLC-Q-TOF/MS) structural analysis. The enrichment and metabolism rules of the metabolites were summarized based on tissue distribution and concentration changes of the three metabolites. The metabolites were mainly found in the liver at 0.1 h after VML injection. The levels of the metabolites were abundant in the bile from 4 h to 12 h and in the skin after 72 h. The levels of the metabolites in the bile first increased, then decreased. The metabolism in the liver was completed at 72 h. The metabolites were detected in the skin following a 72 h period, which increased with time.

As a first-line agent for cholestasis treatment in a clinic, ursodeoxycholic acid rectifies the perturbed bile acids (BAs) submetabolome in a holistic manner. Considering the endogenous distribution of ursodeoxycholic acid and extensive occurrences of isomeric metabolites, it is challenging to point out whether a given bile acid species is impacted by ursodeoxycholic acid in a direct or indirect manner, thus hindering the therapeutic mechanism clarification. Here, an in-depth exploration of the metabolism pattern of ursodeoxycholic acid was attempted. Sequential metabolism in vitro with enzyme-enriched liver microsomes was implemented to simulate the step-wise metabolism and to capture the metabolically labile intermediates in the absence of endogenous BAs. Squared energy-resolved mass spectrometry (ER2-MS) was utilized to achieve isomeric identification of the conjugated metabolites. As a result, 20 metabolites (M1–M20) in total were observed and confirmatively identified. Of those, eight metabolites were generated by hydroxylation, oxidation, and epimerization, which were further metabolized to nine glucuronides and three sulfates by uridine diphosphate-glycosyltransferases and sulfotransferases, respectively. Regarding a given phase II metabolite, the conjugation sites were correlated with first-generation breakdown graphs corresponding to the linkage fission mediated by collision-induced dissociation, and the structural nuclei were identified by matching second-generation breakdown graphs with the known structures. Together, except for intestinal-bacteria-involved biotransformation, the current study characterized BA species directly influenced by ursodeoxycholic acid administration. Moreover, sequential metabolism in vitro should be a meaningful way of characterizing the metabolic pathways of endogenous substances, and squared energy-resolved mass spectrometry is a legitimate tool for structurally identifying phase II metabolites.

Low-density lipoprotein receptor-related protein 6 (LRP6), a member of the low-density lipoprotein receptor (LDLR) family, displays a unique structure and ligand-binding function. As a co-receptor of the Wnt/β-catenin signaling pathway, LRP6 is a novel therapeutic target that plays an important role in the regulation of cardiovascular disease, lipid metabolism, tumorigenesis, and some classical signals. By using capillary electrophoresis–systematic evolution of ligands by exponential enrichment (CE-SELEX), with recombinant human LRP-6 as the target, four candidate aptamers with a stem-loop structure were selected from an ssDNA library—AptLRP6-A1, AptLRP6-A2, AptLRP6-A3, and AptLRP6-A4. The equilibrium dissociation constant KD values between these aptamers and the LRP6 protein were in the range of 0.105 to 1.279 μmol/L, as determined by CE-LIF analysis. Their affinities and specificities were further determined by the gold nanoparticle (AuNP) colorimetric method. Among them, AptLRP6-A3 showed the highest affinity with LRP6-overexpressed human breast cancer cells. Therefore, the LRP6 aptamer identified in this study constitutes a promising modality for the rapid diagnosis and treatment of LRP6-related diseases.

In recent years, the [2.2]paracyclophane (PCP) ring has attracted extensive attention due to its features of providing not only chirality and electron-donating ability but also steric hindrance, which reduces intermolecular π–π stacking interactions and thereby improves the fluorescence properties of dyes. To date, some circularly polarized luminescence (CPL)-active small organic molecules based on the PCP skeleton have been reviewed; however, the application of the PCP ring in improving the photophysical properties of fluorescent dyes is still limited, and new molecular design strategies are still required. This review summarizes and promotes the application of PCP in fluorescent dye design, fluorescence detection, and CPL modulation. We expect that this review will provide readers with a comprehensive understanding of the PCP skeleton and lead to further improvement in fluorescent dye design.

As a type II transmembrane serine protease, fibroblast activation protein (FAP) is specifically expressed on the surface of fibroblasts associated with a variety of epithelial-derived malignancies such as pancreatic cancer, breast cancer, and colon cancer. It participates in the processes of tumorigenesis, progression, and immunosuppression. FAP constitutes an important target for tumor treatment; however, the current studies on FAP are mainly related to structural characteristics, enzymatic properties, and biological functions, and aptamers of FAP have not been investigated. In this work, by using recombinant human FAP as the target, five candidate aptamers, which are AptFAP-A1, AptFAP-A2, AptFAP-A3, AptFAP-A4, and AptFAP-A5, were selected by capillary electrophoresis–systematic evolution of ligands by exponential enrichment (CE-SELEX), and their secondary structures were predicted to be mainly stem-loop. Moreover, the CE-laser-induced fluorescence (LIF) method was used to determine the equilibrium dissociation constant KD values between the FAP protein and candidate aptamers, and the KD value was in the low molar range. Finally, Cy5-labeled aptamers were co-incubated with human pancreatic cancer-associated fibroblasts highly expressing FAP protein, and confocal microscopy imaging showed that aptamer AptFAP-A4 had the highest affinities with the cells. The FAP aptamers screened in this study provide a promising direction for the development of rapid tumor diagnosis and targeted therapy.

Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure extracted from the natural herb Glycyrrhiza glabra. Its anti-inflammatory, antibacterial, antioxidant, and anticancer activities have been extensively studied. Moreover, ISL also possess hypolipidemic and atherosclerosis-reducing effects. However, its cholesterol-lowering mechanisms have not been reported yet. Niemann Pick C1 Like 1 (NPC1L1) is a specific transporter of cholesterol uptake. In this study, we found for the first time that ISL downregulates NPC1L1 expression and competitively inhibits cellular cholesterol uptake by binding to NPC1L1 in a concentration-dependent manner in vitro. This study provides a theoretical basis for further investigation of the molecular mechanisms of its cholesterol-lowering effect in vivo and inspired emerging drug research for cholesterol-lowering purposes through NPC1L1 inhibition.

Elevated cholesterol significantly increases the risk of developing atherosclerosis and coronary heart disease. The key to treating hypercholesterolemia is lowering plasma cholesterol levels. There have been no studies on the cholesterol-lowering potential of parthenolide (PTL), a naturally occurring small molecule from Tanacetum parthenium. Here, we first put forth PTL’s cholesterol-lowering ability to inhibit cellular uptake of cholesterol in a dose-dependent manner. Its performance was on par with the positive control drug, ezetimibe. Niemann–Pick C1 Like-1 (NPC1L1) has been identified as a potential therapeutic target for hypercholesterolemia. The interaction of PTL with NPC1L1 could be explained by the results of molecular docking and filipin staining further reinforces this hypothesis. Furthermore, PTL reduced the expression of NPC1L1 in HepG2 cells in a concentration-dependent manner, which suggests that PTL functions as a potential NPC1L1 inhibitor with therapeutic potential for hypercholesterolemia.