C17 is a small molecule containing 2, 4-diaminoquinazoline and aryl piperazine. Docking was used to compare the affinity of C17 for five dopamine receptor (DR) subtypes. Pancreatic cancer SW1990 and PANC-1 cell lines were used in in vitro and in vivo studies. The effect of C17 on the expression level of D1DR was investigated by immunofluorescence. A cytotoxicity assay, clone formation assay and flow cytometry were used to investigate the ability of C17 to inhibit on cell survival, clone formation, and to suppress cancer stem-like cells (CSCs). The ability to suppress tumorigenesis was investigated by inoculating nude mice with SW1990 cells pre-treated with different concentrations of C17. Finally, the anti-tumor efficacy and safety of C17 and its combination with the multitarget tyrosine kinase inhibitor sunitinib (SUN) were evaluated in SW1990 xenograft mice. Our results demonstrate that C17 is most likely to bind to D1DR among the five DR subtypes. D1DR expression was increased in C17-treated cells, which could be reversed by SCH23390, a D1DR-specific antagonist. The IC₅₀ values of C17 on the survival of SW1990 and PANC-1 cells were 12.56 and 10.56 μmol·L^-1, respectively. C17 could suppress clone formation ability, CSC frequency and in vivo tumorigenesis in a dose-dependent manner. In the SW1990 xenograft model, 50 mg·kg^-1 of C17 could weakly inhibit the tumor growth, and the tumor volume with 50 mg·kg^-1 of C17 in combination with 10 mg·kg^-1 of SUN group was smaller than that in SUN 10 mg·kg^-1, SUN 20 mg·kg^-1 group and gemcitabine (GEM) group. In addition, body weight, blood test, and organ index results showed good safety with all dosing regimens. All animal experiments were in strict accordance with the regulations of the Biomedical Ethics Committee of Peking University. C17 may be a promising candidate for the treatment of pancreatic cancer.

We separated and purified five chemical constituents of dried ginger by Diaion HP-20, Sephadex LH-20, silica gel and semi-preparative high performance liquid chromatography. Five gingerols were identified by physicochemical properties and MS and NMR spectroscopy techniques:4-(2-butyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (1), 4-(2-hexyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (2), 1-(4-hydroxy-3-methoxyphenyl)tridecane-3, 5-diol (3), [10]-gingerdiol (4) and 1-[1-(4-hydroxy-3-methoxy phenyl)-3-oxodecan-5-yl]pyrrolidin-2-one (5a, 5b). Compounds 1-3, 5a, 5b are new compounds.

The fruit of Lycium barbarum L. (FLB) is a food and medicinal herb. Identifying suitable production regions for this plant would be beneficial to its cultivation and production. In this study, the Maxent model was used to identify ecologically suitable regions for the growth of L. barbarum L. In addition, based on its chemical composition, the suitable regions for production were identified by literature analysis and chemometrics. The results show that suitable regions for L. barbarum L. culture are mainly distributed in the northwest of China; suitable regions for the production of medicinal FLB were mainly concentrated in the district of Ningxia, Baiyin, Jiuquan and Zhangye of Gansu, and parts district in west of Inner Mongolia. All are the traditional production regions for FLB, which is consistent with the good quality of FLB produced in Ganzhou in ancient times, and the genuine medicinal materials of FLB produced in Zhongning of Ningxia today. The suitable regions for edible FLB were mainly distributed in northwest of Qinghai, Jiuquan and Zhangye of Gansu, as well as Aksu and Kizi sukirgiz of Xinjiang. The fruit type index of FLB in these regions is large, and the content of fructose and glucose in the fruit is high, which satisfies the edible commodity property. The study results lay a foundation for realizing the regional distribution and development of L. barbarum based on its different uses.

This study was designed to investigate the effect and mechanism of astragaloside IV (ASIV) on mitochondrial morphology and function of rat cardiomyocytes under hypoxia/reoxygenation injury. H9c2 cells were divided into control group, hypoxia/reoxygenation (H/R) group, and H/R + ASIV group. Cell viability and lactate dehydrogenase (LDH) leakage were measured by cell counting kit-8 (CCK-8) and LDH assay kit, respectively. Oxidative stress levels, such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA), were analyzed by commercial kits. Intracellular and mitochondrial reactive oxygen species (ROS) levels were detected by dihydroethidium (DHE) and MitoSOX. Changes of the mitochondrial membrane potential were detected using the fluorescent probe JC-1. Opening of mitochondrial permeability transition pore was examined via calcein acetoxymethyl ester (calcein-AM). Apoptosis was assessed using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay kit. To detect protein expression of dynamin-related protein 1 (Drp1), mitofusin1 (Mfn1), Mfn2, Bax, B-cell lymphoma-2 (Bcl-2), and cleaved cysteine-aspartic protease (caspase)-3, Western blot analysis was carried out. Compared with the control group, ASIV (100 μmol·L^-1) significantly improved H/R induced cell injury, LDH leakage, decrease of SOD activity, and GSH content, increase of MDA content and ROS content, loss of mitochondrial membrane potential, mitochondrial permeability transition pore opening, ROS production activation, mitochondrial fission/fusion imbalance, and cell apoptosis. In addition, the effect of ASIV against H/R injury was also verified on primary rat cardiomyocytes. The animal welfare and experimental process follow the rules of Animal Ethics Committee of Zhejiang Chinese Medical University. In conclusion, ASIV may play a protective role in mitochondria by regulating morphological dynamic stability and mitochondrial function, inhibiting excessive synthesis of ROS, improving the internal environment of oxidative stress, reducing cell apoptosis, and thereby protecting against cardiomyocytes' hypoxia/reoxygenation injury.

Asthma is a chronic inflammatory disease involving eosinophils, mast cells, lymphocytes, neutrophils and other inflammatory cells and immune components. Chinese medicine has unique advantages in the treatment of asthma. In this study an ovalbumin (OVA)-induced asthma model in rats was used to verify the effect of the total sesquiterpenoids of Flos Farfarae (F.F.S) on asthma. The results show that the F.F.S has anti-asthmatic effects. Metabolomic analysis showed that 25 metabolites were changed in asthmatic rats, and 18 of them could be attributed to F.F.S. F.F.S. can block the over-activation of p65 NF-κB, preventing the transmission of pro-inflammatory factor signals to cells. F.F.S. thus could reduce the over-activation of inflammatory cells, inhibiting the secretion of inflammatory factors and further alleviating asthma inflammation. This study lays a foundation for further new drug research. The mechanism of F.F.S. on asthma needs further investigation.

To establish a method for the determination of polymer impurities in cefixime raw materials and preparations, a cefixime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSⁿ method. A new RP-HPLC method for cefixime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.5% formic acid-water solution and 0.5% formic acid-acetonitrile solution. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, three polymer impurities were detected with good specificity, sensitivity and robustness, including two cefixime dimers, and dehydrate dimer. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in cefixime, and cefixime degradation solution can be used as suitable solution for analysis of cefixime polymers.

Dithiocarbamates and their derivatives with unique molecular structures possess diverse biological activities, which have become the research focus in the chemical and pharmaceutical fields in recent years. Here, we will review the structures, synthesis as well as biological activities of dithiocarbamates and their derivatives in anti-oxidation, anti-virus, anti-bacterial, anti-tumor and anti-Alzheimer's disease, and make a prospect for their development in the future.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which is mainly characterized by hyperandrogenemia, rare or anovulation, and polycystic ovarian changes. PCOS is seriously harmful and its causes are complex, which has not yet been clarified. Studies have shown that non-coding RNAs play important roles in the development of PCOS, including the regulation of hormone metabolism and follicle development. Exosomes are natural nano-scale membrane vesicles that contain cell-specific proteins, lipids, nucleic acids, and other biologically active molecules. Exosomes are important mediators for intercellular communication and new targets for disease diagnosis and treatment. Recent studies have shown that as an important component of follicle microenvironment, exosome is closely related to the pathogenesis of PCOS. Exosome and exosomal non-coding RNAs are expected to serve as potential new diagnostic and therapeutic targets for PCOS. In this review, we will summarize the function of exosome and exosomal non-coding RNA in the pathogenesis, diagnosis, and treatment of PCOS.

We prepared moxifloxacin (MXF) loaded nanoparticles by nano-precipitation/self-assembly method, then compared the antibacterial activity of MXF and MXF loaded nanoparticles, and investigated the antibacterial mechanism of MXF loaded nanoparticles against Pseudomonas aeruginosa in vitro. The physicochemical properties such as particle size and zeta potential were investigated by laser particle size analyzer. The in vitro release characteristics were investigated by high performance liquid chromatography (HPLC). The effect of nanoparticles on HBE cells viability was investigated by CCK-8 assay. In addition, the in vitro antibacterial activity was investigated by minimum inhibitory concentration (MIC) assay, biofilm formation assays and transmission electron microscope (TEM) observation, then the antibacterial mechanism was initially explored. The particle size measurement showed that the nanoparticles had a size of 332.5 ±2.7 nm, a polymer dispersion index (PDI) of 0.125 ±0.053, a zeta potential of -24.3 ±1.7 mV, and a uniform particle size distribution, drug loading content was (6.02 ±1.27)%, encapsulation efficiency was (16.69 ±1.17)%. The TEM results show that the nanoparticles have a spheroidal structure, and the particle size and distribution are consistent with the particle size measurement results. The nanoparticles can be effectively and rapidly released in phosphate buffer saline (PBS), releasing about 70% in 24 h, and releasing 87% in 72 h, and almost completely releasing the MXF at 120 h. At the same time, compared with moxifloxacin free drug, its MIC value is 8 μg·mL^-1, which is 1/2 of MXF solution, and can significantly inhibit the formation of bacterial biofilms. It has well antibacterial activity in vitro and can be targeted to the surface of bacteria to exert its efficacy and improve the antibacterial effect. The moxifloxacin nanoparticles prepared in this study has a uniform particle size distribution, well drug release performance and antibacterial effect, and provides new ideas and strategies for the treatment of bacterial lung infection and the development of new antibacterial nanoformulations.

Human pathogenic coronaviruses can be divided into seven types, namely HCoV-229E, HCoV-OC43, HCoV-HKU1, HCoV-NL63, SARS-CoV, MERS-CoV and SARS-CoV-2. Among them, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Corona Virus Disease 2019 (COVID-19), which are caused by the last three coronaviruses respectively, are enormous threats that challenge human health and social and economic development. Despite the huge investment in drug development for pathogenic coronaviruses, there is no specifically effective anti-coronavirus drug approved so far. In this review we systematically summarize 146 representative anti-coronavirus active compounds reported in the past 20 years and list 26 potential target proteins involved in the process of viral infection and replication. In addition, we predict the target proteins of those active compounds with unclear antiviral activity mechanisms. We hope that the information will be useful to accelerate the development of new anti-coronavirus drugs.