The development of tumor tissue is a complicated process, which is closely related to tumor microenvironment. In order to simulate the tumor tissue in vivo, non-contact co-culture of human breast adenocarcinoma cells (MCF-7 cells) and human umbilical vein endothelial cells (HUVECs cells) using transwell cell culture plate was developed in this study. The cell viability, morphology, cell resistance, cell cycle and vascular endothelial growth factor (VEGF) protein content of co-cultured MCF-7 and HUVECs cells were investigated, and compared with those of separately cultivated MCF-7 and HUVECs cells during the same period. Different to the separately cultured MCF-7 and HUVECs cells, co-cultured MCF-7 and HUVECs cells exhibited higher cell viability, deformed cell morphology, lower cell resistance, higher proportion of S and G₂/M phases and higher VEGF protein content (about 1.4-2 times). The double cell model via non-contact co-culture of MCF-7 and HUVECs cells constructed in this study could simulate the interaction between tumor cells and tumor vascular endothelial cells in vivo, which may provide a more realistic model for subsequent study of drug release system in the control of breast cancer in vitro.

Photodynamic therapy (PDT) has emerged as a more effective and promising treatment towards cancer therapy. PDT is a minimally invasive and spatially selective medical technique to destroy cancer cells without drug resistance, which has been increasingly applied in the clinical praxis alongside surgery, chemotherapy and radiotherapy. However, traditional PDTs use a high energy one-photon laser beam, which is far from the efficient optical window of mammalian tissue (650-950 nm). Moreover, it has great limitations in the depth of penetration, and induces the undesired light toxicity. The development of photosensitizers has always been a bottleneck to the effective application of PDT in clinical practice. From the first generation of hematoporphyrin derivatives to the third-generation photosensitizers with tumor targeting ability, they meet the urgent clinical needs to some extent, but they still can not satisfy the requirements of two-photon PDT. Therefore, the development of photosensitizers, which are capable of two-photon activated PDT, has become a promising approach. Among the various two-photon absorption photosensitizers, ruthenium (Ⅱ) polypyridyl complexes have been recognized as excellent candidates due to their attractive photophysical properties. This review is prepared to summarize the recent achievements in the application of ruthenium (Ⅱ) polypyridyl complexes as photosensitizers for two-photon PDT, as well as to provide guidance for the design of two-photon activated photosensitizers in future research.

Autism spectrum disorders (ASD) are a group of behaviorally defined, etiologically heterogeneous neurodevelopmental disorders characterized by impairment in social reciprocity, disturbances in language and various types of repetitive behaviors. The etiology and pathogenic mechanism of ASD are still unclear and there is no effective treatment available yet. ASD treatment includes behavioral and medicinal interventions. Behavioral interventions are the first line of treatment for ASD, alleviating core symptoms. Medicinal treatments, exert limited effect towards the core symptoms, represent an aide to the behavioral intervention and mainly apply to the so-called associated behavioral symptoms, such as irritability, aggression, self-injury, anxiety, insomnia, hyperactivity, low attention and compulsive behavior. A wide range of different agents are currently being tested in the preclinical and clinical studies, which include antipsychotics, antidepressants, anticonvulsants, anxiolytics, anti-infective drugs, glutamate receptor modulators, GABA receptor modulators, mTOR inhibitors and neuropeptides, etc. The purpose of present review is to cover the research advances in drug development and medicinal treatment of autism spectrum disorders.

The antioxidant activities of Vleriana jatamansi Jones were investigated and the relationship between the antioxidant effect and the chemical structure was explored. The free radical scavenging test, 2, 2-diphenyl-1-picrylhydrazyl (DPPH^•), was used to evaluate the antioxidant activities of the extracts of Vleriana jatamansi Jones with 0−100% menthol as extraction solvents. The polar and nonpolar HPLC conditions were conducted to isolate the main chemical compositions. The DPPH^• tests were used in analysis of the free radical scavenging activities. Under polar HPLC separation conditions, 5 kinds of compounds were detected:chlorogenic acid, 3, 5-dicaffeoylquinic acid, 4, 5-dicaffeoylquinic acid, hesperidin, and coffeic acid; under nonpolar HPLC separation conditions, acevaltrate, 1β-acevaltrate and valtrate were founded. Chlorogenic acid, 3, 5-dicaffeoylquinic acid, and 4, 5-dicaffeoylquinic acid presented high DPPH^• free radical scavenging activities. The results of antioxidant activity suggested that the coffee acyl from chlorogenic acid-like compounds had a high DPPH^• free radical scavenging ability. Our investigation indicated that structure of the ortho hydroxyl phenol of chlorogenic acid-like compounds play a significant role in antioxidant activities. In addition, this work can also provide method and theory reference for improving the antioxidant activities of Vleriana jatamansi Jones.

Gambogic acid (GA), the main active ingredient in gamboge, has been reported to have good anti-tumor activity with excellent selectivity.However, its clinical application is limited by the poor water solubility.GA nanosuspensions were designed in this study in order to solve this problem.GA nanosuspensions were prepared by microprecipitation method based on pH adjustment.Suitable stabilizer was screened according to the size and polydispersity index (PDI) of the resultant nanosuspensions.Dynamic light scattering method was used to measure the particle size and transmission electron microscopy was used to observe the morphology.The stability was studied in different medium.The drug release was evaluated using a dialysis method.MTT assay was used to assess their cytotoxicity in vitro against cancer cell line.Anti-tumor effect in vivo was investigated on H22-bearing mice.In result, Poloxamer (P188) was found to be a good stabilizer.The resultant GA nanosuspensions (GA-NSps) were 135.9 ±5.1 nm in diameter, with PDI value being 0.26 ±0.01 and the zeta potential being -35.1 ±1.36) mV.GA-NSps were nearly spherical.They were quite stable in various physiological media.GA-NSps exhibited a sustained drug release pattern, with the cumulative release reaching 90.26% within 312 h.In MTT assay, GA-NSps had a stronger cytotoxicity against HepG2 cells than the free drug (IC₅₀, 0.851 8 μg·mL^-1 vs 2.104 μg·mL^-1, P < 0.05).The pharmacodynamics study suggest that the antitumor effect of GA-NSps was dose-dependent.The anti-tumor effect at the high dose is better than that of paclitaxel (72.35% vs 66.80%, P < 0.01).In summary, we prepared GA-NSps with high drug loading capacity, small particle size and good stability, and provided a solid basis for the effective dosage form of gambogic acid.

A large number of epidemiological data have shown that the high-density lipoprotein cholesterol level is negatively related to atherosclerotic cardiovascular disease, suggesting that high-density lipoprotein may have the effect of anti-atherosclerosis. It may play the role of anti-atherosclerosis, through the promotion of cholesterol reverse transport, anti-inflammatory, antioxidant, and against thrombosis and fibrinolysis and so on. Among them, reverse cholesterol transport which is mainly regulated by apolipoprotein A-I, ATP-binding cassette transporter 1, liver X receptor and cholesteryl ester transfer protein, may play a major role in the maintenance of cholesterol homeostasis and reversing the course of atherosclerosis. These regulatory factors may be potential targets in high density lipoprotein-based drug discovery. In this review, these key proteins are discussed for the current status of small molecule drugs against atherosclerosis.

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to this study to detect heavy metal contents in Coptidis Rhizoma from different habitats, for a comprehensive understanding of heavy metal residues in Coptidis Rhizoma.Decocting method and artificial gastrointestinal digestion model were used to determine transfer rates of heavy metals in assessment of health risk of heavy metals using the target hazard quotient (THQ) developed by the US EPA (1989).The results showed that excess rates of Cu, Pb, As, Cd and Hg of 17 batches of Coptidis Rhizoma were 0, 12%, 0, 0 and 0, respectively, under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metal.The transfer rates of Cu, Pb, As, Cd and Hg were 3.63%, 1.69%, 37.17%, 20.86% and 0 in decoction solution, respectively, and 59.15%, 29.98%, 67.55%, 104.59% and 0 in artificial gastrointestinal solution, respectively.The values of THQ under the two ways of administration in adults and children were 0.001 0, 0.005 3 and 0.000 7, 0.003 6, respectively, and the maximum residue limits (MRL) of heavy metals in Coptidis Rhizoma were higher than the contents of samples in this study.The research showed that the contents of heavy metals in Coptidis Rhizoma were in the safe ranges with no obvious risks to human body, indicating that the excessive of heavy metals in Coptidis Rhizoma might be attributed to the unduly strict standard.The contents of heavy metals in Coptidis Rhizoma of different habitats was estimated for health risks using international risk assessment model, which provides a reference for establishment of heavy metal standards in Coptidis Rhizoma.

Taking cytosine, an unique natural product alkaloid as the lead, we designed thirty cytisinic derivatives with different types of 12N-substituents, which were synthesized and evaluated for their activity in the regulation of glucose metabolism in vitro. The compounds 3d, 3g and 6h exhibited the potential hypoglycemic activity and compound 3d had a good pharmacokinetics profile. In terms of mechanism of glucose consumption, the compounds 3d and 6h increased cellular glucose consumption. which might be associated with up-regulation of glucose transporter Glut4 expression and activation of AMPK. The results revealed important roles of these new skeleton compounds as potential new drug candidates for control of blood glucose.

This study was conducted to improve structural instability of a highly active DHODH inhibitor A found in our group. Twelve prodrugs were synthesized by modifying the carboxyl group. The enzyme activity test of 12 prodrugs A1-A12 demonstrated that A1-A5 displayed weak inhibitory activity, and A6-A12 displayed no activity, which met the action mechanism of designed prodrug. The structural stability of A1-A12 in methanol and pH 2.0, 9.0 buffers were tested, and the results showed that A12 could avoid intramolecular ring-formation in CH₃OH, A1-A8 were easily hydrolyzed under acidic conditions, and A9-A12 were inclined to hydrolyze under alkaline conditions. The cell proliferation inhibitory activity of 12 prodrugs were evaluated, in which compound A12 displayed excellent activity (IC₅₀=0.63 μmol·L^-1) similar to brequinar. These results laid a good foundation for conducting further vivo studies.

As a secondary metabolite in plant, anthocyanins plays an important role in many aspects of plant life, and also exhibits various activities including the anti-oxidation, anti-inflammatory, antibacterial, antitumor and cardio-cerebral vascular protective in animals. They are a group of important natural drug candiadtes in the prevention of cardiovascular and cerebrovascular diseases and metabolic diseases. Therefore, exploration of the biosynthetic pathway and regulatory mechanism of anthocyanins is of great interest for improvement of anthocyanin production and development of low-cost production methods. Circadian clock, as a ubiquitous regulatory system in organisms, affects plant physiological and molecular processes, and also regulate the anthocyanin biosynthesis. To provide new ideas on anthocyanin biosynthesis, we provide a review of the recent progress in circadian rhythm clock with regard on regulation of anthocyanin biosynthesis in this paper.