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.

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.

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.

Tonkinensis is commonly used in the treatment of hepatitis B infection in China with its effecttiveness in reducing clinical symptoms and improving liver function. However, the mechanism of the anti-HBV (hepatitis B virus) effect of Tonkinensis is still not clear. In this study, an integrative analysis using the network pharmacology and metabolomics was employed in identification of the main targets and mechanisms of Tonkinensis in treatment of HBV infections. First, the "drug-target" network was established by predicting the targets of the main chemical components of Tonkinensis; Secondly, the differential metabolites associated with the anti-HBV effect of Tonkinensis were analyzed with the LC-MS based metabolomics in HepG2.2.15 cells; Finally, the "drug ingredients-targets-metabolites" network was constructed to screen the main anti-HBV targets of Tonkinensis. The results suggest that Tonkinensis may act on 16 target proteins in the network of retinol metabolism, peroxisome proliferator activate-receptors (PPAR) signaling pathway and transcriptional regulation of cancer and so on, which contributed to the control of HBV replication and the regulation of immune function and metabolic disorders.

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.

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.

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.

Allene oxide cyclase (AOC), a key enzyme in biosynthesis of jasmonic acid, plays an essential role in the plant defense system.In present study, a full length cDNA of AsAOC gene was cloned by the reverse transcription PCR from Aquilaria sinensis calli.Meanwhile, the bioinformatics, prokaryotic expression, purification, tissue-specific expression analysis, and expression analysis under different abiotic stresses and hormone treatments were performed.The open reading frame (ORF) of AsAOC1 gene was 753 bp, encoding a protein of 251 amino acids with a calculated molecular mass (MW) of 27.46 kD.Bioinformatic analysis showed that AsAOC1 protein contains a conserved allene_ox_cyc domain in C-terminus.The phylogenetic analysis indicated that AsAOC1 protein had the highest level of homology with the AOC protein from Morus notabilis.The recombinant AsAOC1 protein was successfully expressed in Escherichia coli BL21(DE3) cells using the prokaryotic expression vector pET28a-AsAOC1 and was purified by Ni²⁺ affinity chromatography.Expression analysis in different tissues indicated that AsAOC1 was primarily observed in stems, and then stem tips and roots, following by leaves.The transcript level of AsAOC1 was induced by various abiotic stresses including salt, drought, cold, and heavy metal stress.Furthermore, AsAOC1 expression level was enhanced upon methyl jasmonate (MeJA), salicylic acid (SA), gibberellin (GA3), and abscisic acid (ABA) treatments.These results provide valuable insights into the role of JA in the mechanism of agarwood formation and plant defense system.

Immunotherapy is a new strategy for cancer treatment that has the potential to treat all types of cancer. T cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) is a key negative regulator of T cell activation. TIM-3 blockage using anti-TIM-3 monoclonal antibody therapy has a great appeal and special advantages. Nanobodies, derived from heavy chain fragment in camelid animals, are now proving clinical values in the development of antibody drugs. In this study, we have immunized camel with TIM-3 antigens and then constructed phage display library. Moreover, 29 nanobodies with different complementarity-determining regions sequences have been screened from the phage display library by phage display technology. In addition, we successfully constructed the cell line stably expressing TIM-3, and screened 10 TIM-3 nanobodies with high specificity and high affinity using flow cytometry. Our study will lay the foundation for the future screening and development of anti-TIM-3 whole humanized functional nanobody.