The response surface method was used to evaluate the concentration range, property and degree of Scutellaria (HQ) and Coptis (HL) herb pair on improvement of glucose and lipid metabolism in this paper. Type 2 diabetes mellitus (T2DM) was induced in rats by low a dose of streptozotocin (STZ) in combination with high-fat diet feeding. The rats were administered with HQ-HL extract pairs at different ratio (1:0, 3:1, 2:1, 3:2, 1:1, 2:3, 1:2, 1:3, 0:1). To investigate the influence of herb pair extracts on glucose and lipid metabolism of T2DM rats, the multi index synthetic index method was adopted to integrate the indexes, then the response surface method was applied to analyze the integration results. The ratio of HQ and HL from 3:1 to 1:3 showed a synergistic effect (with the value between -0.2 and -0.8). Especially, when the proportion was between 3:2 and 1:3, herb pair extracts possessed stronger synergistic effects (value:-0.8). The high dose of HQ-HL with the ratio of 1:1 exhibited the strongest synergistic effect.

Histone H3 lysine 79 (H3K79) methyltransferase DOT1L plays an important role in the activation and maintenance of gene transcription; it is also essential for maintenance of embryonic development, as well as the normal function of hematopoietic system, heart and kidney. However, the over expression of DOT1L is associated with the occurring and progress of numerous malignant tumors, so more and more attention has been paid to DOT1L. Therefore, it is of great significance to study and develop inhibitors of DOT1L. The inhibitors could serve as a tool in the investigation of the biological function, and have the potential to be developed into novel anti-cancer agents in the anticancer therapy. This paper mainly describes the structure and function of DOT1L, the relationship between DOT1L and tumors as well as the latest research progress of DOT1L inhibitors; with expect to provide some useful references for the subsequent research.

Nanocrystals is a hot topic of poorly soluble drug delivery system under development. Nanocrystals is different from the nanoparticles for drug unloading in polymer materials, and nanocrystals is different from solid dispersion system, in which the drug maintains crystals state. Nanocrystals has a simple preparation process, represents an effective technology in the improvement of solubility and bioavailability of poorly soluble drugs, and has a very promising industrialization application and development potential. In this paper, we retrospect the development history of drug nanocrystals technology, review development of the preparation methods of nanocrystals, and analyze the existing problems to provide a reference to the development of drug nanocrystals preparation.

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.

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.

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.

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.

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.

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.

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.