Vascular endothelial growth factor receptor (VEGFR-2), a member of the super family of protein tyrosine kinase receptors, plays a vital role in the regulation of tumor metastasis and angiogenesis. Several VEGFR-2 inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies. According to the principle of multi-targeted pharmacolgy, in the field of tumor treatment, nonselective drugs targeting on more than one kinase to inhibit different cell pathways can be more effective than drugs specific for one kinase. Multi-target treatment does not mean abandonment of selectivity, but a precise selectivity for several kinases related to tumor, which is also a big challenge in the development of small molecular antitumor drugs. This paper reviews briefly the advances in research of the VEGFR-2 inhibitors and selectivity strategy in recent years.

HSP90 is widely expressed in cells with the main function in assisting the maturation of other proteins that are called clients. Many clients play critical roles in the occurrence and development of cancer. Inhibition of HSP90 can lead to degradation of the oncogenic proteins, and result in potent anti-cancer effects. HSP90-HOP interaction is critical for the chaperone function of HSP90, thereby disruption of the HSP90-HOP interaction is a novel strategy in the inhibition of HSP90. Based on the technology of homogeneous time-resolved fluorescence (HTRF), we developed a new assay for the identification of new inhibitors of HSP90-HOP interaction. This method was evaluated in the study of the HSP90-HOP inhibition activity of the pentapeptide MEEVD from HSP90 C-terminal and its derivatives. This study can provide a basis for the screening and discovery of novel HSP90-HOP disruptors.

L-Glutamate is an important amino acid in protein. It has many physiological functions, such as nutrient metabolism, energy supply, immune response, oxidative stress, and signaling pathways regulation. Recent studies have found that glutamate prevents gastrointestinal damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) and promotes the healing of the lesions. It can inhibit colonization of Helicobacter pylori and cell apoptosis caused by NH₃. Hence, it has a potential value in protection of gastrointestinal from damage caused by NSAIDs and Helicobacter pylori. This article provides a review of the metabolism and physiological function of glutamate and its protective mechanisms of gastrointestinal injury caused by NSAIDs and Helicobacter pylori, which may serve as a reference in the study of glutamate in drug development.

This study was aimed to construct a "drug-target-pathway" network of Xuebijing injection for sepsis treatment in an effort to explore the "multi-components, multi-targets, multi-pathways" mechanism based on "system-system" research mode. Active ingredients of Xuebijing injection were used to predict the potential targets according to reversed pharmacophore matching method. The pathway information was acquired from DAVID and KEGG database. The Cytoscape software was used to construct the "ingredient-target-pathway" network of Xuebijing injection for sepsis treatment. The results showed that 21 major active ingredients of Xuebijing injection regulated 550 targets (HRAS, GSK3B, BTK, AK, et al) and affected 10 inflammation and immune-related pathways, such as B cell receptor signaling pathway, VEGF signaling pathway, natural killer cell mediated cytotoxicity, Toll-like receptor signaling pathway. The sepsis therapeutic effect of Xuebijing injection reflected the action features of traditional Chinese medicine as multi-ingredients, multi-targets, multi-pathways. This research clarifies the material basis of Xuebijing injection for anti-inflammation and immunoregulation, providing a scientific basis for elucidation the mechanism of Xuebijing injection in the treatment of sepsis.

Tianlongtongxin (TLTX) formula is composed of six Chinese herbs including Rhodiola rosea L., Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma and so on. It has been mainly used in the treatment of chest-Bi syndrome in the clinics. To investigate the material foundation and provide reference for clinical dosage regimen, the pharmacokinetics of seven components in the rat plasma were studied after oral administration of TLTX. A high sensitive method was established to determine the seven active components from TLTX in rat plasma based on the LC-MS/MS technique. The method met the requirements of preclinical pharmacokinetic study, through the investigation of linearity, specificity, recovery, accuracy, precision and stability. After administration of TLTX at 4.5 g·kg^-1 dose, all of the components were detectable in the plasma after 5 min. The concentration peaks were observed at 0.11-4.67 h respectively after administration with great difference in levels. The AUC of salidroside was significantly higher than other components, suggesting it as a main active component in TLTX formula. The observations provide scientific evidence for the rationality of salidroside as monarch drug in the formula.

Due to the difference in structure and chemical properties of amino acids, it is difficult to determine amino acids with different properties by GC-MS. A method was established for the simultaneous determination of 20 amino acids by using ethyl chloroformate (ECF) as the derivatization reagent and adjusting pH 9-10 in the second derivatization in this study. The results showed that 20 amino acids were well separated and the compounds in the 2-20 μg·mL^-1 concentrations were detected with a good linear response correlation coefficient r² greater than 0.99. The results of precision and system adaptability show that RSD < 10%, the average recovery of samples in the 78.3%-109.9%. The results showed that the method was simple and easy to use, and the derivatization method could be carried out in aqueous solution. The derivatization product was stable with wide linear range, thus this method could be used for the determination of a variety of biological samples such as Astragalus mongolicus, mouse urine sample and mouse serum sample.

NMR-based metabolomics technique has been applied to botanical studies in recent years. The plant metabolites are complicated and various, metabolomics method can detect the global metabolomic profile of the plant to track valuable metabolites, and provide information for the research of plant physiology, metabolic pathways and functional genes. This paper reviews the application of NMR-based metabolomics technique in medicinal plants, including the biosynthetic mechanism and production of secondary metabolites, the improvement of yield or quality of medicinal plants, the development of effective active ingredient, the identification of medicinal plant species, and the quality control of herbal medicine. In addition, the potential development of this technique in future is discussed.

A new phomapyrone derivative (1), and 9 known compounds were isolated from the ethyl acetate fraction of solid fermentation of Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha, by using various isolation techniques such as Sephadex LH-20, MCI GEL and Semi pre-HPLC, etc. Their structures were identified by spectroscopic analysis, including MS, UV, CD, specific rotation, IR, 1D and 2D NMR, as (+)-7S-4-deoxy-9-hydroxyphomapyrone C (1), uracil (2), uridine (3), 2'-deoxyuridine (4), adenosine (5), 2'-deoxyadenosine (6), cordysinin B (7), ergosterol (8), ergosta-5α, 8β-epidioxy-6, 22-dien-3β-ol (9), and (22E, 24S)-3α-hydroxy-24-methylcholesta-5, 8, 22-trien-7-one (10).

In this study, we aim to develop a pH-sensitive transmembrane peptide TH (AGYLLGHINLHH LAHL (Aib) HHIL-Cys) modified liposome loaded with immunoadjuvant α-galactosylceramides (αGC-TH-Lip) and then investigate its effect on the immune function in tumor-bearing mice and its immune mechanism of action. The liposomes were prepared by membrane dispersion-probe ultrasound method and the size and zeta potential of αGC-TH-Lip were also characterized. The uptake of TH modified liposomes (TH-Lip) and polyethylene glycols modified liposomes (PEG-Lip) in DC2.4 cells in vitro were analyzed and the activation of natural killer T (NKT), natural killer (NK) and macrophages in tumor-bearing mice were also measured after systemic administrations of samples. Besides, the degree of maturation of dendritic cell (DC), the number of cytotoxic T lymphocyte (CTL) and the differentiation of helper T cell (Th) were determined. The results showed the particle size of αGC-TH-Lip was about 117.9 nm and the zeta potential was about-8.37 mV under the neutral condition (pH 7.4) and the αGC-TH-Lip had high serum stability in 50% fetal bovine serum. The uptake of TH-Lip in DC2.4 cells in vitro was 1.48 times higher than that of PEG-Lip. After systemic administrations of the samples, the numbers of NKT cells, NK cells and macrophages in tumor-bearing mice were (0.43±0.048)%, (12.80±0.50)% and (3.13±0.26)%, respectively, and the number of mature DCs and CTLs reached (2.30±0.22)% and (32.30±0.80)% separately, which was significantly different from the con-trol group. Finally, we discovered the αGC-TH-Lip had the strongest induction effect on the differentiation of Th1 cells, while barely promote the differentiation of Th2 cells. All the above results demonstrated that the αGC-TH-Lip can improve the immune the activity of mice, enhance the effect of α-galactosylceramide and promote the differentiation of lymphocytes toward the direction of cellular immunity, which consequently achieve a better anti-cancer immune activity.

The purpose of this study was to investigate the thermodynamics of naringenin (NAR)-isonicotinamide (INT) cocrystal (stoichiometric ratio, 1:2) formed in different solvents. The dissolution behavior of cocrystal was explored in the water. Solubility of NAR-INT cocrystals under various temperatures were measured, followed by fitting the complexation model to calculate the thermodynamic parameters solubility products (K_sp), complexation constants (K₁₂) and Gibbs energy change (ΔG) of cocrystal during formation progress. Ternary phase diagrams (TPDs) of the NAR-INT-solvent systems under various temperatures were plotted. Based on the non-linear simulation, 1:2 complexation model was well fitted to the NAR-INT cocrystal formation in ethanol, isopropanol and ethyl acetate, while no complexation model was more suitable for that in methanol. The cocrystallization reaction was exothermic and spontaneous (ΔG < 0, ΔH < 0, ΔS < 0). K_sp increased while K₁₂ decreased when increasing temperature, suggesting that the two components could cocrystallize more easily at the lower temperature. In comparison to TPDs in other solvents, the area of homogeneous liquid phase in ethyl acetate was the smallest, indicating the easiest formation of NAR-INT cocrystal in ethyl acetate. The current study provides a theoretical foundation for preparation and optimization of scale-up NAR-INT cocrystals.