A new type of L. Bulgaricus microcapsule was prepared to improve stability and resistance of L.Bulgaricus probiotics in harsh environments. An optimal method of preparation of L. Bulgaricus microcapsule is as follow. L. Bulgaricus was mixed with 3% alginate solution. The concentration of bacterial suspension was 1×10⁹ cfu·mL^-1. The mixture was microencapsulated by extrusion into 2% CaCl₂ solution with a dispensing equipment. After 30 min solidification, the gel beads were lyophilized to obtain L.Bulgaricus microcapsules. The microencapsulation technology was aimed to improve the stability and survival rate of L. Bulgaricus. The microcapsule was spherical with uniform particle size and intact structure. The tolerance of acid, high temperature, high humidity and the long-term stability of freeze-dried powder and microcapsule were evaluated. The results indicated that microencapsulation technic could greatly improve stability and resistance of L. Bulgaricus probiotics in harsh environments.

This study aims to synthesize new phospholipids, 1, 3-dipalmaminophospholipid(Pad-PC-Pad), and prepare shear-stress sensitive liposomes(SSSL). ¹H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching(ACQ)characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.

At present, taxol is an internationally acknowledged drug with a unique anticancer activity in the world and mainly come from Taxus plants, these plants have 12 species, all of which have been listed as endangered tree species and protected by the countries concerned. But available wild Taxus plants resources are rather rare, so it is very urgent to strengthen introduction and cultivation of Taxus plants to meet people's demand for taxol. According to the ecological similarity of growth of Taxus plants predict suitable areas in the whole world, which could put forward rational suggestions for introduction and planning production layout of plants. A geographic information system for global medicinal plants(GMPGIS)was developed by Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences independently, and using GMPGIS analyzed in detail the potential ecological suitable areas of Taxus plants. Ecological range of Taxus wallichiana var. chinensis, Taxus wallichiana var. mairei, Taxus baccata, Taxus brevifolia and Taxus wallichiana covered a wide field, and had larger suitable area in the northern and southern hemispheres; Taxus cuspidate mainly distributed in the northern hemisphere, and only scattered in the southern hemisphere; Taxus canadensis, Taxus floridana and Taxus cuspidata var. nana only distributed in the northern hemisphere, and the latter two prediction areas are relatively less areas; Taxus fauna, Taxus globosa and Taxus sumatrana grew up in relatively strict environment, belong to the niche species, scattered distribution and the distribution of the areas are rare. This research would exert an important promoting effect on the cultivation of Taxus plants and the escalation of abundance to guarantee the sufficient supply of raw materials for taxol production. Finally, this paper summarized the research on the ecological quality and resource conservation of Taxus plants, to provide the reference for scientific introduction and cultivation of Taxus plants.

In this study, eleven containing gallic acid moiety derivatives of Matijin-Su(MTS)were synthesized and evaluated for their anti-HBV activities in HepG2 2.2.15 cells in an effort to find novel effective anti-hepatitis B virus(HBV)agents. Compounds 5c, 6c and 6d exhibited significant anti-HBV activity with IC₅₀ values of 6.12, 8.44 and 9.86 μmol·L^-1, respectively. Incorporation of gallic acid moiety into MTS derivatives can lead to profound changes in their anti-HBV activity, and could be worth of further research.

Actinobacteria remain to be one of the major sources for new antibiotics, which historically play an essential role in human's fight against infectious diseases. Due to the emergence of resistant pathogenic microorganisms such as bacteria, fungi and viruses, it is imperative to develop new and effective drugs against these pathogens. The symbiotic actinobacteria residing inside the animals are becoming more and more important as a new source for drug discovery, as well as a "hotspot" in the field of microbial medicine. During the long period of evolution, a specific host-microbe mutualism is formed between the symbiotic bacteria and their hosts of animals. In this unique ecosystem, the secondary metabolites produced by bacteria are well tolerated by the hosts, meanwhile, are able to selectively suppress pathogenic microorganisms, thus providing a specific protection to their hosts. These secondary metabolites encompass a large variety of structural diversities of natural products, and so far, the reported biological activities are including antibacterial, antifungal, antiviral, antitumor, and immunomodulatory effects, which give them a great potential in the field of drug discovery. Herein, we review the secondary metabolites of animal symbiotic actinobacteria and their biological activities within the recent decade, by which to provide a viewpoint for future research of drug discovery from actinobacteria.

To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg^-1), PM group(crude drug, 2.16 g·kg^-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg^-1), PM+LPS group(crude drug 2.16 g·kg^-1, 2.8 mg·kg^-1), PPAR-γ agonist+LPS group(0.5 mg·kg^-1, 2.8 mg·kg^-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg^-1, 2.8 mg·kg^-1, 0.5 mg·kg^-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

This study was designed to establish the method of characterization of surface free energy(SFE)and evaluate the compaction properties of pharmaceutical materials based on SFE. We investigated the contact angles of materials with water and diiodomethane under different compression pressures. The contact angles of materials at 353 MPa compression pressure were utilized to calculate the related parameters of SFE ultimately. The area under tensile strength-compression pressure curve(AUTSC)and pressure yield(Py)were employed to evaluate the compactibility of material. Additionally, Pearson correlation analysis was utilized to analyze the relationship between the SFE and the compaction properties of pharmaceutical materials. The results exhibited that SFE had a significant correlation with the compaction properties of materials(P < 0.05). Moreover, the related parameters of SFE, i.e., cohesive work(W_co)and polarity index(PI)of SFE, were positively correlated with Py of Heckel equation and negatively related with AUTSC. The higher values of W_co and PI, the stronger repulsive force among the particles, led to a worse compaction behavior. In this study, we established the method for characterization of the compaction behavior of materials based on SFE initially. This study also demonstrated that SFE could evaluate the compaction behavior effectively, which provides a better understanding of compaction behavior for pharmaceutical researchers.

The Hedgehog signaling pathway plays a key role in mammalian embryogenesis, while it is quiescent in adult tissues. The aberrant activation of Hedgehog signaling pathway has been linked to multiple types of malignant tumors, which makes it an attractive target for cancer therapy in recent years. Up to now, two Hedgehog inhibitors (vismodegib and sonidegib) have been proved by FDA for the treatment of tumors. However, drug resistance and severe adverse reactions represent the problems in their clinical application. Novel inhibitors targeting Smo, such as taladegib, NVP-LEQ506, MRT-92, and downstream or upstream of Smo receptor such as Shh ligand and Gli have been developed to overcome the drug resistance and adverse reactions. The current Hedgehog inhibitors are used for treatment of basal cell carcinoma only, while many ongoing clinical trials are conducted to investigate the antitumor effect of Hedgehog inhibitors in other malignancies. Here we reviewed the research progress of the new anticancer drugs targeting the Hedgehog signaling pathway and their prospect in variety of cancers therapy.

Annexin is a protein of evolutionarily conserved polygene family that binds to cell membrane phosphatidylserine (PS). PS is closely related to many diseases with a potential as a new drug target. Annexin has a good value in drug discovery and new drug development. Annexin A4 is a member of the annexins family. Annexin A4 involves in a number of cellular functions, such as exocytosis and coagulation. These functions are related to binding of annexin to acidic phospholipids. However, the detail function(s) of annexin A4 has not been fully uncovered. Production of annexin A4 in large quantity is prerequisite for indepth investigation of the structure-function relationship of annexin A4. Human annexin A4 was originally purified from the natural resource at a low yield due to the complex procedure. In the present study, annexin A4 was expressed in a prokaryotic system with a high yield of soluble protein. The plasmid pET28a-annexin A4-EGFP was constructed for the expression. Recombinant annexin A4-EGFP was purified using two methods. Affinity chromatography approach gave a protein yield at purity of 80%. While, the membrane absorption method produced the protein with the purity over 90%. Flow cytometric analysis showed that the annexin A4-EGFP fusion protein could recognize and bind to the apoptotic cells with an affinity PS at 79.58±11.68 nmol·L^-1, which is at the same order of magnitude as A5-EGFP. We successfully achieved the efficient expression of annexin A4-EGFP in prokaryotic system, and provided an easy and convenient method for purifying a large amount of annexin A4-EGFP with a high purity. This study has laid a solid foundation for our study of the function of annexin A4 in the future.