Nanocrystal suspensions drug delivery system is used to solve the delivery difficulty of poorly soluble drug. However, the physical stability of liquid nanocrystal suspensions is very bad. Solid nanocrystal delivery system as a novel technology, can improve the thermokinetics stability of nanocrystal suspensions and have good clinical compliance, which can achieve stabilization of nanocrystal suspension systems as an ideal delivery system. In this paper, we reviewed the research progress of nanotechnology and solidification technology of solid nanocrystal suspension delivery system, which will give the new mirrors and thoughts on the development of solid nanocrystal delivery system.
Drug Delivery Systems ; Nanoparticles ; Nanotechnology ; methods ; Pharmaceutical Preparations ; administration & dosage ; chemistry

Sorafenib, the first oral multikinase inhibitor, can inhibit several kinases involved in tumor proliferation and angiogenesis including Raf, VEGFR, PDGFR, kit and so on. Due to the advantages of multi-mechanisms, broad-spectrum anticancer potency, and well-tolerated results in combination trials, more and more researchers have focused on the optimization of sorafenib in order to develop novel multi-targeted anticancer drugs. The present paper reviews the development of modification of sorafenib in recent years from two aspects: bio-isosterism and scaffold hopping. The structure-activity relationship (SAR) of these compounds is also summarized.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Line, Tumor ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; prevention & control ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; Phenylurea Compounds ; chemical synthesis ; chemistry ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

Chinese agarwood is formed in the aromatic resinous wood formed in Aquilaria sinensis (Lour.) Gilg (botanical family: Thymelaeaceae). Only when suffering stress of wound, etc, can A. sinensis produce sesquiterpenes etc. compounds of agarwood around wounds. However, little is known about how wound induced the biosynthesis pathway of sesquiterpenes. To reveal the molecular mechanism of wound-induced agarwood formation, RNA sequencing (RNA-seq) technology was used to investigate the profile of gene expression in A. sinensis treated by mechanical wounding and elucidate its functional gene. A total of 40,295 ESTs with an average read length of 305 bp were generated and 22 095 unigenes were formed by initial gene splicing. 61.6% of these unigenes (13 611) were annotated using BLAST searches against the SwissProt, KEGG, Nr and Nt databases. Twenty-six unigenes (encoding 7 enzymes) were found to be involved in sesquiterpene of agarwood biosynthesis by bioinformatic tools of Gene Ontology and KEGG. Novel genes that are potentially involved in sesquiterpenes biosynthesis were identified in A. sinensis, providing data for further sesquiterpenes biosynthesis pathway by molecular methods and the EST data establish a foundation for future studies in the molecular mechanisms of wound-induce agarwood formation in A. sinensis.
Drugs, Chinese Herbal ; chemistry ; metabolism ; Expressed Sequence Tags ; Genes, Plant ; genetics ; Plants, Medicinal ; chemistry ; genetics ; Sequence Analysis, RNA ; Sesquiterpenes ; chemistry ; metabolism ; Stress, Physiological ; genetics ; Thymelaeaceae ; chemistry ; genetics ; Transcriptome ; genetics ; Wood ; genetics ; metabolism

In this study, Notopterygii Rhizoma et Radix was used to verify the stability and accuracy of DNA barcodes in identification of Chinese materia medica for the first time. All genomic DNAs from thirty one samples were extracted. The ITS (internal transcribed spacer) regions were amplified and sequenced bi-directionally. Obtained sequences were assembled using the CodonCode Aligner. And the sequences of the ITS regions were aligned through Clustal-W and the genetic distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter (K2P) model. The neighbor-joining (NJ) phylogenetic trees were constructed. The ITS2 regions were obtained by using the hidden Markov model (HMM)-based annotation methods from the ITS sequences. Results indicated that the lengths of ITS regions of Notopterygii Rhizoma et Radix were 603-604 bp, while the lengths of ITS2 regions were 228 bp. The haplotypes of ITS/ITS2 regions of Notopterygii Rhizoma et Radix were the same as those of the original plant leaves. The intra-specific genetic distances were smaller than inter-specific ones in ITS/ITS2 regions of Notopterygium incisum and N. franchetii. The NJ trees showed that N. incisum, N. franchetii and its adulterants can be easily differentiated according to their monophyly. Therefore, ITS/ITS2 regions as DNA barcodes can stably and accurately distinguish Notopterygii Rhizoma et Radix from its adulterants and could provide a new technique to ensure clinical safety in utilization of traditional Chinese medicines.
Apiaceae ; classification ; genetics ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Phylogeny ; Plant Roots ; genetics ; Plants, Medicinal ; genetics ; Rhizome ; genetics

Mevalonate kinase (MVK) is a key enzyme in plant terpenoid biosynthetic pathway. This study focused on cloning and analysis of Panax notoginseng (Burk.) F. H. Chen MVK (PnMVK1) gene. After searching the transcriptome dataset of P. notoginseng, one unique sequence encoding MVK was discovered. The primers were designed according to the transcript sequence of PnMVK1 from the P. notoginseng transcriptome dataset. And then, the open reading frame of PnMVK1 was cloned from P. notoginseng by using RT-PCR strategy. The physical and chemical properties, secondary structure and three-dimensional structure of the PnMVK1 protein were forecasted and analyzed, and its structure and function were predicted. The cDNA (named as PnMVK1) contains a 1164 bp open reading frame and encodes a predicted protein of 387 amino acids. The GenBank accession number for this gene is JQ957844. No transmembrane region and signal peptide were present in PnMVK1. The conserved domain of mevalonate kinase was present in PnMVK1. PnMVK1 was more abundant in P. notoginseng root than other organisms. This study cloned and analyzed PnMVK1 gene from P. notoginseng for the first time. The result will provide a foundation for exploring the mechanism of terpenoid biosynthesis in P. notoginseng plants.
Amino Acid Sequence ; Cloning, Molecular ; Cluster Analysis ; Conserved Sequence ; DNA, Complementary ; genetics ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Molecular Weight ; Open Reading Frames ; Panax notoginseng ; enzymology ; genetics ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; metabolism ; Phylogeny ; Plant Roots ; enzymology ; genetics ; Plants, Medicinal ; enzymology ; genetics ; Protein Structure, Secondary

After searching the transcriptome dataset of Panax notoginseng, one unique sequence Pn02086 encoding UDP-glucosyltransferase (UGT), which may be involved in triterpene saponin biosynthesis, was discovered. The open reading frame of the UGT gene, named as PnUGT1, was cloned by 5'-RACE and RT-PCR method from P. notoginseng. The GenBank accession number for this gene is JX018210. The bioinformatic analysis of this gene and its corresponding protein was performed. The PnUGT1 gene contains a 1488 bp open reading frame and encodes a predicted protein of 495 amino acids. The molecular weight is 55.453 kD and the protein is unstable. In the secondary structure, the percentage of alpha helix, beta turn, random coil were 36.16%, 11.31%, 52.53%, respectively. The PnUGT1 contains 7 conserved domains predicted by InterProScan, including PSPG-box which is a unique consensus sequence of glycosyltransferases involved in plant secondary metabolism. The PnUGT1 was most likely to be located in the cytoplasm, without signal peptide and transmembrane region. Sequence alignment and phylogenetic analysis demonstrated that PnUGT1 had relative close relationship to the triterpene UDP-glucosyltransferase of Medicago truncatula (AAW56092), with the 66% similarity of conserved domain PSPG-box. PnUGT1 was more abundant in P. notoginseng leaf than in flower, stem and root. Therefore, PnUGT1 gene may be involved in notoginsenoside biosynthesis.
Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; DNA, Complementary ; genetics ; DNA, Plant ; genetics ; Gene Expression Regulation, Plant ; Glucosyltransferases ; genetics ; metabolism ; Medicago truncatula ; genetics ; metabolism ; Molecular Sequence Data ; Open Reading Frames ; Panax notoginseng ; enzymology ; genetics ; Phylogeny ; Plant Leaves ; enzymology ; Plants, Medicinal ; enzymology ; genetics ; Protein Structure, Secondary ; Sequence Alignment

Squalene synthase (SQS) is a key enzyme in plant terpenoid biosynthetic pathway. This study focused on cloning and analysis of Huperzia serrata SQS (HsSQS1) gene. After searching the transcriptome dataset of H serrata, one unique sequence encoding SQS was discovered. The primers were designed according to the transcript sequence of HsSQS1 from the H. serrata transcriptome dataset. The open reading frame of HsSQS1 was cloned using RT-PCR strategy. The bioinformatic analysis of this gene and its corresponding protein were performed. The cDNA (named as HsSQS1) contains a 1263 bp open reading frame and encodes a predicted protein of 420 amino acids. The GenBank accession number for this gene is JQ004938. HsSQS1 contains two transmembrane regions, without signal peptide. The conserved domain of squalene synthase was presented in HsSQS1. HsSQS1 was more abundant in H. serrata root than in leaf and stem. This study cloned and analyzed squalene synthase gene from H. serrata for the first time. The result will provide a foundation for exploring the mechanism ofterpenoid biosynthesis in H. serrata plants.
Amino Acid Sequence ; Biosynthetic Pathways ; Cloning, Molecular ; DNA, Complementary ; genetics ; Expressed Sequence Tags ; Farnesyl-Diphosphate Farnesyltransferase ; genetics ; isolation & purification ; metabolism ; Genes, Plant ; genetics ; Huperzia ; enzymology ; genetics ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Plant Leaves ; enzymology ; Plant Roots ; enzymology ; Plant Stems ; enzymology ; Plants, Medicinal ; enzymology ; genetics ; Triterpenes ; chemistry

Traditional Chinese medicine (TCM) genomics and TCM synthetic biology are two hot fields in the TCM modernization. TCM genomics, including transcriptomics, structural genomics, genomic markers and functional genomics, aims to elucidate the biosynthetic pathways of TCM bioactive compounds and mine the related genes encoding enzymes involved in these pathways by analyzing genetic information on the original species of TCM, thus promoting the development of TCM synthetic biology, genome-assisted molecular identification and molecular breeding, and elucidation of the genetic mechanism underlying "Daodi". Genomics and related research provide us much deeper understanding of life process and improve our ability to create new life or modify the present organisms. Based on TCM genomics, TCM synthetic biology sets up a series of procedures to realize the production of TCM pharmacological active compounds in microorganism, including screening and modification of parts and devices, establishment of standardized part and device libraries, and reconstruction and modification of the biosynthetic pathway of TCM pharmacological active compounds in microorganism. TCM synthetic biology will provide a new resource of TCM pharmacological active compounds for the pharmacological study and research & development of new drugs, thus enhancing the core competitiveness of our pharmaceutical industry in the international markets.
Expressed Sequence Tags ; Genomics ; Medicine, Chinese Traditional ; methods ; Plants, Medicinal ; genetics ; Synthetic Biology ; Transcriptome ; genetics

The achenes morphological and micro-morphological characteristics of six species of genus Taraxacum from northeastern China as well as SRAP cluster analysis were observed for their classification evidences. The achenes were observed by microscope and EPMA. Cluster analysis was given on the basis of the size, shape, cone proportion, color and surface sculpture of achenes. The Taraxacum inter-species achene shape characteristic difference is obvious, particularly spinulose distribution and size, achene color and achene size; with the Taraxacum plant achene shape the cluster method T. antungense Kitag. and the T. urbanum Kitag. should combine for the identical kind; the achene morphology cluster analysis and the SRAP tagged molecule systematics's cluster result retrieves in the table with "the Chinese flora". The class group to divide the result is consistent. Taraxacum plant achene shape characteristic stable conservative, may carry on the inter-species division and the sibship analysis according to the achene shape characteristic combination difference; the achene morphology cluster analysis as well as the SRAP tagged molecule systematics confirmation support dandelion classification result of "the Chinese flora".
Base Sequence ; China ; Cluster Analysis ; DNA, Plant ; genetics ; Fruit ; anatomy & histology ; ultrastructure ; Genetic Markers ; genetics ; Genetic Variation ; Genotype ; Phylogeny ; Plants, Medicinal ; anatomy & histology ; genetics ; Polymorphism, Genetic ; Species Specificity ; Taraxacum ; anatomy & histology ; classification ; genetics

The goal of the study is to evaluate the self-microemulsifying drug delivery system (SMEDDS) which enhances the oral bioavailability of the poorly water-soluble drug, total flavones of Hippophae rhamnoides (TFH). It is orally administered for the protection of human cardiovascular system. Self-microemulsifying time, particle size, polydispersity index (PDI), morphological characterization, in vitro dispersity, stability, in situ intestinal absorption and relative bioavailability were investigated in detail. The TFH-SMEDDS rapidly formed fine oil-in-water microemulsions with 0.1 mol x L(-1) hydrochloride solution, with average size of which was less than 40 nm, PDI was below 0.2, and the particles of which were observed round-shaped under transmission electron microscope. Almost 90% of TFH (expressed with quercetin) was released from SMEDDS within 20 min, which was remarkably higher than that from common capsules. The stability test showed the TFH-SMEDDS maintained stable in 6 months under accelerated condition. In situ absorption study demonstrated the absorption rate constant of TFH-SMEDDS (expressed with quercetin) was significantly higher than that of TFH in ethanolic solution (P < 0.05). The absorption of TFH from SMEDDS showed a 4.18-fold increase in relative bioavailability (expressed with quercetin) compared with that of the suspension. The results suggest that SMEDDS is a promising drug delivery system to increase the oral bioavailability of TFH.
Administration, Oral ; Animals ; Biological Availability ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Flavones ; administration & dosage ; isolation & purification ; pharmacokinetics ; Fruit ; chemistry ; Hippophae ; chemistry ; Intestinal Absorption ; Male ; Particle Size ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley