Based on the principle of particle design, the powder of Xiaojin Pills was prepared, and the quality uniformity was investigated by means of powder characterizations and content uniformity. By studying the mixed crushing rules of the classified materials and the design principle of the powder particles of Chinese medicine, the powder of the Xiaojin Pills was prepared. At the same time, the manmade mixed powder and the control powder prepared by pharmacopoeia were prepared. The mixed homogeneity of the three powders was evaluated by particle size distribution and color difference. The GC-MS and LC-MS/MS were used to study the homogeneity of their contents. The best preparation process of particle design powder is:materials easily crushed are smashed for 50 min in the vibrating ultrafine mill with -15℃, then add the materials difficultly crushed into the mill and let them crushed together for 3 min. The particle size range of manmade mixed powder was the largest with the particle size difference being more than 100 microns, the RSD value being 26.07%. The particle size range was more than 50 microns in the powder prepared by pharmacopoeia, and the RSD was nearly 15%. The difference in particle size was only around 4 μm and the RSD value was 3.18%. The color difference test showed that the composite chromatism (dE^*) value of the powder prepared by pharmacopoeia was the largest for the RSD was 84.56%. The RSD of manmade mixed powder and the powder prepared by Pharmacopeia were 53.83% and 32.83%, respectively. The RSD value of the particle designed powder's muscone content is about 50% of the other two kinds of powders. The contents of 10 components in powders were determined by LC-MS/MS. The RSD values of the particle designed powder were much smaller than other two kinds of powders. Results indicate that the uniformity of the particle designed powder is better than other two kinds of powders. Chinese medicine particle design technology can effectively improve the uniformity of traditional Chinese medicine powder.

This study was designed to investigate the molecular mechanism and potential active constituents of Polygala Radix in the treatment of Alzheimer's disease with multiple data bases combined with literature mining to build Polygala Radix chemical composition database. A novel analysis tool Pharmmapper was used to obtain the main active ingredient and potential target of Polygala Radix. By extensive data profiling, the Polygala Radix was found to contain 111 chemical constituents. Among them, a total of 10 active molecules included 3 xanthone, 1 saponins, 3 oligosaccharide esters, and 3 other classes were related to 13 Alzheimer's disease-related targets. Two of the core targets were beta-secretase 1 and glycogen synthase kinase-3 beta. Use the GO analysis and KEGG to explore the molecular mechanism of Polygala Radix in treatment of Alzheimer's disease, which has 3 signaling pathways, and the most important signaling pathway is the cell death signaling pathway. The active constituents of Polygala Radix could control the formation of Aβ and the apoptosis of cells through the interaction with multiple targets, and control the treatment of Alzheimer's disease.

Differences of the individual toxic effects of antitumor drugs have been a concern in clinical treatment of cancers. The drug toxicity was not only related to the age, sex, and drug interactions, but also to the expression of protein involved in the metabolism, targets and transporters of drugs. Drug transporter mediates the absorption, distribution and elimination of some drugs, which exhibits a great significance in pharmacology and clinical practice. The purpose of this review is to provide information regarding trans-porter-medicated toxic effects of antitumor drugs in order to reduce or avoid the transporter-medicated toxic effects, and to promote reasonable drug use and individualized application of antitumor drugs in clinics.

Charge-reversal nanocarrier was constructed to enhance lysosomal escape and improve an-titumor effect. We synthesized the cholesterol-polyethyleneimine-hexahydrophthalic anhydride (Chol-PEI-HHPA) polymer and characterized by ¹H NMR. The charge-reversal liposomes (Lipo-HHPA) were synthesized and the hematoporphyrin monomethyl ether (HMME) was loaded. pH-triggered charge conversion was determined at different pH values. The lysosomal escape and cytotoxicity of the Lipo-HHPA were evaluated in MCF-7 cells. The Lipo-HHPA was uniform with an average particle size of 102 nm. Upon the irradiation of ultrasound, burst release of HMME could be observed. The zeta potential of Lipo-HHPA changed sharply from negative (-23.5 mV) to positive (+21.2 mV) over the pH range of 7.4-4.5. In the cellular uptake experiment, the lysosomal escape of Lipo-HHPA was observed. HMME loaded Lipo-HHPA displayed obviously enhanced cytotoxicity towards MCF-7 cells. These results indicate that the charge-reversal liposomes hold a great potential in improving the cytotoxicity and antitumor effect.

The protein-protein interactions play an important role in life science. At present, many methods are developed with preferences of the amino acid residues, which do not offer the relative spatial information for the residue groups. However, the spatial information for the residue groups is important in the design of the protein-protein interactions. We proposed a new model, which is named 'tri-prism' model, by deep mining the existing protein-protein interaction patterns and refining the preference and the relative spatial information for the combination pairs of the residue groups. The model not only provided the preferences, but also offered the relative spatial information for the triplets combination pairs of the residue groups. The model was able to analyze the triplets combination pairs of the residue groups based on the preference factor, amino acid composition, and protein secondary structure. The model was applied to the interface of the PD-1/PD-L2 protein. According to the diversity characters of the composition and the spatial information between the combination pairs of the residue groups at the interface of the PD-1/PD-L2 protein and the predicted ones, we put forward the suggestions for the mutations of the residues, which offered a new view in the study of protein-protein interactions.

Microfluidics is a technology that involves the use of micro-nanoscale pipelines to manipulate fluid mixing. Precise control of the mixing process of laminar flows or liquid droplets by using microfluidics will contribute to the preparation of nanoparticles, which are difficult to be achieved by the conventional methods. Based on the progress in delivery systems of nanoparticulate drug, we provide a summary to introduce the applications of microfluidics in construction of nanoparticulate drug delivery system such as liposomes, polymer nanoparticles and hybrid nanoparticles, and analyze the assembling mechanisms of different nanostructures by using microfluidic precise control. This review will provide a reference in utilization of microfluidic technology more scientifically and reasonably.

The study aims to establish an LC-MS/MS method for the determination of S-(+)-ibuprofen (S-IBP) and R-(-)-ibuprofen (R-IBP), which may be used subsequently to investigate the pharmacokinetics of ibuprofen enantiomers in healthy Chinese volunteers. Naproxen was used as an internal standard. The separation was achieved on a Chiralpak AD-3R column (4.6 mm×150 mm, 3.0 μm) with a mobile phase consisting of acetonitrile/0.01% formic acid aqueous solution (40:60) at a flow rate of 750 μL·min^-1 within 23.0 min. Naproxen and the internal standard were measured by a triple-quadrupole mass spectrometer in negative electron electronic spray ion (ESI) mode using multiple reaction monitoring (MRM). The extracted ions monitored following MRM transitions were m/z 205.1→161.0 for ibuprofen enantiomers and m/z 229.1→185.0 for the internal standard naproxen. Plasma samples were pretreated through methanol precipitation. The calibration curve of S-IBP and R-IBP in human plasma was linear over the concentration rang of (0.05-30.00) μg·mL^-1. The lower limit of quantitation was 0.05 μg·mL^-1. The intra-and inter-run precisions of S-IBP at three quality control levels were within 2.2%-4.2%, the relative deviation of the assay was within -12.0%-13.0%. The intra-and inter-run precisions of R-IBP at three quality control levels were within 2.0%-8.2%, the relative deviation of the assay was within -11.5%-10.6%. The plasma samples were stable at room temperature (25℃) for 6 h, at -30℃ for 47 days and during three freeze-thaw cycles. The method was proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetics study of ibuprofen enantiomers in healthy Chinese volunteers after a single oral dose of 300 mg ibuprofen extended-release capsule.

The study was designed to test the role of 5, 2', 4'-trihydroxy-6, 7, 5'-trimethoxy flavone nanoparticle (TTF1-NP) on lipopoiysaccharide (LPS)-induced inflammatory response, and to explore the anti-inflammatory mechanism in human hepatocellular carcinoma cells. Inflammatory responses were induced in human hepato-cellular carcinoma HepG2 cells with LPS; Proliferation effect of TTF1-NP in LPS-stimulated HepG2 cells were detected by MTT assay; The expression of TLR4, AKT/mTOR signaling related proteins and IL-6 were detected by Western blot assay. The results showed that TTF1-NP inhibited the proliferation of HepG2 cells induced by LPS in a dose-dependent manner; TTF1-NP inhibited the expression of TLR4, the activation of AKT and mTOR, and expression of IL-6 in a dose-dependent manner; TTF1-NP inhibited the activation of AKT/mTOR signaling pathway and TLR4 proteins leading to suppression of IL-6 expression in HepG2 cells stimulated by insulin. These results suggest that TTF1-NP inhibited inflammatory responses from LPS treatment with a potential mechanisms in the inhibition of AKT/mTOR pathway.

To study the effects of squalene on behavior and related proteins of glutamate toxicity pathways in the mice with chronic unpredictable mild stress (CUMS), thirteen different kinds of CUMS were applied to the male BALB/C mice for 35 days to establish the mouse model of CUMS depression. The stress conditions include food deprivation, noise, stroboscopic lighting, hot stress (45℃), brake, exposure to lower temperature (4℃), shake, soiled cage, clamp tail, water deprivation, swimming, electric shock, presence of a foreign object in the home cage. The mice were treated with squalene at 3 doses (80, 40 and 20 mg·kg^-1·d^-1) through oral administration from the 3rd week continuously. Three weeks later, the impacts were evaluated in the mice with behavioral tests, and malondialdehyde (MDA) and hippocampal glutamate (GLU) contents, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in hippocampus were measured by spectropho-tometry or reversed phase HPLC (RP-HPLC). Western blot was used to examine the expression level of N-methyl-D-aspartate receptor subunits epsilon-2 (NMDAε2), calmodulin kinaseⅡ (CaMKⅡ) and neuronal nitric oxide synthase (NOS1) in hippocampus. Compared with model group, the squalene-treated mice exhibited an increase in body weight, sucrose preference rate and the times of crossing-movement and rearing-movement, shortened the immobility time in the tails suspension test and forced swimming test in the depression mice (P < 0.05). Meanwhile, the treated mice had a significant decrease in the contents of GLU and MDA (P < 0.05) in hippocampus, increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and downregulated the expression of NMDAε2, CaMKⅡ and NOS1 in the hippocampus. In conclusion, squalene shows anti-depressant effect on depressant model in mice, meanwhile the downregulated ROS, related proteins of GLU-NMDAε2-CaMKⅡ-NOS1 signal pathways may be related to the antidepressant effect of squalene.

Rubia cordifolia L. has been used as a traditional Chinese medicine for several centuries. In recent years, the resources of wild Rubia cordifolia have been declined sharply due to increased utilization and rising price. Therefore, it is of great urgency to evaluate and protect resources of wild plant of Rubia cordifolia. In our study, sixty-four individuals that represent eight wild populations of Rubia cordifolia L. were analyzed by Start Codon Targeted Polymorphism (SCoT) molecular markers. Genetic distance was calculated by POPGENE 3.2 software, cluster analysis was generated by NTSYS 2.10 software based on UPGMA method and Mantel Test was used to analysis the relationship between the genetic distances and geographical distance among the wild populations. The results showed a high genetic diversity of wild populations of Rubia cordifolia L. in Shaanxi province. A total of 182 bands were produced by 14 primers, among which 163 bands were polymorphic bands, and the percentage of polymorphic bands was 89.56%. The average value of Nei's genetic diversity index (H) was 0.293 6, Shannon's information index (I) was 0.444 6, genetic differentiation coefficient (Gst) was 0.555 3, and the gene flow (Nm) was 0.440 8, the wild populations were ranked by genetic diversity:AK > YL > SL > BJ > TC > YA > WN > XY. Mantel Test analysis demonstrated that the significant correlation was found between the genetic distances and geographical distances (r=0.776 4, P < 0.05). There is a significant correlation between geographical and genetic distances. This study provides a theoretical basis for the protection and development of the resources of wild Rubia cordifolia L. germplasms.