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.

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.

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.

Using a UHPLC-TOF/MS method combined with software of Masslynx V4.1 and database in the literatures, a total of 20 polygala oligosaccharide esters (POEs) were identified in 60% ethanol extract of Kai Xin San (KXS-60%E). Furthermore, 14 POEs as well as 4 POE-metabolites were identified in rat plasma. The results revealed that POEs and POE-metabolites which were identified in rat plasma, were key components in KXS-60%E and the potential bioactive compounds for KXS action in the treatment of AD.

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.

The anaphase promoting complex (APC) regulates cell cycle progression by forming two functionally distinct E3 ubiquitin ligase complexes, APC^Cdc20 activated by cell division cycle protein 20 (Cdc20) and APC^Cdh1 activated by Cdc20 homologue 1 (Cdh1), respectively. Cdc20 and Cdh1 have different functions in the occurrence and development of the tumor. Cdc20 is a cancer promoter while Cdh1 suppresses tumorigenesis. Emerging evidence has begun to reveal that Cdc20 has positive functions in tumorigenesis, the overexpression of Cdc20 has been observed in many cancers. Currently, Cdc20 inhibitors, mostly non-specific inhibitors except apcin, not only block the combination between Cdc20 and APC, also block the combination between Cdh1 and APC, which leads to a poor selectivity. In this paper, the Cdc20 role in the development and process of cancers and its inhibitors are reviewed.

The study was designed to explore the effects and the underlying mechanism of ginsenoside Rg1 on corticosterone (CORT)-induced astrocytes injury. The primary hippocampal and prefrontal cortical astrocytes from rats were cultured and purified. CORT was used to stimulate stress condition. Western blot was used to detect the effects of ginsenoside Rg1 on the phosphorylation of Cx43. Cell Counting Kit (CCK8) was used to detect the effects of ginsenoside Rg1 on astrocytes viability. The roles of ginsenoside Rg1 was reversed by protein kinase inhibitors in the change of astrocytes morphology. Our results showed that ginsenoside Rg1 reversed the phosphorylation of Cx43 induced by CORT; ginsenoside Rg1 significantly upregulated the cell viability of astrocytes against CORT; the role of ginsenoside Rg1 was obviously inhibited by Src protein kinase inhibitors PP2 and Akt protein kinase inhibitors BAY1125976 in prefrontal cortical astrocytes; in hippocampal astrocytes, Src protein kinase inhibitor PP2, p38 protein kinase inhibitor SB203580, Akt protein kinase inhibitor BAY1125976 significantly inhibited the cell protective effects of ginsenoside Rg1. In conclusion, ginsenoside Rg1 improved the activity of Cx43 gap junctions in astrocytes exposed to CORT; ginsenoside Rg1 protected astrocytes against that CORT activated the Src, p38 and Akt signaling pathways, and the mechanism was different in prefrontal cortical and hippocampal astrocytes.

The drug-loaded ultrasound (US) contrast nanoparticles, which can effectively accumulate in the tumor to penetrate into its deep section, were prepared. After being heated or under the near infrared (NIR) light irradiation, the size of nanoparticles would transform from nanometer-scale to micrometer-scale in vitro, which can vastly enhance the effect of US imaging. We evaluated the size changes of the nanoparticles in vitro, investigating their effect in ultrasound imaging and distribution in vivo. Liposomes containing hydrophobic modified hollow gold nanospheres (HAuNS), doxorubicin (DOX) and perfluorohexane (PFH), which were referred to DOX and HAuNS loaded PFH liposome (DHPL), were prepared by thin film evaporation and ultrasonic technique. The morphology and size of DHPL were measured by transmission electron microscopy and particle size analyzer with dynamic light scattering (DLS) method. The agar gel pore model was used to investigate the enhanced effect of nanoparticles in vitro US imaging under the NIR light irradiation. The biodistribution of DHPL in 4T1 tumor-bearing mice after intravenous injection was measured by the in vivo imaging system. The DHPL were spherical at a particle size of 302 ±5 nm and polydispersity index of 0.195 ±0.018. The HAuNS loaded on phospholipid membrane was observed in transmission electron microscope (TEM) image. Under the NIR light irradiation (1 or 2 W·cm^-2), the temperature of the solution containing the DHPL (0.2, 0.04, 0.02 g·L^-1 in terms of HAuNS) rose rapidly. And a certain amount of micrometer-sized particles could be detected by the particle size analyzer when the temperature of the analyzer was raised to 52℃. The abundant microbubbles, which would enhance the effect of US imaging, were detected by ultrasonic diagnostic apparatus when the nanoparticles were irradiated by NIR light in the in vitro US imaging experiment. The in vivo distribution experiment showed that the DHPL could effectively accumulate in the tumor due to the enhanced permeability and retention effect (EPR effect) of the tumor. In this study, we successfully made a nanometer-micrometer reversible nanoparticles that can accumulate inside the tumor to provide a feasible scheme for US imaging in the tumor site and the combinational photothermal-chemotheraphy simultaneously.

Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by ¹H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).

Five triterpene saponins were isolated from the aqueous extract of the leaves of Panax notoginseng (Burk.) F.H.Chen via various chromatographic approaches, including HPD-100 macroporous resin, silica gel, reverse phase C₁₈ and so on. Spectroscopic and chemical methods were used to elucidated their structures, which were determined to be 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-12β, 23(R)-epoxydammara-24-ene-3β, 6α, 20(S)-triol 20-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (1), 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-12β, 23(R)-epoxydammara-24-ene-3β, 6α, 20(S)-triol 20-O-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (2), notoginsenoside FP2 (3), gypenoside Ⅸ (4), ginsenoside Rg1 (5). Compounds 1 and 2 are new compounds and named as notoginsenoside Fh8 and notoginsenoside Fh9.