This study was conducted to test the effects of schizandrin B (Sch B) on clozapine (CLZ) induced chronic liver injury in mice and the mechanism of action, and this may provide a new approach for clinical prevention of CLZ-induced side effects. The CLZ was given to mice for three weeks alone or co-administration with Sch B. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and antioxidation indexes superoxide dismutase (SOD), malonic dialdehyde (MDA), glutathione (GSH) and liver histological evaluation were determined. Expression of Nrf2 was assayed in hepatic cells by immunohistochemical staining and Western blotting. The changes of relative gene expression of NAD (P) H:quinone oxidoreductase l (NQO1) and heme oxygenase 1 (HO-1) were assayed by real-time Q-PCR. The results showed that pretreatment with a lower dosage of Sch B (25, 50 mg·kg^-1) prevented CLZ-induced liver injury as indicated by the reduced levels of ALT, AST and ALP, and the preserved activities of SOD, GSH and inhibiting MDA. It was shown that Sch B could up-regulate Nrf2 expression leading to nuclear accumulation of Nrf2 to induce oxidative response genes such as NQO1 and HO-1. These results suggest that Sch B could protect against liver injury induced by CLZ via the activation of the Nrf2/ARE signal pathway in a dose-dependent manner.

Human chorionic gonadotrophin (hCG), a glycohormone widely used in treatment of infertility, is a heterodimer composed of an alpha-and a beta-subunit. The heterodimer could be dissociated during production and storage with an impact on its bioactivity. A CE-SDS method for quantitative analysis of hCG subunit dissociation was established in this study by optimization of a variety of method conditions including sample preparation buffer compositions, incubation temperature, separation voltage, and capillary temperature. This method was validated for good sensitivity, linearity, precision, and accuracy for both α-and β-subunit. CE-SDS also showed much better precision and accuracy than SDS-PAGE. The method was successfully used in both recombinant hCG (r-hCG) produced by cell culture and hCG (u-hCG) derived from urine. The CE-SDS method was used in the study of hCG development and stability. Therefore, it is an useful tool for the quality control of hCG.

Transglutaminase (TG) posttranslational modification of antibody permits more precisely conjugating. Based on the amino acid sequence of an anti-CD24 antibody (cG7), this article is aimed to generate a deglycosylated cG7 mutant (cG7Q). Firstly, we introduced additional glutamines at position 297 (N297Q) by site-directed mutagenesis, and then transfected the recombinant plasmids into CHO-s cells via electroporation method and screened by Dot blot assay. Subsequently, cG7Q was expressed and purified through Protein A affinity chromatography, further identified by SDS-PAGE electrophoresis and Western blot. Its affinity was detected with surface plasmon resonance and flow cytometry assay, and ADCC effect was determined by lactate dehydrogenase (LDH) release. Eventually, a cG7 mutant, cG7Q was successfully expressed with sequence-specific conjugation sites for further study.

The pharmacological activities of natural glycosides are closely related to the polyfunctional sugar moieties. Modification of active natural products by glycosylation can change the stereochemical configuration, improve the solubility, tune up the activities and change pharmacokinetic properties for higher efficacy and better selectivity. Compared with the common D-glucose, D-allose, a C-3 epimer of D-glucose rarely exists in nature, but it plays an important role in food, health, medicine, and so on. It is not easily metabolized in the living organisms, but can be used as a safe and low-calorie sweetener. The natural allopyranosides are absolute conjugation forms which are same as other glucopyranosides and rhamno-pyranosides with a broad array of biological activities. This article summarizes the major progresses made in phytochemistry and biological activity studies of these compounds. Structure-activity relationship analyses of partial anti-tumor and anti-diabetic allopyranosides were performed regarding the data reported in the literatures. These insights may provide a theoretical and experimental reference for the discovery of new drug and drug design based on allopyranosides.

Our research was designed for on-line detection of multi-index in the concentration process of Ganmaoling granules by integration of near infrared spectroscopy and automatic control system. First, on-line detection system was set up in the concentration tank for Ganmaoling granules production. Spectra were scanned and values of chlorogenic acid, linarin, solid content and relative density were measured. Models of partial least squares regression were built and imported into near infrared workstation. By connecting the control system, real-time multi-index values were determined automatically in the concentration process. Results showed that correlation coefficients of chlorogenic acid, linarin, solid content and relative density models were 0.963, 0.989, 0.993 and 0.918, respectively. Relative standard errors of prediction were 3.71%, 4.28%, 4.17% and 0.24%, respectively, indicating a good performance and high accuracy of the models. Real-time data collection during the whole process was measured by the near infrared detecting system in the control system. In conclusion, the near infrared detection system is able to perform real-time automatic determination of multi-index in the concentration process of Ganmaoling granules with significant advantages.

This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with ¹H NMR and ¹³C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.

With the method of fluorescence polarization (FP), we screened small molecule inhibitors for PLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit, F083-0063, whose inhibition rate was (99.7±0.4)% at 10 μg·mL^-1. The IC₅₀ was calculated to be 1.9±0.1 μmol·L^-1 using Graphpad Prism 5. The effect of the compound on cells' multiplication was measured by MTT assay which showed that F083-0063 inhibited the proliferation of many tumor cell lines. Flow cytometry analysis indicated that the F083-0063 promoted cell apoptosis and induced cell G2/M arrest. Migration abilities of cells, evaluated using scratch test, increased significantly in the presence of F083-0063 with the mi-gration rate as low as (37.6±0.7)% at 20 μmol·L^-1. Molecular linkage technique found F083-0063 had good affinity with PLK1 PBD. The results of Western blotting showed that the expression of cyclin-dependent proteins was increased after treatment with F083-0063. In summary, F083-0063 has an antitumor activity and is expected to be an antitumor lead compound targeting PLK1 PBD.

Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C₁₈ (50 mm×2.0 mm, 5 μm) column using a gradient elution procedure. The mobile phase consisted of acetonitrile and 5 mmol·L^-1 ammonium acetate (0.2% formic acid) at a flow rate of 0.7 mL·min^-1. The total run time was 5.0 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 468.2→273.2 for donafenib and m/z 465.2→270.2 for its internal standard sorafenib, m/z 484.2→289.2 for donafenib N-oxide and m/z 481.2→286.2 for its internal standard sorafenib N-oxide. The standard curves were linear in the range of 5.00-5 000 ng·mL^-1 for donafenib, and 1.00-1 000 ng·mL^-1 for donafenib N-oxide. The method was validated and successfully applied to the pharmacokinetics study of donafenib tosylate tablets in volunteers.

The biological potency assay and chemical fingerprint chromatogram were applied to quality evaluation of rhubarb. Using the biological potency as indicators, we evaluated the differences in quality of multiple batches of rhubarbs and related products. Using the platelet aggregation analyzer, we determined platelet aggregation rate in the different rhubarbs preparations, and calculated the biological potency based on the simplified probit principle. UPLC was adopted to establish the fingerprint spectra for rhubarbs. The spectral efficiency correlation analysis between chromatograms and biological potencies were conducted using the double variables of SPSS 22.0 software. We used three chemical composition to verify the potency. The biological potency results suggest that Rheum palmatum has a more potent activity than Rheum tanguticum, and wine-treated rhubarb had a higher potentcy than charred. We identified 10 elements in the Fingerprint Spectrum. The relevant elements including rhein-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside and rhein have the strongest activity in the inhibition of platelet aggregation. In conclusion, this study provides a analytical method for rhubarb biological potency based on determination of the maximum antagonism rate model. The rhein may be the effective substance. It may serve as a reference in the quality control of wine processed rhubarb products.

Inhibition of apoptosis induced by oxidative stress is an effective way to reduce myocardial injury. In this study, we used H₂O₂-stimulated rat cardiac myoblast cell line (H9c2) as an oxidative damage model. Curcumin (Cur) was chosen as a model drug and mesoporous silica nanoparticles (MSNs) were chosen as the carrier to construct a Cur-loaded delivery system (Cur@MSNs) and to examine its protective effects against oxidative damage. The MSNs guaranteed efficient loading and controlled release of Cur. Besides, the hydrophilicsilanol groups on the surface of MSNs promoted the Cur solubility in water and increased its cellular uptake amount, which improved the bioavailability of Cur. The results suggest that the Cur@MSNs was pharmacologically active in the reduction of the oxidative damage of H9c2 cells. It was verified that a great decrease of reactive oxygen species was inducted by Cur@MSNs, which led to the protective effects against oxidative damage.