Neural stem cell is a cell type with the ability of self-renewing and the potential to differentiate into neurons, astrocytes or oligodendrocytes. Neurogenesis is beneficial for the recovery of many neurological diseases, such as stroke, Alzheimer's disease and so on. Neurogenesis capacity can maintain through the whole life, which includes the proliferation, migration and differentiation of neural stem cell, as well as the incorporation into the neuronal network of newborn neurons. The self-renewal and differentiation activities of neural stem cell are regulated by the microenvironment, which is defined as neural stem cell niche. Components of neural stem cell niche include cell-cell interactions, cytokines, extracellular matrix and vascular niche. Illustration of neural stem cell niche impact is far more significant for the treatment of certain nervous system diseases. This review summarizes the current understanding of the relationship between neural stem cell niche and the fate of neural stem cell.

In this study, multivariate statistical analysis was applied to characterize the flowability of different types of microcrystalline cellulose (MCC), and the visualization of R language was used to explore the intrinsic correlation on its performances. To verify the operability of multivariate statistical analysis, we compared the results of the conventional methods such as repose angle method, Hausner ratio method, Carr's index method and the parameter a of Kawakita equation to determine whether there are significant differences between the conventional ones and multivariate statistical analysis. Moreover, the fillibility and compressibility were characterized by parameters 1/b of Kawakita equation and the means of pressure-tensile strength and compressibility curve method, respectively. The data was analyzed through R language for visualizing the correlation among the performance parameters of MCC. The flowability of the series of microcrystalline cellulose PH (MCCPH) were superior to the series of microcrystalline cellulose WJ (MCCWJ), the compressibility of MCCPH-302 was optimum, and the flowability and fallibility of MCCPH-102 were better than others. The results of conventional methods were consistent with multivariate statistical analysis. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by analyzing correlation coefficient diagram, which was statistically significant (P < 0.01). It is reasonable that adopting multivariate statistical analysis to character the flowability of powders, which is more objective than the traditional approach. The correlation visualization of performance parameters of powders provides convenience for screening preparation material via the visualization of R language.

Arenaviruses are enveloped RNA viruses. The genus mammarenavirus contains nine members that are known to be human pathogens, and eight of them cause human hemorrhagic fever. Lassa hemorrhagic fever, caused by Lassa virus (LASV) infection, is the most prevalent arenavirus hemorrhagic fever with potential to cause major epidemics. LASV belongs to category A agents, and biosafety level-4 (BSL-4) facility is required for live virus experiments. Currently there are few specific treatments available for arenavirus diseases. Here, we established efficient cell-based pseudovirus infection models using an HIV-1 core (pNL4-3.Luc.R^-E^-) packed with arenavirus glycoproteins. Nine recombinant arenaviruses (arenavirus-GP/HIV-luc) were generated, and 17 cell lines were tested for susceptibilities to these viruses. These pseudovirus infection models were further validated by known arenavirus entry inhibitors. The models are safe and specific to pseudovirus infection, which are readily used for pharmacodynamic evaluation of arenavirus entry inhibitors in BSL-2 laboratory. The models will facilitate screening of the anti-arenavirus drugs and vaccines.

Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.

Shengmaiyin is widely used in the treatment of arrhythmia and has achieved a good effect. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of Shengmaiyin in the treatment of arrhythmia is unclear. In this study, we used the internet-based Computation Platform (www.tcmip.cn) to explore the molecular mechanism. Shengmaiyin was found to treat the arrhythmia by modulating the pathway related to energy metabolism such as carbon metabolism, purine metabolism, carbohydrate metabolism, or by regulating the level of ATP. In this study, we find that the main active drug component in Shengmaiyin may be ginseng.

Interleukin-6 (IL-6)/janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) is a pivotal signaling pathway in the regulation of cell proliferation, survival, differentiation and T cell activation. Aberration of this pathway is involved in multiple autoimmunity diseases and cancers, therefore the pathway is considered as a hot target for drug development. In our study, we validated a cell-based model of IL-6/JAK/STAT3 and used it in screening of its inhibitors. HEK-Blue IL-6 cells of Invivogen Inc. were used to stably express IL-6 receptor and STAT3-induced secreted embryonic alkaline phosphatase (SEAP) report gene. After stimulation by IL-6, SEAP was secreted from cells and reacted with QUANTI-Blue. The product can be detected at 655 nm. The inhibitory effect of compounds on STAT3 signaling showed as IC₅₀ was calculated by OD value. The results shown that IL-6 specifically activated the cells, which could be applied to screen the inhibitors for IL-6/JAK/STAT3 signaling pathway. The optimized screening conditions were described as below:50 000 cells/well, 1 ng·mL^-1 IL-6 incubation for 20 h and reaction with QUANTI-Blue for 1 h. Based on this condition, we screened 14 natural products based on this cell model and arctigenin, cryptotanshinone and curcumin showed potential inhibitory activities on STAT3 signaling pathway with IC₅₀ of 1.28, 2.96 and 6.61 μmol·L^-1. Our study suggests that HEK-Blue IL-6 cells were suitable for screening inhibitors for the IL-6/JAK/STAT3 signaling pathway.

The hepatotoxicity of gefitinib is an important factor limiting its clinical application. In order to control the toxicity, we conducted this study to find the gene variation that can explain and predict the occurrence and severity of hepatotoxicity of gefitinib. Ninety patients with non-small cell lung cancer were included in the retrospective clinical study. Detailed hepatotoxicity induced by gefitinib and epidemiological characteristics were recorded. Twenty-six candidate single-nucleotide polymorphisms of molecular targets, metabolic enzymes, transporters and chemokines were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform. Various confounding factors, such as age, gender and smoking status, were included in the follow-up analysis and variability in the extent of hepatotoxicity was best explained by a multivariate logistic regression model incorporating. The severity of hepatotoxicity was associated with mitogen-activated protein kinase 1 rs13515 (OR=9.467, P=0.074). The research about pharmacogenomic of gefitinib identified the determinants of the drug-induced liver injury. These findings provide a basis to design clinical trials targeting a particular toxicity of gefitinib or similarly targeted agents to benefit patients on long-term gefitinib treatment.

The chemical constituents of Sabia limoniacea var. ardisioides were investigated using chromatographic methods, such as silica gel, Sephadex LH-20 and preparative HPLC. Eight compounds were isolated and their structures were elucidated by spectral data and physicochemical properties, which were identified as 5-methoxy-1, 2-methylenedioxyl oxoaporphine (1), fuseine (2), N-p-feruloyltyramine (3), N-trans-coumaroyl tyramin (4), quercetin (5), rutin (6), mutabiloside (7), and protocatechuic acid (8). Among those, compound 1 is a new compound, compounds 2-8 were isolated from this plant for the first time.

The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (P < 0.05), and IMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (P < 0.05). Above all, IMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

This study was designed to explore the intervention of muscle fatigue in rats with Astragali Radix using ¹H NMR metabolomics methods. The fatigue model was induced in rats by forced swimming plus food restriction, and the effects of Astragali Radix (3, 6 and 12 g·kg^-1) were investigated using the exhaustive time of rat swimming. After 3 weeks, the gastrocnemius was collected for ¹H NMR detection, and the anti-fatigue effects of Astragali Radix were explored using multivariate statistical analysis. Astragali Radix significantly improved the exhaustive swimming time of rats. Compared with control group, the levels of isoleucine, leucine, creatine, phosphatidylcholine, trimethylamine oxide, taurine, guanidinoacetate, AMP, inosine, histidine, hypoxanthine, anserine in rat gastrocnemius of model group were increased. While the levels of lactate, acetone, choline, glycerophosphocholine, glycine were decreased. These 6, 11, 5 potential biomarkers could be reversely regulated by treatment with Astragali Radix (high dose, middle dose, low dose), respectively. Metabolomics analysis revealed that Astragali Radix has a certain anti-fatigue effects and the mechanism may be related to regulation of amino metabolism.