About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC=0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

This study was designed to investigate the inhibitory effect and mechanism of neferine (Nef) on invasion and metastasis of nasopharyngeal carcinoma cells (NPC). The viability of CNE-1 and 5-8F cells was detected by CCK-8 assay after treatment with different concentrations of Nef. The effects of Nef on cell migration and invasion were detected by the scratch test and Transwell assay. Western blot analysis was used to detect the effects of Nef on levels of epithelial-mesenchymal transition (EMT)-associated proteins and transcription factors. The differentially expressed gene profiles between control group and Nef group were analyzed by microRNA microarray, combined with bioinformation analysis. It was observed that 30 μmol·L^-1 Nef had no significant effect on the viability of CNE-1 and 5-8F cells. Western blot assay showed that the expression level of neurotroponin cadherin (N-cadherin) and vimentin decreased after treatment with Nef, while the expression of epithelial cadherin(E-cadherin) increased. The expression of transcription factors including Twist, Snail, and Slug exhibited no significant difference. Results of the microRNA microarray suggest that 10 microRNAs showed significant differences when compared with the control group. Bioinformatics analysis showed that hsa-let-7c-5p and hsamicroRNA-423-5p targeted the same downstream genes:small integral membrane protein 3 (SMIM3) and nerve growth factor (NGF). Overexpression of hsa-let-7c-5p and hsa-miR-423-5p promoted the invasion and migration ability of 5-8F cells and decreased the expression of SMIM3 and NGF. The results from this study suggest that Nef may inhibit the invasion and metastasis of NPC cells by inhibiting the expression of hsa-let-7c-5p and hsamiR-423-5p followed by the upregulation of SMIM3 and NGF; thus, regulating the expression of EMT-associated proteins. Our data have provided experimental evidence for the inhibition of tumor invasion and metastasis by Nef.

Utilization of traditional Chinese medicine (TCM) resources for pharmaceutical development is an important part of modernization of TCM. The classical TCM prescriptions provide an important insight for developing new drugs. Based on the advantages of local TCM resources, focusing on the key scientific problems in the quality evaluation of medicinal materials and the study of classical prescriptions, this research group takes the quality evaluation of medicinal materials as the starting point. Metabolomics serves as a technical means of "quality evaluation of TCM, to support scientific connotation of classical prescriptions and development of new drugs from TCM. Using Radix Bupleurum as an example, this paper systematically and thoroughly expounds the above research ideas and strategies from the aspects:quality evaluation of medicinal materials, basic research of Xiaoyansan, and research and development of new anti-depressants. This provides the scientific basis for the modernization of TCM.

Aging is a normal physiological process involving coaction of many factors. The anti-aging effects of natural products have been studied by many domestic and international scholars, but not far enough, which still needed to be explored. Flavonoids, as natural products, have a variety of pharmacological activities and present in many traditional Chinese medicines. In recent years, research results indicate that flavonoids can delay the aging process of the nervous, immune, and reproductive systems, and the liver, skin and other tissues. The anti-aging effects of flavonoids have attracted more and more attention. Therefore, development of anti-aging drugs from flavonoids is of great significance to improve the quality of life for the elderly and slow the process of aging. However, the mechanism of the anti-aging effect of flavonoids remains unknown at present. This review will discuss the anti-aging effect and mechanisms of flavonoids in traditional Chinese medicine from the aspects of cellular signaling pathways and metabolic pathways based on the modern theories of aging.

The surface hydrophobicity of nanoparticles plays an important role in drug delivery process. The aim of this study was to verify the feasibility of using self-assembly method to prepare drug-loaded nanoparticles with tunable surface hydrophobicity. Here, Soluplus was selected as the polymeric carrier to prepare panobinostat (PNB) loaded micelles. Three different monoglycerides, glycerly monooleate (GMO), glycerly linoleate (GML) and glycerly linolenate (GMLO), were used to modify the surface of PNB-Soluplus micelles to prepare polymerlipid hybrid nanoparticles (PLHNs). The effect of monoglyceride type and amount on the physico-chemical properties of PNB-loaded PLHNs was investigated, and the surface hydrophobicity of PLHNs was characterized by Rose Bengal (RB) binding method and mucin particle method. The results suggested that compared with the PNB-Soluplus micelles (particle size 77.97±0.78 nm, zeta potential 0.44±0.29 mV, entrapment efficiency 99.45%±1.47%, the RB binding constant (K) value 0.008±0.002, the increased particle size after mixing with mucin particles 7.90±1.41 nm), surface hydrophobicity of the PLHNs increased significantly when modified by GMO, GML, GMLO, with K values of 0.055±0.010, 0.050±0.011 and 0.058±0.008, respectively. The increased particle sizes after mixing with mucin particles were 17.37±4.48 nm, 22.60±2.10 nm and 25.13±3.89 nm, respectively. Among them, the physico-chemical properties of the GMLO modified PNB-loaded PLHNs (particle size 81.60±4.52 nm, zeta potential 0.77±0.03 mV, entrapment efficiency 99.59%±0.20%) kept constant, thus GMLO was selected to further investigate the effect of GMLO mass ratio (1%-3%) to Soluplus on the properties of the nanoparticles. While no statistical significant difference in particle size, zeta potential, entrapment efficiency or in vitro release behavior was found when GMLO ratio increased, the surface lipophilicity of the PLHNs, as characterized by K values and the increased particle sizes after mixing with mucin particles, increased almost linearly with the increase of GMLO amount. In conclusion, we demonstrated that drug-loaded PLHNs based on Soluplus and GMLO can be prepared by self-assembly method, and the surface hydrophobicity was tunable by modifying the mass ratio of GMLO to Soluplus. This approach could be used for related basic science research aiming to elucidate the effect of surface hydrophobicity on in vivo behavior of drug-loaded system.

Based on dehydrogenation of monocrotaline-induced Beagle dog model of pulmonary hypertension (PH), GC-TOF-MS metabolomics technique was used to identify potential biomarkers and biologically significant changes in the serum. Pattern recognition method was used for processing metabolomics data to compare PH Beagle dogs (n=11) versus healthy controls (n=8). The results show that 514 compounds were detected in the serum. The profiles of PH models and healthy controls can be distinguished clearly, indicating that there are significant differences in the metabolic profiles. Data analysis revealed 15 types of potential biomarkers, including amino acids glycine and 3-cyanoalanine, glucose, fructose, 1-monopalmitic acid glycerin, and malic acid. Diversified metabolites and their metabolic pathways have been analyzed. We found that different degrees of turbulence and disorganization occurred in glyoxylate and dicarboxylate metabolism, TCA cycle, starch and sucrose metabolism pathways in the Beagle dogs. A soluble guanylate cyclase activator, 4, 6-diamino-2-[1-(3-fluorothiophen-2-yl) methyl-1H-pyrazolo[3, 4-b]pyridin-3-yl] -5-pyrimidinyl-N-methyl methyl carbamate (sGC003), was administered (n=15) for comparison with the model and the control. We found that three groups were clearly clustered, indicating that there were differences in the three groups of metabolites. ANOVA statistical analysis results suggested that sGC003 exhibited pharmacodynamic effect, and at the same time, it also changed the endogenous metabolites to some extent. This study laid a foundation for the application of metabolomics in early diagnosis of pulmonary hypertension and provided experimental evidence for the application of sGC003 compound. In this study, the program of animal testing had been approved by Committee on the management of experimental animal in the Beijing Rixin Technology Co. Ltd.

Network pharmacology and rat ischemia-reperfusion injury (MIRI) model was used to analyze the mechanism of cardiac protection by Trichosanthes. The animal experiments were approved by the Medical Ethics Committee of Wannan Medical College. Compounds were screened by TCMSP database and TCM Database@Taiwan according to oral bioavailability (OB > 30%) and drug like activity (DL > 0.18). The PDBID value of the compound (Z'-score < 0.5) was obtained in DRAR-CPI database and converted into a target protein by UniProt database. Human genes of target proteins were identified using the term "myocardial ischemia reperfusion injury" as the keyword through the CoolGeN database. GOTERM_BP _DIRECT enrichment analysis of target proteins related to MIRI and KEGG PATHWAY annotation analysis were performed using the DAVID database. The component-target protein-signal pathway network was constructed using Giphi0.9.2 software. The expression of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins in MIRI rats pretreated with Trichosanthes (0.2, 1.0 and 2.0 g·kg^-1) was analyzed by Western blot with compound Danshen (85.05 mg·kg^-1) as a positive control. Network pharmacology found that 12 compounds, including schottenol in Trichosanthes, synergistically inhibit MIRI through multiple targets or biological pathways, involving target proteins such as extracellular regulated protein kinase 2 (ERK2), c-jun-N-terminal kinase-1 (JNK1) and p38MAPK in MAPK signaling pathways. Western blot results showed that phosphorylation of ERK1/2 was dose-dependently up-regulated in MIRI rats pretreated with Trichosanthes, while the level of p38MAPK or JNK1 phosphorylation was down-regulated in a dose-dependent manner. Compared with the control group, phosphorylation of ERK1/2, JNK1 and p38MAPK protein showed significant difference in medium and high dose groups (1.0 and 2.0 g·kg^-1) (P < 0.01). Therefore, Trichosanthes could play an anti-MIRI role by regulating phosphorylation of ERK1/2, JNK1 and p38MAPK proteins in rats. In conclusion, the targets and pathways of Trichosanthes on anti-MIRI were revealed by network pharmacology and verified in rat MIRI model, providing the scientific basis for further study on the mechanism of Trichosanthes for cardiac protection.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), as a label-free imaging technique with high coverage and sensitivity is widely used for visualizing the spatial distribution of proteins, peptides and small metabolites in tissues. With the development of MALDI technique, MALDI-MSI is also employed to monitor the spatial distribution of phytochemical constituents of medicinal plants. In this review, we first briefly introduce MALDI-MSI technique, and we focus on its application in the spatial distribution and accumulation of secondary metabolites in medicinal plants. The ultimate advantage of using MALDI-MSI for spatial distribution analysis at the molecular level, offers crucial evidence of synthesis, transfer and accumulation of bioactive molecules in medicinal plants.

Using column chromatographic and preparative HPLC technologies, we isolated a new sesquiterpene glycoside from the stem of Dendrobium nobile. With spectroscopic techniques including NMR and MS, the new compound was identified as cadalene-12-O-β-D-glucopyranoside. This type of compound was dehydrogenated from cadinane sesquiterpene to achieve a naphthalene ring, and it is rare from a natural resource.

This study aims to investigate the effect of down-regulation of miR-205-5p by transfection of miR-205-5p inhibitor on the sensitivity of HNE1/DDP cells to cisplatin (DDP) induced apoptosis and explore the underlying mechanism. qRT-PCR was used to detect the expression of miR-205-5p in HNE1 or HNE1/DDP cells. The expression level of miR-205-5p was analyzed after transfecting HNE1/DDP cells with miR-205-5p inhibitor. MTT assay was used to evaluate the inhibitory effect of DDP alone or in combination with miR-205-5p inhibitor on the proliferation of HNE1/DDP or HNE1 cells. Apoptosis of cells treated with miR-205-5p inhibitor alone or in combination with DDP (8 μmol·L^-1) was assessed using flow cytometry with PI staining, with the nucleus was counterstained with DAPI staining. The expression of Bax, Bak, Mcl-1, or Bcl-2 was analyzed by Western blot. HNE1/DDP cells showed a high level of expression of miR-205-5p, and the expression of miR-205-5p was significantly decreased by transfection of miR-205-5p inhibitor. Down-regulation of miR-205-5p significantly increased the sensitivity of HNE1/DDP cells to DDP (P < 0.05). Transfection of miR-205-5p inhibitor enhanced the sensitivity of HNE1/DDP cells to DDP induced apoptosis. Treatment of HNE1/DDP cells with miR-205-5p inhibitor combined with DDP (8 μmol·L^-1) for 24 h resulted in an apoptotic rate of 28.93% ±2.50%, significantly higher than that treated with miR-205-5p inhibitor (9.83% ±1.31%) or DDP alone (10.83% ±1.70%) (P < 0.05). DAPI staining showed that HNE1/DDP cell nucleus became significantly condensed and fragmented in miR-205-5p inhibitor combined with DDP group. The combined group up-regulated the expression of Bax and down-regulated the expression of Bcl-2 in HNE1/DDP cells. Therefore, down-regulation of miR-205-5p can enhance the sensitivity of HNE1/DDP cells to cisplatin induced apoptosis, and the mechanism may involve up-regulation of Bax and down-regulation of Bcl-2 expression.