In this study, the change of intestinal microflora in rat fecal samples after amoxicillin administration was observed. In vitro incubation experiments combined with LC-MS/MS assay were used to test the role of intestinal flora in the metabolism of nifedipine. The effect of changes of intestinal flora was determined after amoxicillin administration on the metabolism of nifedipine. We found that the number and types of intestinal flora decreased after taking amoxicillin. After incubation for 12 h, the results showed that the remaining amounts of nifedipine in the N1 group (nifedipine) and N2 group (amoxicillin + nifedipine) were 0.057 6 and 0.064 8 μmol·L^-1, respectively, while the remaining amounts of nifedipine after 24 h of incubation were 0.039 6 and 0.050 4 μmol·L^-1, respectively. These results show that the intestinal flora is involved in the metabolism of nifedipine. After administration of amoxicillin, the metabolism of nifedipine was slowed down, the AUC_0-t was increased by 39.10%, t_max was advanced by 0.45 h, and the CL was reduced 34.71%. The data suggest that the combination may enhance the therapeutic effect of nifedipine. Therefore, drug-drug interactions mediated by gut microbiota cannot be ignored when combined with antibiotics and nifedipine, one of the important factors affecting drug efficacy.

Atherosclerosis (AS) is a complex metabolic syndrome that seriously harms human health, and its occurrence and development are directly related to the metabolic disturbances of free fatty acids (FFA). In this study, macrophage-derived foam cells were established as the model of early AS. Therefore, the metabolic disturbances of FFA in ox-LDL induced foamy macrophages were analyzed using target metabolomics. Then the effect of hydroxysafflor yellow A (HSYA) on regulating FFA was also explored. The quantitative analysis of 27 fatty acids was obtained within 20 min based on dynamic MRM mode. Thirteen metabolic biomarkers of macrophage-derived foam cells were identified using multivariate statistical analysis. It was found that upregulation of total SFA and downregulation of C12:0, C14:0, C18:1, total MUFA were the typical metabolic features in macrophage-derived foam cells. Furthermore, HSYA displayed obvious repairing effect on C12:0, C14:0 and C18:1, which were involved in de novo fatty acid biosynthesis pathway. Oleoyl-(acyl-carrier-protein) hydrolase (OLAH), as the key enzyme in de novo fatty acid biosynthesis pathway, may be a drug target of HSYA.

As the common pathway of chronic renal diseases leading to end-stage renal failure, renal tubulointerstitial fibrosis is characterized by the deposition of extracellular matrix and scar hardening. Our study aimed to construct an in vitro cell culture platform to explore the impact of matrix stiffness on cell morphology and function of renal tubular epithelial cells. Photopolymerized polyacrylamide gels (PAA gel) with varying stiffnesses as model substrates was selected to simulate the matrix stiffness of normal and fibrotic renal tissues with elastic moduli ranging from 1 to 40 kPa. The human renal tubular epithelial cells (HK-2) were seeded on the surface of PAA gels. The impact of matrix stiffness on the morphology of HK-2 were investigated via immunofluorescence staining and confocal microscopy. The expression levels of glucose transporter 1 (GLUT1), glucose transporter 2 (GLUT2), glucose transporter 5 (GLUT5) were semi-quantitatively analyzed. With increasing matrix stiffness, both the levels of GLUT1 and GLUT5 in HK-2 cells were significantly decreased, whereas the expression level and the distribution pattern of GLUT2 in HK-2 remained unchanged with stiffness variation.

Oral formulations of nanoemulsions (NE) were systematically designed, and then their effects on oral absorption of raloxifene (RAL), including their absorption mechanisms were investigated. RAL solubility in water and various excipients of NE and oil-water partition coefficient[P_(O/W)] of RAL were examined. Next the optimal compatibility between emulsifiers and oils in NE were ascertained by emulsification ability. Proportions of each component and optimal RAL-NE were fully confirmed by a pseudo-ternary phase diagram and drug loading, respectively. RAL-NE quality was evaluated by particle size, zeta potential, morphology, entrapment efficiency and stability in simulated gastrointestinal fluid. A MDCK cell model was used to study the in vitro transport mechanism of RAL-NE. Oral bioavailability of RAL-NE was eventually performed in SD rats. RAL can be classified as BCSⅡ based on the solubility and P_(O/W). The best formulation of RAL-NE was composed of linoleic acid (LOA):isopropyl palmitate (IPP):cremophor RH40 (RH40):alcohol as 1.67:3.33:3:2. Drug loading in pre-nanoemulsion was 15 mg·g^-1 andentrapment efficiency of RAL in NE was (79.4 ±0.4)%. The particle size, zeta potential and drug content of RAL-NE were maintained in the simulated gastrointestinal fluid. The in vitro transport mechanism of RAL-NE in MDCK cells was mainly clathrin-mediated endocytosis. The oral bioavailability of RAL in RAL-NE relative to RAL-suspension was 171.9%. The best formulation of RAL-NE studied systematically was confirmed to significantly improve the RAL absorption by in vitro and in vivo evaluations (P < 0.05). This paper provides references for oral NE research and development.

On base of traditional physiological studies, building a comprehensive evaluation system for the efficacy of Liuwei Dihuang Wan (LW) for regulating the growth and development of rats by indicators that the overall metabolic profile and biomarkers of urinary metabonomics. Sixty-seven day-old Sprague-Dawley rats were randomly divided into four groups that are the control group and low-dose, medium-dose, and high-dose groups of LW. At the age of 28 days, different doses of LW extracts were continuously administered for 16 days. On the basis of behavior, body weight, organ index and femur length, a UPLC-HDMS technique was used to establish urine metabolomics method to characterize the profile of urine metabolism before and after intervention of LW, analysis and identificate related to drug effects of differential metabolism markers, and study the effect of LW on the growth and development of rats. LW could improve the overall behavioral ability of rats, promote weight gain and the growth of organs and bones, and 36 differential metabolites and 13 target metabolic pathways of urine under the intervention of LW were identified, and 8 metabolic markers were regarded as a key marker that LW effect the growth and development of rats. LW has a significant regulatory effect on the urine metabolic network during the growth and development of rats. This study interpreted the scientific implications of the effect of "Nourishing Kidney Yin" on the growth and development of rats.

S-adenosylmethionine synthetase, a key enzyme in plant metabolism, plays an essential role in the plant defence system. In present study, a full length cDNA sequence of AsSAMS1 gene was cloned by RACE and reverse transcription PCR from Aquilaria sinensis calli. Meanwhile, the bioinformatics, prokaryotic expression, tissue-specific expression analysis, and expression analysis under different abiotic stresses and hormone treatments were performed. The open reading frame (ORF) of AsSAMS1 gene was 1 183 bp, encoding a protein of 393 amino acids with a calculated molecular mass (MW) of 43.13 kDa. Bioinformatic analysis indicated that AsSAMS1 contained 3 SAMS characteristic sequences. The phylogenetic analysis indicated that AsSAMS1 protein had the highest level of homology with SAMS protein from Glycine soja. The recombinant AsSAMS1 protein was successfully expressed in Escherichia coli BL21 (DE3) cells using the prokaryotic expression vector pET28a-AsSAMS1 and the recombinant AsSAMS1 was purified by Ni²⁺ affinity chromatography. Expression analysis results in different tissues indicated that AsSAMS1 was primarily observed in stems, and then stem tips and leaves, following by roots. The transcript level of AsSAMS1 and the content of S-adenosylmethionine (SAM) were induced by various abiotic stresses including salt, drought, cold, and heavy metal stress. Furthermore, AsSAMS1 expression level was enhanced upon methyl jasmonate (MeJA), salicylic acid (SA), gibberellin (GA3), and abscisic acid (ABA) treatment. These results provided valuable insights for further study on the role of SAMS in the mechanism of agarwood formation and plant resistance.

Fructose 1, 6-bisphosptase (FBPase), a second rate-limiting enzyme in gluconeogenesis, has an important role in the control of gluconeogenesis, which involves in energy metabolism and glucose homeostasis. Inhibitors of FBPase exhibit an anti-diabetic activity. Some of FBPase inhibitors have entered the stage of clinical trials, which indicates that FBPase is a promising therapeutic target for the discovery and development of hypoglycemic drugs. In addition, recent studies have shown that FBPase can be used to treat other diseases such as the initiation and development of tumors in several cancer types. Here, we provide a review of the biological characteristics of FBPase and contributions of FBPase on gluconeogenesis and insulin secretion, the research and development of FBPase inhibitors and the regulatory role of FBPase in other diseases.

Gold nanoclusters (AuNCs) are gold atom aggregates less than 2 nm (excluding the ligand shell) or 150 atoms. It has been widely studied due to its small size effect, fluorescence property, and catalytic activity. In this review, research progress in the preparation of gold nanoclusters containing accurate atom numbers using biomolecules and chemically synthesized molecules as ligands have been summarized. The factors that affect the preparation of gold nanoclusters have been discussed. The applications of AuNCs having accurate atomic numbers in the fields of analyte assay, catalysis, bioimaging, and drug delivery have been introduced. This review provides references to the further researches on the preparation technology and biomedical applications of AuNCs.

Dendrobium officinale is a member of the family Orchidaceae. The dried stem of D. officinale is used as a valuable traditional Chinese medicine, known as Dendrobii Officamlis Caulis (called TiepiShihu in Chinese). According to Chinese Pharmacopoeia, Dendrobii Officamlis Caulis has effects of tonifying stomach, promoting fluid, nourishing Yin and clearing heat. At present, the planting area of D. officinale is over 100 000 Mu (over 6 670 hm²) and the annual output of its fresh stem is in excess of 10 000 tons. Good variety is the guarantee of herbal medicine's quality, while germplasm resource is the base for breeding excellent variety. In this paper, we summed the characteristics of present main varieties of D. officinale and reviewed the progress on germplasm resources and genetics and breeding of the plant, in order to provide a scientific basis for the further research.

The study was designed to explore the active components and mechanism of Kai Xin San in the treatment of Alzheimer's disease (AD) based on network pharmacology. All targets related to AD were researched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Therapeutic Targets Database (TTD). The common targets obtained by two databases were determined as candidate proteins involved in AD. All active components related to Kai Xin San were researched from ADME (absorption, distribution, metabolism and excretion). PharmMapper was used to obtain the primary candidate targets of Kai Xin San. The corresponding gene name of each target protein was obtained from the UniProt database and selected human target proteins. Finally, the target proteins related to AD by Kai Xin San were acquired; Cytoscape 3.5.1 was used to construct the topology analysis for the active ingredient-AD target interaction network of Kai Xin San. According to STRING database and DAVID annotation databases, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the targets was performed. The network pharmacology analysis results were verified by Discovery Studio molecular docking software. There were 31 components meeting the conditions of ADME and 8 targets relating to AD. Thirteen kinds of biological process, 7 related to molecular function and 11 related to cellar components, were included in 31 GO entries. There were 5 KEGG pathways, involving the calcium signaling pathway and PI3K-Akt signaling pathway. The docking results of Discovery Studio showed that active ingredients of Kai Xin San and the positive controls all have good binding activity with important targets. In conclusion, the Kai Xin San as applied for treating AD has the advantages of multi-components and targets, to investigate the active components and mechanism of Kai Xin San for treating AD based on network pharmacology to eludicate possible studies of the mechanisms of action.