Timolol maleate cubic nanoparticles (TM-LCNPs) were prepared via fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by high-pressure homogenization. The optimal prescription was selected based on particle size and entrapment efficiency by orthogonal design method. Malvern particle sizer, polarized light microscopy, and differential scanning calorimetry were used to characterize the cubic nanoparticles. Commercial eye drops were used as a control for the release and corneal permeation experiment in vitro. Fluorescence imaging was used to observe the retention of Rhodamine B cubic nanoparticles (RhB-LCNPs) in rabbit cornea. The results indicated that the optimal prescription and preparation of TM-LCNPs was oil-water ratio (7:3), homogenous pressure (900 bar), the number of homogenizations (6) and drug loading (1%). Corneal permeability of TM-LCNPs was significantly higher than that of commercially available eye drops. The residence time in eyes was longer which suggested a sustained release behavior. The pathology result of rabbit corneal after multiple administration of TM-LCNPs showed that there was no apparent damage.

The aim of this study is to apply 3D printing technology to hospital drug dosing operations, and explore its feasibility and scalability. Drugs often dosed in hospitals are selected as models. The commercially available drug was ground into powder, diluted with medicinal excipients and then mixed with 75% ethanol and binder to prepare a paste for 3D printing. The dose and physicochemical properties of divided tablets were controlled by setting print parameters and printing models in computer software. Different 3D printers were employed to evaluate the impact of the device on the dosing tablet. Two drugs were dosed in this study to explore the scalability of 3D printing technology between different drugs. The drug content of the three divided dose tablets (warfarin sodium 1 mg, 2 mg, hydrochlorothiazide 5 mg) was 1.02±0.03, 1.96±0.01, 5.19±0.06 mg. The content uniformity was 1.0, 5.3, 2.6, respectively. The drug dissolution rate was (99.3±1.2)%, (101.5±0.3)%, (98.1±0.8)% in 45, 45 and 30 min. The mechanical properties of the three sub-doses and the stability within 30 days were in line with the Chinese Pharmacopoeia (2015) requirements. At the same time, it was found that the printing parameters and prescriptions can affect the properties of the divided dose tablets. By controlling the dilution ratio of commercial drug and printing parameters, the drug release rate can be customized to achieve individualized treatment. Both different modes of 3D printers can produce qualified sub-doses, and 3D print dispensing technology was also versatile between the two drugs. 3D printing can prepare small-volume, high-precision, high-repetition dosing tablets, with all properties in compliance with pharmacopoeia regulations. Thus, this method can be used as a new and scalable sub-dosing method.

Multidrug resistance (MDR) seriously affects the clinical efficacy of chemotherapeutic drugs. One of the main mechanisms of MDR is the overexpression of P-glycoprotein (P-gp) in tumor cells that reduces the intracellular drug concentrations and limits the effective use of chemotherapeutic drugs. Accordingly, application of P-gp inhibitors that can reverse tumor MDR is an effective strategy to enhance the anti-tumor effect of chemotherapeutic drugs. In recent years, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely applied as the potential P-gp inhibitor for its excellent P-gp inhibition effect as well as good safety. In this paper, we reviewed the P-gp inhibitors, the mechanisms of TPGS in reversing P-gp-mediated MDR and the application of TPGS-based nano-drug delivery system.

Free fatty acid receptor 1 (FFAR1), also known as G protein-coupled receptor 40 (GPR40), is a receptor for diverse free fatty acids. This review aims at summarizing effects and mechanisms of FFAR1 on insulin secretion and related blood glucose and lipids metabolism. FFAR1 is involved in the occurrence and development of type 2 diabetes, but its specific mechanism has not been clarified. FFAR1 is expressed in the wide variety of issues, especially β-cells in the pancreatic islets, as well as α-cells in islets, central nervous tissue, subcutaneous fat, skeletal muscle, gastrointestinal tract, etc. FFAR1 can act on islet β-cells to promote the secretion of insulin, promote α-cells on glucagon secretion, and regulate the secretion of endocrine cells in the gastrointestinal tract to balance the level of glucose and lipids. Existing research found that FFAR1 agonists have significant advantages. They promote insulin release, reduce weight and protect pancreatic β-cells, and have no risk of hypoglycemia. To in-depth understand the role of FFAR1 as a drug target in the treatment of diabetes, further pharmacological studies are still needed in order to obtain safer and more effective drugs against type 2 diabetes.

Traditional Chinese medicine Baitouweng have a long history of application. The pharmacopoeia included dry roots of Pulsatilla chinensis (Bge.) Regel of Ranunculaceae. There are easily confused species in the market circulation, such as P. cernua (Thunb.) Bercht. et Opiz., P. dahurica (Fisch.) Spreng., P. turczaninovii Kryl. et Serg., and P. chinensis (Bge.) Regel var. kissii (Mandl) S. H. Li et Y. H. Huang, etc. In this study, using the method of metagenomics, based on high-throughput sequencing technology, the ITS2 sequence of mixed samples of five species of Baitouweng medicinal materials was sequenced. First, the total DNA extraction of medicinal materials mixing powder, and the ITS2 fragment of total DNA was amplified by PCR. Second, the Illumina MiSeq platform was used to carry out Paired-end sequencing for DNA fragments. Last, using FLASH, QⅡME and GraPhlAn software to arrange and analyze, and clustering analysis with the sequences of uploaded to GenBank by our group in the early stage. The results showed that a total of 53 024 sequences of ITS2 were obtained from the mixed samples, there are 52 295 effective sequences, there are a total of 49 079 of five species of medicinal materials of P. Miller. After the representative sequences and the sequence of uploaded to GenBank by our group in the early stage were clustering analysis, 5 species of Baitouweng medicinal materials were clustered into one branch separately, presenting monophyletic. The results showed that using the high-throughput sequencing technology, using ITS2 sequence as DNA barcode, the mix powder of 5 species of Baitouweng medicinal materials could be effectively identified. It provides a new method and thought for the origin identification of mixed Chinese medicinal materials.

Macrophage migration inhibitory factor (MIF) is a classical pro-inflammatory cytokine that plays an important role in the innate and adaptive immune regulation. In recent years, a large number of studies have demonstrated that the expression level of MIF is significantly increased in a variety of tumor tissues and MIF promotes the occurrence and development of tumors. MIF participates in the regulation of tumor growth, metastasis, angiogenesis, as well as induces and maintains the tumor microenvironment. Targeting MIF has been considered as a candidate strategy against cancer. In this review, the structural features, the signaling pathway, the biological functions of MIF are briefly outlined. Moreover, approaches that target MIF in the treatment of cancer are also summarized.

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.

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.