Jasmonic acid (JA) is an important signal molecule involved in plant resistance, and allene oxide synthase (AOS) is a key enzyme in the biosynthesis of jasmonates. In this study, a full-length cDNA of AsAOS1 gene was cloned from Aquilaria sinensis. Meanwhile, the sequence analysis, prokaryotic expression, purification, tissue-specific expression analysis and expression analysis under different abiotic stresses and hormone treatments were performed. The open reading frame (ORF) of AsAOS1 gene was 1 575 bp, encoding a protein of 524 amino acid residues, with a predicted molecular mass of 58.70 kDa. AsAOS1 protein possessed the conserved sequences of cytochrome P450 (CYP450). The phylogenetic analysis indicated that AsAOS1 protein had the highest level of homology with AOS protein of Citrus sinensis. The recombinant AsAOS1 protein was successfully expressed in Escherichia coli BL21(DE3) cells using the prokaryotic expression vector pET28a-AsAOS1 and the recombinant AsAOS1 was purified by Ni²⁺ affinity chromatography. Expression analysis results in different tissues showed that AsAOS1 was primarily observed in stems, and then roots, followed by leaves. AsAOS1 transcript level was significantly induced after 12 h treatment of NaCl, cold temperature and CdCl₂. Furthermore, AsAOS1 expression level was enhanced upon methyl jasmonate (MeJA), salicylic acid (SA) and abscisic acid (ABA) treatment. However, mannitol and gibberellin (GA₃) treatments had little influence on the expression level of AsAOS1. These results provides valuable insights into the role of JA in the mechanism of agarwood formation and plant resistance.

This study was designed to investigate the therapeutic effect and mechanisms of action of novel compound N-(Z)-9-octadecenyl-2-propanesulfonamide (N15) on type 2 diabetes (T2DM). A mouse model of T2DM was established with multiple injection of streptozotocin (STZ) at a low dose. N15 at different doses (50, 100 and 200 mg·kg^-1·d^-1) and pioglitazone (6 mg·kg^-1·d^-1) were administrated orally for 6 weeks. The level of fasting blood glucose (FBG) and fasting insulin (FIns) were measured in the course of the experiment for insulin resistance index (HOMA-IR). Oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were determined in the treated mice. The expression of Akt, AMPK and Glut4 in liver were analyzed by Western blot. N15 was found to reduce the level of FBG, FIns and HOMA-IR (P < 0.01) and ameliorate the glucose and insulin tolerance (P < 0.01, P < 0.001). Simultaneously the protein expression of p-Akt, p-AMPK and Glut4 was significantly increased in liver by N15 (P < 0.01). These effects were similar to those of pioglitazone (P > 0.05). These results suggested that the novel compound N15 can ameliorate insulin resistance and the potential mechanism may be associated with increased insulin signaling in liver and promotion of phosphatidyl inositol 3 phosphate phosphorylation.

Photo-sensitive reactive oxygen species (ROS) responsive liposomes loaded with 1, 4, 8, 11, 15, 18, 22, 25-octabutoxypalladium phthalocyanine[PdPC(OBu)₈] and doxorubicin hydrochloride (DOX) (LPD) were prepared by (NH4)₂SO₄-gradient method. LPD was characterized with transmission electron microscopy (TEM), dynamic light scattering particle size, zeta potentials, photo-sensitive ROS-responsive DOX release behaviors and the serum stability in vitro. LPD cytotoxicity, DOX uptake and singlet oxygen production in MCF-7 cells were evaluated. The results showed that the particle size of LPD was (169.3 ±1.2) nm, PDI of LPD was 0.198 ±0.003 and zeta potentials of LPD was (-39.8 ±0.8) mV. The accumulated release of DOX reached 95.5% in 5 min under 730 nm laser irradiation (300 mW·cm^-2). The DOX uptake of liposome was increased and ¹O₂ was generated. The half inhibition concentration (IC₅₀) of DOX in LPD with irradiation group was decreased by 85.7% and no irradiation group was decreased by 67.9% compared with free DOX group in MCF-7 cells. Therefore, photo-sensitive ROS-responsive liposomes would be a promising drug delivery system for tumor therapy.

In this study, we used low molecular weight heparin (LH) as hydrophilic sides, doxorubicin (DOX) as hydrophobic sides, and indocyanine green (ICG) as a photosensitive drug to prepare pH-sensitive self-assembled polymeric micelles (LH-DOX/ICG). The micelles were prepared by dialysis, and evaluated for stability, pH sensibility in vitro, hemolytic test and photo-thermal effect. Wound healing test was used to evaluate the anti-metastatic effects. MTT assay and apoptosis detection kit were used to evaluate the cytotoxicity of micelles against melanoma B16F10 cells. The size of the micelles was (148.7 ±2.1) nm and the zeta potential was (-30.7 ±1.1) mV. The drug-loading content of DOX and ICG were 11.82% and 5.59%, respectively. The micelles exhibited spherical in shape, fairly uniform size. The micelles were stable within 48 h in 50% fetal bovine serum phosphate buffer. The release of DOX was pH-sensitive, while the release of ICG was sustained. The micelles were biocompatible and safe as indicated by the hemolytic test. In vitro photo-thermal effect indicated LH-DOX/ICG micelles had similar photo-thermal effect to the free ICG. Wound healing test showed that the micelles had a good ability to inhibit tumor migration with laser irradiation. MTT assay and cell apoptosis assay indicated that LH-DOX/ICG micelles displayed more efficient anti-tumor effect after near infrared laser compared to LH-DOX micelles. LH-DOX/ICG micelles are promising for the therapeutic effect of phototherapy and chemotherapy in combination for melanoma.

The purpose of this article was to study the pharmacokinetic characteristics of YZG-331, plasma protein binding and metabolic stability in vivo and in vitro. Plasma and tissue concentrations of YZG-331 were determined in mice and rats after administration by LC-MS/MS analysis orally or intravenously. The plasma protein binding of YZG-331 with human, dog, monkey, rat and mouse were measured by ultrafiltration method. The stability of YZG-331 in animal and human plasma, liver microsomes, intestinal bacteria and artificial gastrointestinal fluid was also investigated in vitro. The results show that YZG-331 was absorbed rapidly in both mice and rats after oral administration, while the absorption and elimination saturation YZG-331 were also observed. The bioavailability of YZG-331 was much higher in male mice (51.2%) than that in female mice (27.7%), however, the bioavailability in male rats (27.1%) was lower than that in female rats (78.7%). YZG-331 was widely distributed in different tissues of mice, especially in certain regains of brain, including thalamus, hippocampi, cortical and striatal. YZG-331 was found to bind to human, dog, monkey, rat and mouse plasma protein in vitro (93.3%-98.9%) without significant concentration dependences and species differences. YZG-331 was stable in animal and human plasma, simulated gastric/intestinal fluid and liver microsomal incubations, except rat liver microsomes and intestinal flora. Therefore, we concluded that:the pharmacokinetics of YZG-331 in mice and rats have gender and species differences; YZG-331 was widely distributed in vivo including brain, the targets of the agent; YZG-331 had a high affinity to plasma protein and was metabolized by rat liver microsomes and intestinal flora.

Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4^CRBN, CRL2^VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.

Depression is a complex heterogeneous psychiatric disorder with a potential to cause patient disability worldwide. In the past decades, a number of the first-line drugs (tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) had been discovered for the treatment of depression. CYP450 superfamily is involved in the biotransformation of antidepressants mainly through the CYP2D6, CYP2C19, CYP3A4 isoenzymes. Their genetic polymorphisms are closely related to clinical use and the interactions have been already identified between enzymes and antidepressants. This review focuses on drug metabolism and the interaction for CYP450 enzymes. The content may contribute to the development of antidepressant, improvement of the safety of antidepressants and the efficacy of treatment.

This study was designed to investigate the effect of Yinxing Mihuan oral solution on rats with myocardial ischemia injury. Left anterior descending (LAD) coronary artery was occluded in rats to establish the model. Yinxing Mihuan oral solution was given by intragastric administration daily for one week at dosage of 309 and 618 mg·kg^-1. Cardiac ultrasound function, pathologic change and serum myocardial enzymes were determined to evaluate the effect of Yinxing Mihuan oral solution. The heart function was significantly reduced in the model group compared with sham operation group, and the pathologic damage was clear. The changes were significantly improved by Diltiazem hydrochloride tablets in heart function and ejection fraction (P < 0.01). The ejection fraction and stroke volume was improved by Yinxing Mihuan oral solution (618 mg·kg^-1) (P < 0.05, P < 0.01). In addition, Yinxing Mihuan oral solution decreased the myocardial damage and inhibited inflammatory reaction, and inhibited platelet activation factor. Yinxing Mihuan oral solution can protect against myocardial ischemia injury, inflammation and platelet activation in the rat model.

The acquired immunodeficiency syndrome (AIDS) is a serious infectious disease infected by human immunodeficiency virus type 1 (HIV-1). HIV-1 nucleocapsid protein 7 (HIV-1 NCp7) plays an important role in the progress of virus reverse transcription and integration. Thus, the central role and conservative nature of the NCp7 protein make it an attractive target for development of novel anti-HIV agents. This review summarizes the research progress of HIV-1 NCp7 inhibitors in the past decade.

Direct-PCR technology was using a 15 minutes heat-lysis step instead of DNA extraction to get DNA templates with small amount of plant materials followed by sensitive PCR process to amplify target genes. In order to facilitate DNA barcoding in medicinal herb identification with Direct-PCR, we collected different tissues from 80 medicinal plants as material to amplify the ITS fragments. Through optimizing the PCR reaction, ITS of 80 plant samples was all successfully amplified. PCR products were sequenced and to do Blast analysis. These results suggest that Direct-PCR would improve the efficiency of DNA barcoding in the application of medicinal herb molecular authentication.