ABSTRACT
Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
ABSTRACT
Liver is the main place of drug metabolism. Mitochondria of hepatocytes are important targets of drug-induced liver injury. Mitochondrial autophagy could maintain the healthy operation of mitochondria in cells and the stable proliferation of cells. Therefore, the use of mitochondrial autophagy to remove damaged mitochondria is an important strategy of anti-drug-induced liver injury. Active ingredients that could enhance mitochondrial autophagy are contained in many traditional Chinese medicines, which could regulate the mitochondrial autophagy to alleviate relevant diseases. However, there are only a few reports on how to accurately and efficiently identify and evaluate such components targeting mitochondria from traditional Chinese medicine. Liquid chromatography-mass spectro-metry(LC-MS) combined with serum pharmacology in vivo can be used to accurately and efficiently find active ingredients of traditional Chinese medicine acting on mitochondrial targets. This paper reviewed the research ideas and methods of traditional Chinese medicine ingredients for increasing the hepatotoxicity of mitochondrial autophagy, in order to provide new ideas and methods for the study of active ingredients of traditional Chinese medicine targeting mitochondria.
Subject(s)
Humans , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , MitochondriaABSTRACT
@#AIM: To observe and compare the changes of macular vascular density and retinal thickness in children and adolescents with different degrees using optical coherence tomography angiography(OCTA), then analyze their correlation.<p>METHODS: Our prospective cross-sectional study included 230 eyes of 115 children and adolescents aged 6-18a. According to spherical equivalent power(SE), they were divided into four groups: emmetropia group(32 eyes of 16 cases), mild myopia group(94 eyes of 47 cases), moderate myopia group(68 eyes of 34 cases), and high myopia group(36 eyes of 18 cases). Using RTVue XR scans of the 6mm×6mm region of the macula, the system automatically divided it into three rings: 1mm(fovea)ring, 1mm-3mm(parafovea)ring, and 3mm-6mm(perifovea)ring. And each ring was further divided into four quadrants: temporal(T), superior(S), nasal(N), and inferior(I). Quantitatively analysis was performed for the superficial and deep capillary densities and retinal thickness of each sector.<p>RESULTS: The superficial capillary density in the macula was in turn significantly decreased as in emmetropia(44.4±3.5)%, mild myopia(44.8±3.8)%, moderate myopia(44.3±3.8)%, and high myopia(42.6±4.5)% groups(<i>F</i>=2.963,<i>P</i>=0.033). The superficial capillary density of parafovea's temporal side were(46.1±3.5)%,(46.8±5.1)%,(46.2±4.3)%, and(43.8±5.5)% in the four groups, respectively(<i>F</i>=3.436, <i>P</i>=0.018). Similarly, the deep capillary density of the four groups was(49.9±4.1)%,(48.4±4.7)%,(47.9±5.5)%, and(45.3±4.7)%, respectively(<i>F</i>=4.806, <i>P</i>=0.003). The deep capillary density of the perifovea was(49±4.4)%,(47.2±5.2)%,(46.6±6)%, and(43.6±5.1)% in the 4 groups, respectively(<i>F</i>=5.495, <i>P</i>=0.001). The retinal thickness of the four groups was 293.9±12.9, 295.5±13.0, 290.9±12.0, and 284.5±10.7 μm(<i>F</i>=6.606, <i>P</i><0.001). The superficial capillary densities of parafoveal's temporal and nasal sides were positively correlated with SE(<i>r</i>=0.221, 0.219, <i>P</i>=0.001, 0.001). The deep capillary density of perifovea's temporal, superior, nasal and inferior side were positively correlated with SE(<i>r</i>=0.172, 0.200, 0.250, 0.296, <i>P</i>=0.011, 0.003, <0.001, <0.001). The central retinal thickness except the fovea were positively correlated with SE(<i>P</i><0.05).<p>CONCLUSION: With the increase of myopia degree of children and adolescents, the superficial capillaries density in the macula decreases, especially in the parafovea's temporal side; as well as the deep capillaries density, especially decreases in the perifovea. The central retinal thickness decreases in both parafovea and perifovea. With the myopia degree of children and adolescents increases, the structure and capillary circulation of the macula will be influenced, especially in the high myopia group.
ABSTRACT
This study aimed to investigate the influence of combinating Huangqi with Fuzi on the pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA). The plasma concentrations of the drugs were determined by LC-MS for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.3, and SPSS 12.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. Comparing with Fuzi group, the AUC0-t and AUC0-∞ of six alkaloids in Fuzi-Huangqi group was significantly decreased, the CLz/Fof six alkaloids except HA was significantly increased; the Cmax was decreased and the tmax was prolonged in 3 monoester alkaloids, and the apparent volume of distribution of BMA and MA (Vz/F) increases. These data indicated that Huangqi can inhibit the absorption of aconite alkaloids, induce the distribution of aconite alkaloids to the whole body, and accelerate the elimination of aconite alkaloids. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.
ABSTRACT
Echinostoma hortense (Digenea: Echinostomatidae) is one of the intestinal flukes with medical importance in humans. However, the mitochondrial (mt) genome of this fluke has not been known yet. The present study has determined the complete mt genome sequences of E. hortense and assessed the phylogenetic relationships with other digenean species for which the complete mt genome sequences are available in GenBank using concatenated amino acid sequences inferred from 12 protein-coding genes. The mt genome of E. hortense contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region. The length of the mt genome of E. hortense was 14,994 bp, which was somewhat smaller than those of other trematode species. Phylogenetic analyses based on concatenated nucleotide sequence datasets for all 12 protein-coding genes using maximum parsimony (MP) method showed that E. hortense and Hypoderaeum conoideum gathered together, and they were closer to each other than to Fasciolidae and other echinostomatid trematodes. The availability of the complete mt genome sequences of E. hortense provides important genetic markers for diagnostics, population genetics, and evolutionary studies of digeneans.