ABSTRACT
Biocompatible lipo-histidine hybrid materials conjugated with IR820 dye show pH-sensitivity, efficient intracellular delivery of doxorubicin (Dox), and intrinsic targetability to cancer cells. These new materials form highly uniform Dox-loaded nanosized vesicles via a self-assembly process showing good stability under physiological conditions. The Dox-loaded micelles are effective for suppressing MCF-7 tumors, as demonstrated in vitro and in vivo. The combined mechanisms of the EPR effect, active internalization, endosomal-triggered release, and drug escape from endosomes, and a long blood circulation time, clearly prove that the IR820 lipopeptide DDS is a safe theranostic agent for imaging-guided cancer therapy.
Subject(s)
Histidine/chemistry , Hydrogen-Ion Concentration , Humans , MCF-7 Cells , Microscopy, Electron, TransmissionABSTRACT
BACKGROUND AND AIM: The significance of incidentally detected bile duct dilatation has not yet been elucidated and there are only a few studies on asymptomatic patients with a dilated bile duct. This study aimed to investigate the causes and natural course of bile duct dilatation in asymptomatic patients. METHODS: A retrospective review of medical records was conducted for individuals in whom bile duct dilatation was detected by routine screening abdominal ultrasound at a health promotion center in Samsung Medical Center from January 2005 to April 2008. RESULTS: A total of 514 patients were included; the mean age was 60.1 ± 9.9 and the median follow-up period was 72 (interquartile range 56-85) months. Thirty-eight individuals who had a definite cause or biliary disease requiring treatment at the time of detection of bile duct dilatation were compared with 476 individuals who did not have a definitive cause or who did not need treatment. Both common bile duct (CBD) dilatation and intrahepatic bile duct (IHBD) dilatation were significantly related to the presence of a definitive causative lesion (OR 3.95; 95 % CI 1.77-8.82; p = 0.001). In the IHBD dilatation group, the severity of dilatation was also associated with the presence of a definitive causative lesion (OR 5.77; 95 % CI 1.32-25.26; p = 0.020). CONCLUSION: Incidentally found biliary dilatation could be a prodrome of significant biliary tree disease. Therefore, further evaluation and regular follow up should be considered especially for marked IHBD dilatation or concomitant dilatation of CBD and IHBD detected on ultrasound.
Subject(s)
Bile Duct Diseases/diagnosis , Aged , Aged, 80 and over , Bile Duct Diseases/pathology , Female , Humans , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk FactorsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum hydropiper L. (Polygonaceae) has been traditionally used to treat various inflammatory diseases such as rheumatoid arthritis. However, no systematic studies on the anti-inflammatory actions of Polygonum hydropiper and its inhibitory mechanisms have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 99% methanol extracts (Ph-ME) of this plant. MATERIALS AND METHODS: The effects of Ph-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages were investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, were elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the kinase activities of target enzymes. Additionally, a dextran sulphate sodium (DSS)-induced colitis model was employed to see whether this extract can be used as an orally available drug. RESULTS: Ph-ME dose-dependently suppressed the release of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ph-ME inhibited mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, activator protein (AP-1), and cAMP responsive element binding protein (CREB), and simultaneously inhibited its upstream inflammatory signalling cascades, including cascades involving Syk, Src, and IRAK1. Consistent with these findings, the extract strongly suppressed the kinase activities of Src and Syk. Based on HPLC analysis, quercetin, which inhibits NO and PGE(2) activities, was found as one of the active ingredients in Ph-ME. CONCLUSION: Ph-ME exerts strong anti-inflammatory activity by suppressing Src/Syk/NF-κB and IRAK/AP-1/CREB pathways, which contribute to its major ethno-pharmacological role as an anti-gastritis remedy.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Colitis, Ulcerative/prevention & control , Macrophages/drug effects , Methanol/chemistry , Plant Extracts/pharmacology , Polygonum , Solvents/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/immunology , Colitis, Ulcerative/metabolism , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dextran Sulfate , Dinoprostone/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Inflammation Mediators/metabolism , Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors , Interleukin-1 Receptor-Associated Kinases/metabolism , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , Lipopolysaccharides/pharmacology , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal , Polygonum/chemistry , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , RNA, Messenger/metabolism , Signal Transduction/drug effects , Syk Kinase , Time Factors , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Transfection , Tumor Necrosis Factor-alpha/metabolism , src-Family Kinases/antagonists & inhibitorsABSTRACT
During brown planthopper (BPH) feeding on rice plants, we employed a modified representational difference analysis (RDA) method to detect rare transcripts among those differentially expressed in SNBC61, a BPH resistant near-isogenic line (NIL) carrying the Bph1 resistance gene. This identified 3 RDA clones: OsBphi237, OsBphi252 and OsBphi262. DNA gel-blot analysis revealed that the loci of the RDA clones in SNBC61 corresponded to the alleles of the BPH resistant donor Samgangbyeo. Expression analysis indicated that the RDA genes were up-regulated in SNBC61 during BPH feeding. Interestingly, analysis of 64 SNBC NILs, derived from backcrosses of Samgangbyeo with a BPH susceptible Nagdongbyeo, using a cleaved amplified polymorphic sequence (CAPS) marker indicated that OsBphi252, which encodes a putative lipoxygenase (LOX), co-segregates with BPH resistance. Our results suggest that OsBphi252 is tightly linked to Bph1, and may be useful in marker-assisted selection (MAS) for resistance to BPH.
Subject(s)
Genes, Plant , Hemiptera/pathogenicity , Oryza/genetics , Oryza/parasitology , Animals , Base Sequence , Chromosome Mapping , Chromosomes, Plant/genetics , DNA, Plant/genetics , Gene Expression , Host-Pathogen Interactions/genetics , Phenotype , Plant Diseases/genetics , Plant Diseases/parasitologyABSTRACT
The development of rice varieties (Oryza sativa L.) that are resistant to the brown planthopper (BPH; Nilaparvata lugens Stål) is an important objective in current breeding programs. In this study, we generated 132 BC(5)F(5) near-isogenic rice lines (NILs) by five backcrosses of Samgangbyeo, a BPH resistant indica variety carrying the Bph1 locus, with Nagdongbyeo, a BPH susceptible japonica variety. To identify genes that confer BPH resistance, we employed representational difference analysis (RDA) to detect transcripts that were exclusively expressed in one of our BPH resistant NIL, SNBC61, during insect feeding. The chromosomal mapping of the RDA clones that we subsequently isolated revealed that they are located in close proximity either to known quantitative trait loci or to an introgressed SSR marker from the BPH resistant donor parent Samgangbyeo. Genomic DNA gel-blot analysis further revealed that loci of all RDA clones in SNBC61 correspond to the alleles of Samgangbyeo. Most of the RDA clones were found to be exclusively expressed in SNBC61 and could be assigned to functional groups involved in plant defense. These RDA clones therefore represent candidate defense genes for BPH resistance.
