An G

References (9)

Title : A Quantitative Systems Pharmacology Model of the Incretin Hormones GIP and GLP1, Glucagon, Glucose, Insulin, and the Small Molecule DPP-4 Inhibitor, Linagliptin - Wu_2023_J.Pharm.Sci__
Author(s) : Wu N , An G
Ref : J Pharm Sci , : , 2023
Abstract : In the current study, we established a comprehensive quantitative systems pharmacology (QSP) model using linagliptin as the model drug, where drug disposition, drug intervention on dipeptidyl peptidase-4 (DPP-4), glucose-dependent insulinotropic peptide (GIP), Glucagon-like peptide-1 (GLP-1), glucagon, glucose, and insulin are integrated together with the cross talk and feedback loops incorporated among the whole glycemic control system. In the final linagliptin QSP model, the complicated disposition of linagliptin was characterized by a 2-compartment pharmacokinetic (PK) model with an enterohepatic cycling (EHC) component as well as target-mediated drug disposition (TMDD) processes occurring in both tissues and plasma, and the inhibitory effect of linagliptin on DPP-4 was determined by the linagliptin-DPP-4 complex in the central compartment based on target occupancy principle. The integrated GIP-GLP1-glucagon-glucose-insulin system contains five indirect response models as the "skeleton" structure with 12 feedback loops incorporated within the glucose control system. Our model adequately characterized the substantial nonlinear PK of linagliptin, time course of DPP-4 inhibition, as well as the kinetics of GIP, GLP-1, glucagon and glucose simultaneously in human. Our model provided valuable insights on linagliptin pharmacokinetics/pharmacodynamics and complicated glucose homeostasis. Since the glucose regulation modeling framework within the QSP model is "drug-independent", our model can be easily adopted by others to evaluate the effect of other DPP-4 inhibitors on glucose control system. In addition, our QSP model, which contains more components than other reported glucose regulation models, can potentially be used to evaluate the effect of combination antidiabetic therapy targeting different components of glucose control system.
ESTHER : Wu_2023_J.Pharm.Sci__
PubMedSearch : Wu_2023_J.Pharm.Sci__
PubMedID: 37716531

Title : Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones - Yi_2023_Plant.Physiol__
Author(s) : Yi F , An G , Song A , Cheng K , Liu J , Wang C , Wu S , Wang P , Zhu J , Liang Z , Chang Y , Chu Z , Cai C , Zhang X , Chen A , Xu J , Burritt DJ , Herrera-Estrella L , Tran LP , Li W , Cai Y
Ref : Plant Physiol , : , 2023
Abstract : Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.
ESTHER : Yi_2023_Plant.Physiol__
PubMedSearch : Yi_2023_Plant.Physiol__
PubMedID: 36718522

Title : Thiobencarb induces phenotypic abnormalities, apoptosis, and cardiovascular toxicity in zebrafish embryos through oxidative stress and inflammation - An_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_261_109440
Author(s) : An G , Park J , Lim W , Song G
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 261 :109440 , 2022
Abstract : Thiobencarb is a representative herbicide used on rice paddies. Because thiobencarb is used extensively on agricultural lands, especially on paddy fields, there is a high risk of unintended leaks into aquatic ecosystems. For this reason, several studies have investigated and reported on the toxicity of thiobencarb to aquatic species. In European eels, thiobencarb affected acetylcholinesterase levels in plasma and impaired adenosine triphosphatase activity in their gills. In medaka, thiobencarb-exposed embryos showed lower viability. However, molecular mechanisms underlying thiobencarb-mediated embryotoxicity have yet to be clarified. Therefore, the objective of our study was to investigate its mechanism of toxicity using zebrafish embryos. The viability of zebrafish embryos decreased upon exposure to thiobencarb and various phenotypic abnormalities were observed at concentrations lower than the lethal dose. The developmental toxicity of thiobencarb was mediated by pro-inflammatory cytokines (il1b, cxcl8, cxcl18b, and cox2a) and excessive generation of reactive oxygen species due to the downregulation of genes such as catalase, sod1, and sod2, which encode antioxidant enzymes. In addition, severe defects of the cardiovascular system were identified in response to thiobencarb exposure. Specifically, deformed cardiac looping, delayed common cardinal vein (CCV) regression, and interrupted dorsal aorta (DA)-posterior cardinal vein (PCV) segregation were observed. Our results provide an essential resource that demonstrates molecular mechanisms underlying the toxicity of thiobencarb on non-target organisms, which may contribute to the establishment of a mitigation strategy.
ESTHER : An_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_261_109440
PubMedSearch : An_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_261_109440
PubMedID: 35961533

Title : Target-Mediated Drug Disposition-A Class Effect of Soluble Epoxide Hydrolase Inhibitors - An_2021_J.Clin.Pharmacol_61_531
Author(s) : An G , Lee KSS , Yang J , Hammock BD
Ref : Journal of Clinical Pharmacology , 61 :531 , 2021
Abstract : Pharmacological target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TMDD can also happen in small-molecule compounds, it has been largely overlooked. In this mini-review, we summarize the occurrence of TMDD that we discovered recently in a series of small-molecule soluble epoxide hydrolase (sEH) inhibitors. Our journey started with an accidental discovery of target-mediated kinetics of 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU), a potent sEH inhibitor, in a pilot clinical study. To confirm what we observed in humans, we conducted a series of mechanism experiments in animals, including pharmacokinetic experiments using sEH knockout mice as well as in vivo displacement experiments with co-administration of another potent sEH inhibitor. Our mechanism studies confirmed that the TMDD of TPPU is due to its pharmacological target sEH. We further expanded our evaluation to various other sEH inhibitors and found that TMDD is a class effect of this group of small-molecule sEH inhibitors. In addition to summarizing the occurrence of TMDD in sEH inhibitors, in this mini-review we also highlighted the importance of recognizing TMDD of small-molecule compounds and its impact in clinical development as well as using pharmacometric modeling in facilitating quantitative understanding of TMDD.
ESTHER : An_2021_J.Clin.Pharmacol_61_531
PubMedSearch : An_2021_J.Clin.Pharmacol_61_531
PubMedID: 33078430

Title : The negative regulator SMAX1 controls mycorrhizal symbiosis and strigolactone biosynthesis in rice - Choi_2020_Nat.Commun_11_2114
Author(s) : Choi J , Lee T , Cho J , Servante EK , Pucker B , Summers W , Bowden S , Rahimi M , An K , An G , Bouwmeester HJ , Wallington EJ , Oldroyd G , Paszkowski U
Ref : Nat Commun , 11 :2114 , 2020
Abstract : Most plants associate with beneficial arbuscular mycorrhizal (AM) fungi that facilitate soil nutrient acquisition. Prior to contact, partner recognition triggers reciprocal genetic remodelling to enable colonisation. The plant Dwarf14-Like (D14L) receptor conditions pre-symbiotic perception of AM fungi, and also detects the smoke constituent karrikin. D14L-dependent signalling mechanisms, underpinning AM symbiosis are unknown. Here, we present the identification of a negative regulator from rice, which operates downstream of the D14L receptor, corresponding to the homologue of the Arabidopsis thaliana Suppressor of MAX2-1 (AtSMAX1) that functions in karrikin signalling. We demonstrate that rice SMAX1 is a suppressor of AM symbiosis, negatively regulating fungal colonisation and transcription of crucial signalling components and conserved symbiosis genes. Similarly, rice SMAX1 negatively controls strigolactone biosynthesis, demonstrating an unexpected crosstalk between the strigolactone and karrikin signalling pathways. We conclude that removal of SMAX1, resulting from D14L signalling activation, de-represses essential symbiotic programmes and increases strigolactone hormone production.
ESTHER : Choi_2020_Nat.Commun_11_2114
PubMedSearch : Choi_2020_Nat.Commun_11_2114
PubMedID: 32355217

Title : Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis - Cai_2020_Plant.Biotechnol.J_18_814
Author(s) : Cai Y , Cai X , Wang Q , Wang P , Zhang Y , Cai C , Xu Y , Wang K , Zhou Z , Wang C , Geng S , Li B , Dong Q , Hou Y , Wang H , Ai P , Liu Z , Yi F , Sun M , An G , Cheng J , Shi Q , Xie Y , Shi X , Chang Y , Huang F , Chen Y , Hong S , Mi L , Sun Q , Zhang L , Zhou B , Peng R , Zhang X , Liu F
Ref : Plant Biotechnol J , 18 :814 , 2020
Abstract : The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes.
ESTHER : Cai_2020_Plant.Biotechnol.J_18_814
PubMedSearch : Cai_2020_Plant.Biotechnol.J_18_814
PubMedID: 31479566
Gene_locus related to this paper: gosra-a0a0d2pzd7

Title : Complete Genome Sequence of Fish Pathogen Aeromonas hydrophila JBN2301 - Yang_2016_Genome.Announc_4_
Author(s) : Yang W , Li N , Li M , Zhang D , An G
Ref : Genome Announc , 4 : , 2016
Abstract : Aeromonas hydrophila is one of the most important fish pathogens in China. Here, we report complete genome sequence of a virulent strain, A. hydrophila JBN2301, which was isolated from diseased crucian carp.
ESTHER : Yang_2016_Genome.Announc_4_
PubMedSearch : Yang_2016_Genome.Announc_4_
PubMedID: 26823580
Gene_locus related to this paper: aerhy-a0a0s3bhm4

Title : Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak - Olivas_2012_PLoS.One_7_e44326
Author(s) : Olivas AD , Shogan BD , Valuckaite V , Zaborin A , Belogortseva N , Musch M , Meyer F , Trimble WL , An G , Gilbert J , Zaborina O , Alverdy JC
Ref : PLoS ONE , 7 :e44326 , 2012
Abstract : The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high ( approximately 10%) even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; p<0.01) when colonized by P. aeruginosa compared to radiated tissues alone (0%). Phenotype analysis comparing the original inoculating strain (MPAO1- termed P1) and the strain retrieved from leaking anastomotic tissues (termed P2) demonstrated that P2 was altered in pyocyanin production and displayed enhanced collagenase activity, high swarming motility, and a destructive phenotype against cultured intestinal epithelial cells (i.e. apoptosis, barrier function, cytolysis). Comparative genotype analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP) mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that in vivo transformation of microbial pathogens to a tissue destroying phenotype may have important implications in the pathogenesis of anastomotic leak.
ESTHER : Olivas_2012_PLoS.One_7_e44326
PubMedSearch : Olivas_2012_PLoS.One_7_e44326
PubMedID: 22952955
Gene_locus related to this paper: pseae-PA1558 , pseae-PA2927 , pseae-PA2949 , pseae-PA3695 , pseae-PA5080 , pseae-q9i252

Title : The Rice Annotation Project Database (RAP-DB): 2008 update - Tanaka_2008_Nucleic.Acids.Res_36_D1028
Author(s) : Tanaka T , Antonio BA , Kikuchi S , Matsumoto T , Nagamura Y , Numa H , Sakai H , Wu J , Itoh T , Sasaki T , Aono R , Fujii Y , Habara T , Harada E , Kanno M , Kawahara Y , Kawashima H , Kubooka H , Matsuya A , Nakaoka H , Saichi N , Sanbonmatsu R , Sato Y , Shinso Y , Suzuki M , Takeda J , Tanino M , Todokoro F , Yamaguchi K , Yamamoto N , Yamasaki C , Imanishi T , Okido T , Tada M , Ikeo K , Tateno Y , Gojobori T , Lin YC , Wei FJ , Hsing YI , Zhao Q , Han B , Kramer MR , McCombie RW , Lonsdale D , O'Donovan CC , Whitfield EJ , Apweiler R , Koyanagi KO , Khurana JP , Raghuvanshi S , Singh NK , Tyagi AK , Haberer G , Fujisawa M , Hosokawa S , Ito Y , Ikawa H , Shibata M , Yamamoto M , Bruskiewich RM , Hoen DR , Bureau TE , Namiki N , Ohyanagi H , Sakai Y , Nobushima S , Sakata K , Barrero RA , Souvorov A , Smith-White B , Tatusova T , An S , An G , S OO , Fuks G , Messing J , Christie KR , Lieberherr D , Kim H , Zuccolo A , Wing RA , Nobuta K , Green PJ , Lu C , Meyers BC , Chaparro C , Piegu B , Panaud O , Echeverria M
Ref : Nucleic Acids Research , 36 :D1028 , 2008
Abstract : The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: and
ESTHER : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedSearch : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedID: 18089549
Gene_locus related to this paper: orysa-Q9FW17 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q5N7L1 , orysa-pir7a , orysa-q2qyj1 , orysj-q6yse8 , orysa-q6yzk1 , orysa-Q8S0U8 , orysa-q33aq0 , orysa-Q0J0A4 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-b9fkb0 , orysj-cgep , orysj-q0djj0 , orysj-q0dud7 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1 , orysj-pla4 , orysj-pla1