He Y

References (113)

Title : A commentary on The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs -
Author(s) : He Y , Jiang Z , Zhang Y
Ref : Int J Surg , : , 2024
PubMedID: 38768040

Title : Neurotoxicities induced by micro\/nanoplastics: A review focusing on the risks of neurological diseases - Liu_2024_J.Hazard.Mater_469_134054
Author(s) : Liu S , He Y , Yin J , Zhu Q , Liao C , Jiang G
Ref : J Hazard Mater , 469 :134054 , 2024
Abstract : Pollution of micro/nano-plastics (MPs/NPs) is ubiquitously prevalent in the environment, leading to an unavoidable exposure of the human body. Despite the protection of the blood-brain barrier, MPs/NPs can be transferred and accumulated in the brain, which subsequently exert negative effects on the brain. Nevertheless, the potential neurodevelopmental and/or neurodegenerative risks of MPs/NPs remain largely unexplored. In this review, we provide a systematic overview of recent studies related to the neurotoxicity of MPs/NPs. It covers the environmental hazards and human exposure pathways, translocation and distribution into the brain, the neurotoxic effects, and the possible mechanisms of environmental MPs/NPs. MPs/NPs are widely found in different environment matrices, including air, water, soil, and human food. Ambient MPs/NPs can enter the human body by ingestion, inhalation and dermal contact, then be transferred into the brain via the blood circulation and nerve pathways. When MPs/NPs are present in the brain, they can initiate a series of molecular or cellular reactions that may harm the blood-brain barrier, cause oxidative stress, trigger inflammatory responses, affect acetylcholinesterase activity, lead to mitochondrial dysfunction, and impair autophagy. This can result in abnormal protein folding, loss of neurons, disruptions in neurotransmitters, and unusual behaviours, ultimately contributing to the initiation and progression of neurodegenerative changes and neurodevelopmental abnormalities. Key challenges and further research directions are also proposed in this review as more studies are needed to focus on the potential neurotoxicity of MPs/NPs under realistic conditions.
ESTHER : Liu_2024_J.Hazard.Mater_469_134054
PubMedSearch : Liu_2024_J.Hazard.Mater_469_134054
PubMedID: 38503214

Title : Treatment of Organophosphorus Poisoning with 6-Alkoxypyridin-3-ol Quinone Methide Precursors: Resurrection of Methylphosphonate-Aged Acetylcholinesterase - Clay_2024_Chem.Res.Toxicol__
Author(s) : Clay WK , Buck AK , He Y , Hernandez Sanchez DN , Ward NA , Lear JM , Nguyen KQ , Clark BH , Sapia RJ , Lalisse RF , Sriraman A , Cadieux CL , McElroy CA , Callam CS , Hadad CM
Ref : Chemical Research in Toxicology , : , 2024
Abstract : Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.2 min, so immediate recovery (resurrection) of OP-aged AChE is needed. In 2018, we showed pyridin-3-ol-based quinone methide precursors (QMPs) can resurrect OP-aged electric eel AChE in vitro, achieving 2% resurrection after 24 h of incubation (pH 7, 4 mM). We prepared 50 unique 6-alkoxypyridin-3-ol QMPs with 10 alkoxy groups and five amine leaving groups to improve AChE resurrection. These compounds are predicted in silico to cross the blood-brain barrier and treat AChE in the central nervous system. This library resurrected 7.9% activity of OP-aged recombinant human AChE after 24 h at 250 microM, a 4-fold increase from our 2018 report. The best QMP (1b), with a 6-methoxypyridin-3-ol core and a diethylamine leaving group, recovered 20.8% (1 mM), 34% (4 mM), and 42.5% (predicted maximum) of methylphosphonate-aged AChE activity over 24 h. Seven QMPs recovered activity from AChE aged with Soman and a VX degradation product (EA-2192). We hypothesize that QMPs form the quinone methide (QM) to realkylate the phosphylated serine residue as the first step of resurrection. We calculated thermodynamic energetics for QM formation, but there was no trend with the experimental biochemical data. Molecular docking studies revealed that QMP binding to OP-aged AChE is not the determining factor for the observed biochemical trends; thus, QM formation may be enzyme-mediated.
ESTHER : Clay_2024_Chem.Res.Toxicol__
PubMedSearch : Clay_2024_Chem.Res.Toxicol__
PubMedID: 38556765

Title : Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders - Liu_2024_Brain__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev YV , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski MR , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent AL , Siskind CE , Traboulsi EI , Blackstone C , Sisk RA , Miraldi Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Brain , : , 2024
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2024_Brain__
PubMedSearch : Liu_2024_Brain__
PubMedID: 38735647

Title : LET-767 determines lipid droplet protein targeting and lipid homeostasis - Fu_2024_J.Cell.Biol_223_
Author(s) : Fu L , Zhang J , Wang Y , Wu H , Xu X , Li C , Li J , Liu J , Wang H , Jiang X , Li Z , He Y , Liu P , Wu Y , Zou X , Liang B
Ref : Journal of Cell Biology , 223 : , 2024
Abstract : Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.
ESTHER : Fu_2024_J.Cell.Biol_223_
PubMedSearch : Fu_2024_J.Cell.Biol_223_
PubMedID: 38551495

Title : Preclinical Evaluation of the Reversible Monoacylglycerol Lipase PET Tracer (R)-[(11) C]YH132: Application in Drug Development and Neurodegenerative Diseases - He_2024_Chembiochem__e202300819
Author(s) : He Y , Delparente A , Jie C , Keller C , Humm R , Heer D , Collin L , Schibli R , Gobbi L , Grether U , Mu L
Ref : Chembiochem , :e202300819 , 2024
Abstract : Monoacylglycerol lipase (MAGL) plays a crucial role in the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids in the brain. Inhibiting MAGL could lead to increased levels of 2-AG, which showed beneficial effects on pain management, anxiety, inflammation, and neuroprotection. In the current study, we report the characterization of an enantiomerically pure (R)-[(11) C]YH132 as a novel MAGL PET tracer. It demonstrates an improved pharmacokinetic profile compared to its racemate. High invitro MAGL specificity of (R)-[(11) C]YH132 was confirmed by autoradiography studies using mouse and rat brain sections. In vivo, (R)-[(11) C]YH132 displayed a high brain penetration, and high specificity and selectivity toward MAGL by dynamic PET imaging using MAGL knockout and wild-type mice. Pretreatment with a MAGL drug candidate revealed a dose-dependent reduction of (R)-[(11) C]YH132 accumulation in WT mouse brains. This result validates its utility as a PET probe to assist drug development. Moreover, its potential application in neurodegenerative diseases was explored by invitro autoradiography using brain sections from animal models of Alzheimer's disease and Parkinson's disease.
ESTHER : He_2024_Chembiochem__e202300819
PubMedSearch : He_2024_Chembiochem__e202300819
PubMedID: 38441502

Title : Identification of metabolizing enzyme genes associated with xenobiotics and odorants in the predatory stink bug Arma custos based on transcriptome analysis - Li_2023_Heliyon_9_e18657
Author(s) : Li W , Zou J , Yang X , Yang M , Jiang P , Wang X , Huang C , He Y
Ref : Heliyon , 9 :e18657 , 2023
Abstract : The predatory stink bug, Arma custos, is a highly effective beneficial predator of crop pests. The lack of gene information related to xenobiotic detoxification and odorant degrading enzymes in the predator stink bugs to date has limited our ability for more in-depth studies of biological control. Hence, we conducted de novo assembly of the A. custos transcriptome from guts, antennae, and other tiussue samples of 5th instar larvae using Illumina sequencing technology. A total of 91, 50 and 23 genes of cytochrome P450 monooxygenases (CYPs), carboxyl/choline esterases (CCEs) and glutathione S-transferases (GSTs) genes were identified, respectively. Gene expansions of CYP3 and CYP4 clans and the hormone and pheromone processing CCE class were found in A. custos. Analysis of tissue-specific expression patterns showed that 37 CYPs, 14 CCEs and 8 GSTs were enriched in guts, and 6 CYPs, 5 CCEs and 2 GSTs were up-regulated in antennae, suggesting their potential roles on xenobiotics detoxification and ordorant degradation. Gene information data presented here could be useful for a deeper understanding of the ecology, physiology and behavior of this beneficial species and could be helpful to improve their bio-control efficiency.
ESTHER : Li_2023_Heliyon_9_e18657
PubMedSearch : Li_2023_Heliyon_9_e18657
PubMedID: 37576196

Title : Secondary Metabolites from the Coral-Derived Fungus Aspergillus austwickii SCSIO41227 with Pancreatic Lipase and Neuraminidase Inhibitory Activities - Chen_2023_Mar.Drugs_21_
Author(s) : Chen Y , He Y , Pang X , Zhou X , Liu Y , Yang B
Ref : Mar Drugs , 21 : , 2023
Abstract : The coral-derived fungus Aspergillus austwickii SCSIO41227 from Beibu Gulf yielded four previously uncharacterized compounds, namely asperpentenones B-E (1-4), along with twelve known compounds (5-16). Their structures were elucidated using HRESIMS and NMR ((1)H and (13)C NMR, HSQC, HMBC), among which the stereo-structure of compounds 1-3 was determined by calculated ECD. Furthermore, compounds 1-16 were evaluated in terms of their enzyme (acetylcholinesterase (AChE), pancreatic lipase (PL), and neuraminidase (NA)) inhibitory activities. These bioassay results revealed that compounds 2 and 14 exerted noticeable NA inhibitory effects, with IC(50) values of 31.28 and 73.64 microM, respectively. In addition, compound 3 exhibited a weak inhibitory effect against PL. Furthermore, these compounds showed the potential of inhibiting enzymes in silico docking analysis to demonstrate the interactions between compounds and proteins.
ESTHER : Chen_2023_Mar.Drugs_21_
PubMedSearch : Chen_2023_Mar.Drugs_21_
PubMedID: 37999391

Title : Role of cholinergic innervation in biliary remnants of patients with biliary atresia - Yang_2023_Front.Pediatr_11_1278978
Author(s) : Yang J , Chen X , Wang W , Su Y , Liu K , Abudusalamu A , Li D , He Y , Wang P , Xiong X , Feng J
Ref : Front Pediatr , 11 :1278978 , 2023
Abstract : OBJECTIVE: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. METHODS: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. RESULTS: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R(2 )= 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). CONCLUSIONS: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
ESTHER : Yang_2023_Front.Pediatr_11_1278978
PubMedSearch : Yang_2023_Front.Pediatr_11_1278978
PubMedID: 38259596

Title : Combined exposure to titanium dioxide and tetracycline induces neurotoxicity in zebrafish - Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
Author(s) : Xu L , Yang X , He Y , Hu Q , Fu Z
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109562 , 2023
Abstract : In aquatic environment, engineered materials may inevitably interact with the coexisted organic pollutants, which affect their bioavailability and toxicity. In this contribution, the combined impacts of tetracycline (TC) and titanium dioxide nanoparticles (TiO(2) NPs) on the neurodevelopment of zebrafish larvae were investigated, and the underlying mechanisms were further elucidated. Firstly, it was confirmed that the co-existence of TC would increase the size and decrease the zeta potential of TiO(2) NPs. Following, developmental indicators and motor behaviors were investigated. Our results indicated that co-exposure to TC and TiO(2) NPs exhibited enhanced embryonic malformation rates and abnormal nervous system development in zebrafish embryos. Meanwhile, the locomotor behavior was increased upon treatment of TC and TiO(2) NP. Further, pathway enrichment analyses of transcriptomic sequencing provided detailed information that either lipid metabolism or PPAR signaling pathway were significantly affected in the co-exposure group. Also, TC + TiO(2) NP exposure significantly changed the mRNA expression of neural development-related genes and up-regulated the expression levels of neurotransmitters like 5-hydroxytryptamine, dopamine, acetylcholinesterase, and gamma-aminobutyric acid. Taken together, our results demonstrated that the co-exposure of TC and TiO(2) NPs had the potential to cause neurotoxicity in zebrafish embryos.
ESTHER : Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
PubMedSearch : Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
PubMedID: 36764589

Title : Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders - Liu_2023_bioRxiv__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev Y , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski M , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent A , Siskind CE , Traboulsi EI , Blackstone C , Sisk R , Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Biorxiv , : , 2023
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. PNPLA6 encodes Neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a clinical meta-analysis of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 10 variants as likely pathogenic and 36 variants as pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship and the generation of a preclinical animal model pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2023_bioRxiv__
PubMedSearch : Liu_2023_bioRxiv__
PubMedID: 37333224

Title : Citrobacter sp. Y3 harbouring novel gene HBCD-hd-1 mineralizes hexabromocyclododecane via new metabolic pathways according to multi-omics characterization - Peng_2023_J.Hazard.Mater_442_130071
Author(s) : Peng X , Li T , Zheng Q , Lu Y , He Y , Tang Y , Qiu R
Ref : J Hazard Mater , 442 :130071 , 2023
Abstract : Hexabromocyclododecane (HBCD) is a typical persistent organic pollutant that is widely detected in the environment. Despite the significant efforts put into its mineralisation, there is still a lack of microorganism resources that can completely mineralise HBCD. Stable isotope analysis revealed that the Citrobacter sp. Y3 can use [(13)C]HBCD as its sole carbon source and degrade or even mineralise it into (13)CO(2), with a maximum conversion rate of 100% in approximately 14 days. Strain Y3 could completely mineralise HBCD, which it used as its only carbon source, and six debromination enzymes related to HBCD degradation were found in Y3, including haloalkane dehalogenase (DhaA), haloacid dehalogenase (HAD), etc. A functional gene named HBCD-hd-1, encoding a HAD, was found to be upregulated during HBCD degradation and heterologously expressed in Escherichia coli. Recombinant E. coli with the HBCD-hd-1 gene transformed the typical intermediate 4-bromobutyric acid to 4-hydroxybutanoic acid and showed excellent degradation performance on HBCD, accompanied by nearly 100% bromine (Br) ion generation. The expression of HBCD-hd-1 in Y3 rapidly accelerated the biodegradation of HBCD. With HBCD as its sole carbon source, strain Y3 could potentially degrade HBCD, especially in a low-nutrient environment.
ESTHER : Peng_2023_J.Hazard.Mater_442_130071
PubMedSearch : Peng_2023_J.Hazard.Mater_442_130071
PubMedID: 36183513

Title : Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhou_2023_J.Enzyme.Inhib.Med.Chem_38_2231661
Author(s) : Zhou Y , He Y , Teng X , Mi J , Yang J , Wei R , Liu W , Ma Q , Tan Z , Sang Z
Ref : J Enzyme Inhib Med Chem , 38 :2231661 , 2023
Abstract : Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC(50) = 0.53 microM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.
ESTHER : Zhou_2023_J.Enzyme.Inhib.Med.Chem_38_2231661
PubMedSearch : Zhou_2023_J.Enzyme.Inhib.Med.Chem_38_2231661
PubMedID: 37414563

Title : The roles of serine hydrolases and serum albumin in alisol B 23-acetate hydrolysis in humans - Zhang_2023_Front.Pharmacol_14_1160665
Author(s) : Zhang T , Zhang F , Zhang Y , Li H , Zhu G , Weng T , Huang C , Wang P , He Y , Hu J , Ge G
Ref : Front Pharmacol , 14 :1160665 , 2023
Abstract : Introduction: Alisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (Rhizoma Alismatis), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects. Methods: The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level. Results: AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis via its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect. Discussion: This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.
ESTHER : Zhang_2023_Front.Pharmacol_14_1160665
PubMedSearch : Zhang_2023_Front.Pharmacol_14_1160665
PubMedID: 37089921

Title : Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats - Zeng_2023_Scand.J.Rheumatol__1
Author(s) : Zeng M , Issotina Zibrila A , Li X , Liu X , Wang X , Zeng Z , Wang Z , He Y , Meng L , Liu J
Ref : Scand J Rheumatol , :1 , 2023
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
ESTHER : Zeng_2023_Scand.J.Rheumatol__1
PubMedSearch : Zeng_2023_Scand.J.Rheumatol__1
PubMedID: 37339380

Title : Mechanism of the Change in the Intestinal Microbiota of C-Strain Spodoptera frugiperda (Lepidoptera: Noctuidae) after an Interspecific Transference between Rice and Corn - Di_2023_Microorganisms_11_
Author(s) : Di T , Li Y , Du G , He Y , Wang W , Shen Y , Meng J , Xiao W , Xiao G , Chen B
Ref : Microorganisms , 11 : , 2023
Abstract : Spodoptera frugiperda (J.E.Smith) (Lepidoptera: Noctuidae) was first found in 2019 in Yunnan, China, and it was characterized as a corn strain; it was also found on rice strains there, and it damages rice in China, but little is known about the effect of host plant transfer on the intestinal microbiota and the activities of detoxification enzymes in the C-strain (corn strain) S. frugiperda. The intestinal microbiota and the protective enzyme activity of S. frugiperda that were transferred from rice plants were assessed, and the fourth generation of insects transferred from corn were studied; the gene types of S. frugiperda that were transferred from rice plants were tested using mitochondrial Tpi gene sequences. The results showed that the intestinal microbiota in the C-strain S. frugiperda were changed after the host transference, and the diversity and richness of the intestinal bacterial communities of the S. frugiperda feeding on rice were significantly reduced after the transfer of the host from corn. The predominant species of intestinal bacteria of the S. frugiperda on rice transferred from corn were Enterococcus and Enterobacter, with relative abundances of 28.7% and 66.68%; the predominant species of intestinal bacteria of the S. frugiperda that were transferred from rice and feeding on corn were Enterococcus (22.35%) and Erysipelatoclostridium (73.92%); and the predominant species of intestinal bacteria of S. frugiperda feeding on corn was Enterococcus, with a relative abundance of 61.26%. The CAT (catalase) activity of the S. frugiperda transferred from corn onto rice from corn was reduced, the POD (peroxidase) activity was significantly increased after the transfer from corn, and no significant variations were found for the SOD (superoxide dismutase), CarE (carboxylesterase), and GST (glutathione S-transferase) activities of S. frugiperda after the host plant transfer. The results showed that after feeding on rice, the activities of CAT and POD in the in S. frugiperda body changed in order to resist plant secondary metabolites from corn or rice, but there was no significant change in the detoxification enzymes in the body. In summary, switching the host plant between corn and rice induced variations in the intestinal microbiota in C-strain S. frugiperda owing to the strain difference between the C-strain and the R-strain (rice strain), and this was consistent with the results of the activities of detoxification enzymes. The results indicat that changes in intestinal microbiota and physiological enzymes may be important reasons for the adaptive capacity of C-strain S. frugiperda to rice.
ESTHER : Di_2023_Microorganisms_11_
PubMedSearch : Di_2023_Microorganisms_11_
PubMedID: 37894172

Title : Proof-of-concept optimization of a copper-mediated (18)F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation - Lu_2023_Lab.Chip__
Author(s) : Lu Y , He Y , Schibli R , Mu L , van Dam RM
Ref : Lab Chip , : , 2023
Abstract : Copper-mediated radiofluorination has demonstrated remarkable potential in forming aromatic C-(18)F bonds of radioligands for positron emission tomography (PET). Achieving optimal results often requires optimization efforts, requiring a substantial amount of radiolabeling precursor and time, severely limiting the experimental throughput. Recently, we successfully showcased the feasibility of performing and optimizing Cu-mediated radiosynthesis on a high-throughput microdroplet platform using the well-known and clinically used radioligand [(18)F]FDOPA as an illustrative example. In our current work, we optimized the Cu-mediated synthesis of a novel monoacylglycerol lipase (MAGL) PET tracer ([(18)F]YH149), showing the versatility of droplet-based techniques for early stage tracer development. Across 5 days, we conducted a total of 117 experiments, studying 36 distinct conditions, while utilizing <15 mg of total organoboron precursor. Compared to the original report in which the radiochemical yield (RCY) was 4.4 +/- 0.5% (n = 5), the optimized droplet condition provided a substantial improvement in RCY (52 +/- 8%, n = 4) and showed excellent radiochemical purity (100%) and molar activity (77-854 GBq micromol(-1)), using a starting activity of 0.2-1.45 GBq. Furthermore, we showed for the first time a translation of the optimized microscale conditions to a vial-based method. With similar starting activity (0.2-1.44 GBq), the translated synthesis exhibited a comparable RCY of 50 +/- 10% (n = 4) while maintaining excellent radiochemical purity (100%) and acceptable molar activity (20-46 GBq micromol(-1)). The successful translation to vial-based reactions ensures wider applicability of the optimized synthesis by leveraging widely available commercial vial-based synthesis modules.
ESTHER : Lu_2023_Lab.Chip__
PubMedSearch : Lu_2023_Lab.Chip__
PubMedID: 37818614

Title : Impact of Donepezil Supplementation on Alzheimer's Disease-like Pathology and Gut Microbiome in APP\/PS1 Mice - Li_2023_Microorganisms_11_
Author(s) : Li Y , Wu M , Kong M , Sui S , Wang Q , He Y , Gu J
Ref : Microorganisms , 11 : , 2023
Abstract : Based on published information, the occurrence and development of Alzheimer's disease (AD) are potentially related to gut microbiota changes. Donepezil hydrochloride (DH), which enhances cholinergic activity by blocking acetylcholinesterase (AChE), is one of the first-line drugs for AD treatment approved by the Food and Drug Administration (FDA) of the USA. However, the potential link between the effects of DH on the pathophysiological processes of AD and the gut microbiota remains unclear. In this study, pathological changes in the brain and colon, the activities of superoxide dismutase (SOD) and AChE, and changes in intestinal flora were observed. The results showed that Abeta deposition in the prefrontal cortex and hippocampus of AD mice was significantly decreased, while colonic inflammation was significantly alleviated by DH treatment. Concomitantly, SOD activity was significantly improved, while AChE was significantly reduced after DH administration. In addition, the gut microbiota community composition of AD mice was significantly altered after DH treatment. The relative abundance of Akkermansia in the AD group was 54.8% higher than that in the N group. The relative abundance of Akkermansia was increased by 18.3% and 53.8% in the AD_G group and the N_G group, respectively. Interestingly, Akkermansia showed a potential predictive value and might be a biomarker for AD. Molecular docking revealed the binding mode and major forces between DH and membrane proteins of Akkermansia. The overall results suggest a novel therapeutic mechanism for treating AD and highlight the critical role of gut microbiota in AD pathology.
ESTHER : Li_2023_Microorganisms_11_
PubMedSearch : Li_2023_Microorganisms_11_
PubMedID: 37764150

Title : Influence of Cry1Ab protein on growth and development of a predatory spider, Pardosa pseudoannulata, from protective perspectives - He_2023_Ecotoxicol.Environ.Saf_269_115799
Author(s) : He Y , Lv B , Chao Y , Tang YE , Wang J , Wang Z , Peng YD
Ref : Ecotoxicology & Environmental Safety , 269 :115799 , 2023
Abstract : The expression of Cry proteins in genetically modified rice varieties safeguards the crop from lepidopteran pests. These proteins have the potential to be transferred through the food chain to arthropods like planthoppers and predatory spiders, triggering defensive responses in these unintended organisms. Hence, we hypothesized that Cry protein might influence the growth and development of spiders by altering protective enzyme activities. The results showed that Cry1Ab protein could accumulate in tissues and subcellular organelles of Pardosa pseudoannulata from Nilaparvata lugens. Cry1Ab protein exposure prolonged the developmental duration in the 5th and 7th instar spiderlings but induced no alterations of other growth indicators, such as body length, median ocular area, and survival rate. In addition, Cry1Ab protein exerted no adverse impacts on several detoxifying enzymes (i.e., superoxide dismutase, catalase, glutathione peroxidase, and acetylcholine esterase) in muscle, midgut, ganglia, and hemolymph at subcellular components (i.e., microsome and cytoplasm). To further explore the effects of Cry1Ab protein on the spiderlings, we performed an integrated transcriptome analysis on spiderlings exposed to Cry1Ab protein. The results showed that Cry1Ab protein might prolong the development duration of P. pseudoannulata via the altered cuticle metabolism (e.g., chitin metabolic process and structural constituent of cuticle). In addition, the gene expression profile associated with detoxifying enzymes and three stress-responsive pathways (JAK/STAT, JNK/SAPK, and Hippo pathways) also displayed no significant alterations under Cry1Ab exposure. Collectively, this integrated analysis generates multidimensional insights to assess the effects of Cry1Ab protein on non-target spiders and demonstrates that Cry1Ab protein exerts no toxicity in P. pseudoannulata.
ESTHER : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedSearch : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedID: 38070414

Title : Enantioselective Metabolism of Fenpropathrin Enantiomers by carboxyl\/choline esterase 6 (CCE06) in Tetranychus cinnabarinus - Yang_2023_Pest.Manag.Sci__
Author(s) : Yang F , Ran L , He Y , Xu Z , He L , Zhang P
Ref : Pest Manag Sci , : , 2023
Abstract : BACKGROUND: Tetranychus cinnabarinus is a polyphagous pest mite commonly found in agriculture. As an excellent acaricide, fenpropathrin (FEN) is frequently used to control T. cinnabarinus in agriculture. However, commercial FEN is a racemate with two enantiomers, R-FEN and S-FEN. Considering that investigations on the metabolism of FEN by T. cinnabarinus are based on racemate FEN, it is important to investigate the enantioselective metabolism of FEN in T. cinnabarinus. RESULTS: S-FEN was more toxic to T. cinnabarinus than R-FEN by more than 68.8-fold. Moreover, the synergist bioassay revealed that carboxylesterase and cytochrome P450 were the primary enzymes engaged in the detoxification of FEN in T. cinnabarinus, with carboxylesterase playing a leading role. Seven genes were substantially different after the induction of S-FEN and R-FEN, respectively. TcCCE06 was screened and selected as a key gene that related to FEN metabolism in T. cinnabarinus. The metabolic results showed that the recombinant TcCCE06 effectively metabolized 32.1% of the R-FEN and 13.8% of the S-FEN within 4 hours of incubation. Moreover, R-FEN was demonstrated a higher affinity for the TcCCE06 protein than S-FEN based on molecular docking. CONCLUSION: Our results indicated that TcCCE06 mediates the enantioselective metabolism of FEN in T. cinnabarinus. Our findings will contribute to a more comprehensive understanding of the mechanisms underlying the differential toxicity of the FEN enantiomers against T. cinnabarinus. Furthermore, it also provides a new perspective for the development of enantiomer-enriched acaricides with higher activity and lower pesticide dosage and pollution risks. This article is protected by copyright. All rights reserved.
ESTHER : Yang_2023_Pest.Manag.Sci__
PubMedSearch : Yang_2023_Pest.Manag.Sci__
PubMedID: 37948435
Gene_locus related to this paper: tetur-t1jsk0

Title : Comparison of in vivo pharmacokinetic behaviors of R- and S-flurbiprofen after intravenous injection of flurbiprofen axetil - He_2023_Chirality__
Author(s) : He Y , Qin M , Li M , Zhi D , Tian B , Qin F
Ref : Chirality , : , 2023
Abstract : Flurbiprofen axetil (FA) is a prodrug of flurbiprofen (FP), and it is hydrolyzed to the active FP by carboxylesterase in plasma after intravenous injection. The pharmacological action of FP is closely related to its chirality, and S-FP shows better analgesic effects than R-FP. Therefore, it is of great significance to compare the in vivo pharmacokinetic behaviors of R-FP and S-FP. In this study, we designed a sensitive high performance liquid chromatography-tandem mass spectrometry method and used CHIRALPAK-IG3 column for chiral separation to quantify the concentrations of R-FP and S-FP in rat plasma. The results show that this method can accurately and effectively analyze the contents of R-FP and S-FP in plasma. In addition, the systemic exposure was approximately 3.09-folds for the S-FP compared with the R-FP following intravenous administration of the FA to rats at a single dose of 4.5 mg/kg. More importantly, the clearance rate of S-FP is significantly smaller than that of R-FP. Therefore, the development of S-FA injectable emulsion for clinical treatment of postoperative pain is very necessary.
ESTHER : He_2023_Chirality__
PubMedSearch : He_2023_Chirality__
PubMedID: 36759185

Title : Identification of (R)-[(18)F]YH134 for Monoacylglycerol Lipase Neuroimaging and Exploration of Its Use for Central Nervous System and Peripheral Drug Development - He_2023_J.Nucl.Med__
Author(s) : He Y , Kramer SD , Grether U , Wittwer MB , Collin L , Kuhn B , Topp A , Heer D , O'Hara F , Honer M , Pavlovic A , Richter H , Ritter M , Rombach D , Keller C , Gobbi L , Mu L
Ref : J Nucl Med , : , 2023
Abstract : This study aimed to evaluate (R)-[(18)F]YH134 as a novel PET tracer for imaging monoacylglycerol lipase (MAGL). Considering the ubiquitous expression of MAGL throughout the whole body, the impact of various MAGL inhibitors on (R)-[(18)F]YH134 brain uptake and its application in brain-periphery crosstalk were explored. Methods: MAGL knockout and wild-type mice were used to evaluate (R)-[(18)F]YH134 in in vitro autoradiography and PET experiments. To explore the impact of peripheral MAGL occupancy on (R)-[(18)F]YH134 brain uptake, PET kinetics with an arterial input function were studied in male Wistar rats under baseline and blocking conditions. Results: In in vitro autoradiography, (R)-[(18)F]YH134 revealed a heterogeneous distribution pattern with high binding to MAGL-rich brain regions in wild-type mouse brain slices, whereas the radioactive signal was negligible in MAGL knockout mouse brain slices. The in vivo brain PET images of (R)-[(18)F]YH134 in wild-type and MAGL knockout mice demonstrated its high specificity and selectivity in mouse brain. A Logan plot with plasma input function was applied to estimate the distribution volume (V (T)) of (R)-[(18)F]YH134. V (T) was significantly reduced by a brain-penetrant MAGL inhibitor but was unchanged by a peripherally restricted MAGL inhibitor. The MAGL target occupancy in the periphery was estimated using (R)-[(18)F]YH134 PET imaging data from the brain. Conclusion: (R)-[(18)F]YH134 is a highly specific and selective PET tracer with favorable kinetic properties for imaging MAGL in rodent brain. Our results showed that blocking of the peripheral target influences brain uptake but not the V (T) of (R)-[(18)F]YH134. (R)-[(18)F]YH134 can be used for estimating the dose of MAGL inhibitor at half-maximal peripheral target occupancy.
ESTHER : He_2023_J.Nucl.Med__
PubMedSearch : He_2023_J.Nucl.Med__
PubMedID: 38164615

Title : OsGELP77, a QTL for broad-spectrum disease resistance and yield in rice, encodes a GDSL-type lipase - Zhang_2023_Plant.Biotechnol.J__
Author(s) : Zhang M , Chen D , Tian J , Cao J , Xie K , He Y , Yuan M
Ref : Plant Biotechnol J , : , 2023
Abstract : Lipids and lipid metabolites have essential roles in plant-pathogen interactions. GDSL-type lipases are involved in lipid metabolism modulating lipid homeostasis. Some plant GDSLs modulate lipid metabolism altering hormone signal transduction to regulate host-defence immunity. Here, we functionally characterized a rice lipase, OsGELP77, promoting both immunity and yield. OsGELP77 expression was induced by pathogen infection and jasmonic acid (JA) treatment. Overexpression of OsGELP77 enhanced rice resistance to both bacterial and fungal pathogens, while loss-of-function of osgelp77 showed susceptibility. OsGELP77 localizes to endoplasmic reticulum and is a functional lipase hydrolysing universal lipid substrates. Lipidomics analyses demonstrate that OsGELP77 is crucial for lipid metabolism and lipid-derived JA homeostasis. Genetic analyses confirm that OsGELP77-modulated resistance depends on JA signal transduction. Moreover, population genetic analyses indicate that OsGELP77 expression level is positively correlated with rice resistance against pathogens. Three haplotypes were classified based on nucleotide polymorphisms in the OsGELP77 promoter where OsGELP77(Hap3) is an elite haplotype. Three OsGELP77 haplotypes are differentially distributed in wild and cultivated rice, while OsGELP77(Hap3) has been broadly pyramided for hybrid rice development. Furthermore, quantitative trait locus (QTL) mapping and resistance evaluation of the constructed near-isogenic line validated OsGELP77, a QTL for broad-spectrum disease resistance. In addition, OsGELP77-modulated lipid metabolism promotes JA accumulation facilitating grain yield. Notably, the hub defence regulator OsWRKY45 acts upstream of OsGELP77 by initiating the JA-dependent signalling to trigger immunity. Together, OsGELP77, a QTL contributing to immunity and yield, is a candidate for breeding broad-spectrum resistant and high-yielding rice.
ESTHER : Zhang_2023_Plant.Biotechnol.J__
PubMedSearch : Zhang_2023_Plant.Biotechnol.J__
PubMedID: 38100249

Title : Tanshinone IIA regulates glycogen synthase kinase-3beta-related signaling pathway and ameliorates memory impairment in APP\/PS1 transgenic mice - Peng_2022_Eur.J.Pharmacol__174772
Author(s) : Peng X , Chen L , Wang Z , He Y , Ruganzu JB , Guo H , Zhang X , Ji S , Zheng L , Yang W
Ref : European Journal of Pharmacology , :174772 , 2022
Abstract : Our previous findings indicated that tanshinone IIA (tan IIA), a natural component extracted from the root and rhizome of danshen, significantly attenuated beta-amyloid accumulation, neuroinflammation, and endoplasmic reticulum stress, as well as improved learning and memory deficits in APP/PS1 transgenic mouse model of Alzheimer's disease (AD). However, whether tan IIA can ameliorate tau pathology and the underlying mechanism in APP/PS1 mice remains unclear. In the current study, tan IIA (15 mg/kg and 30 mg/kg) or saline was intraperitoneally administered to the 5-month-old APP/PS1 mice once daily for 4 weeks. The open-field test, novel object recognition test, Y-maze test, and Morris water maze test were performed to assess the cognitive function. Nissl staining, immunohistochemistry, TUNEL, and western blotting were conducted to explore tau hyperphosphorylation, neuronal injury, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway. The activity of GSK-3beta, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) were measured using commercial kits. Our results revealed that tan IIA treatment significantly ameliorated behavioral deficits and improved spatial learning and memory ability of APP/PS1 mice. Additionally, tan IIA markedly attenuated tau hyperphosphorylation and prevented neuronal loss and apoptosis in the parietal cortex and hippocampus. Simultaneously, tan IIA reversed cholinergic dysfunction and reduced oxidative stress. Furthermore, tan IIA activated the PI3K/Akt signaling pathway and suppressed GSK-3beta. Taken together, the above findings suggested that tan IIA improves cognitive decline and tau pathology may through modulation of PI3K/Akt/GSK-3beta signaling pathway.
ESTHER : Peng_2022_Eur.J.Pharmacol__174772
PubMedSearch : Peng_2022_Eur.J.Pharmacol__174772
PubMedID: 35090935

Title : Discovery, synthesis and evaluation of novel reversible monoacylglycerol lipase radioligands bearing a morpholine-3-one scaffold - He_2022_Nucl.Med.Biol_108-109_24
Author(s) : He Y , Gobbi LC , Herde AM , Rombach D , Ritter M , Kuhn B , Wittwer MB , Heer D , Hornsperger B , Bell C , O'Hara F , Benz J , Honer M , Keller C , Collin L , Richter H , Schibli R , Grether U , Mu L
Ref : Nucl Med Biol , 108-109 :24 , 2022
Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays an important role in the endocannabinoid degradation in the brain. It has recently emerged as a promising therapeutic target in the treatment of neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Development of MAGL-specific radioligands for non-invasive imaging by positron-emission tomography (PET) would deepen our knowledge on the relevant pathological changes in diseased states and accelerate drug discovery. In this study, we report the selection and synthesis of two morpholine-3-one derivatives as potential reversible MAGL PET tracer candidates based on their multiparameter optimization scores. Both compounds ([(11)C]1, [(11)C]2) were radiolabeled by direct [(11)C]CO(2) fixation and the in vitro autoradiographic studies demonstrated their specificity and selectivity towards MAGL. Dynamic PET imaging using MAGL knockout and wild-type mice confirmed the in vivo specificity of [(11)C]2. Our preliminary results indicate that morpholine-3-one derivative [(11)C]2 ([(11)C]RO7279991) binds to MAGL in vivo, and this molecular scaffold could serve as an alternative lead structure to image MAGL in the central nervous system.
ESTHER : He_2022_Nucl.Med.Biol_108-109_24
PubMedSearch : He_2022_Nucl.Med.Biol_108-109_24
PubMedID: 35248850

Title : A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase - Xia_2022_Biosensors.(Basel)_12_
Author(s) : Xia M , Li C , Liu L , He Y , Li Y , Jiang G , Wang J
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.
ESTHER : Xia_2022_Biosensors.(Basel)_12_
PubMedSearch : Xia_2022_Biosensors.(Basel)_12_
PubMedID: 35884287

Title : Multi-parameter optimization: Development of a morpholin-3-one derivative with an improved kinetic profile for imaging monoacylglycerol lipase in the brain - He_2022_Eur.J.Med.Chem_243_114750
Author(s) : He Y , Grether U , Taddio MF , Meier C , Keller C , Edelmann MR , Honer M , Huber S , Wittwer MB , Heer D , Richter H , Collin L , Hug MN , Hilbert M , Postmus AGJ , Stevens AF , van der Stelt M , Kramer SD , Schibli R , Mu L , Gobbi LC
Ref : Eur Journal of Medicinal Chemistry , 243 :114750 , 2022
Abstract : Monoacylglycerol lipase (MAGL) is a gatekeeper in regulating endocannabinoid signaling and has gained substantial attention as a therapeutic target for neurological disorders. We recently discovered a morpholin-3-one derivative as a novel scaffold for imaging MAGL via positron emission tomography (PET). However, its slow kinetics in vivo hampered the application. In this study, structural optimization was conducted and eleven novel MAGL inhibitors were designed and synthesized. Based on the results from MAGL inhibitory potency, in vitro metabolic stability and surface plasmon resonance assays, we identified compound 7 as a potential MAGL PET tracer candidate. [(11)C]7 was synthesized via direct (11)CO(2) fixation method and successfully mapped MAGL distribution patterns on rodent brains in in vitro autoradiography. PET studies in mice using [(11)C]7 demonstrated its improved kinetic profile compared to the lead structure. Its high specificity in vivo was proved by using MAGL KO mice. Although further studies confirmed that [(11)C]7 is a P-glycoprotein (P-gp) substrate in mice, its low P-gp efflux ratio on cells transfected with human protein suggests that it should not be an issue for the clinical translation of [(11)C]7 as a novel reversible MAGL PET tracer in human subjects. Overall, [(11)C]7 ([(11)C]RO7284390) showed promising results warranting further clinical evaluation.
ESTHER : He_2022_Eur.J.Med.Chem_243_114750
PubMedSearch : He_2022_Eur.J.Med.Chem_243_114750
PubMedID: 36137365
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : A full-length transcriptome and gene expression analysis of three detoxification gene families in a predatory stink bug, Picromerus lewisi - Li_2022_Front.Physiol_13_1016582
Author(s) : Li W , Wang X , Jiang P , Yang M , Li Z , Huang C , He Y
Ref : Front Physiol , 13 :1016582 , 2022
Abstract : The predatory stink bug P. Lewisi shows potential for Integrated Pest Management programs for controlling Lepidoptera pest insects in crops and forests. The importance of this insect for biological control has stimulated several studies into its biology and ecology. However, P. lewisi has little genetic information available. In the present study, PacBio single-molecule real-time (SMRT) sequencing and Illumina RNA-seq sequencing technologies were used to reveal the full-length transcriptome profiling and tissue-specific expression patterns of P. lewisi. A total of 12,997 high-quality transcripts with an average length of 2,292 bp were obtained from different stages of P. lewisi using SMRT sequencing. Among these, 12,101 were successfully annotated in seven public databases. A total of 67 genes of cytochrome P450 monooxygenases, 43 carboxylesterase genes, and 18 glutathione S-transferase genes were identified, most of which were obtained with full-length ORFs. Then, tissue-specific expression patterns of 5th instar nymphs were analyzed using Illumina sequencing. Several candidate genes related to detoxification of insecticides and other xenobiotics as well as the degradation of odors, were identified in the guts and antennae of P. lewisi. The current study offered in-depth knowledge to understand the biology and ecology of this beneficial predator and related species.
ESTHER : Li_2022_Front.Physiol_13_1016582
PubMedSearch : Li_2022_Front.Physiol_13_1016582
PubMedID: 36299261

Title : The Acaricidal Potential of a New Agent GC16 for Tetranychus pueraricola (Acari: Tetranychidae) Based on Developmental Performance and Physiological Enzyme Activity - He_2022_J.Econ.Entomol__
Author(s) : He Y , Du G , Xie S , Long X , He X , Zhu Y , Chen B
Ref : J Econ Entomol , : , 2022
Abstract : The spider mite, Tetranychus pueraricola (Ehara & Gotoh; Acari: Tetranychidae), is a serious pest in agriculture and horticulture. Application of chemical pesticides is the main mode of this pest control. Due to pesticide residues and resistance-induced resurgence of pests, there is a need to discover alternatives for spider mite management. GC16 comprises a mixture of calcium chloride (CaCl2, 45%) and lecithin (55%), which was recently found to have acaricidal properties. We evaluated the sublethal effects of GC16 on T. pueraricola using life table and enzyme [catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), carboxylesterase (CarE), glutathione S-transferases (GST), and Ca2+-ATPase (Ca2+-ATP)] activity assays. The results showed that fecundity of T. pueraricola increased at LC30 but decreased at LC50 of GC16. The intrinsic rate of increase (r) of T. pueraricola decreased under the LC30 and LC50 of GC16. GC16 concentration and exposure time significantly influenced the activities of CAT, POD, CarE, GST, and Ca2+-ATP in adult mites. Twelve hours later after the treatment, GST and Ca2+-ATP activities were significantly inhibited by LC30 but enhanced by LC50. Moreover, the demographic parameter r and enzyme activities were negatively correlated. In sum, sublethal amounts of GC16 had an adverse effect on mites, and there was a trade-off between developmental performance and physiological enzyme activity of mites under GC16 stress, and GC16 showed an acaricidal potential for T. pueraricola. This work provides guidance for the application of GC16 to control T. pueraricola.
ESTHER : He_2022_J.Econ.Entomol__
PubMedSearch : He_2022_J.Econ.Entomol__
PubMedID: 35512629

Title : Isorhapontigenin prevents beta-amyloid-associated cognitive impairments through activation of the PI3K\/AKT\/GSK-3beta pathway - Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
Author(s) : Ma Q , Li C , He Y , Liu P , Gong F , Zhang W
Ref : Acta Neurobiol Exp (Wars) , 82 :389 , 2022
Abstract : Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Abeta1-42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti-tumor, and anti-inflammatory effects. However, it is still unclear whether ISO can affect beta-amyloid-associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Abeta1-42 in rats. It inhibited the Abeta-induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta-induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Abeta-induced inflammation and oxidative stress by activating the PI3K/AKT/GSK-3beta pathway and ultimately improved cognitive dysfunction in AD rats.
ESTHER : Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
PubMedSearch : Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
PubMedID: 36214721

Title : Ethanol and its nonoxidative metabolites promote acute liver injury by inducing ER stress, adipocyte death and lipolysis - Park_2022_Cell.Mol.Gastroenterol.Hepatol__
Author(s) : Park SH , Seo W , Xu MJ , Mackowiak B , Lin Y , He Y , Fu Y , Hwang S , Kim SJ , Guan Y , Feng D , Yu L , Lehner R , Liangpunsakul S , Gao B
Ref : Cell Mol Gastroenterol Hepatol , : , 2022
Abstract : BACKGROUND & AIMS: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease (ALD). However, the underlying mechanisms remain elusive. We investigated if oxidative and non-oxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influence the development of acute liver injury in a single ethanol binge model. METHODS & RESULTS: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. Oral administration of a single dose of ethanol induced acute liver injury and hepatic ER stress in chow- or HFD-fed mice. Disruption of the alcohol dehydrogenase 1 (Adh1) gene elevated blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the aldehyde dehydrogenase 2 (Aldh2) gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies revealed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, increased adipocyte death and lipolysis, contributing to acute liver injury. Elevated serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice post ethanol gavage with higher levels in Adh1 knockout mice than that in wild-type mice. Deletion of the carboxylesterase 1d (Ces1d) gene in mice markedly reduced acute ethanol-induced elevation of blood FAEE levels with slight but significant reduction of serum aminotransferase levels. CONCLUSION: Ethanol and its non-oxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.
ESTHER : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedSearch : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedID: 36243320

Title : Development of naringenin-O-carbamate derivatives as multi-target-directed liagnds for the treatment of Alzheimer's disease - Mi_2022_Bioorg.Med.Chem.Lett_60_128574
Author(s) : Mi J , He Y , Yang J , Zhou Y , Zhu G , Wu A , Liu W , Sang Z
Ref : Bioorganic & Medicinal Chemistry Lett , 60 :128574 , 2022
Abstract : In this work, a series of naringenin-O-carbamate derivatives was designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD) through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c showed good antioxidant potency (ORAC = 1.0 eq), and it was a reversible huAChE (IC(50) = 9.7 microM) inhibitor. In addition, compound 3c significantly inhibited self-induced Abeta(1-42) aggregation, and it could activate UPS degradation pathway in HT22 cells and clear the aggregated proteins associated with AD. Moreover, compound 3c was a selective metal chelator, and it significantly inhibited and disaggregated Cu(2+)-mediated Abeta(1-42) aggregation. Furthermore, compound 3c displayed remarkable neuroprotective effect and anti-inflammatory property. Interestingly, compound 3c displayed good hepatoprotective effect by its antioxidant activity. More importantly, compound 3c demonstrated favourable blood-brain barrier penetration in vitro and drug-like property. Therefore, compound 3c was a promising multifunctional agent for the treatment of AD.
ESTHER : Mi_2022_Bioorg.Med.Chem.Lett_60_128574
PubMedSearch : Mi_2022_Bioorg.Med.Chem.Lett_60_128574
PubMedID: 35065231

Title : Development of High Brain-Penetrant and Reversible Monoacylglycerol Lipase PET Tracers for Neuroimaging - He_2022_J.Med.Chem_65_2191
Author(s) : He Y , Schild M , Grether U , Benz J , Leibrock L , Heer D , Topp A , Collin L , Kuhn B , Wittwer M , Keller C , Gobbi LC , Schibli R , Mu L
Ref : Journal of Medicinal Chemistry , 65 :2191 , 2022
Abstract : Monoacylglycerol lipase (MAGL) is one of the key enzymes in the endocannabinoid system. Inhibition of MAGL has been proposed as an attractive approach for the treatment of various diseases. In this study, we designed and successfully synthesized two series of piperazinyl pyrrolidin-2-one derivatives as novel reversible MAGL inhibitors. (R)-[(18)F]13 was identified through the preliminary evaluation of two carbon-11-labeled racemic structures [(11)C]11 and [(11)C]16. In dynamic positron-emission tomography (PET) scans, (R)-[(18)F]13 showed a heterogeneous distribution and matched the MAGL expression pattern in the mouse brain. High brain uptake and brain-to-blood ratio were achieved by (R)-[(18)F]13 in comparison with previously reported reversible MAGL PET radiotracers. Target occupancy studies with a therapeutic MAGL inhibitor revealed a dose-dependent reduction of (R)-[(18)F]13 accumulation in the mouse brain. These findings indicate that (R)-[(18)F]13 ([(18)F]YH149) is a highly promising PET probe for visualizing MAGL non-invasively in vivo and holds great potential to support drug development.
ESTHER : He_2022_J.Med.Chem_65_2191
PubMedSearch : He_2022_J.Med.Chem_65_2191
PubMedID: 35089028
Gene_locus related to this paper: human-MGLL

Title : CRISPR-Cas12a based fluorescence assay for organophosphorus pesticides in agricultural products - Fu_2022_Food.Chem_387_132919
Author(s) : Fu R , Wang Y , Liu Y , Liu H , Zhao Q , Zhang Y , Wang C , Li Z , Jiao B , He Y
Ref : Food Chem , 387 :132919 , 2022
Abstract : Herein, we propose a sensitive fluorescent assay for organophosphorus pesticides (OPs) detection based on a novel strategy of activating the CRISPR-Cas12a system. Specifically, acetylcholinesterase (AChE) hydrolyzes acetylthiocholine into thiocholine (TCh). Subsequently, TCh induces the degradation of MnO(2) nanosheets and generates sufficient Mn(2+) ions to activate the Mn(2+)-dependent DNAzyme. Then, as the catalytic product of activated DNAzyme, the short DNA strand activates the CRISPR-Cas12a system to cleave the fluorophore-quencher-labeled DNA reporter (FQ) probe effectively; thus, increasing the fluorescence intensity (FI) in the solution. However, in the presence of OPs, the activity of AChE is suppressed, resulting in a decrease in FI. Under optimized conditions, the limits of detection for paraoxon, dichlorvos, and demeton were 270, 406, and 218 pg/mL, respectively. Benefiting from the outstanding MnO(2) nanosheets properties and three rounds of enzymatic signal amplification, the proposed fluorescence assay holds great potential for the detection of OPs in agricultural products.
ESTHER : Fu_2022_Food.Chem_387_132919
PubMedSearch : Fu_2022_Food.Chem_387_132919
PubMedID: 35421656

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) - Zhang_2022_Pest.Manag.Sci__
Author(s) : Zhang L , Wang L , Chen J , Zhang J , He Y , Lu Y , Cai J , Chen X , Wen X , Xu Z , Wang C
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2022_Pest.Manag.Sci__
PubMedSearch : Zhang_2022_Pest.Manag.Sci__
PubMedID: 35192738

Title : Potentially tunable ratiometric electrochemiluminescence sensing based on conjugated polymer nanoparticle for organophosphorus pesticides detection - He_2022_J.Hazard.Mater_432_128699
Author(s) : He Y , Yang G , Zhao J , Tan K , Yuan R , Chen S
Ref : J Hazard Mater , 432 :128699 , 2022
Abstract : In general, suitable double luminophores and their coreactants are necessary for constructing electrochemiluminescence (ECL) ratio strategy. However, the complexity of matching double luminophores and the stability and repeatability problem suffered by introducing exogenous coreactant would greatly limit the application of ratio detection. An original single-luminophore-based ECL ratio sensing was developed excluding any exogenous coreactants in this work. The poly [9,9-bis(3'-(N,N-dimethylamino)propyl)- 2,7-fluorene]-alt-2,7-(9,9-dioctylfluorene)] nanoparticles (PFN NPs) were explored to emit two anodic ECL signals. One centered at + 1.25 V (ECL-1) with the scanning potential of 0 ~ + 1.25 V and the other at + 1.95 V (ECL-2) with the scanning potential of 0 ~ + 1.95 V. ECL-1 showed a very strong emission without any exogenous coreactant. Importantly, hydrogen peroxide (H(2)O(2)) was able to efficiently weaken ECL-1 but strengthen ECL-2. When organophosphorus pesticides (OPs) were absent, the immobilized acetylcholinesterase-choline oxidase (AChE-ChOx) would catalyze the substrate acetylthiocholine chloride (ATCl) to produce H(2)O(2), resulting in a quenched ECL-1 and an enhanced ECL-2. With the introduction of OPs, ECL-1 increased while ECL-2 accordingly decreased as OPs prohibited production of H(2)O(2) by inhibiting activity of AChE. Highly sensitive ECL ratio detection for OPs was realized based on the change of the ratio of two signals. The dual anode emission properties of PFN NPs coupled with the opposite regulation of H(2)O(2) on the two signals paved a new avenue for potentially tunable ECL ratio sensing strategy, and showed enormous potential applications for OPs analysis.
ESTHER : He_2022_J.Hazard.Mater_432_128699
PubMedSearch : He_2022_J.Hazard.Mater_432_128699
PubMedID: 35325864

Title : Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation - Qiu_2021_Front.Cardiovasc.Med_8_639541
Author(s) : Qiu H , Zhang Y , Li Z , Jiang P , Guo S , He Y , Guo Y
Ref : Front Cardiovasc Med , 8 :639541 , 2021
Abstract : Background: The beneficial effects of parasympathetic stimulation in pulmonary arterial hypertension (PAH) have been reported. However, the specific mechanism has not been completely clarified. Donepezil, an oral cholinesterase inhibitor, enhances parasympathetic activity by inhibiting acetylcholinesterase, whose therapeutic effects in PAH and its mechanism deserve to be investigated. Methods: The PAH model was established by a single intraperitoneal injection of monocrotaline (MCT, 50 mg/kg) in adult male Sprague-Dawley rats. Donepezil was administered via intraperitoneal injection daily after 1 week of MCT administration. At the end of the study, PAH status was confirmed by echocardiography and hemodynamic measurement. Testing for acetylcholinesterase activity and cholinergic receptor expression was used to evaluate parasympathetic activity. Indicators of pulmonary arterial remodeling and right ventricular (RV) dysfunction were assayed. The proliferative and apoptotic ability of pulmonary arterial smooth muscle cells (PASMCs), inflammatory reaction, macrophage infiltration in the lung, and activation of bone marrow-derived macrophages (BMDMs) were also tested. PASMCs from the MCT-treated rats were co-cultured with the supernatant of BMDMs treated with donepezil, and then, the proliferation and apoptosis of PASMCs were evaluated. Results: Donepezil treatment effectively enhanced parasympathetic activity. Furthermore, it markedly reduced mean pulmonary arterial pressure and RV systolic pressure in the MCT-treated rats, as well as reversed pulmonary arterial remodeling and RV dysfunction. Donepezil also reduced the proliferation and promoted the apoptosis of PASMCs in the MCT-treated rats. In addition, it suppressed the inflammatory response and macrophage activation in both lung tissue and BMDMs in the model rats. More importantly, donepezil reduced the proliferation and promoted the apoptosis of PASMCs by suppressing M2-macrophage activation. Conclusion: Donepezil could prevent pulmonary vascular and RV remodeling, thereby reversing PAH progression. Moreover, enhancement of the parasympathetic activity could reduce the proliferation and promote the apoptosis of PASMCs in PAH by suppressing M2-macrophage activation.
ESTHER : Qiu_2021_Front.Cardiovasc.Med_8_639541
PubMedSearch : Qiu_2021_Front.Cardiovasc.Med_8_639541
PubMedID: 33791350

Title : Oxidase-like Nanozyme-Mediated Altering of the Aspect Ratio of Gold Nanorods for Breaking through H(2)O(2)-Supported Multicolor Colorimetric Assay: Application in the Detection of Acetylcholinesterase Activity and Its Inhibitors - Fu_2021_ACS.Appl.Bio.Mater_4_3539
Author(s) : Fu R , Zhou J , Wang Y , Liu Y , Liu H , Yang Q , Zhao Q , Jiao B , He Y
Ref : ACS Appl Bio Mater , 4 :3539 , 2021
Abstract : A convenient, fast, and colorful colorimetric platform with high resolution for acetylcholinesterase (AChE) activity and its inhibitors detection based on the regulation of oxidase-like nanozyme-mediated etching of gold nanorods (AuNRs) has been proposed in this work. MnO(2) nanosheets are selected as the nanozyme. Their excellent oxidase-like activity enables the etching process to proceed smoothly without the usage of unstable H(2)O(2). When AChE is present, it catalytically hydrolyzes acetylthiocholine (ATCh) to thiocholine (TCh). With high reducing ability, TCh induces the decomposition of MnO(2) nanosheets, causing them to lose their oxidase-like activity. Thus, the etching of AuNRs is hampered. Consequently, with the increasing concentration of AChE, an apparent change in the AuNRs solution color is observed. The proposed platform achieves high-sensitivity detection of AChE (limit of detection = 0.18 mU/mL). Furthermore, the proposed platform also has been demonstrated its applicability for its inhibitors detection. Benefiting from the advantages of convenient and high resolution of visual readout, the proposed platform holds great potential for the detection of AChE and its inhibitors in clinical diagnosis.
ESTHER : Fu_2021_ACS.Appl.Bio.Mater_4_3539
PubMedSearch : Fu_2021_ACS.Appl.Bio.Mater_4_3539
PubMedID: 35014439

Title : Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure - Lv_2021_Environ.Pollut_280_117000
Author(s) : Lv B , Wang J , He Y , Zeng Z , Tang YE , Li N , Chen LJ , Wang Z , Song QS
Ref : Environ Pollut , 280 :117000 , 2021
Abstract : Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure.
ESTHER : Lv_2021_Environ.Pollut_280_117000
PubMedSearch : Lv_2021_Environ.Pollut_280_117000
PubMedID: 33784568

Title : Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes - Bi_2021_Cell_184_1377
Author(s) : Bi X , Wang K , Yang L , Pan H , Jiang H , Wei Q , Fang M , Yu H , Zhu C , Cai Y , He Y , Gan X , Zeng H , Yu D , Zhu Y , Qiu Q , Yang H , Zhang YE , Wang W , Zhu M , He S , Zhang G
Ref : Cell , 184 :1377 , 2021
Abstract : Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.
ESTHER : Bi_2021_Cell_184_1377
PubMedSearch : Bi_2021_Cell_184_1377
PubMedID: 33545088
Gene_locus related to this paper: atrsp-a0a8j7tiu5

Title : Toxicity of gabapentin-lactam on the early developmental stage of zebrafish (Danio rerio) - He_2021_Environ.Pollut_287_117649
Author(s) : He Y , Jia D , Du S , Zhu R , Zhou W , Pan S , Zhang Y
Ref : Environ Pollut , 287 :117649 , 2021
Abstract : Gabapentin-lactam (GBP-L) is a transformation product (TP) of gabapentin (GBP), a widely used anti-epileptic pharmaceutical. Due to its high persistence, GBP-L has been frequently detected in the surface water. However, the effects of GBP-L on aquatic organisms have not been thoroughly investigated. In the present study, zebrafish (Danio rerio) embryos as a model organism were used to study the impacts of GBP-L in terms of embryos LC(50), spontaneous movement at 24 hpf (hours post fertilization), heartbeat rates at 48 hpf, and body length at 72 hpf, with the concentrations of GBP-L down to 0.01 microg/L, covering its environmental concentrations. Various biomarkers from nervous, antioxidant and immune systems of zebrafish larvae were analyzed, including acetylcholinesterase, acetylcholine, dopamine, gamma-aminobutyric acid, superoxide dismutase, catalase, glutathione S-transferase, C reactive protein, and lysozyme, to assess its toxicity on these systems. RT-qPCR was then used to further verify the results and explain the toxicological mechanism at the gene level. The results demonstrated that GBP-L is much more toxic than its parent compound, and could lead to adverse impacts on the aquatic organisms even at every low concentrations.
ESTHER : He_2021_Environ.Pollut_287_117649
PubMedSearch : He_2021_Environ.Pollut_287_117649
PubMedID: 34182397

Title : A BCNO QDs-MnO(2) nanosheets based fluorescence off-on-off and colorimetric sensor with smartphone detector for the detection of organophosphorus pesticides - Liu_2021_Anal.Chim.Acta_1184_339026
Author(s) : Liu F , Lei T , Zhang Y , Wang Y , He Y
Ref : Anal Chim Acta , 1184 :339026 , 2021
Abstract : In this work, boron carbon oxynitride quantum dots (BCNO QDs) were prepared by a one-step hydrothermal process of ethanolamine and boric acid. BCNO QDs exhibited blue fluorescence with the optimal excitation/emission fluorescence peak at 335 and 420 nm, respectively. As an efficient fluorescence quencher, manganese dioxide (MnO(2)) nanosheets can effectively quench the fluorescence of BCNO QDs via the inner filter effect (IFE). Acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylcholine (ATCh) to produce thiocholine (TCh). TCh can reductively degrade MnO(2) nanosheets to generate Mn(2+), thereby recovering the fluorescence of BCNO QDs. Organophosphorus pesticides (OPs) can inhibit the activity of AChE enzymes, thereby preventing the production of TCh and the decomposition of MnO(2) nanosheets, resulting in the fluorescence "turn-off". Therefore, the concentration of OPs can be detected by measuring the fluorescence intensity change of AChE-ATCh-MnO(2)-BCNO-QDs system. Under optimal experimental conditions, the dynamic detection range of paraoxon is 0.1-250 ng mL(-1), and the detection limit is 0.03 ng mL(-1). Meanwhile, the reaction system also showed concentration-dependent visual color changes from colorless to brownish. Furthermore, we prepared a portable BCNO QDs test paper. By using a smartphone to identify the RGB values of the reaction solution and the corresponding test paper, we carried out the digital image chromaticity analysis, which can shorten the detection time and reduce the detection cost, and provide an effective solution for the rapid detection of OPs on site.
ESTHER : Liu_2021_Anal.Chim.Acta_1184_339026
PubMedSearch : Liu_2021_Anal.Chim.Acta_1184_339026
PubMedID: 34625266

Title : Fluorine-free synthesis of Ti(3)C(2) MQDs for smartphone-based fluorescent and colorimetric determination of acetylcholinesterase and organophosphorus pesticides - Pei_2021_Mikrochim.Acta_189_7
Author(s) : Pei T , He Y , Wang Y , Song G
Ref : Mikrochim Acta , 189 :7 , 2021
Abstract : Ti(3)C(2) MQDs were synthesized using an effective fluorine-free method with excitation/emission maxima at 390/490 nm and a fluorescence quantum yield of 11.78%. In contrast to the traditional, hazardous, and time-consuming process of HF pretreatment, our fluorine-free method is safe and simple. Acetylcholinesterase (AChE) could catalyze the hydrolysis of acetylthiocholine (ATCh) to produce thiocholine which was further reacted with Ehrman's reagent and decomposed to form a yellow product 2-nitro-5-thiobenate anion (TNB). Due to the obvious overlap between the excitation spectrum of Ti(3)C(2) MQDs and the absorption spectrum of TNB, AChE catalyzed the hydrolysis of substrate DTNB/ATCh to form TNB, which can effectively quench the fluorescence of Ti(3)C(2) MQDs through the inner filter effect (IFE). However, the presence of organophosphorus (OPs) inhibited the activity of AChE, leading to a less expressed IFE and increasing recovery of fluorescence. This was used for the quantification of OPs with a detection limit of 0.20 microg.L(-1). Moreover, with the constant increase of AChE activity, the color of the reaction system changed visibly from colorless to yellow, and then from yellow to colorless with further continuous addition of OPs. A colorimetric detection with a paper-based sensor of AChE activity and OP concentration was also fabricated by analyzing changes in RGB value using a smartphone APP. In this work, we proposed an effective fluorescence/colorimetric two-mode detection method, which opened a new horizon to detect other targets.
ESTHER : Pei_2021_Mikrochim.Acta_189_7
PubMedSearch : Pei_2021_Mikrochim.Acta_189_7
PubMedID: 34862575

Title : Development of reversible monoacylglycerol lipase PET tracers with improved brain uptake - He_2021_Nucl.Med.Biol_96-97_S36
Author(s) : He Y , Schild M , Grether U , Humm R , Keller C , Schibli R , Gobbi L , Mu L
Ref : Nucl Med Biol , 96-97 :S36 , 2021
Abstract : Objectives: Monoacylglycerol lipase (MAGL) is the key enzyme for degradation of the most abundant brain endocannabinoid, 2-ara-chidonoylglycerol (2-AG). It is considered as an attractive drug target for oncological and psychiatric diseases [1]. During the last decade, several irreversible MAGL PET ligands have been disclosed, however, reversible MAGL radiotracers with sufficient brain penetration are barely reported. To the best of our knowledge, [18F]T-401 is the only available reversible MAGL tracer with moderate brain uptake in mice. In this study, we synthesized a series of reversible MAGL inhibitors based on the piperazinyl pyrrolidin-2-one core structure [2,3]. The most potent compounds were radiolabeled with either C-11 or F-18. Their utilities as PET imaging agents were evaluated. Methods: Novel series of piperazinyl pyrrolidin-2-one derivatives were designed and prepared via multi-step synthetic approaches. Their IC 50 values towards MAGL were determined by tracing the hydrolysis of natural substrate 2-AG. The most potent ligands YH132 and YH135 were labeled with C-11, and YH149 was labeled with F-18. In vitro autoradiography and PET imaging were performed in MAGL knockout and wild-type mice to evaluate their in vitro and in vivo specificity. [18F]YH149 was further evaluated in ex vivo biodistribution and drug-occupancy studies to assess its utility for imaging MAGL in the rodent brain. Results: IC50 values of the novel MAGL inhibitors ranged from 3 nM to 10.7 M. YH132 (IC50 = 6 nM),YH135 (IC50 = 18 nM), andYH149 (IC50 = 12 nM) that possess IC 50 values in a nano-molar range for human MAGL were further evaluated as radioligands. Both [11C]YH132 and [11C]YH135 showed high accumulation in MAGL-rich brain regions in in vitro autoradiographic studies. In PET studies using MAGL knock-out and wild-type mice, [11C]YH132 revealed higher brain permeability and specificity than [11C]YH135. Therefore, [18F]YH149, the F-18 labeled analog of YH132, was synthesized via copper-mediated fluorination. [18F]YH149 demonstrated excellent in vitro and in vivo specificity towards MAGL. The averaged PET image (12.5-52.5 min p.i.) was in high accordance with MAGL expression pattern in the mouse brain. In ex vivo biodistribution in mice, [18F]YH149 exhibited significantly higher brain uptake than the benchmark radiotracer [18F]T-401 at 30 min post-injection [2]. Blocking effects were observed in the brain and MAGL-expressive peripheral organs using PF-06795071, an irreversible MAGL inhibitor. Furthermore, the drug occupancy study indicated that [18F]YH149 can be used to determine the D50 value of PF-06795071 in the mouse brain. Conclusions: The fluorinated PET probe, [18F]YH149, revealed high in vitro/in vivo specificity towards MAGL and increased brain permeability compared to the previously reported reversible MAGL PET radiotracers. Preliminary results indicate that [18F]YH149 is a very promising PET tracer for imaging MAGL and capable to evaluate target occupancy in vivo
ESTHER : He_2021_Nucl.Med.Biol_96-97_S36
PubMedSearch : He_2021_Nucl.Med.Biol_96-97_S36

Title : Bifunctional Moderator-Powered Ratiometric Electrochemiluminescence Enzymatic Biosensors for Detecting Organophosphorus Pesticides Based on Dual-Signal Combined Nanoprobes - He_2021_Anal.Chem__
Author(s) : He Y , Hu F , Zhao J , Yang G , Zhang Y , Chen S , Yuan R
Ref : Analytical Chemistry , : , 2021
Abstract : The bifunctional moderator is urgently needed in the field of ratiometric electrochemiluminescence (ECL) sensing since it can mediate simultaneously two ECL signals to conveniently realize their opposite change trend. This work designed a novel dual-signal combined nanoprobe with carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] nanoparticles (c-PFBT NPs) as the anodic ECL probe and L-cysteine capped CdS quantum dots (L-CdS QDs) as the cathodic ECL probe, which performed a dual-signal output capability without any additional coreactants. More importantly, hydrogen peroxide (H(2)O(2)) produced in situ by enzyme-catalyzed reaction was developed as a bifunctional moderator for simultaneously regulating two signals. The dual-signal combined nanoprobe (c-PFBT NPs@CdS QDs) served as the matrix to immobilize acetylcholinesterase (AChE) and choline oxidase for organophosphorus (OPs) analysis. In the absence of OPs, H(2)O(2) was produced by catalyzing the substrate acetylthiocholine (ATCl) with enzymes and it quenched the anodic ECL signal from c-PFBT NPs and simultaneously promoted the cathodic ECL signal from L-CdS QDs. When OPs was present, the activity of AChE was inhibited, the anodic signal would increase, and the cathodic signal would accordingly decrease. The integration of the bifunctional moderator H(2)O(2) and dual-signal combined nanoprobe c-PFBT NPs@CdS QDs not only provides an attractive ECL platform for enzymatic sensing involving the generation or consumption of H(2)O(2) but also paves a new pathway for other ratiometric ECL systems involving enzyme catalytic amplification for detecting antigens, antibodies, DNA, RNA, etc.
ESTHER : He_2021_Anal.Chem__
PubMedSearch : He_2021_Anal.Chem__
PubMedID: 34133127

Title : miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT\/p70S6K and JNK Pathways through ABHD2 - He_2020_Mol.Ther.Oncolytics_17_83
Author(s) : He Y , Yang Y , Liao Y , Xu J , Liu L , Li C , Xiong X
Ref : Mol Ther Oncolytics , 17 :83 , 2020
Abstract : Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2.
ESTHER : He_2020_Mol.Ther.Oncolytics_17_83
PubMedSearch : He_2020_Mol.Ther.Oncolytics_17_83
PubMedID: 32322665
Gene_locus related to this paper: human-ABHD2

Title : Toxicity assessment of municipal sewage treatment plant effluent by an integrated biomarker response in the liver of crucian carp (Carassius auratus) - Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
Author(s) : Chang T , Wei B , Wang Q , He Y , Wang C
Ref : Environ Sci Pollut Res Int , 27 :7280 , 2020
Abstract : In this study, crucian carp (Carassius auratus) was exposed to the increasing concentrations of municipal sewage treatment plant effluent (MSTPE) for 15 days, and the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE), together with the contents of malondialdehyde (MDA) and glutathione (GSH) in the liver of C. auratus were investigated. Moreover, the integrated biomarker response (IBR) approach was applied to assess the adverse effects of MSTPE in freshwater. The aim of the study was to provide an effective biological indicator for evaluating the toxicity effects and ecological risks of MSTPE in the freshwater environment quantitatively. Results showed that MSTPE could cause oxidative damage to the liver of C. auratus, which reflected through the increasing MDA content over the exposure period. MSTPE also led to the biochemical responses of antioxidant defense in C. auratus liver, such as the enhancement of SOD, CAT, and GPx activities, as well as the inhibition of AChE activity and GSH content. It was found that MDA, SOD, GPx, and GSH could be used as the biomarkers for reflecting the adverse effects of MSTPE in the receiving freshwater on the 12th day of exposure. A significant increase of IBR values was observed as the increasing concentration of MSTPE, and the IBR values presented a significant positive correlation (r = 0.891, P < 0.05) with the increasing concentrations of MSTPE, indicating that IBR approach is a promising tool for assessing the toxicity effects of MSTPE in environmental freshwater.
ESTHER : Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
PubMedSearch : Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
PubMedID: 31883072

Title : Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I \/ II) - Ye_2020_Trials_21_520
Author(s) : Ye Q , Wang H , Xia X , Zhou C , Liu Z , Xia ZE , Zhang Z , Zhao Y , Yehenala J , Wang S , Zhou G , Hu K , Wu B , Wu CT , He Y
Ref : Trials , 21 :520 , 2020
Abstract : OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m(2)) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x10(7) human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h +/- 30min, 24h +/- 30min after the injection) and follow-up period D90 +/- 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h +/- 30min, 24h +/- 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 +/- 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 +/- 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 beta, IL-2, TNF-a, ITN-gamma), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood beta-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 +/- 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h +/- 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16(th) April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
ESTHER : Ye_2020_Trials_21_520
PubMedSearch : Ye_2020_Trials_21_520
PubMedID: 32532356

Title : Single and combined effects of carbamazepine and copper on nervous and antioxidant systems of zebrafish (Danio rerio) - Jia_2020_Environ.Toxicol__
Author(s) : Jia D , Li X , Du S , Xu N , Zhang W , Yang R , Zhang Y , He Y
Ref : Environ Toxicol , : , 2020
Abstract : Various pollutants co-exist in the aquatic environment such as carbamazepine (CBZ) and copper (Cu), which can cause complex effects on inhabiting organisms. The toxic impacts of the single substance have been studied extensively. However, the studies about their combined adverse impacts are not enough. In the present study, zebrafish were exposed to environmental relevant concentrations of CBZ (1, 10, and 100 mug/L), Cu (0.5, 5, and 10 mug/L) and the mixtures (1 mug/L CBZ + 0.5 mug/L Cu, 10 mug/L CBZ + 5 mug/L Cu, 100 mug/L CBZ + 10 mug/L Cu) for 45 days, the effects on nervous and antioxidant systems of zebrafish were investigated. The results demonstrated that, in comparison with single exposure group, the combined presence of CBZ and Cu exacerbated the effect of antioxidant system (the ability of inhibition of hydroxyl radicals (IHR), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)) but not nervous system (Acetylcholinesterase [AChE]). The qPCR results supported the changes of corresponding enzymes activities. Hepatic histopathological analysis verified the results of biomarkers. Our work illustrated that the toxicity of mixed pollutants is very complicated, which cannot simply be inferred from the toxicity of single pollutant, and calls for more co-exposure experiments to better understanding of the co-effects of pollutants on aquatic organisms.
ESTHER : Jia_2020_Environ.Toxicol__
PubMedSearch : Jia_2020_Environ.Toxicol__
PubMedID: 32485069

Title : Liver Function of Male Rats Exposed to Manganese at Different Time Points - Zhu_2020_Biol.Trace.Elem.Res__
Author(s) : Zhu X , Yang L , He Y , Sun Y , Shi W , Ou C
Ref : Biol Trace Elem Res , : , 2020
Abstract : As an essential trace element in the human body, manganese (Mn) is involved in many important biochemical reactions. However, excessive exposure to manganese can cause multiple systematic damages to the body. This study aims to investigate the effects of manganese exposure on serum hepatic enzymes in male rats at different time points. After adaptive feeding for 7 days, male Sprague-Dawley (SD) rats were injected intraperitoneally with 30 mg/kg MnCl2.4H2O once a day for 21 days at zeitgeber time point 2 (ZT2), ZT8, ZT14, and ZT20, respectively. We found that short-term repeated exposure to manganese caused slower body weight gain and increased relative liver and spleen weight index in male rats at different time points. Moreover, serum total bile acid (TBA) increased while aspartate aminotransferase (AST) decreased at ZT2, ZT8, and ZT20. Cholinesterase (ChE) decreased at ZT2 and ZT20, lactic dehydrogenase (LDH) decreased at ZT2, ZT14, and ZT20, and acid phosphatase (ACP) decreased at ZT2 and ZT14. Alkaline phosphatase (ALP) decreased at ZT2, ZT14, and ZT20, but increased at ZT8. Alanine amino transferase (ALT) decreased at ZT2 and ZT20, but increased at ZT8. There was a negative correlation between relative liver weight index with AST, ACP, ALP, and LDH, while a positive correlation with TBA. However, relative spleen weight index had a positive correlation with relative liver weight index and TBA, while a negative correlation with ALT, AST, ACP, ALP, LDH, and ChE. Our study shows that the injury of liver function is caused by short-term repeated manganese exposure at different time points. The time effect should be considered in manganese toxicity evaluation.
ESTHER : Zhu_2020_Biol.Trace.Elem.Res__
PubMedSearch : Zhu_2020_Biol.Trace.Elem.Res__
PubMedID: 32100273

Title : Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Tian_2019_Bioorg.Chem__103477
Author(s) : Tian C , Qiang X , Song Q , Cao Z , Ye C , He Y , Deng Y , Zhang L
Ref : Bioorg Chem , :103477 , 2019
Abstract : The complex pathogenesis of Alzheimer's disease (AD) calls for multitarget approach for disease management. Herein, a series of novel flurbiprofen-chalcone hybrid Mannich base derivatives were designed and synthesized. The biological screening results indicated that most of the derivatives exhibited potent multi-target effects involved in AD. In particular, compound 6c bearing a pyrrolidine group showed the highest activities against self- and Cu(2+)-induced Abeta1-42 aggregation (70.65% and 54.89% at 25.0 microM, respectively), highly selective inhibition towards AChE and MAO-B (IC50 = 7.15 muM and 0.43 muM respectively), good antioxidant ability and metal-chelating property. Moreover, 6c displayed excellent anti-neuroinflammatory activity and appropriate BBB permeability in vitro. These outstanding results qualified compound 6c as a promising multifunctional agent for further development of disease-modifying treatment of AD.
ESTHER : Tian_2019_Bioorg.Chem__103477
PubMedSearch : Tian_2019_Bioorg.Chem__103477
PubMedID: 31818478

Title : A transcriptomics-based analysis of the toxicity mechanisms of gabapentin to zebrafish embryos at realistic environmental concentrations - He_2019_Environ.Pollut_251_746
Author(s) : He Y , Li X , Jia D , Zhang W , Zhang T , Yu Y , Xu Y , Zhang Y
Ref : Environ Pollut , 251 :746 , 2019
Abstract : Gabapentin (GPT) has become an emerging contaminant in aquatic environments due to its wide application in medical treatment all over the world. In this study, embryos of zebrafish were exposed to gabapentin at realistically environmental concentrations, 0.1mug/L and 10mug/L, so as to evaluate the ecotoxicity of this emergent contaminant. The transcriptomics profiling of deep sequencing was employed to illustrate the mechanisms. The zebrafish (Danio rerio) embryo were exposed to GPT from 12 hpf to 96 hpf resulting in 136 and 750 genes differentially expressed, respectively. The results of gene ontology (GO) analysis and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis illustrated that a large amount of differentially expressed genes (DEGs) were involved in the antioxidant system, the immune system and the nervous system. RT-qPCR was applied to validate the results of RNA-seq, which provided direct evidence that the selected genes involved in those systems mentioned above were all down-regulated. Acetylcholinesterase (AChE), lysozyme (LZM) and the content of C-reactive protein (CRP) were decreased at the end of exposure, which is consistent with the transcriptomics results. The overall results of this study demonstrate that GPT simultaneously affects various vital functionalities of zebrafish at early developmental stage, even at environmentally relevant concentrations.
ESTHER : He_2019_Environ.Pollut_251_746
PubMedSearch : He_2019_Environ.Pollut_251_746
PubMedID: 31121539

Title : Coreactant-free electrochemiluminescence biosensor for the determination of organophosphorus pesticides - He_2019_Biosens.Bioelectron__111898
Author(s) : He Y , Du J , Luo J , Chen S , Yuan R
Ref : Biosensors & Bioelectronics , :111898 , 2019
Abstract : Poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] (PFBT) was functionalized with carboxyl groups via nanoprecipitation method to prepare polymer nanoparticles (PNPs). Remarkable electrochemiluminescence (ECL) was observed at PFBT PNPs without any external species or dissolved O2 as coreactants. Furthermore, such an ECL emission could be efficiently quenched by hydrogen peroxide (H2O2). A coreactant-free ECL enzyme-based biosensor is making use of PFBT PNPs as luminophore for detecting organophosphorus (OPs) pesticides. In the absence of OPs, H2O2 stemmed from the enzymatic reaction would quench the ECL signal of PFBT PNPs, resulting in an ECL signal-off state. In the presence of OPs, the ECL signal obviously increased because the enzyme activity of the acetylcholinesterase (AChE) was inhibited by OPs. The linear range for OPs detection was 1.0 x 10(-12)-1.0 x 10(-7) M and the detection limit was low as 1.5 x 10(-13) M. Such a coreactant-free ECL strategy could avoid the drawbacks resulted from the addition of exogenous species or dissolved O2 as coreactant. More importantly, H2O2 was released by many oxidases-induced reactions, and its quenching effect on the ECL of PFBT PNPs would pave a new avenue for constructing coreactant-free enzyme-based ECL biosensor for environmental monitoring and biological analysis.
ESTHER : He_2019_Biosens.Bioelectron__111898
PubMedSearch : He_2019_Biosens.Bioelectron__111898
PubMedID: 31767347

Title : Carbon dots co-doped with nitrogen and chlorine for off-on fluorometric determination of the activity of acetylcholinesterase and for quantification of organophosphate pesticides - Yang_2019_Mikrochim.Acta_186_585
Author(s) : Yang M , Liu M , Wu Z , He Y , Ge Y , Song G , Zhou J
Ref : Mikrochim Acta , 186 :585 , 2019
Abstract : Nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) were hydrothermally prepared starting from 4-chloro-1,2-diaminobenzene and dopamine. The N,Cl-CDs exhibit strong orange fluorescence, with excitation/emission maxima at 420/570 nm and a relative high quantum yield (15%). The N,Cl-CDs were employed to detect acetylcholinesterase (AChE) activity and organophosphate pesticides (OPs) which are enzyme inhibitors. Acetylthiocholine is enzymatically split by AChE to produce thiocholine which triggers the decomposition of Ellmans's reagent to form a yellow colored product (2-nitro-5-thiobenzoate anion). The product causes an inner filter effect (IEF) on the fluorescence of the N,Cl-CDs. Fluorescence decreases linearly in the 0.017 to 5.0 Unit.L(-1) AChE activity range, and the detection limit is 2 mUnit.L(-1). If organophosphates are present, the activity of AChE becomes increasingly blocked, and this leads to a less expressed IFE and an increasing recovery of fluorescence. This was used for the quantification of OPs. Response is linear in the 0.3-1000 mug.L(-1) OP concentration range with a 30 ng.L(-1) detection limit. Graphical abstractSchematic representation of the synthesis of nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) and the recognition of organophosphate pesticides by N,Cl-CDs.
ESTHER : Yang_2019_Mikrochim.Acta_186_585
PubMedSearch : Yang_2019_Mikrochim.Acta_186_585
PubMedID: 31363918

Title : Fluctuations between high- and low-modularity topology in time-resolved functional connectivity - Fukushima_2018_Neuroimage_180_406
Author(s) : Fukushima M , Betzel RF , He Y , de Reus MA , van den Heuvel MP , Zuo XN , Sporns O
Ref : Neuroimage , 180 :406 , 2018
Abstract : Modularity is an important topological attribute for functional brain networks. Recent human fMRI studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate basic spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (respectively, low) modularity period are relatively homogeneous (respectively, heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.
ESTHER : Fukushima_2018_Neuroimage_180_406
PubMedSearch : Fukushima_2018_Neuroimage_180_406
PubMedID: 28823827

Title : Hierarchical nanocomposites with an N-doped carbon shell and bimetal core: Novel enzyme nanocarriers for electrochemical pesticide detection - Ma_2018_Biosens.Bioelectron_121_166
Author(s) : Ma L , Zhou L , He Y , Wang L , Huang Z , Jiang Y , Gao J
Ref : Biosensors & Bioelectronics , 121 :166 , 2018
Abstract : Core-shell structured nanocomposites (named PtPd@NCS) with N-doped carbon shell and bimetal core (Pt and Pd) were fabricated through a facile strategy for the first time. The PtPd@NCS nanocomposites were obtained through reduction of K2PtCl4, H2PtCl6 and Na2PdCl4 species, self-polymerization of dopamine (DA) and co-assembly of Pluronic F127 using a one-pot approach. DA serves as a reductant, as well as a carbon and nitrogen source. The core-shell structure of the PtPd@NCS nanocomposites was characterized and the result indicated that Pt-Pd nanoparticle core with a diameter of approximately 15nm was encased in the N-doped carbon shells with a thickness of approximately 35nm. The PtPd@NCS nanocomposites were used as an electrode material to prepare acetylcholinesterase (AChE) biosensors for detecting organophosphate pesticides. The obtained AChE biosensor exhibited a linear range of 1x10(-14) to 1x10(-10) M and 1x10(-9) to 1x10(-5) M within the detection limit of 7.9x10(-15) M for malathion, 1x10(-13) to 1x10(-6) within the detection limit of 7.1x10(-14) M for chlopyrifos, and 1x10(-14) to 1x10(-11) M and 1x10(-10) to 1x10(-5) M within the detection limit of 8.6x10(-15) M for parathion methyl. The proposed biosensor also exhibited high selectivity, reproducibility and stability. The AChE biosensor was also applied in real samples for detecting organophosphate pesticides and exhibited acceptable recovery. This work demonstrated that the PtPd@NCS had great potential in constructing biosensors to detect organophosphate pesticides and other analytes.
ESTHER : Ma_2018_Biosens.Bioelectron_121_166
PubMedSearch : Ma_2018_Biosens.Bioelectron_121_166
PubMedID: 30218924

Title : Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats - Ma_2018_Lipids.Health.Dis_17_152
Author(s) : Ma L , Xiao H , Wen J , Liu Z , He Y , Yuan F
Ref : Lipids Health Dis , 17 :152 , 2018
Abstract : BACKGROUND: This study explored the possible mechanism of flavones from Vitis vinifera L. (VTF) on neurotransmitters, synaptic transmission and related learning and memory in rats with Alzheimer disease (AD). METHODS: The researchers injected amyloid-beta(25-35) into the hippocampus to establish AD model rats. The Sprague-Dawley (SD) rats were divided into a control group, a donepezil group, an AD model group, a VTF low-dose group, a VTF medium-dose group and a VTF high-dose group. The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats' hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: VTF may enhance the protein expression of p-CREB, BDNF and SYT1 in rat hippocampi, depending on dose. The messenger RNA (mRNA) level of CREB was significantly higher in the VTF high-dose group than in the model group, which was consistent with the results of Western blotting. VTF may reduce the activity of AChE and increase that of ChAT in rat hippocampi. Finally, VTF effectively improved the learning and memory abilities of AD rats. CONCLUSIONS: VTF can promote synaptic plasticity and indirectly affect the expression of cholinergic neurotransmitters, which may be one mechanism of VTF protection in AD rats.
ESTHER : Ma_2018_Lipids.Health.Dis_17_152
PubMedSearch : Ma_2018_Lipids.Health.Dis_17_152
PubMedID: 29973282

Title : Network-Based Asymmetry of the Human Auditory System - Misic_2018_Cereb.Cortex_28_2655
Author(s) : Misic B , Betzel RF , Griffa A , de Reus MA , He Y , Zuo XN , van den Heuvel MP , Hagmann P , Sporns O , Zatorre RJ
Ref : Cerebral Cortex , 28 :2655 , 2018
Abstract : Converging evidence from activation, connectivity, and stimulation studies suggests that auditory brain networks are lateralized. Here we show that these findings can be at least partly explained by the asymmetric network embedding of the primary auditory cortices. Using diffusion-weighted imaging in 3 independent datasets, we investigate the propensity for left and right auditory cortex to communicate with other brain areas by quantifying the centrality of the auditory network across a spectrum of communication mechanisms, from shortest path communication to diffusive spreading. Across all datasets, we find that the right auditory cortex is better integrated in the connectome, facilitating more efficient communication with other areas, with much of the asymmetry driven by differences in communication pathways to the opposite hemisphere. Critically, the primacy of the right auditory cortex emerges only when communication is conceptualized as a diffusive process, taking advantage of more than just the topologically shortest paths in the network. Altogether, these results highlight how the network configuration and embedding of a particular region may contribute to its functional lateralization.
ESTHER : Misic_2018_Cereb.Cortex_28_2655
PubMedSearch : Misic_2018_Cereb.Cortex_28_2655
PubMedID: 29722805

Title : Planarian cholinesterase: molecular and functional characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity - Hagstrom_2018_Arch.Toxicol_92_1161
Author(s) : Hagstrom D , Zhang S , Ho A , Tsai ES , Radic Z , Jahromi A , Kaj KJ , He Y , Taylor P , Collins ES
Ref : Archives of Toxicology , 92 :1161 , 2018
Abstract : The asexual freshwater planarian Dugesia japonica has emerged as a medium-throughput alternative animal model for neurotoxicology. We have previously shown that D. japonica are sensitive to organophosphorus pesticides (OPs) and characterized the in vitro inhibition profile of planarian cholinesterase (DjChE) activity using irreversible and reversible inhibitors. We found that DjChE has intermediate features of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Here, we identify two candidate genes (Djche1 and Djche2) responsible for DjChE activity. Sequence alignment and structural homology modeling with representative vertebrate AChE and BChE sequences confirmed our structural predictions, and show that both DjChE enzymes have intermediate sized catalytic gorges and disrupted peripheral binding sites. Djche1 and Djche2 were both expressed in the planarian nervous system, as anticipated from previous activity staining, but with distinct expression profiles. To dissect how DjChE inhibition affects planarian behavior, we acutely inhibited DjChE activity by exposing animals to either an OP (diazinon) or carbamate (physostigmine) at 1 microM for 4 days. Both inhibitors delayed the reaction of planarians to heat stress. Simultaneous knockdown of both Djche genes by RNAi similarly resulted in a delayed heat stress response. Furthermore, chemical inhibition of DjChE activity increased the worms' ability to adhere to a substrate. However, increased substrate adhesion was not observed in Djche1/Djche2 (RNAi) animals or in inhibitor-treated day 11 regenerates, suggesting this phenotype may be modulated by other mechanisms besides ChE inhibition. Together, our study characterizes DjChE expression and function, providing the basis for future studies in this system to dissect alternative mechanisms of OP toxicity.
ESTHER : Hagstrom_2018_Arch.Toxicol_92_1161
PubMedSearch : Hagstrom_2018_Arch.Toxicol_92_1161
PubMedID: 29167930
Gene_locus related to this paper: dugja-CHE1 , dugja-CHE2

Title : Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Chronic Ethanol-Induced Cardiac Fibrosis by Restoring Autophagic Flux - Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
Author(s) : Zhou C , Huang J , Li Q , Zhan C , He Y , Liu J , Wen Z , Wang DW
Ref : Alcohol Clin Exp Res , 42 :1970 , 2018
Abstract : BACKGROUND: Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alcoholic injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) to less bioactive diols, and EETs have cardioprotective properties. However, the effects of sEH inhibition in ethanol (EtOH)-induced cardiac fibrosis are unknown. METHODS: This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic EtOH feeding-induced cardiac fibrosis. C57BL/6J mice were fed a 4% Lieber-DeCarli EtOH diet for 8 weeks, and the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered throughout the experimental period. RESULTS: The results showed that chronic EtOH intake led to cardiac dilatation, collagen deposition, and autophagosome accumulation, while TPPU administration ameliorated these effects. In vitro, treating primary cardiac fibroblasts (CFs) with EtOH resulted in CF activation, including alpha smooth muscle actin overexpression, collagen synthesis, and cell migration. Moreover, EtOH disturbed CF autophagic flux, as evidenced by the increased LC3 II/I ratio and SQSTM1 expression, and by the enhanced autophagosome accumulation. TPPU treatment prevented the activation of CF induced by EtOH and restored the impaired autophagic flux by suppressing mTOR activation. CONCLUSIONS: Taken together, these findings suggest that sEH pharmacological inhibition may be a unique therapeutic strategy for treating EtOH-induced cardiac fibrosis.
ESTHER : Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
PubMedSearch : Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
PubMedID: 30047995

Title : Epigallocatechin-3-gallate attenuates cerebral cortex damage and promotes brain regeneration in acrylamide-treated rats - He_2017_Food.Funct_8_2275
Author(s) : He Y , Tan D , Mi Y , Zhou Q , Ji S
Ref : Food Funct , 8 :2275 , 2017
Abstract : Acrylamide (ACR) is a neurotoxic industrial chemical intermediate, which is also present in food and water. We investigated the neuroprotective effects of epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, on ACR-treated rat brain. Rats were pre-treated with EGCG for 4 d and then administered ACR and EGCG for 14 d. EGCG increased acetylcholinesterase (AChE) activity and the rate of Nissl-positive cells in ACR-treated rats. Senescence-associated beta-galactosidase (SA-beta-gal) staining indicated that EGCG attenuated ACR-induced senescence. Tumour necrosis factor alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) protein expression indicated that EGCG inhibited ACR-induced inflammation. In addition, immunohistochemical analysis of nestin and brain-derived neurotrophic factor (BDNF) revealed that EGCG promoted brain regeneration in ACR-treated rats. Altogether, our results suggest that EGCG can attenuate ACR-induced brain damage and promote regeneration in the cerebral cortex of rats. Therefore, we hypothesized that EGCG may alleviate ACR-related nerve injury.
ESTHER : He_2017_Food.Funct_8_2275
PubMedSearch : He_2017_Food.Funct_8_2275
PubMedID: 28561817

Title : Effect of epigallocatechin-3-gallate on acrylamide-induced oxidative stress and apoptosis in PC12 cells - He_2017_Hum.Exp.Toxicol_36_1087
Author(s) : He Y , Tan D , Mi Y , Bai B , Jiang D , Zhou X , Ji S
Ref : Hum Exp Toxicol , 36 :1087 , 2017
Abstract : Acrylamide (ACR) is a chemical intermediate utilized in industry. ACR is also formed during heating of foods containing carbohydrates and amino acids. Therefore, humans are widely exposed to ACR, and ACR neurotoxicity in humans is a significant public health issue attracting wide attention. In this study, we investigated the potential neuroprotective effects of epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic compound in green tea, in PC12 cells treated with ACR. ACR-treated PC12 cells pretreated with various concentrations of EGCG (2.5, 5 and 10 muM) for 24 h had increased viability and acetylcholinesterase activity and reduced apoptosis and necrosis compared to cells exposed to ACR alone. EGCG reduced the expression of bax mRNA, decreased cytochrome c release, reduced intracellular calcium levels, inactivated caspase 3 and increased mitochondrial membrane potential, suggesting that EGCG prevents ACR-induced apoptosis through a mitochondrial-mediated pathway. In addition, EGCG inhibited the formation of reactive oxygen species and lipid peroxidation while enhancing superoxide dismutase activity and glutathione levels, thereby reducing oxidative stress. Our results indicate that pretreatment of PC12 cells with EGCG attenuates ACR-induced apoptosis by reducing oxidative stress. Therefore, drinking green tea may reduce nerve injury induced by ACR.
ESTHER : He_2017_Hum.Exp.Toxicol_36_1087
PubMedSearch : He_2017_Hum.Exp.Toxicol_36_1087
PubMedID: 27920337

Title : Shengjiang Xiexin Decoction Alters Pharmacokinetics of Irinotecan by Regulating Metabolic Enzymes and Transporters: A Multi-Target Therapy for Alleviating the Gastrointestinal Toxicity - Guan_2017_Front.Pharmacol_8_769
Author(s) : Guan HY , Li PF , Wang XM , Yue JJ , He Y , Luo XM , Su MF , Liao SG , Shi Y
Ref : Front Pharmacol , 8 :769 , 2017
Abstract : Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medical formula chronicled in Shang Han Lun, is used in modern clinical practice to decrease gastrointestinal toxicity induced by the chemotherapeutic drug irinotecan (CPT-11). In this study, the effect of SXD on the pharmacokinetics of CPT-11 and its active metabolites (SN-38 and SN-38G), and the underlying mechanisms were further examined. An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous quantification of CPT-11, SN-38, and SN-38G in the plasma, bile, liver, intestine, and intestinal contents of control and SXD-pre-treated rats after intravenous administration of CPT-11. SXD pretreatment increased the area under the curve (AUC) and the initial plasma concentration (C0) of CPT-11 but decreased the plasma clearance (CL). The AUC and the maximum plasma concentration (Cmax) of SN-38 decreased, whereas the Cmax of SN-38G increased. Compared with that of the control group, the biliary excretion of CPT-11, SN-38, and SN-38G was inhibited. The CPT-11, SN-38, and SN-38G concentrations in the liver, intestine, and intestinal contents were different between the two groups. Furthermore, the hepatic expression of multidrug resistance-associated protein-2 (Mrp-2), P-glycoprotein (P-gp), and carboxylesterase 2 (CES2) was significantly down-regulated by SXD, while the hepatic and jejunal uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) expression was elevated. The hydrolysis of CPT-11 to SN-38 by CES and the glucuronidation of SN-38 to SN-38G by UGT were affected by liver and jejunum S9 fractions from rats pre-treated with SXD. Therefore, this study demonstrated for the first time that SXD could alter the pharmacokinetics of CPT-11 and its metabolites to alleviate CPT-11-induced diarrhea. And the underlying mechanism of drug interaction between CPT-11 and SXD involves decreasing hepatic Mrp-2 and P-gp expression and altering the activities of CES and UGT.
ESTHER : Guan_2017_Front.Pharmacol_8_769
PubMedSearch : Guan_2017_Front.Pharmacol_8_769
PubMedID: 29163158

Title : Rationale behind the near-ideal catalysis of Candida antarctica lipase A (CAL-A) for highly concentrating omega-3 polyunsaturated fatty acids into monoacylglycerols - He_2017_Food.Chem_219_230
Author(s) : He Y , Li J , Kodali S , Chen B , Guo Z
Ref : Food Chem , 219 :230 , 2017
Abstract : Dramatic decline in the quality and quantity of omega-3 PUFAs from marine resource demands new environmental-friendly technology to produce high quality omega-3 PUFAs concentrates in a better bioavailable form. Accordingly this work demonstrated an exceptionally highly efficient non-aqueous approach that non-regiospecific and non omega-3 PUFAs preferential Candida antarctica lipase A (CAL-A), functioning as a near-ideal biocatalyst, is capable to directly concentrate omega-3 PUFAs from 20% to 30% in oils to up to >90% in monoacylglycerols form through one step reaction. The rationale behind the experimental observation is justified and the catalytic property and specificity of an ideal enzyme tackling this task are defined. High selectivity and efficiency, excellent reusability of biocatalyst, general applicability for concentrating omega-3 PUFAs from both fish and microalgae oils, simple process for product recovery (e.g. by short path distillation), make this novel approach a highly industrially relevant and with potential application in food and drug industries.
ESTHER : He_2017_Food.Chem_219_230
PubMedSearch : He_2017_Food.Chem_219_230
PubMedID: 27765222
Gene_locus related to this paper: canan-lipasA

Title : Effect of single-wall carbon nanotubes on bioconcentration and toxicity of perfluorooctane sulfonate in zebrafish (Danio rerio) - Li_2017_Sci.Total.Environ_607-608_509
Author(s) : Li Y , Men B , He Y , Xu H , Liu M , Wang D
Ref : Sci Total Environ , 607-608 :509 , 2017
Abstract : The wide application of nanoparticles will lead its release into the aquatic environment, which may alter the bioavailability and toxicity of other contaminants to aquatic organisms. This work aimed to study the effects of perfluorooctane sulfonate (PFOS), single-wall carbon nanotubes (SWCNT), and their mixture on PFOS accumulation, antioxidant defenses and acetylcholinesterase (AChE) activity in zebrafish. The fish was dissected after being exposed (24, 48, 72 and 96h) separately to PFOS, SWCNT and PFOS+SWCNT co-exposure. The bioaccumulation of PFOS in fish tissues (liver, intestines, gills and brain) decreased with increasing dosage of SWCNT, however, the opposite trend was observed in fish skin, which indicated that the bioavailability of PFOS changed by adsorption on SWCNT. Meanwhile, co-exposure induced more reactive oxygen species (ROS) than PFOS alone and enhanced the effect of PFOS on the superoxide dismutase (SOD), and catalase (CAT) and AChE activities. Furthermore, the integrated biomarker response (IBR) showed that co-exposure was the most stressful circumstance.
ESTHER : Li_2017_Sci.Total.Environ_607-608_509
PubMedSearch : Li_2017_Sci.Total.Environ_607-608_509
PubMedID: 28704675

Title : DWARF14, A Receptor Covalently Linked with the Active Form of Strigolactones, Undergoes Strigolactone-Dependent Degradation in Rice - Hu_2017_Front.Plant.Sci_8_1935
Author(s) : Hu Q , He Y , Wang L , Liu S , Meng X , Liu G , Jing Y , Chen M , Song X , Jiang L , Yu H , Wang B , Li J
Ref : Front Plant Sci , 8 :1935 , 2017
Abstract : Strigolactones (SLs) are the latest confirmed phytohormones that regulate shoot branching by inhibiting bud outgrowth in higher plants. Perception of SLs depends on a novel mechanism employing an enzyme-receptor DWARF14 (D14) that hydrolyzes SLs and becomes covalently modified. This stimulates the interaction between D14 and D3, leading to the ubiquitination and degradation of the transcriptional repressor protein D53. However, the regulation of SL perception in rice remains elusive. In this study, we provide evidences that D14 is ubiquitinated after SL treatment and degraded through the 26S proteasome system. The Lys280 site of the D14 amino acid sequence was important for SL-induced D14 degradation, but did not change the subcellular localization of D14 nor disturbed the interaction between D14 and D3, nor D53 degradation. Biochemical and genetic analysis indicated that the key amino acids in the catalytic center of D14 were essential for D14 degradation. We further showed that D14 degradation is dependent on D3 and is tightly correlated with protein levels of D53. These findings revealed that D14 degradation takes place following D53 degradation and functions as an important feedback regulation mechanism of SL perception in rice.
ESTHER : Hu_2017_Front.Plant.Sci_8_1935
PubMedSearch : Hu_2017_Front.Plant.Sci_8_1935
PubMedID: 29170677

Title : Production of new human milk fat substitutes by enzymatic acidolysis of microalgae oils from Nannochloropsis oculata and Isochrysis galbana - He_2017_Bioresour.Technol_238_129
Author(s) : He Y , Qiu C , Guo Z , Huang J , Wang M , Chen B
Ref : Bioresour Technol , 238 :129 , 2017
Abstract : Human milk fat substitutes (HMFs) with four kinds of n-3 fatty acid for infant formula were firstly synthesized using triacylglycerols (TAGs) from Nannochloropsis oculata rich in PA at the sn-2 position and free fatty acids (FFAs) from Isochrysis galbana rich in n-3 polyunsaturated fatty acids (n-3 PUFAs-ALA/SDA/DHA) via solvent-free acidolysis with Novozym 435, Lipozyme 435, TL-IM and RM-IM as biocatalysts. The results show that the resulting HMFs contain total n-3 PUFA of 13.92-17.12% and PA of 59.38-68.13% at the sn-2 position under the optimal conditions (mole ratio FFAs/TAG 3:1, 60 degC (Novozym 435 and Lipozyme TL-IM) and 50 degC (Lipozyme 435 and RM-IM), lipase loading 10%, reaction time 24h). Moreover, among the tested enzymes, Lipozyme 435, TL-IM, and RM-IM display the fatty acid selectivity towards SDA, LA and ALA, and OA, respectively. Overall, the examined lipases are promising biocatalysts for producing high-value microalgal HMFs in a cost-effective manner.
ESTHER : He_2017_Bioresour.Technol_238_129
PubMedSearch : He_2017_Bioresour.Technol_238_129
PubMedID: 28433900

Title : MicroRNA-132 attenuates neurobehavioral and neuropathological changes associated with intracerebral hemorrhage in mice - Zhang_2017_Neurochem.Int_107_182
Author(s) : Zhang Y , Han B , He Y , Li D , Ma X , Liu Q , Hao J
Ref : Neurochem Int , 107 :182 , 2017
Abstract : Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.
ESTHER : Zhang_2017_Neurochem.Int_107_182
PubMedSearch : Zhang_2017_Neurochem.Int_107_182
PubMedID: 27940326

Title : The near-ideal catalytic property of Candida antarctica lipase A to highly concentrate n-3 polyunsaturated fatty acids in monoacylglycerols via one-step ethanolysis of triacylglycerols - He_2016_Bioresour.Technol_219_466
Author(s) : He Y , Li J , Kodali S , Chen B , Guo Z
Ref : Bioresour Technol , 219 :466 , 2016
Abstract : Declining quantity/quality of available n-3 polyunsaturated fatty acids (n-3 PUFAs) resources demand innovative technology to concentrate n-3 PUFAs from low quality oils into value-added products/health-beneficial ingredients rich in n-3 PUFAs. This work proposed the catalytic property and specificity of an ideal enzyme required to tackle this task and identified Candida antarctica lipase A (CAL-A) is such a near-ideal enzyme in practice, which concentrates n-3 PUFAs from 25% to 27% in oils to a theoretically closer value 90% in monoacylglycerols (MAGs) via one-step enzymatic ethanolysis. Non-regiospecificity and high non-n-3 PUFAs preference of CAL-A are the catalytic feature to selectively cleave non-n-3 PUFAs in all 3 positions of triacylglycerols (TAGs); while high ethanol/TAGs ratio, low operation temperature and high tolerance to polar ethanol are essential conditions beyond biocatalyst itself. C-13 Nuclear magnetic resonance ((13)C NMR) analysis and competitive factor estimation verified the hypothesis and confirmed the plausible suggestion of catalytic mechanism of CAL-A.
ESTHER : He_2016_Bioresour.Technol_219_466
PubMedSearch : He_2016_Bioresour.Technol_219_466
PubMedID: 27521783

Title : The molecular steps of citrinin biosynthesis in fungi - He_2016_Chem.Sci_7_2119
Author(s) : He Y , Cox RJ
Ref : Chem Sci , 7 :2119 , 2016
Abstract : The individual steps of citrinin 1 biosynthesis in Monascus ruber M7 were determined by a combination of targeted gene knockout and heterologous gene expression in Aspergillus oryzae. The pathway involves the synthesis of an unreduced trimethylated pentaketide 10 by a non-reducing polyketide synthase (nrPKS) known as CitS. Reductive release yields the keto-aldehyde 2 as the first enzyme-free intermediate. The nrPKS appears to be assisted by an as-yet cryptic hydrolysis step catalysed by CitA which was previously wrongly annotated as an oxidase. CitB is a non-heme iron oxidase which oxidises the 12-methyl of 2 to an alcohol. Subsequent steps are catalysed by CitC which oxidises the 12-alcohol to an aldehyde and CitD which converts the 12-aldehyde to a carboxylic acid. Final reduction of C-3 by CitE yields citrinin. The pathway rules out alternatives involving intramolecular rearrangements, and fully defines the molecular steps for the first time and corrects previous errors in the literature. The activity of CitB links the pathway to fungal tropolone biosynthesis and the observation of aminated shunt products links the pathway to azaphilone biosynthesis. Production of citrinin by coordinated production of CitS + CitA-CitE in the heterologous host A. oryzae, in which each gene was driven by a constitutive promoter, was achieved in high yield.
ESTHER : He_2016_Chem.Sci_7_2119
PubMedSearch : He_2016_Chem.Sci_7_2119
PubMedID: 29899939
Gene_locus related to this paper: monpu-cita

Title : Discovery of Multitarget-Directed Ligands against Alzheimer's Disease through Systematic Prediction of Chemical-Protein Interactions - Fang_2015_J.Chem.Inf.Model_55_149
Author(s) : Fang J , Li Y , Liu R , Pang X , Li C , Yang R , He Y , Lian W , Liu AL , Du GH
Ref : J Chem Inf Model , 55 :149 , 2015
Abstract : To determine chemical-protein interactions (CPI) is costly, time-consuming, and labor-intensive. In silico prediction of CPI can facilitate the target identification and drug discovery. Although many in silico target prediction tools have been developed, few of them could predict active molecules against multitarget for a single disease. In this investigation, naive Bayesian (NB) and recursive partitioning (RP) algorithms were applied to construct classifiers for predicting the active molecules against 25 key targets toward Alzheimer's disease (AD) using the multitarget-quantitative structure-activity relationships (mt-QSAR) method. Each molecule was initially represented with two kinds of fingerprint descriptors (ECFP6 and MACCS). One hundred classifiers were constructed, and their performance was evaluated and verified with internally 5-fold cross-validation and external test set validation. The range of the area under the receiver operating characteristic curve (ROC) for the test sets was from 0.741 to 1.0, with an average of 0.965. In addition, the important fragments for multitarget against AD given by NB classifiers were also analyzed. Finally, the validated models were employed to systematically predict the potential targets for six approved anti-AD drugs and 19 known active compounds related to AD. The prediction results were confirmed by reported bioactivity data and our in vitro experimental validation, resulting in several multitarget-directed ligands (MTDLs) against AD, including seven acetylcholinesterase (AChE) inhibitors ranging from 0.442 to 72.26 muM and four histamine receptor 3 (H3R) antagonists ranging from 0.308 to 58.6 muM. To be exciting, the best MTDL DL0410 was identified as an dual cholinesterase inhibitor with IC50 values of 0.442 muM (AChE) and 3.57 muM (BCHE) as well as a H3R antagonist with an IC50 of 0.308 muM. This investigation is the first report using mt-QASR approach to predict chemical-protein interaction for a single disease and discovering highly potent MTDLs. This protocol may be useful for in silico multitarget prediction of other diseases.
ESTHER : Fang_2015_J.Chem.Inf.Model_55_149
PubMedSearch : Fang_2015_J.Chem.Inf.Model_55_149
PubMedID: 25531792

Title : The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration - Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
Author(s) : Xiao L , Yang G , Zhang L , Yang X , Zhao S , Ji Z , Zhou Q , Hu M , Wang Y , Chen M , Xu Y , Jin H , Xiao X , Hu G , Bao F , Hu Y , Wan P , Li L , Deng X , Kuang T , Xiang C , Zhu JK , Oliver MJ , He Y
Ref : Proc Natl Acad Sci U S A , 112 :5833 , 2015
Abstract : "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes.
ESTHER : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedSearch : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedID: 25902549
Gene_locus related to this paper: 9lami-a0a2z7c6k4 , 9lami-a0a2z7bgj4

Title : Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis - Wen_2015_Int.J.Clin.Exp.Med_8_20343
Author(s) : Wen Y , Huang Z , Zhang X , Gao B , He Y
Ref : Int J Clin Exp Med , 8 :20343 , 2015
Abstract : OBJECTIVE: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk.
METHODS: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals.
RESULTS: The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). CONCLUSION: For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer.
ESTHER : Wen_2015_Int.J.Clin.Exp.Med_8_20343
PubMedSearch : Wen_2015_Int.J.Clin.Exp.Med_8_20343
PubMedID: 26884950

Title : Contribution of Disulfide Bridges to the Thermostability of a Type A Feruloyl Esterase from Aspergillus usamii - Yin_2015_PLoS.One_10_e0126864
Author(s) : Yin X , Hu D , Li JF , He Y , Zhu TD , Wu MC
Ref : PLoS ONE , 10 :e0126864 , 2015
Abstract : The contribution of disulfide bridges to the thermostability of a type A feruloyl esterase (AuFaeA) from Aspergillus usamii E001 was studied by introducing an extra disulfide bridge or eliminating a native one from the enzyme. MODIP and DbD, two computational tools that can predict the possible disulfide bridges in proteins for thermostability improvement, and molecular dynamics (MD) simulations were used to design the extra disulfide bridge. One residue pair A126-N152 was chosen, and the respective amino acid residues were mutated to cysteine. The wild-type AuFaeA and its variants were expressed in Pichia pastoris GS115. The temperature optimum of the recombinant (re-) AuFaeAA126C-N152C was increased by 6 degreesC compared to that of re-AuFaeA. The thermal inactivation half-lives of re-AuFaeAA126C-N152C at 55 and 60 degreesC were 188 and 40 min, which were 12.5- and 10-folds longer than those of re-AuFaeA. The catalytic efficiency (kcat/Km) of re-AuFaeAA126C-N152C was similar to that of re-AuFaeA. Additionally, after elimination of each native disulfide bridge in AuFaeA, a great decrease in expression level and at least 10 degreesC decrease in thermal stability of recombinant AuEaeA variants were also observed.
ESTHER : Yin_2015_PLoS.One_10_e0126864
PubMedSearch : Yin_2015_PLoS.One_10_e0126864
PubMedID: 25969986
Gene_locus related to this paper: aspni-FAEA

Title : Aberrant soluble epoxide hydrolase and oxylipin levels in a porcine arteriovenous graft stenosis model - Terry_2014_J.Vasc.Res_51_269
Author(s) : Terry CM , Carlson ML , He Y , Ulu A , Morisseau C , Blumenthal DK , Hammock BD , Cheung AK
Ref : J Vasc Res , 51 :269 , 2014
Abstract : Synthetic arteriovenous grafts (AVGs) used for hemodialysis frequently fail due to the development of neointimal hyperplasia (NH) at the vein-graft anastomosis. Inflammation and smooth-muscle cell (SMC) and myofibroblast proliferation and migration likely play an important role in the pathogenesis of NH. Epoxyeicosatrienoic acids (EETs), the products of the catabolism of arachidonic acid by cytochrome P450 enzymes, possess anti-inflammatory, antiproliferative, antimigratory and vasodilatory properties that should reduce NH. The degradation of vasculoprotective EETs is catalyzed by the enzyme, soluble epoxide hydrolase (sEH). sEH upregulation may thus contribute to NH development by the enhanced removal of vasculoprotective EETs. In this study, sEH, cytochrome P450 and EETs were examined after AVG placement in a porcine model to explore their potential roles in AVG stenosis. Increased sEH protein expression, decreased P450 epoxygenase activity and dysregulation of 5 oxylipin mediators were observed in the graft-venous anastomotic tissues when compared to control veins. Pharmacological inhibitors of sEH decreased the growth factor-induced migration of SMCs and fibroblasts, although they had no significant effect on the proliferation of these cells. These results provide insights on epoxide biology in vascular disorders and a rationale for the development of novel pharmacotherapeutic strategies to prevent AVG failure due to NH and stenosis.
ESTHER : Terry_2014_J.Vasc.Res_51_269
PubMedSearch : Terry_2014_J.Vasc.Res_51_269
PubMedID: 25196102

Title : Application of fully automatic hollow fiber liquid phase microextraction to assess the distribution of organophosphate esters in the Pearl River Estuaries - Wang_2014_Sci.Total.Environ_470-471_263
Author(s) : Wang X , He Y , Lin L , Zeng F , Luan T
Ref : Sci Total Environ , 470-471 :263 , 2014
Abstract : Organophosphate esters (OPEs) are widespread organic pollutants that could be detected in various environmental matrices. In this study, a sample pretreatment method was developed for the determination of 9 OPEs by automatic hollow fiber-liquid phase microextraction (HF-LPME) coupled with gas chromatography-mass spectrometry (GC-MS). High sensitivity of OPEs could be achieved after optimization of several important parameters with the limits of detection (LODs) ranging from 2.6 to 120ngL(-1) for different individual OPEs, and the relative standard deviations (RSDs) ranged from 2.1% to 10.4%. Acceptable recoveries were observed and the proposed method was then successfully applied to determine OPEs in seawaters collected from 23 sampling sites of the Pearl River Estuaries in dry and wet seasons, respectively. All of the OPEs could be detected, except tris(2-ethylhexyl) phosphate (TEHP). The total concentrations of 9 OPEs in seawaters were ranging from 2.04 (Hemen) to 3.12 (Humen) mugL(-1) in the dry season and from 1.08 (Hemen) to 2.50 (Jitimen) mugL(-1) in the wet season. By using spatial interpolation method of ordinary kriging, the most polluted area of SigmaOPEs was found in Humen in the dry season, while it was Jitimen in the wet season. Moreover, the annual input of SigmaOPEs discharged via eight estuaries ranged from 384tons (Jitimen) to 1225tons (Modaomen), and the total annual input was 5694tons.
ESTHER : Wang_2014_Sci.Total.Environ_470-471_263
PubMedSearch : Wang_2014_Sci.Total.Environ_470-471_263
PubMedID: 24140697

Title : Activation of alpha-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress - Han_2014_PLoS.One_9_e105711
Author(s) : Han Z , Shen F , He Y , Degos V , Camus M , Maze M , Young WL , Su H
Ref : PLoS ONE , 9 :e105711 , 2014
Abstract : Activation of alpha-7 nicotinic acetylcholine receptor (alpha-7 nAchR) has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that alpha-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1) and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, alpha-7 nAchR agonist), methyllycaconitine (MLA, nAchR antagonist), or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO). Behavior test, lesion volume, CD68(+), M1 (CD11b(+)/Iba1(+)) and M2 (CD206/Iba1+) microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68(+) and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in alpha-7 nAchR neuro-protective effect.
ESTHER : Han_2014_PLoS.One_9_e105711
PubMedSearch : Han_2014_PLoS.One_9_e105711
PubMedID: 25157794

Title : A Novel Risk Haplotype of ALOX5AP Gene is Associated with Ischemic Stroke in Chinese Han Population - Yang_2014_J.Mol.Neurosci_53_493
Author(s) : Yang D , He Y , Li M , Shi C , Song G , Wang Q , Fan Y , Feng Q , Zheng H
Ref : Journal of Molecular Neuroscience , 53 :493 , 2014
Abstract : Previous studies have implicated that two at-risk haplotypes (HapA and HapB) of gene-encoding 5-lipoxygenase-activating protein (ALOX5AP) were significantly associated with stroke. The aim of this study was to explore the association between haplotypes of ALOX5AP gene and risk for ischemic stroke (IS) in Chinese Han population. A total of 492 patients with IS and 490 matched control subjects were recruited. Six ALOX5AP SNPs (SG13S377, SG13S114, SG13S41, SG13S89, SG13S32 and SG13S35) were genotyped by SNaPshot minisequence technique. A common genetic variant SG13S114/AA in the ALOX5AP gene was associated with IS in this Chinese cohort (OR = 2.514, 95 % CI = 1.667 ~ 3.790). HapA (TGA) and HapB (AAAG) had no significant difference in the patients (36.3 and 18.5 %, respectively) and controls (37.6 and 16.3 %, respectively) (P = 0.631 and P = 0.375, respectively). But, the frequency of Hap (GAAG) was significantly higher in the patients than that in the controls after Bonferroni's adjustment (P = 0.006). To conclude, SG13S114/AA of the ALOX5AP gene was associated with an increased risk for IS. A novel risk haplotype, Hap (GAAG) was a genetic risk factor for IS in this Chinese population.
ESTHER : Yang_2014_J.Mol.Neurosci_53_493
PubMedSearch : Yang_2014_J.Mol.Neurosci_53_493
PubMedID: 24198186

Title : Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage - He_2014_Neural.Regen.Res_9_1985
Author(s) : He Y , Zhu J , Huang F , Qin L , Fan W , He H
Ref : Neural Regen Res , 9 :1985 , 2014
Abstract : The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.
ESTHER : He_2014_Neural.Regen.Res_9_1985
PubMedSearch : He_2014_Neural.Regen.Res_9_1985
PubMedID: 25598781

Title : Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - He_2013_Eur.J.Med.Chem_63C_299
Author(s) : He Y , Yao PF , Chen SB , Huang ZH , Huang SL , Tan JH , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 63C :299 , 2013
Abstract : A series of 7,8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer's disease (AD). All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0.60 to 196.7 nM, and good selectivity for AChE over butyrylcholinesterase (BCHE) (125- to 3225-fold). A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE. Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (Abeta) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators. Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment.
ESTHER : He_2013_Eur.J.Med.Chem_63C_299
PubMedSearch : He_2013_Eur.J.Med.Chem_63C_299
PubMedID: 23501115

Title : Crystal structures of two phytohormone signal-transducing alpha\/beta hydrolases: karrikin-signaling KAI2 and strigolactonesignaling DWARF14 -
Author(s) : Zhao LH , Zhou XE , Wu ZS , Yi W , Xu Y , Li S , Xu TH , Liu Y , Chen RZ , Kovach A , Kang Y , Hou L , He Y , Xie C , Song W , Zhong D , Wang Y , Li J , Zhang C , Melcher K , Xu HE
Ref : Cell Res , 23 :436 , 2013
PubMedID: 23381136
Gene_locus related to this paper: orysj-Q10QA5

Title : Genome Sequencing of Bacillus subtilis Strain XF-1 with High Efficiency in the Suppression of Plasmodiophora brassicae - Guo_2013_Genome.Announc_1_e0006613
Author(s) : Guo S , Mao Z , Wu Y , Hao K , He P , He Y
Ref : Genome Announc , 1 :e0006613 , 2013
Abstract : The genome of the rhizobacterium Bacillus subtilis XF-1 is 4.06 Mb in size and harbors 3,853 coding sequences (CDS). Giant gene clusters were dedicated to the nonribosomal synthesis of antimicrobial lipopeptides and polyketides. Remarkably, XF-1 possesses a gene cluster involved in the synthesis of chitosanase that is related to the suppression of the pathogen Plasmodiophora brassicae.
ESTHER : Guo_2013_Genome.Announc_1_e0006613
PubMedSearch : Guo_2013_Genome.Announc_1_e0006613
PubMedID: 23558530
Gene_locus related to this paper: bacsu-pnbae , bacsu-YVAK

Title : Butyrylcholinesterase genotype and gender influence Alzheimer's disease phenotype - Lane_2013_Alzheimers.Dement_9_e1
Author(s) : Lane RM , He Y
Ref : Alzheimers Dement , 9 :e1 , 2013
Abstract : Retrospective data are presented to support a spectrum of early Alzheimer's disease (AD) along a continuum defined by gender and genotype. The putative neurodegenerative mechanisms driving distinct phenotypes at each end of the spectrum are glial hypoactivity associated with early failure of synaptic cholinergic neurotransmission and glial overactivation associated with loss of neural network connectivity due to accelerated age-related breakdown of myelin. In early AD, male butyrylcholinesterase K-variant carriers with one or two apolipoprotein varepsilon4 alleles have prominent medial temporal atrophy, synaptic failure, cognitive decline, and accumulation of aggregated beta-amyloid peptide. Increasing synaptic acetylcholine in damaged but still functional cholinergic synapses improves cognitive symptoms, whereas increasing the ability of glia to support synapses and to clear beta-amyloid peptide might be disease-modifying. Conversely, chronic glial overactivation can also drive degenerative processes and in butyrylcholinesterase K-variant negative females generalized glial overactivation may be the main driver from mild cognitive impairment to AD. Females are more likely than males to have accelerated age-related myelin breakdown, more widespread white matter loss, loss of neural network connectivity, whole brain atrophy, and functional decline. Increasing extracellular acetylcholine levels blocks glial activation, reduces myelin loss and damage to neural network connectivity, and is disease-modifying. Between extremes characterized by gender, genotype, and age, pathophysiology may be mixed and this spectrum may explain much of the heterogeneity of amnestic mild cognitive impairment. Preservation of the functional integrity of the neural network may be an important component of strengthening cognitive reserve and significantly delaying the onset and progression of dementia, particularly in females. Prospective confirmation of these hypotheses is required. Implications for future research and therapeutic opportunities are discussed.
ESTHER : Lane_2013_Alzheimers.Dement_9_e1
PubMedSearch : Lane_2013_Alzheimers.Dement_9_e1
PubMedID: 22402324

Title : DWARF 53 acts as a repressor of strigolactone signalling in rice - Jiang_2013_Nature_504_401
Author(s) : Jiang L , Liu X , Xiong G , Liu H , Chen F , Wang L , Meng X , Liu G , Yu H , Yuan Y , Yi W , Zhao L , Ma H , He Y , Wu Z , Melcher K , Qian Q , Xu HE , Wang Y , Li J
Ref : Nature , 504 :401 , 2013
Abstract : Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF(D3) ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.
ESTHER : Jiang_2013_Nature_504_401
PubMedSearch : Jiang_2013_Nature_504_401
PubMedID: 24336200

Title : Genome Sequence of an Environmental Isolate of the Bacterial Pathogen Legionella pneumophila - Ma_2013_Genome.Announc_1_E00320
Author(s) : Ma J , He Y , Hu B , Luo ZQ
Ref : Genome Announc , 1 : , 2013
Abstract : We report here the genomic sequence of Legionella pneumophila strain LPE509 from the water distribution system of a hospital in Shanghai, China. This is the first complete genome sequence of an environmental L. pneumophila isolate. Genomic analyses identified approximately 600 genes unique to LPE509 compared to those of the 7 available L. pneumophila genomes.
ESTHER : Ma_2013_Genome.Announc_1_E00320
PubMedSearch : Ma_2013_Genome.Announc_1_E00320
PubMedID: 23792742
Gene_locus related to this paper: legpa-q5x473 , legph-q5zwi2 , legpn-i7i328

Title : The genome of plant growth-promoting Bacillus amyloliquefaciens subsp. plantarum strain YAU B9601-Y2 contains a gene cluster for mersacidin synthesis - Hao_2012_J.Bacteriol_194_3264
Author(s) : Hao K , He P , Blom J , Rueckert C , Mao Z , Wu Y , He Y , Borriss R
Ref : Journal of Bacteriology , 194 :3264 , 2012
Abstract : The genome of rhizobacterium Bacillus amyloliquefaciens subsp. plantarum YAU B9601-Y2 was 4.24 Mb in size and harbored 3,991 coding sequences (CDS). Giant gene clusters were dedicated to nonribosomal synthesis of antimicrobial lipopeptides and polyketides. Remarkably, CAU B946 possessed a gene cluster involved in synthesis of mersacidin.
ESTHER : Hao_2012_J.Bacteriol_194_3264
PubMedSearch : Hao_2012_J.Bacteriol_194_3264
PubMedID: 22628498
Gene_locus related to this paper: baca2-a7z811

Title : Genome sequence of the plant growth promoting strain Bacillus amyloliquefaciens subsp. plantarum B9601-Y2 and expression of mersacidin and other secondary metabolites - He_2012_J.Biotechnol_164_281
Author(s) : He P , Hao K , Blom J , Ruckert C , Vater J , Mao Z , Wu Y , Hou M , He Y , Borriss R
Ref : J Biotechnol , 164 :281 , 2012
Abstract : The plant-associated Bacillus amyloliquefaciens subsp. plantarum strain B9601-Y2, isolated from wheat rhizosphere, is a powerful plant growth-promoting rhizobacterium. Its relative large genome size of 4.24Mbp, exceeding that of other representatives of the B. amyloliquefaciens subsp. plantarum taxon, is mainly due to the presence of 18 DNA-islands containing remnants of phages, a unique restriction modification system, a gene cluster for mersacidin synthesis, and an orphan gene cluster devoted to non-ribosomal synthesis of an unidentified peptide. Like other members of the taxon, the Y2 genome contains giant gene clusters for non-ribosomal synthesis of the polyketides macrolactin, difficidin, and bacillaene, the antifungal lipopeptides bacillomycin D, and fengycin, the siderophore bacillibactin, and the dipeptide bacilysin. A gene cluster encoding enzymes for a degradative pathway with 2-keto-3-deoxygluconate and 2-keto-3-deoxy-phosphogluconate as intermediates was explored by genome mining and found as being a unique feature for representatives of the plantarum subspecies. A survey of the Y2 genome against other B. amyloliquefaciens genomes revealed 130 genes only occurring in subsp. plantarum but not in subsp. amyloliquefaciens. Notably, the surfactin gene cluster is not functional due to a large deletion removing parts of the Srf synthetases B and C. Expression of polyketides, lipopeptides, mersacidin, and of the growth hormone indole-3-acetic acid in Y2 was demonstrated by matrix-assisted laser desorption ionization-time of flight mass spectroscopy and high-performance liquid chromatography, respectively.
ESTHER : He_2012_J.Biotechnol_164_281
PubMedSearch : He_2012_J.Biotechnol_164_281
PubMedID: 23357245
Gene_locus related to this paper: baca2-a7z924 , bacsu-YVAK

Title : [Expression and molecular evolution of recombinant acetylcholinesterase for detection of pesticide residues: a review] - Dong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_557
Author(s) : Dong J , Li Z , Lei H , He Y , Wang H , Sun Y
Ref : Sheng Wu Gong Cheng Xue Bao , 28 :557 , 2012
Abstract : Acetylcholinesterase (AChE) plays a key role in the pesticide determination. However, the extraction of AChE from natural materials has the disadvantages of low yield, complex purification and poor stability. Therefore, the preparation of recombinant AChE with high performance becomes the hot topic of researchers in recent years. In this article we summarize the progress in the expression of recombinant AChE and the improvement of its analytical characteristic. Finally, we point out that the directed evolution strategy combined with surface display technology is the future trend on improving recombinant AChE activity.
ESTHER : Dong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_557
PubMedSearch : Dong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_557
PubMedID: 22916494

Title : Complete genome sequence of Brucella melitensis biovar 3 strain NI, isolated from an aborted bovine fetus - Liu_2012_J.Bacteriol_194_6321
Author(s) : Liu W , Jing Z , Ou Q , Cui B , He Y , Wu Q
Ref : Journal of Bacteriology , 194 :6321 , 2012
Abstract : From an aborted bovine fetus in China, a bacterial strain named NI was isolated and identified as Brucella melitensis by a PCR assay. Strain NI was further characterized as B. melitensis biovar 3 using biochemical assays. Here we report the complete genome sequence of strain NI.
ESTHER : Liu_2012_J.Bacteriol_194_6321
PubMedSearch : Liu_2012_J.Bacteriol_194_6321
PubMedID: 23105063
Gene_locus related to this paper: brume-PCAD

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : The identification of cutin synthase: formation of the plant polyester cutin - Yeats_2012_Nat.Chem.Biol_8_609
Author(s) : Yeats TH , Martin LB , Viart HM , Isaacson T , He Y , Zhao L , Matas AJ , Buda GJ , Domozych DS , Clausen MH , Rose JK
Ref : Nat Chemical Biology , 8 :609 , 2012
Abstract : A hydrophobic cuticle consisting of waxes and the polyester cutin covers the aerial epidermis of all land plants, providing essential protection from desiccation and other stresses. We have determined the enzymatic basis of cutin polymerization through characterization of a tomato extracellular acyltransferase, CD1, and its substrate, 2-mono(10,16-dihydroxyhexadecanoyl)glycerol. CD1 has in vitro polyester synthesis activity and is required for cutin accumulation in vivo, indicating that it is a cutin synthase.
ESTHER : Yeats_2012_Nat.Chem.Biol_8_609
PubMedSearch : Yeats_2012_Nat.Chem.Biol_8_609
PubMedID: 22610035

Title : Microarray analysis of gene regulations and potential association with acephate-resistance and fitness cost in Lygus lineolaris - Zhu_2012_PLoS.One_7_e37586
Author(s) : Zhu YC , Guo Z , He Y , Luttrell R
Ref : PLoS ONE , 7 :e37586 , 2012
Abstract : The tarnished plant bug has become increasingly resistant to organophosphates in recent years. To better understand acephate resistance mechanisms, biological, biochemical, and molecular experiments were systematically conducted with susceptible (LLS) and acephate-selected (LLR) strains. Selection of a field population with acephate significantly increased resistance ratio to 5.9-fold, coupled with a significant increase of esterase activities by 2-fold. Microarray analysis of 6,688 genes revealed 329 up- and 333 down-regulated (>/=2-fold) genes in LLR. Six esterase, three P450, and one glutathione S-transferase genes were significantly up-regulated, and no such genes were down-regulated in LLR. All vitellogenin and eggshell protein genes were significantly down-regulated in LLR. Thirteen protease genes were significantly down-regulated and only 3 were up-regulated in LLR. More than twice the number of catalysis genes and more than 3.6-fold of metabolic genes were up-regulated, respectively, as compared to those down-regulated with the same molecular and biological functions. The large portion of metabolic or catalysis genes with significant up-regulations indicated a substantial increase of metabolic detoxification in LLR. Significant increase of acephate resistance, increases of esterase activities and gene expressions, and variable esterase sequences between LLS and LLR consistently demonstrated a major esterase-mediated resistance in LLR, which was functionally provable by abolishing the resistance with esterase inhibitors. In addition, significant elevation of P450 gene expression and reduced susceptibility to imidacloprid in LLR indicated a concurrent resistance risk that may impact other classes of insecticides. This study demonstrated the first association of down-regulation of reproductive- and digestive-related genes with resistance to conventional insecticides, suggesting potential fitness costs associated with resistance development. This study shed new light on the understanding of the molecular basis of insecticide resistance, and the information is highly valuable for development of chemical control guidelines and tactics to minimize resistance and cross-resistance risks.
ESTHER : Zhu_2012_PLoS.One_7_e37586
PubMedSearch : Zhu_2012_PLoS.One_7_e37586
PubMedID: 22655059
Gene_locus related to this paper: lygli-i3wnt1 , lygli-q5sex5

Title : Activation of transcription factor MEF2D by bis(3)-cognitin protects dopaminergic neurons and ameliorates Parkinsonian motor defects - Yao_2012_J.Biol.Chem_287_34246
Author(s) : Yao L , Li W , She H , Dou J , Jia L , He Y , Yang Q , Zhu J , Capiro NL , Walker DI , Pennell KD , Pang Y , Liu Y , Han Y , Mao Z
Ref : Journal of Biological Chemistry , 287 :34246 , 2012
Abstract : Parkinson disease (PD) is characterized by the selective demise of dopaminergic (DA) neurons in the substantial nigra pars compacta. Dysregulation of transcriptional factor myocyte enhancer factor 2D (MEF2D) has been implicated in the pathogenic process in in vivo and in vitro models of PD. Here, we identified a small molecule bis(3)-cognitin (B3C) as a potent activator of MEF2D. We showed that B3C attenuated the toxic effects of neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) by activating MEF2D via multiple mechanisms. B3C significantly reduced MPP(+)-induced oxidative stress and potentiated Akt to down-regulate the activity of MEF2 inhibitor glycogen synthase kinase 3beta (GSK3beta) in a DA neuronal cell line SN4741. Furthermore, B3C effectively rescued MEF2D from MPP(+)-induced decline in both nucleic and mitochondrial compartments. B3C offered SN4741 cells potent protection against MPP(+)-induced apoptosis via MEF2D. Interestingly, B3C also protected SN4741 cells from wild type or mutant A53T alpha-synuclein-induced cytotoxicity. Using the in vivo PD model of C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), we showed that B3C maintained redox homeostasis, promoted Akt function activity, and restored MEF2D level in midbrain neurons. Moreover, B3C greatly prevented the loss of tyrosine hydroxylase signal in substantial nigra pars compacta DA neurons and ameliorated behavioral impairments in mice treated with MPTP. Collectedly, our studies identified B3C as a potent neuroprotective agent whose effectiveness relies on its ability to effectively up-regulate MEF2D in DA neurons against toxic stress in models of PD in vitro and in vivo.
ESTHER : Yao_2012_J.Biol.Chem_287_34246
PubMedSearch : Yao_2012_J.Biol.Chem_287_34246
PubMedID: 22891246

Title : Synthesis and evaluation of heterobivalent tacrine derivatives as potential multi-functional anti-Alzheimer agents - Luo_2011_Eur.J.Med.Chem_46_2609
Author(s) : Luo W , Li YP , He Y , Huang SL , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 46 :2609 , 2011
Abstract : A new series of heterobivalent tacrine derivatives were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents for their inhibitory activity on cholinesterases, antioxidant activity and self-induced beta-amyloid (Abeta) aggregation. All these synthesized compounds had potent inhibition activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at nanomolar range. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The compounds containing hydroxyl group showed potent peroxyl radical absorbance activity. In addition, compound 5j exhibited higher self-induced Abeta aggregation inhibitory activity than curcumin, which could become a multi-functional agent for further development for the treatment of AD.
ESTHER : Luo_2011_Eur.J.Med.Chem_46_2609
PubMedSearch : Luo_2011_Eur.J.Med.Chem_46_2609
PubMedID: 21497959

Title : Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation - Luo_2011_Bioorg.Med.Chem_19_763
Author(s) : Luo W , Li YP , He Y , Huang SL , Tan JH , Ou TM , Li D , Gu LQ , Huang ZS
Ref : Bioorganic & Medicinal Chemistry , 19 :763 , 2011
Abstract : A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced beta-amyloid (Abeta) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC(5)(0) values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Abeta aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD.
ESTHER : Luo_2011_Bioorg.Med.Chem_19_763
PubMedSearch : Luo_2011_Bioorg.Med.Chem_19_763
PubMedID: 21211982

Title : Genome sequence and analysis of the tuber crop potato - Xu_2011_Nature_475_189
Author(s) : Xu X , Pan S , Cheng S , Zhang B , Mu D , Ni P , Zhang G , Yang S , Li R , Wang J , Orjeda G , Guzman F , Torres M , Lozano R , Ponce O , Martinez D , De la Cruz G , Chakrabarti SK , Patil VU , Skryabin KG , Kuznetsov BB , Ravin NV , Kolganova TV , Beletsky AV , Mardanov AV , Di Genova A , Bolser DM , Martin DM , Li G , Yang Y , Kuang H , Hu Q , Xiong X , Bishop GJ , Sagredo B , Mejia N , Zagorski W , Gromadka R , Gawor J , Szczesny P , Huang S , Zhang Z , Liang C , He J , Li Y , He Y , Xu J , Zhang Y , Xie B , Du Y , Qu D , Bonierbale M , Ghislain M , Herrera Mdel R , Giuliano G , Pietrella M , Perrotta G , Facella P , O'Brien K , Feingold SE , Barreiro LE , Massa GA , Diambra L , Whitty BR , Vaillancourt B , Lin H , Massa AN , Geoffroy M , Lundback S , DellaPenna D , Buell CR , Sharma SK , Marshall DF , Waugh R , Bryan GJ , Destefanis M , Nagy I , Milbourne D , Thomson SJ , Fiers M , Jacobs JM , Nielsen KL , Sonderkaer M , Iovene M , Torres GA , Jiang J , Veilleux RE , Bachem CW , De Boer J , Borm T , Kloosterman B , van Eck H , Datema E , Hekkert B , Goverse A , van Ham RC , Visser RG
Ref : Nature , 475 :189 , 2011
Abstract : Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.
ESTHER : Xu_2011_Nature_475_189
PubMedSearch : Xu_2011_Nature_475_189
PubMedID: 21743474
Gene_locus related to this paper: soltu-q2tqv0 , soltu-q4h433 , soltu-m0zl00 , soltu-m1aw23 , soltu-m0zxh5 , soltu-m1d3q4 , soltu-m1bz14 , soltu-m1d3q6 , sollc-k4b1g3 , soltu-m0zzn8 , soltu-m1ba60 , sollc-k4bf33 , soltu-m1c8d8 , soltu-m1ced9 , soltu-m1a385 , soltu-m1bz15 , soltu-m1a7s9 , soltu-m1bc84 , soltu-m1bpd1 , sollc-k4bm34 , soltu-m1a487 , soltu-m1a5u0 , soltu-m1cjx7 , soltu-m1bvq8 , soltu-m1baq1 , soltu-m1cfh4 , soltu-m1azl4 , soltu-m0ztj0 , soltu-m1d6d0 , soltu-m1cap1 , soltu-m1a7m1 , soltu-m1d3s6

Title : Group XV phospholipase A, a lysosomal phospholipase A - Shayman_2011_Prog.Lipid.Res_50_1
Author(s) : Shayman JA , Kelly R , Kollmeyer J , He Y , Abe A
Ref : Prog Lipid Res , 50 :1 , 2011
Abstract : A phospholipase A was identified from MDCK cell homogenates with broad specificity toward glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The phospholipase has the unique ability to transacylate short chain ceramides. This phospholipase is calcium-independent, localized to lysosomes, and has an acidic pH optimum. The enzyme was purified from bovine brain and found to be a water-soluble glycoprotein consisting of a single peptide chain with a molecular weight of 45 kDa. The primary structure deduced from the DNA sequences is highly conserved between chordates. The enzyme was named lysosomal phospholipase A (LPLA) and subsequently designated group XV phospholipase A. LPLA has 49% of amino acid sequence identity to lecithin-cholesterol acyltransferase and is a member of the alphabeta-hydrolase superfamily. LPLA is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA(-/-) mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA(-/-) mice develop a phenotype similar to human autoimmune disease. These observations indicate that LPLA may play a primary role in phospholipid homeostasis, drug toxicity, and host defense.
ESTHER : Shayman_2011_Prog.Lipid.Res_50_1
PubMedSearch : Shayman_2011_Prog.Lipid.Res_50_1
PubMedID: 21074554
Gene_locus related to this paper: human-PLA2G15

Title : Natural variation in GS5 plays an important role in regulating grain size and yield in rice - Li_2011_Nat.Genet_43_1266
Author(s) : Li Y , Fan C , Xing Y , Jiang Y , Luo L , Sun L , Shao D , Xu C , Li X , Xiao J , He Y , Zhang Q
Ref : Nat Genet , 43 :1266 , 2011
Abstract : Increasing crop yield is one of the most important goals of plant science research. Grain size is a major determinant of grain yield in cereals and is a target trait for both domestication and artificial breeding(1). We showed that the quantitative trait locus (QTL) GS5 in rice controls grain size by regulating grain width, filling and weight. GS5 encodes a putative serine carboxypeptidase and functions as a positive regulator of grain size, such that higher expression of GS5 is correlated with larger grain size. Sequencing of the promoter region in 51 rice accessions from a wide geographic range identified three haplotypes that seem to be associated with grain width. The results suggest that natural variation in GS5 contributes to grain size diversity in rice and may be useful in improving yield in rice and, potentially, other crops(2).
ESTHER : Li_2011_Nat.Genet_43_1266
PubMedSearch : Li_2011_Nat.Genet_43_1266
PubMedID: 22019783
Gene_locus related to this paper: orysa-q5w727

Title : BuChE-K and APOE epsilon4 allele frequencies in Lewy body dementias, and influence of genotype and hyperhomocysteinemia on cognitive decline - Lane_2009_Mov.Disord_24_392
Author(s) : Lane R , He Y , Morris C , Leverenz JB , Emre M , Ballard C
Ref : Movement Disordersord , 24 :392 , 2009
Abstract : Apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase-K (BuChE-K) are associated with an increased risk for Alzheimer's disease. The primary objective was to evaluate frequencies of these alleles in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A secondary objective was to evaluate influences on rate of cognitive decline. This analysis used data from participants consenting to pharmacogenetic testing in placebo-controlled rivastigmine studies. Allele frequencies in DLB and PDD were compared using logistic regression. Within the PDD placebo sample, associations with cognitive decline were evaluated (the DLB sample was too small for these evaluations). Fifty-seven DLB and 323 PDD subjects provided APOE and BuChE data. Allelic frequencies were higher in DLB, relative to PDD subjects, for BuChE-K (P = 0.06), APOE epsilon4 (P < 0.001), or both alleles together (P < 0.001). More rapid cognitive decline was seen in PDD patients carrying both alleles, compared with other genotypes. Subjects with hyperhomocysteinemia were associated with more rapid decline in the presence of BuChE-K, with or without APOE epsilon4. These results suggest that genetic and biochemical risk factors for AD and PDD pathology may be important in dementia onset and progression in these Lewy body disorders.
ESTHER : Lane_2009_Mov.Disord_24_392
PubMedSearch : Lane_2009_Mov.Disord_24_392
PubMedID: 19006190

Title : Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes - D'Alessio_2009_J.Clin.Endocrinol.Metab_94_81
Author(s) : D'Alessio DA , Denney AM , Hermiller LM , Prigeon RL , Martin JM , Tharp WG , Saylan ML , He Y , Dunning BE , Foley JE , Pratley RE
Ref : J Clinical Endocrinology Metab , 94 :81 , 2009
Abstract : CONTEXT: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state.
OBJECTIVE: The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. DESIGN: We conducted a randomized, double-blind, placebo-controlled trial.
SETTING: The study was performed in General Clinical Research Centers at two University Hospitals.
SUBJECTS: Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2-7.5%.
INTERVENTION: Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout.
RESULTS: There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P < 0.05) and increased the slope of the C-peptide response to glucose (33%; P = 0.023).
CONCLUSION: Vildagliptin improves islet function in T2DM under fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.
ESTHER : D'Alessio_2009_J.Clin.Endocrinol.Metab_94_81
PubMedSearch : D'Alessio_2009_J.Clin.Endocrinol.Metab_94_81
PubMedID: 18957505

Title : Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients - Boschmann_2009_J.Clin.Endocrinol.Metab_94_846
Author(s) : Boschmann M , Engeli S , Dobberstein K , Budziarek P , Strauss A , Boehnke J , Sweep FC , Luft FC , He Y , Foley JE , Jordan J
Ref : J Clinical Endocrinology Metab , 94 :846 , 2009
Abstract : CONTEXT: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extrapancreatic mechanisms.
OBJECTIVE: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism.
DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at an academic clinical research center.
PATIENTS: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2), participated.
INTERVENTION: INTERVENTION included 7 d treatment with the selective DPP-4 inhibitor vildagliptin or placebo and a standardized test meal on d 7.
MAIN OUTCOME MEASURES: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin, dialysate glucose, lactate, pyruvate, glycerol were measured. RESULTS: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides, and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptin increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. CONCLUSIONS: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.
ESTHER : Boschmann_2009_J.Clin.Endocrinol.Metab_94_846
PubMedSearch : Boschmann_2009_J.Clin.Endocrinol.Metab_94_846
PubMedID: 19088168

Title : Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes - Azuma_2008_J.Clin.Endocrinol.Metab_93_459
Author(s) : Azuma K , Radikova Z , Mancino J , Toledo FG , Thomas E , Kangani C , Dalla Man C , Cobelli C , Holst JJ , Deacon CF , He Y , Ligueros-Saylan M , Serra D , Foley JE , Kelley DE
Ref : J Clinical Endocrinology Metab , 93 :459 , 2008
Abstract : OBJECTIVE: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. RESEARCH DESIGN AND
METHODS: Participants with T2DM (n = 16) who had a baseline hemoglobin A(1c) of 7.1 +/- 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min x m(2) insulin infusions.
RESULTS: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 +/- 0.3 mmol/liter and 1.6 +/- 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01).
CONCLUSIONS: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.
ESTHER : Azuma_2008_J.Clin.Endocrinol.Metab_93_459
PubMedSearch : Azuma_2008_J.Clin.Endocrinol.Metab_93_459
PubMedID: 18042650

Title : Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease - Lane_2008_Pharmacogenet.Genomics_18_289
Author(s) : Lane R , Feldman HH , Meyer J , He Y , Ferris SH , Nordberg A , Darreh-Shori T , Soininen H , Pirttila T , Farlow MR , Sfikas N , Ballard C , Greig NH
Ref : Pharmacogenet Genomics , 18 :289 , 2008
Abstract : OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI).
METHODS: This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study.
RESULTS: Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 allele. CONCLUSION: In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon4 alleles.
ESTHER : Lane_2008_Pharmacogenet.Genomics_18_289
PubMedSearch : Lane_2008_Pharmacogenet.Genomics_18_289
PubMedID: 18334913

Title : Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study - Ballard_2008_Curr.Med.Res.Opin_24_2561
Author(s) : Ballard C , Sauter M , Scheltens P , He Y , Barkhof F , van Straaten EC , van der Flier WM , Hsu C , Wu S , Lane R
Ref : Curr Med Res Opin , 24 :2561 , 2008
Abstract : OBJECTIVE: The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD). METHODS: VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects. TRIAL REGISTRATION: NCT00099216. RESULTS: 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance. CONCLUSION: Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.
ESTHER : Ballard_2008_Curr.Med.Res.Opin_24_2561
PubMedSearch : Ballard_2008_Curr.Med.Res.Opin_24_2561
PubMedID: 18674411

Title : Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's disease - Bullock_2006_Curr.Med.Res.Opin_22_483
Author(s) : Bullock R , Bergman H , Touchon J , Gambina G , He Y , Nagel J , Lane R
Ref : Curr Med Res Opin , 22 :483 , 2006
Abstract : BACKGROUND: Younger Alzheimer's disease (AD) patients appear to differ genetically and neuropathologically from older AD patients, and may experience a more aggressive disease course compared with older patients. A randomised trial investigated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with AD over a 2-year period. This retrospective analysis investigated whether younger and older patients showed differential tolerability and efficacy responses to cholinesterase inhibitor treatment.
METHODS: For the current analysis, patients were divided according to age at baseline: those aged < 75 years and those aged >or= 75 years. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Changes in efficacy parameters and adverse event frequencies were calculated for rivastigmine and donepezil-treated patients in both age groups. Exploratory analyses were also conducted on SIB, ADCS-ADL and NPI in patients who consented to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE) epsilon4 allele and the BuChE K-variant was conducted using the TaqMan assay. Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population.
RESULTS: Of the 994 patients who received the study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75 years or over. Rivastigmine provided significant benefits in younger patients compared with donepezil on the NPI-10, NPI-12, NPI-D, GDS and ADCS-ADL (all p < 0.05, ITT-LOCF). With the exception of the NPI-D in favour of donepezil (p < 0.05, ITT-LOCF), no significant treatment differences were observed in older patients. Younger patients with two wild-type BuChE alleles had a significantly greater response to rivastigmine than donepezil on the ADCS-ADL (p < 0.01, ITT-LOCF) and SIB (p < 0.05, ITT-LOCF). The most common adverse events were nausea and vomiting and these were more frequent in rivastigmine-treated patients. CONCLUSION: In this sub group analysis, patients younger than 75 years of age showed greater treatment responses to rivastigmine than donepezil. Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine.
ESTHER : Bullock_2006_Curr.Med.Res.Opin_22_483
PubMedSearch : Bullock_2006_Curr.Med.Res.Opin_22_483
PubMedID: 16574032

Title : Effect of butyrylcholinesterase genotype on the response to rivastigmine or donepezil in younger patients with Alzheimer's disease - Blesa_2006_Pharmacogenet.Genomics_16_771
Author(s) : Blesa R , Bullock R , He Y , Bergman H , Gambina G , Meyer J , Rapatz G , Nagel J , Lane R
Ref : Pharmacogenet Genomics , 16 :771 , 2006
Abstract : A randomized double-blind trial evaluated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with Alzheimer's disease over a 2-year period. A retrospective analysis showed differential responses to cholinesterase inhibitors (ChE-Is) in patients younger than 75 years. This analysis investigated the effect of BuChE genotype on response to ChE-I therapy in these patients. In a retrospective analysis, patients younger than 75 who had consented to pharmacogenetic analysis were divided into groups according to BuChE genotype. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). Changes on efficacy parameters were calculated for rivastigmine-treated and donepezil-treated patients in both groups. Of 114 (34.1%) patients younger than 75 who were successfully assessed for BuChE genotype, 76 (66.7%) were homozygous for wild-type BuChE, and 38 (33.3%) carried at least one BuChE K-variant allele. Wild-type BuChE carriers showed significantly greater responses to rivastigmine than to donepezil on the SIB, ADCS-ADL, GDS and NPI. No significant between-treatment differences in efficacy were observed in BuChE K-variant carriers, although adverse events were more frequent in rivastigmine-treated patients. In this retrospective analysis, Alzheimer's disease patients younger than 75 with wild-type BuChE exhibited differential efficacy to rivastigmine, while BuChE K-variant carriers experienced similar long-term treatment effects with both agents. These differences may reflect rivastigmine's ability to inhibit BuChE and AChE.
ESTHER : Blesa_2006_Pharmacogenet.Genomics_16_771
PubMedSearch : Blesa_2006_Pharmacogenet.Genomics_16_771
PubMedID: 17047484

Title : Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period - Bullock_2005_Curr.Med.Res.Opin_21_1317
Author(s) : Bullock R , Touchon J , Bergman H , Gambina G , He Y , Rapatz G , Nagel J , Lane R
Ref : Curr Med Res Opin , 21 :1317 , 2005
Abstract : OBJECTIVES: Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period.
METHODS: Patients were randomly assigned to rivastigmine 3-12 mg/day or donepezil 5-10 mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs.
RESULTS: In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT-LOCF population. However, this was not maintained in the non-ITT-LOCF populations. In secondary subgroup analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment.
CONCLUSIONS: Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.
ESTHER : Bullock_2005_Curr.Med.Res.Opin_21_1317
PubMedSearch : Bullock_2005_Curr.Med.Res.Opin_21_1317
PubMedID: 16083542

Title : A gene encoding an acyl hydrolase is involved in leaf senescence in Arabidopsis - He_2002_Plant.Cell_14_805
Author(s) : He Y , Gan S
Ref : Plant Cell , 14 :805 , 2002
Abstract : SAG101, a leaf senescence-associated gene, was cloned from an Arabidopsis leaf senescence enhancer trap line and functionally characterized. Reporter gene and RNA gel blot analyses revealed that SAG101 was not expressed until the onset of senescence in leaves. A recombinant SAG101 fusion protein overexpressed in Escherichia coli displayed acyl hydrolase activity. Antisense RNA interference in transgenic plants delayed the onset of leaf senescence for approximately 4 days. Chemically induced overexpression of SAG101 caused precocious senescence in both attached and detached leaves of transgenic Arabidopsis plants. These data suggest that SAG101 plays a significant role in leaf senescence.
ESTHER : He_2002_Plant.Cell_14_805
PubMedSearch : He_2002_Plant.Cell_14_805
PubMedID: 11971136
Gene_locus related to this paper: arath-At5g14930

Title : Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice - Holladay_1998_Bioorg.Med.Chem.Lett_8_2797
Author(s) : Holladay MW , Bai H , Li Y , Lin NH , Daanen JF , Ryther KB , Wasicak JT , Kincaid JF , He Y , Hettinger AM , Huang P , Anderson DJ , Bannon AW , Buckley MJ , Campbell JE , Donnelly-Roberts D , Gunther KL , Kim DJ , Kuntzweiler TA , Sullivan JP , Decker MW , Arneric SP
Ref : Bioorganic & Medicinal Chemistry Lett , 8 :2797 , 1998
Abstract : Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays.
ESTHER : Holladay_1998_Bioorg.Med.Chem.Lett_8_2797
PubMedSearch : Holladay_1998_Bioorg.Med.Chem.Lett_8_2797
PubMedID: 9873625

Title : Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors - Holladay_1998_J.Med.Chem_41_407
Author(s) : Holladay MW , Wasicak JT , Lin NH , He Y , Ryther KB , Bannon AW , Buckley MJ , Kim DJ , Decker MW , Anderson DJ , Campbell JE , Kuntzweiler TA , Donnelly-Roberts D , Piattoni-Kaplan M , Briggs CA , Williams M , Arneric SP
Ref : Journal of Medicinal Chemistry , 41 :407 , 1998
Abstract : New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (i.p.) or oral (p.o.) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.
ESTHER : Holladay_1998_J.Med.Chem_41_407
PubMedSearch : Holladay_1998_J.Med.Chem_41_407
PubMedID: 9484491

Title : Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist - Lin_1998_Bioorg.Med.Chem.Lett_8_249
Author(s) : Lin NH , Gunn DE , Li Y , He Y , Bai H , Ryther KB , Kuntzweiler T , Donnelly-Roberts D , Anderson DJ , Campbell JE , Sullivan JP , Arneric SP , Holladay MW
Ref : Bioorganic & Medicinal Chemistry Lett , 8 :249 , 1998
Abstract : Analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, (A-84543, 1) with 2-, 4-, 5-, and 6-substituents on the pyridine ring were synthesized. These analogs exhibited Ki values ranging from 0.15 to > 9,000 nM when tested in vitro for neuronal nicotinic acetylcholine receptor binding activity. Assessment of functional activity at subtypes of neuronal nicotinic acetylcholine receptors indicates that pyridine substitution can have a profound effect on efficacy at these subtypes, and several subtype-selective agonists and antagonists have been identified.
ESTHER : Lin_1998_Bioorg.Med.Chem.Lett_8_249
PubMedSearch : Lin_1998_Bioorg.Med.Chem.Lett_8_249
PubMedID: 9871663

Title : ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties - Sullivan_1997_J.Pharmacol.Exp.Ther_283_235
Author(s) : Sullivan JP , Donnelly-Roberts D , Briggs CA , Anderson DJ , Gopalakrishnan M , Xue IC , Piattoni-Kaplan M , Molinari E , Campbell JE , McKenna DG , Gunn DE , Lin NH , Ryther KB , He Y , Holladay MW , Wonnacott S , Williams M , Arneric SP
Ref : Journal of Pharmacology & Experimental Therapeutics , 283 :235 , 1997
Abstract : Accumulating preclinical and clinical evidence data suggests that compounds that selectively activate neuronal nicotinic acetylcholine receptor (nAChR) subtypes may have therapeutic utility for the treatment of several neurological disorders. In the present study, the in vitro pharmacological properties of the novel cholinergic channel modulator ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine], are described. In radioligand binding studies, ABT-089 was shown to display selectivity toward the high-affinity (-)-cytisine binding site present on the alpha4beta2 nAChR subtype (Ki = 16 nM) relative to the [125I]alpha-bungarotoxin binding site present on the alpha7 (Ki > or = 10,000 nM) and alpha1beta1deltagamma (Ki > 1000 nM) nAChR subtypes. In cation flux and channel current studies, ABT-089 displayed a more complex profile than (-)-nicotine having agonist, partial agonist and inhibitory activities depending on the nAChR subtype with which it interacts. ABT-089 differentially stimulated neurotransmitter release. The compound displayed a similar potency and efficacy to (-)-nicotine to facilitate ACh release (ABT-089, EC50 = 3 microM; (-)-nicotine, EC50 = 1 microM), but was markedly less potent and less efficacious than (-)-nicotine to stimulate dopamine release (ABT-089, EC50 = 1.1 microM; (-)-nicotine, EC50 = 0.04 microM). Additionally, ABT-089 was neuroprotective against the excitotoxic insults elicited by exposure to glutamate in both rat cortical cell cultures (EC50 = 10 +/- 3 microM) and differentiated human IMR32 cells (EC50 = 3 +/- 2 microM). The differential full agonist/partial agonist profile of ABT-089, as compared with (-)-nicotine and ABT-418, illustrates the complexity of nAChR activation and the potential to target responses at subclasses of the neuronal and peripheral receptors.
ESTHER : Sullivan_1997_J.Pharmacol.Exp.Ther_283_235
PubMedSearch : Sullivan_1997_J.Pharmacol.Exp.Ther_283_235
PubMedID: 9336329