Deng J

References (28)

Title : Donepezil promotes skin flap survival through activation of the HIF-1alpha\/VEGF signalling pathway - Lin_2024_Wound.Repair.Regen__
Author(s) : Lin H , Wang K , Yang J , Wang A , Deng J , Lin D
Ref : Wound Repair Regen , : , 2024
Abstract : Flaps are mainly used to repair wounds in the clinical setting but can sometimes experience ischaemic necrosis postoperatively. This study investigated whether donepezil, an acetylcholinesterase inhibitor, can enhance the survival rate of flaps. We randomly allocated 36 rats into control, low-dose (3 mg/kg/day), and high-dose (5 mg/kg/day) groups. On Postoperative day 7, we assessed flap viability and calculated the mean area of viable flap. After euthanizing the rats, we employed immunological and molecular biology techniques to examine the changes in flap tissue vascularization, apoptosis, autophagy, and inflammation. Donepezil enhanced the expression of hypoxia-inducible factor and vascular endothelial growth factor to facilitate angiogenesis. In addition, it elevated the expression of LC3B, p62, and beclin to stimulate autophagy. Furthermore, it increased the expression of Bcl-2 while reducing the expression of Bax, thus inhibiting apoptosis. Finally, it had anti-inflammatory effects by reducing the levels of IL-1beta, IL-6, and TNF-alpha. The results suggest that donepezil can enhance the viability of randomly generated skin flaps by upregulating HIF-1alpha/VEGF signalling pathway, facilitating vascularization, inducing autophagy, suppressing cell apoptosis, and mitigating inflammation within the flap tissue.
ESTHER : Lin_2024_Wound.Repair.Regen__
PubMedSearch : Lin_2024_Wound.Repair.Regen__
PubMedID: 38551210

Title : In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase - Shang_2024_Sci.Rep_14_10952
Author(s) : Shang L , Wei H , Deng J , Stewart MJ , LeSaint JE , Kyomuhangi A , Park S , Maul EC , Zhan CG , Zheng F
Ref : Sci Rep , 14 :10952 , 2024
Abstract : It is recognized as a promising therapeutic strategy for cocaine use disorder to develop an efficient enzyme which can rapidly convert cocaine to physiologically inactive metabolites. We have designed and discovered a series of highly efficient cocaine hydrolases, including CocH5-Fc(M6) which is the currently known as the most efficient cocaine hydrolase with both the highest catalytic activity against (-)-cocaine and the longest biological half-life in rats. In the present study, we characterized the time courses of protein appearance, pH, structural integrity, and catalytic activity against cocaine in vitro and in vivo of a CocH5-Fc(M6) bulk drug substance produced in a bioreactor for its in vitro and in vivo stability after long-time storage under various temperatures (-80, -20, 4, 25, or 37 degreesC). Specifically, all the tested properties of the CocH5-Fc(M6) protein did not significantly change after the protein was stored at any of four temperatures including -80, -20, 4, and 25 degreesC for~18 months. In comparison, at 37 degreesC, the protein was less stable, with a half-life of~82 days for cocaine hydrolysis activity. Additionally, the in vivo studies further confirmed the linear elimination PK profile of CocH5-Fc(M6) with an elimination half-life of~9 days. All the in vitro and in vivo data on the efficacy and stability of CocH5-Fc(M6) have consistently demonstrated that CocH5-Fc(M6) has the desired in vitro and in vivo stability as a promising therapeutic candidate for treatment of cocaine use disorder.
ESTHER : Shang_2024_Sci.Rep_14_10952
PubMedSearch : Shang_2024_Sci.Rep_14_10952
PubMedID: 38740850

Title : Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis - Nham_2024_J.Am.Geriatr.Soc__
Author(s) : Nham T , Garcia MC , Tsang KJ , Silva JM , Schneider T , Deng J , Lohit S , Mbuagbaw L , Holbrook A
Ref : J Am Geriatr Soc , : , 2024
Abstract : BACKGROUND: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. METHODS: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age <=18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. RESULTS: Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I(2) = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up <=52 weeks (RR: 1.32, 0.98-1.79). CONCLUSIONS: This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.
ESTHER : Nham_2024_J.Am.Geriatr.Soc__
PubMedSearch : Nham_2024_J.Am.Geriatr.Soc__
PubMedID: 38580328

Title : Recovery of dopaminergic system after cocaine exposure and impact of a long-acting cocaine hydrolase - Deng_2022_Addict.Biol_27_e13179
Author(s) : Deng J , Zhang T , Zheng X , Shang L , Zhan CG , Zheng F
Ref : Addict Biol , 27 :e13179 , 2022
Abstract : Dysregulation of dopamine transporters (DAT) within the dopaminergic system is an important biomarker of cocaine exposure. Depending on cocaine amount in-taken, one-time exposure in rats could lead to most (>95% of total) of DAT translocating to plasma membrane of the dopaminergic neurons compared to normal DAT distribution (~5.7% on the plasma membrane). Without further cocaine exposure, the time course of striatal DAT distribution, in terms of intracellular and plasma membrane fractions of DAT, represents a recovery process of the dopaminergic system. In this study, we demonstrated that after an acute cocaine exposure of 20 mg/kg (i.p.), the initial recovery process from days 1 to 15 in rats was relatively faster (from >95% on day 1 to ~35.4% on day 15). However, complete recovery of the striatal DAT distribution may take about 60 days. In another situation, with repeated cocaine exposures for once every other day for a total of 17 doses of 20 mg/kg cocaine (i.p.) from days 0 to 32, the complete recovery of striatal DAT distribution may take an even longer time (about 90 days), which represents a consequence of chronic cocaine use. Further, we demonstrated that a highly efficient Fc-fused cocaine hydrolase, CocH5-Fc(M6), effectively blocked cocaine-induced hyperactivity and DAT trafficking with repeated cocaine exposures by maintaining a plasma CocH5-Fc(M6) concentration <=58.7 +/- 2.9 nM in rats. The cocaine hydrolase protected dopaminergic system and helped the cocaine-altered DAT distribution to recover by preventing the dopaminergic system from further damage by cocaine.
ESTHER : Deng_2022_Addict.Biol_27_e13179
PubMedSearch : Deng_2022_Addict.Biol_27_e13179
PubMedID: 35754103

Title : Development of a Highly Efficient Long-Acting Cocaine Hydrolase Entity to Accelerate Cocaine Metabolism - Zheng_2022_Bioconjug.Chem__
Author(s) : Zheng F , Jin Z , Deng J , Chen X , Zheng X , Wang G , Kim K , Shang L , Zhou Z , Zhan CG
Ref : Bioconjug Chem , : , 2022
Abstract : It is particularly challenging to develop a truly effective pharmacotherapy for cocaine use disorder (CUD) treatment. Accelerating cocaine metabolism via hydrolysis at cocaine benzoyl ester using an efficient cocaine hydrolase (CocH) is known as a promising pharmacotherapeutic approach to CUD treatment. Preclinical and clinical studies on our first CocH (CocH1), in its human serum albumin-fused form known as TV-1380, have demonstrated the promise of a general concept of CocH-based pharmacotherapy for CUD treatment. However, the biological half-life of TV-1380 (t(1/2) = 8 h in rats, associated with t(1/2) = 43-77 h in humans) is not long enough for practical treatment of cocaine dependence, which requires enzyme injection for no more than once weekly. Through protein fusion of a human butyrylcholinesterase mutant (denoted as CocH5) with a mutant (denoted as Fc(M6)) of Fc from human IgG1, we have designed, prepared, and tested a new fusion protein (denoted as CocH5-Fc(M6)) for its pharmacokinetic profile and in vivo catalytic activity against (-)-cocaine. CocH5-Fc(M6) represents the currently most efficient long-acting cocaine hydrolase with both the highest catalytic activity against (-)-cocaine and the longest elimination half-life (t(1/2) = 229 +/- 5 h) in rats. As a result, even at a single modest dose of 3 mg/kg, CocH5-Fc(M6) can significantly and effectively accelerate the metabolism of cocaine in rats for at least 60 days. In addition, -70 nM CocH5-Fc(M6) in plasma was able to completely block the toxicity and physiological effects induced by intraperitoneal injection of a lethal dose of cocaine (60 mg/kg).
ESTHER : Zheng_2022_Bioconjug.Chem__
PubMedSearch : Zheng_2022_Bioconjug.Chem__
PubMedID: 35767675

Title : Effects of alcohol on metabolism and toxicity of cocaine in rats - Shang_2022_Toxicol.Rep_9_1586
Author(s) : Shang L , Zheng X , Zhang T , Deng J , Zhan CG , Zheng F
Ref : Toxicol Rep , 9 :1586 , 2022
Abstract : As most cocaine users drink alcohol, it is interesting to understand how a non-lethal dose of alcohol affects the metabolism and toxicity of cocaine. In this study, we examined the correlation between dose-dependent toxicity and the metabolism/pharmacokinetic (PK) profile of cocaine with or without alcohol (ethanol, 1sg/kg) co-administration in rats. The cocaine toxicity in rats with or without alcohol co-administration is characterized by not only the commonly used LD(50), but also the average times for the appearance of convulsion and death as well as total toxicity level (TTL) in the blood. All these data have consistently demonstrated that co-administration of alcohol increased cocaine toxicity, and that the alcohol-enhanced toxicity of cocaine is mainly attributed to the observed two additional metabolites (cocaethylene and norcocaethylene - products of chemical reactions of cocaine with alcohol catalyzed by metabolic enzymes carboxylesterase-1 and liver microsomal cytochrome P450 3A4) that are more toxic than cocaine itself. So, evaluation of the substance TTL should account for the blood levels of not only cocaine itself, but also its all toxic metabolites. In addition, for rats died of a lethal dose of cocaine (60 or 100smg/kg) combined with 1sg/kg alcohol, we also determined the TTL at the time of death, demonstrating that death would occur once the TTL reached a threshold (~16smicroM).
ESTHER : Shang_2022_Toxicol.Rep_9_1586
PubMedSearch : Shang_2022_Toxicol.Rep_9_1586
PubMedID: 36518391

Title : Cu(2+)-Regulated reversible coordination interaction of GQD@Tb\/GMP ICP nanoparticles: towards directly monitoring cerebrospinal acetylcholinesterase as a biomarker for cholinic brain dysfunction - Liu_2021_Analyst_145_7849
Author(s) : Liu C , Huang C , Ma R , Zhai W , Deng J , Zhou T
Ref : Analyst , 145 :7849 , 2021
Abstract : This work demonstrates a new strategy for sensing cerebrospinal acetylcholinesterase (AChE) as a cholinergic biomarker for brain dysfunction based on graphene quantum dot (GQD)-functionalized lanthanide infinite coordination polymer (Ln-ICP) nanoparticles. The ICPs used in this work were comprised of two components, i.e. a supramolecular Ln-ICP host formed by the coordination between the GMP ligand and central metal ion Tb3+, and guest GQDs with abundant functional groups, which were utilized as antenna ligands to further sensitize the fluorescence of Tb/GMP. Upon excitation at 300 nm, the obtained GQD@Tb/GMP ICP nanoparticles exhibited enhanced green fluorescence from Tb/GMP. With the addition of Cu2+, the competitive coordination between Cu2+ and GQDs weakened the antenna effect, leading to a decrease in the fluorescence of GQD@Tb/GMP ICPs. However, in the presence of thiocholine (TCh), a thiol-containing compound hydrolyzed from acetylthiocholine (ATCh) by AChE, a stronger coordination interaction between Cu2+ and TCh occurred, resulting in the restoration of the fluorescence of GQD@Tb/GMP ICPs. Using the method established herein, the cerebrospinal AChE fluctuation of rats with acute organophosphorus pesticide (OP) poisoning or chronic Alzheimer's disease (AD) could be monitored. This study essentially provides a novel approach to realize the direct monitoring of a biomarker for brain dysfunction by regulating the competitive coordination interaction reversibly, which is critical in the early diagnosis and therapy of brain diseases.
ESTHER : Liu_2021_Analyst_145_7849
PubMedSearch : Liu_2021_Analyst_145_7849
PubMedID: 33410430

Title : Red-to-blue paper-based colorimetric sensor integrated with smartphone for point-of-use analysis of cerebral AChE upon Cd(2+) exposure - Liu_2021_Nanoscale__
Author(s) : Liu C , Luo Y , Wen H , Qi Y , Shi G , Deng J , Zhou T
Ref : Nanoscale , : , 2021
Abstract : Herein, combined with a pervasive smartphone installed with a color recognition app, dual-responsive CDs@Eu/GMP ICPs were designed as a red-to-blue paper-based colorimetric sensor for the point-of-use analysis of cerebral acetylcholinesterase (AChE) upon Cd2+ exposure. Blue-emitting CDs with multi-functional groups as guests were encapsulated into the network of Eu/GMP ICPs to obtain CDs@Eu/GMP ICPs with the sensitized red fluorescence of Eu3+. With the presence of thiocholine (TCh), derived from acetylthiocholine (ATCh) hydrolyzed by AChE, the coordination environment of the CDs@Eu/GMP ICPs was interrupted, leading to the collapse of the CDs@Eu/GMP ICP network and the corresponding release of guest CDs into the surrounding environment. Consequently, the sensitized red fluorescence of Eu3+ decreased and the blue fluorescence of the CDs increased. This obvious red-to-blue fluorescent color changes of CDs@Eu/GMP ICPs on test paper could then be integrated with the smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure, which not only offers a new analytical platform for a better understanding of the environmental risk of Alzheimer's Dementia (AD), but also holds great potential in the early diagnosis of AD even at the asymptomatic stage with the decrease in CSF AChE as an early biomarker.
ESTHER : Liu_2021_Nanoscale__
PubMedSearch : Liu_2021_Nanoscale__
PubMedID: 33406172

Title : Effect of Selenium on Brain Injury in Chickens with Subacute Arsenic Poisoning - Ren_2021_Biol.Trace.Elem.Res__
Author(s) : Ren Z , Deng H , Wu Q , Jia G , Wen N , Deng Y , Zhu L , Zuo Z , Deng J
Ref : Biol Trace Elem Res , : , 2021
Abstract : The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage.
ESTHER : Ren_2021_Biol.Trace.Elem.Res__
PubMedSearch : Ren_2021_Biol.Trace.Elem.Res__
PubMedID: 33594525

Title : Stimulus Response of GQD-Sensitized Tb\/GMP ICP Nanoparticles with Dual-Responsive Ratiometric Fluorescence: Toward Point-of-Use Analysis of Acetylcholinesterase and Organophosphorus Pesticide Poisoning with Acetylcholinesterase as a Biomarker - Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
Author(s) : Ma R , Xu M , Liu C , Shi G , Deng J , Zhou T
Ref : ACS Appl Mater Interfaces , 12 :42119 , 2020
Abstract : In this study, by rationally designing the stimulus response of graphene quantum dot (GQD)-sensitized terbium/guanine monophosphate (Tb/GMP) infinite coordination polymer (ICP) nanoparticles, we have constructed a smartphone-based colorimetric assay with ratiometric fluorescence, which could be applied for the detection of acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) directly. First, GQDs with abundant functional groups were chosen as the guest, which not only could be used as one of the signal readouts but also served as the antenna ligand to further sensitize the fluorescence of the host Tb/GMP. Upon being excited at 330 nm, the green fluorescence of the Tb/GMP host is highly enhanced, while the blue fluorescence of GQDs is suppressed due to the confinement of the ICP host. With the presence of thiocholine (TCh), an enzymatic product hydrolyzed from acetylthiocholine (ATCh) by AChE, the competitive coordination of Tb(3+) between GMP and TCh results in the collapse of the ICP network and thereby the release of GQDs into the solution; thus, the fluorescence of Tb/GMP turns off and the fluorescence of GQDs turns on. The dual-responsive ratiometric fluorescent intensity change leads to the corresponding green-to-blue fluorescent color change obviously, which constitutes a novel mechanism for the colorimetric analysis of AChE. Moreover, when OPs are subsequently introduced, the activity of AChE is blocked, thus preventing the stimulus response of GQD@Tb/GMP ICP nanoparticles, leading to the fluorescent color change from greenish-blue to green, which could also be employed for OP detection. Benefitting from the high sensitivity, good reliability, and the obvious color changes, the method demonstrated here is a promising candidate to realize smartphone-based point-of-use applications, which is of great importance for timely clinical diagnosis and treatment of OPs related to health issues with AChE as an exposure biomarker in less industrialized countries, in remote settings, or even in home care services.
ESTHER : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedSearch : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedID: 32805836

Title : Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic - Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
Author(s) : Su X , Guo Y , Deng J , Xu J , Zhou G , Zhou T , Li Y , Zhong D , Kong L , Wang X , Liu M , Wu K , Yan G , Chen XG
Ref : PLoS Negl Trop Dis , 13 :e0007665 , 2019
Abstract : Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.
ESTHER : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedSearch : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedID: 31525199

Title : ATGL promotes the proliferation of hepatocellular carcinoma cells via the p-AKT signaling pathway - Liu_2019_J.Biochem.Mol.Toxicol__e22391
Author(s) : Liu M , Yu X , Lin L , Deng J , Wang K , Xia Y , Tang X , Hong H
Ref : J Biochem Mol Toxicol , :e22391 , 2019
Abstract : Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of adipose triglyceride lipase (ATGL) in hepatocellular carcinoma cells has not been elucidated. We evaluated the function of ATGL in hepatocellular carcinoma using methyl azazolyl blue and migration assay through overexpression of ATGL in HepG2 cells. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses were used to assess the mechanisms of ATGL in hepatocellular carcinoma. In the current study, we first constructed and transiently transfected ATGL into hepatocellular carcinoma cells. Secondly, we found that ATGL promoted the proliferation of hepatoma cell lines via upregulating the phosphorylation of AKT, but did not affect the metastatic ability of HCC cells. Moreover, the p-AKT inhibitor significantly eliminated the effect of ATGL on the proliferation of hepatoma carcinoma cells. Taken together, our results indicated that ATGL promotes hepatocellular carcinoma cells proliferation through upregulation of the AKT signaling pathway.
ESTHER : Liu_2019_J.Biochem.Mol.Toxicol__e22391
PubMedSearch : Liu_2019_J.Biochem.Mol.Toxicol__e22391
PubMedID: 31476254

Title : Reengineering of Albumin-Fused Cocaine Hydrolase CocH1 (TV-1380) to Prolong Its Biological Half-Life - Cai_2019_AAPS.J_22_5
Author(s) : Cai Y , Zhou S , Jin Z , Wei H , Shang L , Deng J , Zhan CG , Zheng F
Ref : AAPS J , 22 :5 , 2019
Abstract : Therapeutic treatment of cocaine toxicity or addiction is a grand medical challenge. As a promising therapeutic strategy for treatment of cocaine toxicity and addiction to develop a highly efficient cocaine hydrolase (CocH) capable of accelerating cocaine metabolism to produce physiologically/biologically inactive metabolites, our previously designed A199S/S287G/A328W/Y332G mutant of human butyrylcholinesterase (BChE), known as cocaine hydrolase-1 (CocH1), possesses the desirably high catalytic activity against cocaine. The C-terminus of CocH1, truncated after amino acid #529, was fused to human serum albumin (HSA) to extend the biological half-life. The C-terminal HSA-fused CocH1 (CocH1-HSA), known as Albu-CocH1, Albu-CocH, AlbuBChE, Albu-BChE, or TV-1380 in literature, has shown favorable preclinical and clinical profiles. However, the actual therapeutic value of TV-1380 for cocaine addiction treatment is still limited by the short half-life. In this study, we designed and tested a new type of HSA-fused CocH1 proteins, i.e., N-terminal HSA-fused CocH1, with or without a linker between the HSA and CocH1 domains. It has been demonstrated that the catalytic activity of these new fusion proteins against cocaine is similar to that of TV-1380. However, HSA-CocH1 (without a linker) has a significantly longer biological half-life (t1/2 = 14 +/- 2 h) compared to the corresponding C-terminal HSA-fused CocH1, i.e., CocH1-HSA (TV-1380 with t1/2 = 5-8 h), in rats. Further, the N-terminal HSA-fused CocH1 proteins with a linker have further prolonged biological half-lives: t1/2 = 17 +/- 2 h for both HSA-EAAAK-CocH1 and HSA-PAPAP-CocH1, and t1/2 = 18 +/- 3 h for HSA-(PAPAP)2-CocH1. These N-terminal HSA-fused CocH1 proteins may serve as more promising protein drug candidates for cocaine addiction treatment.
ESTHER : Cai_2019_AAPS.J_22_5
PubMedSearch : Cai_2019_AAPS.J_22_5
PubMedID: 31754920

Title : Development of a long-acting Fc-fused cocaine hydrolase with improved yield of protein expression - Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
Author(s) : Chen X , Deng J , Zheng X , Zhang J , Zhou Z , Wei H , Zhan CG , Zheng F
Ref : Chemico-Biological Interactions , 306 :89 , 2019
Abstract : Human butyrylcholinesterase (BChE) is known as a safe and effective protein for detoxification of organophosphorus (OP) nerve agents. Its rationally designed mutants with considerably improved catalytic activity against cocaine, known as cocaine hydrolases (CocHs), are recognized as the most promising drug candidates for the treatment of cocaine abuse. However, it is a grand challenge to efficiently produce active recombinant BChE and CocHs with a sufficiently long biological half-life. In the present study, starting from a promising CocH, known as CocH3 (i.e. A199S/F227A/S287G/A328W/Y332G mutant of human BChE), which has a approximately 2000-fold improved catalytic activity against cocaine compared to wild-type BChE, we designed an N-terminal fusion protein, Fc(M3)-(PAPAP)2-CocH3, which was constructed by fusing Fc of human IgG1 to the N-terminal of CocH3 and further optimized by inserting a linker between the two protein domains. Without lowering the enzyme activity, Fc(M3)-(PAPAP)2-CocH3 expressed in Chinese hamster ovary (CHO) cells has not only a long biological half-life of 105+/-7h in rats, but also a high yield of protein expression. Particularly, Fc(M3)-(PAPAP)2-CocH3 has a approximately 21-fold increased protein expression yield in CHO cells compared to CocH3 under the same experimental conditions. Given the observations that Fc(M3)-(PAPAP)2-CocH3 has not only a high catalytic activity against cocaine and a long biological half-life, but also a high yield of protein expression, this new protein entity reported in this study would be a more promising candidate for therapeutic treatment of cocaine overdose and addiction.
ESTHER : Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
PubMedSearch : Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
PubMedID: 30986387

Title : Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition -
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 24 :2795 , 2018
PubMedID: 30184511
Gene_locus related to this paper: human-ABHD5

Title : [Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases] - Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
Author(s) : Liu ZM , Fang F , Ding CH , Zhang WH , Deng J , Chen CH , Wang X , Liu J , Li Z , Jia XL , Zeng JS , Qian SY
Ref : Zhonghua Er Ke Za Zhi , 56 :216 , 2018
Abstract : Objective: To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT) Methods: The clinical data of 2 patients with congenital myasthenia syndrome were collected, and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital, Capital Medical University. The clinical features and gene mutation characteristics were analyzed, and the patients were followed-up for therapeutic efficacy. Results: The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively. The two patients were admitted to the PICU due to dyspnea, cyanotic episodes that required intubation. The patients had repeated apnea and became ventilator dependent. Case 1 died due to refusal of any treatment. Case 2 had a tracheotomy, and gradually weaned from ventilator after using pyridostigmine. The hospitalization of case 2 lasted 162 days. Case 2 was followed up to the age of 3 years and 4 months, and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation. Both cases were negative for anti-AChR, anti-acetylcholinesterase, anti-MuSK antibodies. Neostigmine test was negative in case 1 and suspiciously positive in case 2. Low-frequency repetitive nerve stimulation testing of case 2 was negative. Cranial MRI scans of both cases showed brain atrophy-like change. Genetic testing showed compound heterozygous deletions (exon 4, 5, 6) and pathogenic variant c.914T>C (p.I305T) in CHAT in case 1, compound heterozygous variants c.1007T>C (p.I336T) and c.64C>T (p.Q22X) in CHAT in case 2. To our knowledge, compound heterozygous deletions (exon 4, 5, 6) and p.Q22X were novel, previously unreported variants. Conclusion: CMS-EA usually presents at birth or in the neonatal period with hypotonia, ptosis, dysphagia due to severe bulbar weakness, and respiratory insufficiency with cyanosis and apnea. Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.
ESTHER : Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
PubMedSearch : Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
PubMedID: 29518833

Title : Highly sensitive GQDs-MnO2 based assay with turn-on fluorescence for monitoring cerebrospinal acetylcholinesterase fluctuation: A biomarker for organophosphorus pesticides poisoning and management - Deng_2017_Environ.Pollut_224_436
Author(s) : Deng J , Lu D , Zhang X , Shi G , Zhou T
Ref : Environ Pollut , 224 :436 , 2017
Abstract : In this study, we demonstrated an assay with turn-on fluorescence for monitoring cerebrospinal acetylcholinesterase (AChE) fluctuation as a biomarker for organophosphorus pesticides (OPs) poisoning and management based on single layer MnO2 nanosheets with graphene quantum dots (GQDs) as signal readout. Initially, the fluorescence of GQDs was quenched by MnO2 nanosheets mainly due to the inner filter effect (IFE). However, with the presence of reductive thiocholine (TCh), the enzymatic product, hydrolyzed from acetylthiocholine (ATCh) by AChE, the redox reaction between MnO2 and TCh occurred, leading to the destruction of the MnO2 nanosheets, and thereby IFE was diminished gradually. As a consequence, the turn-on fluorescence of GQDs with the changes in the spectrum of the dispersion constituted a new mechanism for sensing of cerebrospinal AChE. With the method developed here, we could monitor cerebrospinal AChE fluctuation of rats exposed to OPs before and after therapy, and could thereby open up the pathway to a new sensing platform for better understanding the mechanism of brain dysfunctions associate with OPs poisoning.
ESTHER : Deng_2017_Environ.Pollut_224_436
PubMedSearch : Deng_2017_Environ.Pollut_224_436
PubMedID: 28258856

Title : Potential anti-obesity effects of a long-acting cocaine hydrolase - Zheng_2016_Chem.Biol.Interact_259_99
Author(s) : Zheng X , Deng J , Zhang T , Yao J , Zheng F , Zhan CG
Ref : Chemico-Biological Interactions , 259 :99 , 2016
Abstract : A long-acting cocaine hydrolase, known as CocH3-Fc(M3), engineered from human butyrylcholinesterase (BChE) was tested, in this study, for its potential anti-obesity effects. Mice on a high-fat diet gained significantly less body weight when treated weekly with 1 mg/kg CocH3-Fc(M3) compared to control mice, though their food intake was similar. There is no correlation between the average body weight and the average food intake, which is consistent with the previously reported observation in BChE knockout mice. In addition, molecular modeling was carried out to understand how ghrelin binds with CocH3, showing that ghrelin binds with CocH3 in a similar mode as ghrelin binding with wild-type human BChE. The similar binding structure mode explains why CocH3 has a similar catalytic activity against ghrelin.
ESTHER : Zheng_2016_Chem.Biol.Interact_259_99
PubMedSearch : Zheng_2016_Chem.Biol.Interact_259_99
PubMedID: 27163854

Title : Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models - Li_2016_Sci.Rep_6_34387
Author(s) : Li YF , Chang YQ , Deng J , Li WX , Jian J , Gao JS , Wan X , Gao H , Kurihara H , Sun PH , He RR
Ref : Sci Rep , 6 :34387 , 2016
Abstract : The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2'R,3'R)-desgalloyloolongtheanin-3,3'-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 mug/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.
ESTHER : Li_2016_Sci.Rep_6_34387
PubMedSearch : Li_2016_Sci.Rep_6_34387
PubMedID: 27694956

Title : Polyacrylic acid-coated cerium oxide nanoparticles: An oxidase mimic applied for colorimetric assay to organophosphorus pesticides - Zhang_2016_Biosens.Bioelectron_85_457
Author(s) : Zhang SX , Xue SF , Deng J , Zhang M , Shi G , Zhou T
Ref : Biosensors & Bioelectronics , 85 :457 , 2016
Abstract : It is important and urgent to develop reliable and highly sensitive methods that can provide on-site and rapid detection of extensively used organophosphorus pesticides (OPs) for their neurotoxicity. In this study, we developed a novel colorimetric assay for the detection of OPs based on polyacrylic acid-coated cerium oxide nanoparticles (PAA-CeO2) as an oxidase mimic and OPs as inhibitors to suppress the activity of acetylcholinesterase (AChE). Firstly, highly dispersed PAA-CeO2 was prepared in aqueous solution, which could catalyze the oxidation of TMB to produce a color reaction from colorless to blue. And the enzyme of AChE was used to catalyze the substrate of acetylthiocholine (ATCh) to produce thiocholine (TCh). As a thiol-containing compound with reducibility, TCh can decrease the oxidation of TMB catalyzed by PAA-CeO2. Upon incubated with OPs, the enzymatic activity of AChE was inhibited to produce less TCh, resulting in more TMB catalytically oxidized by PAA-CeO2 to show an increasing blue color. The two representative OPs, dichlorvos and methyl-paraoxon, were tested using our proposed assay. The novel assay showed notable color change in a concentration-dependent manner, and as low as 8.62 ppb dichlorvos and 26.73 ppb methyl-paraoxon can be readily detected. Therefore, taking advantage of such oxidase-like activity of PAA-CeO2, our proposed colorimetric assay can potentially be a screening tool for the precise and rapid evaluation of the neurotoxicity of a wealth of OPs.
ESTHER : Zhang_2016_Biosens.Bioelectron_85_457
PubMedSearch : Zhang_2016_Biosens.Bioelectron_85_457
PubMedID: 27208478

Title : Suppressive subtractive hybridization reveals different gene expression between high and low virulence strains of Cladosporium cladosporioides - Gu_2016_Microb.Pathog_100_276
Author(s) : Gu Y , Liu Y , Cao S , Huang X , Zuo Z , Yu S , Deng J , Ding C , Yuan M , Shen L , Wu R , Wen Y , Ren Z , Zhao Q , Peng G , Zhong Z , Wang C , Ma X
Ref : Microb Pathog , 100 :276 , 2016
Abstract : Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the unigenes in the forward library corresponded to 5 different pathways and the reverse library unigenes were involved in 3 different pathways. The qRT-PCR results indicated that expressions of APL1, GUD1, CSE1, SPBC3E7.04c and MFS were significantly different between Z20 and Zt strains, while genes encoding the senescence-associated proteins, pse1, nup107, mip1, pex2, icl1 and alpha/beta hydrolase exhibited no significant differences between the two strains. In addition, we found that 5 unigenes encoding mip1, chk1, icl1, alpha/beta hydrolase and beta-glucosidase may be associated with pathogenicity. One unigene (MFS) may be related to the resistance to 14 alpha-demethylase inhibitor fungicides, and 5 unigenes (PEX2, NUP107, PSE1, APL1, and SPBC3E7.04c) may be related to either low spore yield or earlier aging of the Zt strain. Our study may help better understand the molecular mechanism of C. cladosporioides infection, and therefore improve the treatment and prevention of C. cladosporioides induced diseases.
ESTHER : Gu_2016_Microb.Pathog_100_276
PubMedSearch : Gu_2016_Microb.Pathog_100_276
PubMedID: 27744104

Title : Determination of a novel dipeptidyl peptidase IV inhibitor in monkey plasma by HPLC-MS\/MS and its application in a pharmacokinetics study - Deng_2015_J.Pharm.Biomed.Anal_117_99
Author(s) : Deng J , Guo J , Dai R , Zhang G , Xie H
Ref : J Pharm Biomed Anal , 117 :99 , 2015
Abstract : A lot of attention has been given to novel diabetes treatment, which is used to replace injectable insulin. A novel dipeptidyl peptidase IV inhibitor (HWH-10d) for treating type 2 diabetes was previously determined to have comparable efficacy to the marketed drug (alogliptin) in ICR male mice. Therefore, a sensitive and rapid liquid chromatography-tandem mass spectrometric method was developed and validated for the further evaluation of HWH-10d in monkey. The analytes were extracted through a liquid-liquid extraction with ethyl acetate. The linear detection range for HWH-10d in monkey plasma was from 0.5 to 2000ng/mL with the lower limit of quantification of 0.5ng/mL. The relative standard deviation was measured to be less than 10.4% for determination of inter- and intra-day precisions, and the relative error was determined to be within +/-7.2% for all accuracy measurements. The simple and rapid LC-MS/MS method for HWH-10d in monkey plasma could be used for the pharmacokinetics studies of HWH-10d in monkeys. The oral bioavailability of HWH-10d in monkeys is 57.8%.
ESTHER : Deng_2015_J.Pharm.Biomed.Anal_117_99
PubMedSearch : Deng_2015_J.Pharm.Biomed.Anal_117_99
PubMedID: 26344384

Title : Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition - Ou_2014_Cell.Rep_9_1798
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 9 :1798 , 2014
Abstract : How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of alpha/beta-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKalpha-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis.
ESTHER : Ou_2014_Cell.Rep_9_1798
PubMedSearch : Ou_2014_Cell.Rep_9_1798
PubMedID: 25482557
Gene_locus related to this paper: human-ABHD5

Title : Finding the missing honey bee genes: lessons learned from a genome upgrade - Elsik_2014_BMC.Genomics_15_86
Author(s) : Elsik CG , Worley KC , Bennett AK , Beye M , Camara F , Childers CP , de Graaf DC , Debyser G , Deng J , Devreese B , Elhaik E , Evans JD , Foster LJ , Graur D , Guigo R , Hoff KJ , Holder ME , Hudson ME , Hunt GJ , Jiang H , Joshi V , Khetani RS , Kosarev P , Kovar CL , Ma J , Maleszka R , Moritz RF , Munoz-Torres MC , Murphy TD , Muzny DM , Newsham IF , Reese JT , Robertson HM , Robinson GE , Rueppell O , Solovyev V , Stanke M , Stolle E , Tsuruda JM , Vaerenbergh MV , Waterhouse RM , Weaver DB , Whitfield CW , Wu Y , Zdobnov EM , Zhang L , Zhu D , Gibbs RA
Ref : BMC Genomics , 15 :86 , 2014
Abstract : BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes.
RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data.
CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.
ESTHER : Elsik_2014_BMC.Genomics_15_86
PubMedSearch : Elsik_2014_BMC.Genomics_15_86
PubMedID: 24479613

Title : Genome sequencing of five Shewanella baltica strains recovered from the oxic-anoxic interface of the Baltic Sea - Caro-Quintero_2012_J.Bacteriol_194_1236
Author(s) : Caro-Quintero A , Auchtung J , Deng J , Brettar I , Hofle M , Tiedje JM , Konstantinidis KT
Ref : Journal of Bacteriology , 194 :1236 , 2012
Abstract : Here we describe five Shewanella baltica genomes recovered from the same sample, as well as 12 years apart from the same sampling station. These genomes expand the collection of previously sequenced S. baltica strains and represent a valuable resource for assessing the role of environmental settings on genome adaptation.
ESTHER : Caro-Quintero_2012_J.Bacteriol_194_1236
PubMedSearch : Caro-Quintero_2012_J.Bacteriol_194_1236
PubMedID: 22328742
Gene_locus related to this paper: sheb8-a6wty5 , sheb5-a3d2c0 , sheb5-a3d659 , sheb5-a3dai0 , sheb9-a9l1s9

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus) - Stajich_2010_Proc.Natl.Acad.Sci.U.S.A_107_11889
Author(s) : Stajich JE , Wilke SK , Ahren D , Au CH , Birren BW , Borodovsky M , Burns C , Canback B , Casselton LA , Cheng CK , Deng J , Dietrich FS , Fargo DC , Farman ML , Gathman AC , Goldberg J , Guigo R , Hoegger PJ , Hooker JB , Huggins A , James TY , Kamada T , Kilaru S , Kodira C , Kues U , Kupfer D , Kwan HS , Lomsadze A , Li W , Lilly WW , Ma LJ , Mackey AJ , Manning G , Martin F , Muraguchi H , Natvig DO , Palmerini H , Ramesh MA , Rehmeyer CJ , Roe BA , Shenoy N , Stanke M , Ter-Hovhannisyan V , Tunlid A , Velagapudi R , Vision TJ , Zeng Q , Zolan ME , Pukkila PJ
Ref : Proc Natl Acad Sci U S A , 107 :11889 , 2010
Abstract : The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.
ESTHER : Stajich_2010_Proc.Natl.Acad.Sci.U.S.A_107_11889
PubMedSearch : Stajich_2010_Proc.Natl.Acad.Sci.U.S.A_107_11889
PubMedID: 20547848
Gene_locus related to this paper: copc7-a8n2b8 , copc7-a8n3e0 , copc7-a8n3e1 , copc7-a8n6a5 , copc7-a8n8h4 , copc7-a8n702 , copc7-a8n941 , copc7-a8nkc7 , copc7-a8nll5 , copc7-a8nll6 , copc7-a8nqf4 , copc7-a8nqg3 , copc7-a8nqv8 , copc7-a8nvb5 , copc7-a8nwm2 , copc7-a8nz18 , copc7-a8p0p4 , copc7-d6rlx1 , copc7-d6rnh7 , copc7-kex1 , copci-b9u444 , copc7-a8nb05 , copc7-a8nha0 , copci-b9u443 , copc7-a8nq30 , copc7-a8nh79 , copc7-d6rm78 , copc7-a8nzs7 , copc7-axe1

Title : Increased lipolysis in adipose tissues is associated with elevation of systemic free fatty acids and insulin resistance in perilipin null mice - Zhai_2010_Horm.Metab.Res_42_247
Author(s) : Zhai W , Xu C , Ling Y , Liu S , Deng J , Qi Y , Londos C , Xu G
Ref : Hormone & Metabolic Research , 42 :247 , 2010
Abstract : Elevated plasma levels of free fatty acids (FFAs) are thought to restrict glucose utilization and induce insulin resistance. Plasma FFA concentrations are primarily governed by lipolysis in adipocytes. Perilipin surrounds the lipid droplet in adipocytes and has a dual role in lipolysis regulation. Perilipin null mice studied by two independent laboratories exhibited similar phenotypes of reduced adipose mass and resistance to diet-induced obesity, but have inconsistent metabolic parameters such as plasma levels of FFA, glucose, and insulin. This discrepancy may be due to differences in genetic background, generation, and nutritional status of the animals examined. In this study, we examined the major metabolic parameters in 129/SvEv perilipin null mice fasted for 4 h and observed increased plasma concentrations of FFA, glycerol, glucose, and insulin. An increase in the score for the homeostasis model assessment of insulin resistance index confirmed the insulin resistance in perilipin null mice, which may be attributed to the plasma FFA elevation. Basal lipolysis was increased in adipose tissues or primary adipocytes isolated from perilipin null mice with increased mass and activity of hormone-sensitive lipase and adipose triglyceride lipase. The increased lipolytic action may accelerate FFA efflux from the adipose tissues to the bloodstream, thereby accounting for systemic FFA elevation and, hence, insulin resistance in perilipin null mice.
ESTHER : Zhai_2010_Horm.Metab.Res_42_247
PubMedSearch : Zhai_2010_Horm.Metab.Res_42_247
PubMedID: 20091459