Xie C

References (13)

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : An Esterase-Responsive SLC7A11 shRNA Delivery System Induced Ferroptosis and Suppressed Hepatocellular Carcinoma Progression - Zhang_2024_Pharmaceutics_16_
Author(s) : Zhang H , Wang J , Xiang X , Xie C , Lu X , Guo H , Sun Y , Shi Z , Song H , Qiu N , Xu X
Ref : Pharmaceutics , 16 : , 2024
Abstract : Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G-LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G-LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G-LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment.
ESTHER : Zhang_2024_Pharmaceutics_16_
PubMedSearch : Zhang_2024_Pharmaceutics_16_
PubMedID: 38399303

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression - He_2021_Cell.Death.Dis_12_992
Author(s) : He W , Huang J , Liu Y , Xie C , Zhang K , Zhu X , Chen J , Huang H
Ref : Cell Death Dis , 12 :992 , 2021
Abstract : Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
ESTHER : He_2021_Cell.Death.Dis_12_992
PubMedSearch : He_2021_Cell.Death.Dis_12_992
PubMedID: 34689162

Title : Deciphering the venomic transcriptome of killer-wasp Vespa velutina - Liu_2015_Sci.Rep_5_9454
Author(s) : Liu Z , Chen S , Zhou Y , Xie C , Zhu B , Zhu H , Liu S , Wang W , Chen H , Ji Y
Ref : Sci Rep , 5 :9454 , 2015
Abstract : Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world.
ESTHER : Liu_2015_Sci.Rep_5_9454
PubMedSearch : Liu_2015_Sci.Rep_5_9454
PubMedID: 25896434
Gene_locus related to this paper: vesve-pa1

Title : Bacillus ligniniphilus sp. nov., an alkaliphilic and halotolerant bacterium isolated from sediments of the South China Sea - Zhu_2014_Int.J.Syst.Evol.Microbiol_64_1712
Author(s) : Zhu D , Tanabe SH , Xie C , Honda D , Sun J , Ai L
Ref : Int J Syst Evol Microbiol , 64 :1712 , 2014
Abstract : An alkaliphilic and halotolerant Gram-stain-positive bacterium, which was isolated from sediment samples from the South China Sea, was subjected to a taxonomic study. The isolate, strain L1T, grew well at a wide range of temperatures and pH values, 10.0-45.0 degrees C and pH 6-11, with optima at 30 degrees C and pH 9.0, respectively. The growth of strain L1T occurred at total salt concentrations of 0-10% (w/v) with an optimum at 2% (w/v). Phylogenetic analysis based on 16S rRNA sequence comparison indicated that the isolate represented a member of the genus Bacillus. The strains most closely related to strain L1T were Bacillus nanhaiisediminis JCM 16507T, Bacillus halodurans DSM 497T and Bacillus pseudofirmus DSM 8715T, with 16S rRNA similarities of 96.5%, 95.9% and 95.7%, respectively. DNA-DNA hybridization of strain L1T with the type strains of the most closely related species, B. nanhaiisediminis JCM 16507T, B. halodurans DSM 497T and B. pseudofirmus DSM 8715T, showed reassociation values of about 21.7%, 14.3% and 13.9%, respectively. The DNA G+C content of strain L1T was 40.76 mol%. The predominant isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant cellular fatty acids of strain L1T were iso-C14 : 0 and anteiso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the phenotypic and phylogenetic characteristics, it is proposed that strain L1T (=JCM 18543T=DSM 26145T) should be classified as the type strain of Bacillus ligniniphilus sp. nov.
ESTHER : Zhu_2014_Int.J.Syst.Evol.Microbiol_64_1712
PubMedSearch : Zhu_2014_Int.J.Syst.Evol.Microbiol_64_1712
PubMedID: 24554634

Title : Silencing of an aphid carboxylesterase gene by use of plant-mediated RNAi impairs Sitobion avenae tolerance of Phoxim insecticides - Xu_2014_Transgenic.Res_23_389
Author(s) : Xu L , Duan X , Lv Y , Zhang X , Nie Z , Xie C , Ni Z , Liang R
Ref : Transgenic Res , 23 :389 , 2014
Abstract : RNA interference (RNAi) describes the ability of double-stranded RNA (dsRNA) to inhibit homologous gene expression at the RNA level. Its specificity is sequence-based and depends on the sequence of one strand of the dsRNA corresponding to part or all of a specific gene transcript. In this study we adopted plant-mediated RNAi technology that targets Sitobion avenae (S. avenae) to enable gene silencing in the aphid and to minimize handling of the insects during experiments. S. avenae was selected for this study because it causes serious economic losses to wheat throughout the world. The carboxylesterase (CbE E4) gene in S. avenae was homologously cloned, which increased synthesis of a protein known to be critical to the resistance (tolerance) this species has developed to a wide range of pesticides. A plant RNAi vector was constructed, and transgenic Triticum aesticum (dsCbE1-5 and dsCbE2-2 lines) expressing CbE E4 dsRNA were developed. S. avenae were fed on dsCbE1-5 and dsCbE2-2 lines stably producing the CbE E4 dsRNA. CbE E4 gene expression in S. avenae was reduced by up to 30-60 %. The number of aphids raised on dsCbE1-5 and dsCbE2-2 was lower than the number raised on non-transgenic plants. A solution of CbE E4 enzyme from S. avenae fed on dsCbE1-5 and dsCbE2-2 plants hydrolyzed only up to 20-30 % Phoxim solution within 40 min whereas a solution of the enzyme from CbE E4 fed on control plants hydrolyzed 60 % of Phoxim solution within 40 min. CbE E4 gene silencing was achieved by our wheat-mediated RNAi approach. This plant-mediated RNAi approach for addressing degradation-based pesticide resistance mechanisms in aphids and may prove useful in pest management for diverse agro-ecosystems.
ESTHER : Xu_2014_Transgenic.Res_23_389
PubMedSearch : Xu_2014_Transgenic.Res_23_389
PubMedID: 24242160

Title : The effects of CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease - Xie_2014_Pharmacogenet.Genomics_24_204
Author(s) : Xie C , Ding X , Gao J , Wang H , Hang Y , Zhang H , Zhang J , Jiang B , Miao L
Ref : Pharmacogenet Genomics , 24 :204 , 2014
Abstract : OBJECTIVE: Carboxylesterase 1 hydrolyzes the majority of clopidogrel to the inactive metabolite. The aim of this study was to assess the effects of the CES1A2 A(-816)C polymorphism and other genetic and clinical factors on clopidogrel response variability. An additional aim was to investigate the relationship between genetic variations and development of stent thrombosis (ST).
METHODS: We recruited 162 coronary heart disease patients treated with aspirin and clopidogrel, and we genotyped them for the CES1A2 A(-816)C, CYP2C19 *2/*3, PON1 Q192R, and ABCB1 C3435T polymorphisms. Platelet reactivity was analyzed using the VASP-PRI assay. We also carried out a case-control study in which 22 patients undergoing stent implantation who had ST were matched with 86 ST-free controls.
RESULTS: The VASP-PRI values were significantly higher in the carriers of the CES1A2 -816C allele (P=0.014) and CYP2C19 loss of function (LOF) alleles (P=0.004). Furthermore, the patients with CYP2C19 LOF alleles showed an increased risk of ST (ORadj=4.28, P=0.033). However, there was no significant association between the CES1A2 -816C allele and the development of ST. The CYP2C19 and CES1A2 genotypes alone could explain 6.1 and 3.7% of the interindividual variability in the VASP-PRI results, respectively. The value increased to 12.5% when clinical factors (e.g. BMI and triglycerides) were also considered. The PON1 Q192R and ABCB1 C3435T genetic variations produced no significant impact. CONCLUSION: The CES1A2 -816C and the CYP2C19 LOF alleles were associated with attenuated platelet reactivity to clopidogrel. CYP2C19 LOF was also predictive of ST; however, the association between the CES1A2 -816C allele and development of ST requires further study.
ESTHER : Xie_2014_Pharmacogenet.Genomics_24_204
PubMedSearch : Xie_2014_Pharmacogenet.Genomics_24_204
PubMedID: 24535487

Title : Metabolism and pharmacokinetics of allitinib in cancer patients: the roles of cytochrome p450s and epoxide hydrolase in its biotransformation - Lin_2014_Drug.Metab.Dispos_42_872
Author(s) : Lin L , Xie C , Gao Z , Chen X , Zhong D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :872 , 2014
Abstract : Allitinib, a novel irreversible selective inhibitor of the epidermal growth factor receptor (EGFR) 1 and human epidermal receptor 2 (ErbB2), is currently in clinical trials in China for the treatment of solid tumors. It is a structural analog of lapatinib but has an acrylamide side chain. Sixteen metabolites of allitinib were detected by ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. The pharmacologically active alpha,beta-unsaturated carbonyl group was the major metabolic site. The metabolic pathways included O-dealkylation, amide hydrolysis, dihydrodiol formation, hydroxylation, and secondary phase 2 conjugation. The metabolite of amide hydrolysis (M6) and 27,28-dihydrodiol allitinib (M10) were the major pharmacologically active metabolites in the circulation. The steady-state exposures to M6 and M10 were 11% and 70% of that of allitinib, respectively. The biotransformation of allitinib was determined using microsomes and recombinant metabolic enzymes. In vitro phenotyping studies demonstrated that multiple cytochrome P450 (P450) isoforms, mainly CYP3A4/5 and CYP1A2, were involved in the metabolism of allitinib. Thiol conjugates (M14 and M16) and dihydrodiol metabolites (M5 and M10) were detected in humans, implying the formation of reactive intermediates. The formation of a glutathione conjugate of allitinib was independent of NADPH and P450 isoforms, but was catalyzed by glutathione-S-transferase. P450 enzymes and epoxide hydrolase were involved in M10 formation. Overall, our study showed that allitinib was metabolized by the O-dealkylation pathway similar to lapatinib, but that amide hydrolysis and the formation of dihydrodiol were the dominant metabolic pathways. The absorbed allitinib was extensively metabolized by multiple enzymes.
ESTHER : Lin_2014_Drug.Metab.Dispos_42_872
PubMedSearch : Lin_2014_Drug.Metab.Dispos_42_872
PubMedID: 24598282

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 : Discovery of XEN445: A potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice - Sun_2013_Bioorg.Med.Chem_21_7724
Author(s) : Sun S , Dean R , Jia Q , Zenova A , Zhong J , Grayson C , Xie C , Lindgren A , Samra P , Sojo L , van Heek M , Lin L , Percival D , Fu JM , Winther MD , Zhang Z
Ref : Bioorganic & Medicinal Chemistry , 21 :7724 , 2013
Abstract : Endothelial lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related cardiovascular disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice.
ESTHER : Sun_2013_Bioorg.Med.Chem_21_7724
PubMedSearch : Sun_2013_Bioorg.Med.Chem_21_7724
PubMedID: 24211162
Gene_locus related to this paper: human-LIPG

Title : Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer's disease after 12-week donepezil treatment - Li_2012_Neuroimage_60_1083
Author(s) : Li W , Antuono PG , Xie C , Chen G , Jones JL , Ward BD , Franczak MB , Goveas JS , Li SJ
Ref : Neuroimage , 60 :1083 , 2012
Abstract : Acetylcholinesterase inhibitors (AChEIs), such as donepezil, have been shown to improve cognition in mild to moderate Alzheimer's disease (AD) patients. In this paper, our goal is to determine the relationship between altered cerebral blood flow (CBF) and intrinsic functional network connectivity changes in mild AD patients before and after 12-week donepezil treatment. An integrative neuroimaging approach was employed by combining pseudocontinuous arterial spin labeling (pCASL) MRI and resting-state functional MRI (R-fMRI) methods to determine the changes in CBF and functional connectivity (FC) in the cholinergic pathway. Linear regression analyses determined the correlations of the regional CBF alterations and functional connectivity changes with cognitive responses. These were measured with the Mini-Mental Status Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-cog) scores. Our results show that the regional CBF in mild AD subjects after donepezil treatment was significantly increased in the middle cingulate cortex (MCC) and posterior cingulate cortex (PCC), which are the neural substrates of the medial cholinergic pathway. In both brain regions, the baseline CBF and its changes after treatment were significantly correlated with the behavioral changes in ADAS-cog scores. The intrinsic FC was significantly enhanced in the medial cholinergic pathway network in the brain areas of the parahippocampal, temporal, parietal and prefrontal cortices. Finally, the FC changes in the medial prefrontal areas demonstrated an association with the CBF level in the MCC and the PCC, and also were correlated with ADAS-cog score changes. These findings indicate that regional CBF and FC network changes in the medial cholinergic pathway were associated with cognitive performance. It also is suggested that the combined pCASL-MRI and R-fMRI methods could be used to detect regional CBF and FC changes when using drug treatments in mild AD subjects.
ESTHER : Li_2012_Neuroimage_60_1083
PubMedSearch : Li_2012_Neuroimage_60_1083
PubMedID: 22245641

Title : Association between schizophrenia and single nucleotide polymorphisms in lipoprotein lipase gene in a Han Chinese population - Xie_2011_Psychiatr.Genet_21_307
Author(s) : Xie C , Wang ZC , Liu XF , Wang L , Yang MS
Ref : Psychiatr Genet , 21 :307 , 2011
Abstract : OBJECTIVE: Many studies have suggested that certain types of lipids such as phospholipids, fatty acids, and cholesterols are involved in the pathology of nervous system diseases. Lipoprotein lipase (LPL), as the key enzyme of triglyceride hydrolysis, is expressed in the brain regions functionally relevant to learning, memory, and other cognitive functions. In addition, both genome-wide linkage and association studies in schizophrenia have implicated the chromosome 8p22 region, in which the LPL gene is located. Therefore, LPL is an attractive candidate gene for schizophrenia and we tested this hypothesis in a case-control sample. METHODS: In this study, we investigated allele and genotype frequencies distributions of nine single nucleotide polymorphisms (SNPs) within the LPL gene in Han Chinese patients with schizophrenia (n=319) and healthy controls (n=575). RESULTS: Significant differences were detected between case and control groups in the frequencies of rs253 alleles [odds ratio (OR): 1.74; 95% confidence interval (CI): 1.43-2.11; P=3.21x10] and genotypes (OR: 3.08; 95%CI: 2.07-4.56; global P=7.88x10), respectively. Interestingly, this association was observed only in the male (P=5.87x10 for allele; P=1.79x10 for genotype) and not in the female samples (P>0.05). After correcting for multiple testing, the above association remains to be significant (Pc<1x10). These results suggest that rs253 C allele and CC genotype confer risk for schizophrenia in men. CONCLUSION: Our study lends support to the potential role of lipid metabolism in schizophrenia and further investigations are warranted.
ESTHER : Xie_2011_Psychiatr.Genet_21_307
PubMedSearch : Xie_2011_Psychiatr.Genet_21_307
PubMedID: 21862952