Zhou Y

References (217)

Title : Co-Reactive Ligand In Situ Engineered Gold Nanoclusters with Ultra-Bright Near-Infrared Electrochemiluminescence for Ultrasensitive and Label-Free Detection of Carboxylesterase Activity - Guo_2024_Anal.Chem__
Author(s) : Guo W , Xia M , Peng D , Zhao Y , Nie Y , Zhou Y
Ref : Analytical Chemistry , : , 2024
Abstract : Ultrasensitive and accurate monitoring of carboxylesterase (CE) activity is extremely crucial for the early diagnosis of hepatocellular carcinoma (HCC), which is still a considerable challenge. Herein, using a co-reactive ligand engineering strategy, ultra-bright near-infrared (lambda(max) = 830 nm) and self-enhanced electrochemiluminescence (ECL) Au nanoclusters (NCs) were in situ prepared with 2-(diethylamino) ethanethiol (DEAET) as a co-reactive ligand. Remarkably, the co-reactive ligand not only acts as a stabilizer like traditional ligands but also plays a crucial role as a co-reactant to ensure a confinement effect to shorten the charge transfer distance and increase the local concentration, significantly improving the collision efficiency between the electrogenerated free radicals. Consequently, the DEAET Au NCs exhibited a record and stable anodal ECL without the addition of an exogenous co-reactant, dramatically superior to classical Au NCs and Ru(bpy)(3)(2+) with a certain amount of the co-reactant. As a proof of concept, a convenient and label-free CE biosensor was innovatively constructed using 1-naphthyl acetate as a selective substrate, achieving ultrasensitive detection for CE activity with a low limit of detection of 9.1 x 10(-7) U/L. Therefore, this work not only paves a co-reactive ligand engineering strategy for in situ preparation of high-efficiency metal NCs but also provides an ultrasensitive and convenient platform for the early diagnosis of HCC.
ESTHER : Guo_2024_Anal.Chem__
PubMedSearch : Guo_2024_Anal.Chem__
PubMedID: 38310525

Title : Rivastigmine Nasal Spray for the Treatment of Alzheimer's Disease: Olfactory Deposition and Brain Delivery - Guo_2024_Int.J.Pharm__123809
Author(s) : Guo H , Wang G , Zhai Z , Huang J , Huang Z , Zhou Y , Xia X , Yao Z , Huang Y , Zhao Z , Wu C , Zhang X
Ref : Int J Pharm , :123809 , 2024
Abstract : Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F(2) (containing 1% (w/v) viscosity modifier Avicel(a) RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F(2) exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.
ESTHER : Guo_2024_Int.J.Pharm__123809
PubMedSearch : Guo_2024_Int.J.Pharm__123809
PubMedID: 38224760

Title : Alloyed Trimetallic Nanocomposite as an Efficient and Recyclable Solid Matrix for Ideonella sakaiensis Lipase Immobilization - Addai_2024_Langmuir__
Author(s) : Addai FP , Wu J , Lin F , Ma X , Han J , Liu Y , Zhou Y , Wang Y
Ref : Langmuir , : , 2024
Abstract : In this work, a trimetallic (Ni/Co/Zn) organic framework (tMOF), synthesized by a solvothermal method, was calcinated at 400 and 600 degreesC and the final products were used as a support for lipase immobilization. The material annealed at 400 degreesC (Ni-Co-Zn@400) had an improved surface area (66.01 m(2)/g) and pore volume (0.194 cm(3)/g), which showed the highest enzyme loading capacity (301 mg/g) with a specific activity of 0.196 U/mg, and could protect the enzyme against thermal denaturation at 65 degreesC. The optimal pH and temperature for the lipase were 8.0 and 45 degreesC but could tolerate pH levels 7.0-8.0 and temperatures 40-60 degreesC. Moreover, the immobilized enzyme (Ni-Co-Zn@Lipase, Ni-Co-Zn@400@Lipase, or Ni-Co-Zn@600@Lipase) could be recovered and reused for over seven cycles maintaining 80, 90, and 11% of its original activity and maintained a residual activity >90% after 40 storage days. The remarkable thermostability and storage stability of the immobilized lipase suggest that the rigid structure of the support acted as a protective shield against denaturation, while the improved pH tolerance toward the alkaline range indicates a shift in the ionization state attributed to unequal partitioning of hydroxyl and hydrogen ions within the microenvironment of the active site, suggesting that acidic residues may have been involved in forming an enzyme-support bond. The high enzyme loading capacity, specific activity, encouraging stability, and high recoverability of the tMOF@Lipase indicate that a multimetallic MOF could be a better platform for efficient enzyme immobilization.
ESTHER : Addai_2024_Langmuir__
PubMedSearch : Addai_2024_Langmuir__
PubMedID: 38626327

Title : Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation - Kuang_2024_Sci.Total.Environ_932_173117
Author(s) : Kuang HX , Dong CY , Yan L , Zhou Y , Xiang MD , Yu YJ
Ref : Sci Total Environ , 932 :173117 , 2024
Abstract : 2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, gamma-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 microg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.
ESTHER : Kuang_2024_Sci.Total.Environ_932_173117
PubMedSearch : Kuang_2024_Sci.Total.Environ_932_173117
PubMedID: 38734097

Title : Direct detection of acetylcholinesterase by Fe(HCOO)(2.6)(OH)(0.3). H(2)O nanosheets with oxidase-like activity on a smartphone platform - Cao_2024_Talanta_274_126074
Author(s) : Cao Y , Chen Y , Zhou Y , Chen X , Peng J
Ref : Talanta , 274 :126074 , 2024
Abstract : Monitoring acetylcholinesterase (AChE) is crucial in clinical diagnosis and drug screening. Traditional methods for detecting AChE usually require the addition of intermediates like acetylthiocholine, which complicates the detection process and introduces interference risks. Herein, we develop a direct colorimetric assay based on alkaline iron formate nanosheets (Fe(HCOO)(2.6)(OH)(0.3).H(2)O NSs, Fef NSs) for the detection of AChE without any intermediates. The as-prepared Fef NSs exhibit oxidase-like activity, catalyzing the generation of O(2)(.-), (1)O(2) and .OH, which leads to a color change from colorless to blue when exposed to 3,3',5,5'-tetramethylbenzidine. AChE directly inhibits the oxidase-like activity of Fef NSs, resulting in a hindered color reaction, enabling the detection of AChE. The biosensor has a linear detection range of 0.1-30 mU/mL, with a minimum detection limit of 0.0083 mU/mL (S/N = 3), representing a 100-fold improvement in detection sensitivity over the traditional Ellman's method. Satisfactory results were obtained when analyzing real AChE samples. Attractively, a method for the quantitative detection of AChE by a smartphone is established based on the Fef NSs. This method enables instant acquisition of AChE concentrations, achieving real-time visualized detection.
ESTHER : Cao_2024_Talanta_274_126074
PubMedSearch : Cao_2024_Talanta_274_126074
PubMedID: 38608632

Title : Genome-wide association studies of egg production traits by whole genome sequencing of Laiwu Black chicken - Lei_2024_Poult.Sci_103_103705
Author(s) : Lei Q , Zhang S , Wang J , Qi C , Liu J , Cao D , Li F , Han H , Liu W , Li D , Tang C , Zhou Y
Ref : Poult Sci , 103 :103705 , 2024
Abstract : Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 x per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.
ESTHER : Lei_2024_Poult.Sci_103_103705
PubMedSearch : Lei_2024_Poult.Sci_103_103705
PubMedID: 38598913

Title : Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects - Lin_2024_Talanta_274_126060
Author(s) : Lin X , Liu M , Yi Q , Zhou Y , Su J , Qing B , Lu Y , Pu C , Lan W , Zou L , Wang J
Ref : Talanta , 274 :126060 , 2024
Abstract : In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF(2)-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF(2)-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF(2)-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF(2)-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.
ESTHER : Lin_2024_Talanta_274_126060
PubMedSearch : Lin_2024_Talanta_274_126060
PubMedID: 38604044

Title : Frequencies of insecticide resistance mutations detected by the amplicon sequencing in Plutella xylostella (Lepidoptera: Plutellidae) and Spodoptera exigua (Lepidoptera: Noctuidae) from China - Liu_2024_J.Econ.Entomol__
Author(s) : Liu Z , Ma H , Li K , Liu J , Zhu H , Zhou Y , Man Y , Zhou X
Ref : J Econ Entomol , : , 2024
Abstract : The globally prevalent pests, Diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) and Beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), pose significant threats to cruciferous vegetables. They have rapidly developed resistance to a wide range of insecticides, leading to significant yield losses and increased control expenses. In this study, we have established an efficient approach utilizing amplicon sequencing to detect the frequency of 15 target resistance mutant sites in 6 molecular targets, acetylcholinesterase 1 (ACE1), chitin synthase 1 (CHS1), the gamma-aminobutyric acid receptor (GABAR), glutamate-gated chloride channel (GluCl), voltage-gated sodium channels (NaV), and ryanodine receptor (RyR) in P. xylostella and the frequency of 11 mutations in 5 molecular targets (except GluCl) in S. exigua in China. Our findings indicate that P. xylostella exhibits remarkably high frequency (over 88.67%) in pyrethroid resistance-related mutations T929I and L1014F of NaV. In S. exigua, the frequencies of L659F mutation were ranging from 41.92% to 74.89%. In addition, the organophosphorus resistance-related mutations A298S and G324A of ACE1 were detected at frequencies ranging from 34.29% to 75.66%, and these 2 mutations occurred simultaneously (from 29.22% to 65.79%) in P. xylostella. An interannual variation in mutation frequency from 2019 to 2021 was found for P. xylostella in HNCS. The frequency of A298S and G324A mutations steadily increased while the frequency of G4946E and I4790M mutations continuously decreased. These results unveil a worrisome scenario of multiple resistance sites in these 2 pests in China and provide valuable insights for the practical application of pesticides in the field.
ESTHER : Liu_2024_J.Econ.Entomol__
PubMedSearch : Liu_2024_J.Econ.Entomol__
PubMedID: 38748551

Title : Trace Amount of Bi-Doped Core-Shell Pd@Pt Mesoporous Nanospheres with Specifically Enhanced Peroxidase-Like Activity Enable Sensitive and Accurate Detection of Acetylcholinesterase and Organophosphorus Nerve Agents - Lei_2024_Anal.Chem__
Author(s) : Lei M , Ding X , Liu J , Tang Y , Chen H , Zhou Y , Zhu C , Yan H
Ref : Analytical Chemistry , : , 2024
Abstract : The urgent need for sensitive and accurate assays to monitor acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs) arises from the imperative to safeguard human health and protect the ecosystem. Due to its cost-effectiveness, ease of operation, and rapid response, nanozyme-based colorimetry has been widely utilized in the determination of AChE activity and OPs. However, the rational design of nanozymes with high activity and specificity remains a great challenge. Herein, trace amount of Bi-doped core-shell Pd@Pt mesoporous nanospheres (Pd@PtBi(2)) have been successfully synthesized, exhibiting good peroxidase-like activity and specificity. With the incorporation of trace bismuth, there is a more than 4-fold enhancement in the peroxidase-like performance of Pd@PtBi(2) compared to that of Pd@Pt. Besides, no significant improvement of oxidase-like and catalase-like activities of Pd@PtBi(2) was found, which prevents interference from O(2) and undesirable consumption of substrate H(2)O(2). Based on the blocking impact of thiocholine, a colorimetric detection platform utilizing Pd@PtBi(2) was constructed to monitor AChE activity with sensitivity and selectivity. Given the inhibition of OPs on AChE activity, a biosensor was further developed by integrating Pd@PtBi(2) with AChE to detect OPs, capitalizing on the cascade amplification strategy. The OP biosensor achieved a detection limit as low as 0.06 ng mL(-1), exhibiting high sensitivity and anti-interference ability. This work is promising for the construction of nanozymes with high activity and specificity, as well as the development of nanozyme-based colorimetric biosensors.
ESTHER : Lei_2024_Anal.Chem__
PubMedSearch : Lei_2024_Anal.Chem__
PubMedID: 38577757

Title : Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway - Xiang_2024_Neurosci.Lett_830_137769
Author(s) : Xiang X , Xia S , Li S , Zeng Y , Wang L , Zhou Y
Ref : Neuroscience Letters , 830 :137769 , 2024
Abstract : The occurrence and development of Alzheimer's disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.
ESTHER : Xiang_2024_Neurosci.Lett_830_137769
PubMedSearch : Xiang_2024_Neurosci.Lett_830_137769
PubMedID: 38616003

Title : Role of Mn-LIPA in Sex Hormone Regulation and Gonadal Development in the Oriental River Prawn, Macrobrachium nipponense - Cai_2024_Int.J.Mol.Sci_25_
Author(s) : Cai P , Zhang W , Jiang S , Xiong Y , Qiao H , Yuan H , Gao Z , Zhou Y , Jin S , Fu H
Ref : Int J Mol Sci , 25 : , 2024
Abstract : This study investigates the role of lysosomal acid lipase (LIPA) in sex hormone regulation and gonadal development in Macrobrachium nipponense. The full-length Mn-LIPA cDNA was cloned, and its expression patterns were analyzed using quantitative real-time PCR (qPCR) in various tissues and developmental stages. Higher expression levels were observed in the hepatopancreas, cerebral ganglion, and testes, indicating the potential involvement of Mn-LIPA in sex differentiation and gonadal development. In situ hybridization experiments revealed strong Mn-LIPA signaling in the spermatheca and hepatopancreas, suggesting their potential role in steroid synthesis (such as cholesterol, fatty acids, cholesteryl ester, and triglycerides) and sperm maturation. Increased expression levels of male-specific genes, such as insulin-like androgenic gland hormone (IAG), sperm gelatinase (SG), and mab-3-related transcription factor (Dmrt11E), were observed after dsMn-LIPA (double-stranded LIPA) injection, and significant inhibition of sperm development and maturation was observed histologically. Additionally, the relationship between Mn-LIPA and sex-related genes (IAG, SG, and Dmrt11E) and hormones (17beta-estradiol and 17alpha-methyltestosterone) was explored by administering sex hormones to male prawns, indicating that Mn-LIPA does not directly control the production of sex hormones but rather utilizes the property of hydrolyzing triglycerides and cholesterol to provide energy while influencing the synthesis and secretion of self-sex hormones. These findings provide valuable insights into the function of Mn-LIPA in M. nipponense and its potential implications for understanding sex differentiation and gonadal development in crustaceans. It provides an important theoretical basis for the realization of a monosex culture of M. nipponense.
ESTHER : Cai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Cai_2024_Int.J.Mol.Sci_25_
PubMedID: 38338678

Title : Characteristics of a lipase ArEstA with lytic activity against drug-resistant pathogen from a novel myxobacterium, Archangium lipolyticum sp. nov - Zhou_2024_Front.Microbiol_14_1320827
Author(s) : Zhou Y , Chen H , Jiang H , Yao Q , Zhu H
Ref : Front Microbiol , 14 :1320827 , 2024
Abstract : Bacteriolytic myxobacteria are versatile micropredators and are proposed as potential biocontrol agents against diverse bacterial and fungal pathogens. Isolation of new myxobacteria species and exploration of effective predatory products are necessary for successful biocontrol of pathogens. In this study, a myxobacterium strain CY-1 was isolated from a soil sample of a pig farm using the Escherichia coli baiting method. Based on the morphological observation, physiological test, 16S rRNA gene sequence, and genomic data, strain CY-1 was identified as a novel species of the myxobacterial genus Archangium, for which the name Archangium lipolyticum sp. nov. was proposed. Subsequent predation tests indicated that the strain efficiently lysed drug-resistant pathogens, with a higher predatory activity against E. coli 64 than Staphylococcus aureus GDMCC 1.771 (MRSA). The lysis of extracellular proteins against ester-bond-containing substrates (tributyrin, tween 80, egg-yolk, and autoclaved drug-resistant pathogens) inspired the mining of secreted predatory products with lipolytic activity. Furthermore, a lipase ArEstA was identified from the genome of CY-1, and the heterologously expressed and purified enzyme showed bacteriolytic activity against Gram-negative bacteria E. coli 64 but not against Gram-positive MRSA, possibly due to different accessibility of enzyme to lipid substrates in different preys. Our research not only provided a novel myxobacterium species and a candidate enzyme for the development of new biocontrol agents but also reported an experimental basis for further study on different mechanisms of secreted predatory products in myxobacterial killing and degrading of Gram-negative and Gram-positive preys.
ESTHER : Zhou_2024_Front.Microbiol_14_1320827
PubMedSearch : Zhou_2024_Front.Microbiol_14_1320827
PubMedID: 38239728
Gene_locus related to this paper: 9bact-ArEstA

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2024_Ther.Apher.Dial_28_141
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , 28 :141 , 2024
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2024_Ther.Apher.Dial_28_141
PubMedSearch : Wan_2024_Ther.Apher.Dial_28_141
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Dual-Mode Ratiometric Electrochemical and Turn-On Fluorescent Detection of Butyrylcholinesterase Utilizing a Single Probe for the Diagnosis of Alzheimer's Disease - Dong_2023_Anal.Chem_95_8340
Author(s) : Dong H , Zhao L , Wang T , Chen Y , Hao W , Zhang Z , Hao Y , Zhang C , Wei X , Zhang Y , Zhou Y , Xu M
Ref : Analytical Chemistry , 95 :8340 , 2023
Abstract : Biomarkers detection in blood with high accuracy is crucial for the diagnosis and treatment of many diseases. In this study, the proof-of-concept fabrication of a dual-mode sensor based on a single probe (Re-BChE) using a dual-signaling electrochemical ratiometric strategy and a "turn-on" fluorescent method is presented. The probe Re-BChE was synthesized in a single step and demonstrated dual mode response toward butyrylcholinesterase (BChE), a promising biomarker of Alzheimer's disease (AD). Due to the specific hydrolysis reaction, the probe Re-BChE demonstrated a turn-on current response for BChE at -0.28 V, followed by a turn-off current response at -0.18 V, while the fluorescence spectrum demonstrated a turn-on response with an emission wavelength of 600 nm. The developed ratiometric electrochemical sensor and fluorescence detection demonstrated high sensitivity with BChE concentrations with a low detection limit of 0.08 microg mL(-1) and 0.05 microg mL(-1), respectively. Importantly, the dual-mode sensor presents the following advantages: (1) dual-mode readout can correct the impact of systematic or background error, thereby achieving more accurate results; (2) the responses of dual-mode readout originate from two distinct mechanisms and relatively independent signal transduction, in which there is no interference between two signaling routes. Additionally, compared with the reported single-signal electrochemical assays for BChE, both redox potential signals were detected in the absence of biological interference within a negative potential window. Furthermore, it was discovered that the outcomes of direct dual-mode electrochemical and fluorescence quantifications of the level of BChE in serum were in agreement with those obtained from the use of commercially available assay kits for BChE sensing. This method has the potential to serve as a useful point-of-care tool for the early detection of AD.
ESTHER : Dong_2023_Anal.Chem_95_8340
PubMedSearch : Dong_2023_Anal.Chem_95_8340
PubMedID: 37192372

Title : Complementary Homogeneous Electrochemical and Photothermal Dual-Modal Sensor for Highly Sensitive Detection of Organophosphorus Pesticides via Stimuli-Responsive COF\/Methylene Blue@MnO(2) Composite - Wen_2023_Anal.Chem__
Author(s) : Wen SH , Zhang H , Yu S , Ma J , Zhu JJ , Zhou Y
Ref : Analytical Chemistry , : , 2023
Abstract : Credible and on-site detection of organophosphorus pesticides (OPs) in complex matrixes is significant for food security and environmental monitoring. Herein, a novel COF/methylene blue@MnO(2) (COF/MB@MnO(2)) composite featured abundant signal loading, a specific recognition unit, and robust oxidase-like activity was successfully prepared through facile assembly processes. The multifunctional composite acted as a homogeneous electrochemical and photothermal dual-mode sensing platform for OPs detection through stimuli-responsive regulation. Without the presence of OPs, the surface MnO(2) coating could recognize thiocholine (TCh), originating from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine (ATCh), and exhibited a distinctly amplified diffusion current due to the release of plentiful MB; while the residual MnO(2) nanosheets could only catalyze less TMB into oxidized TMB (oxTMB) with a typical near-infrared (NIR) absorption, enabling NIR-driven photothermal assay with a low temperature using a portable thermometer. Based on the inhibitory effect of OPs on AChE activity and OP-regulated generation of TCh, chlorpyrifos as a model target can be accurately detected with a low limit of detection of 0.0632 and 0.108 ng/mL by complementary electrochemical and photothermal measurements, respectively. The present dual-mode sensor was demonstrated to be excellent for application to the reliable detection of OPs in complex environmental and food samples. This work can not only provide a complementary dual-mode method for convenient and on-site detection of OPs in different scenarios but also expand the application scope of the COF-based multifunctional composite in multimodal sensors.
ESTHER : Wen_2023_Anal.Chem__
PubMedSearch : Wen_2023_Anal.Chem__
PubMedID: 37769195

Title : Biosynthesis of diisooctyl 2,5-furandicarboxylate by Candida antarctica lipase B (CALB) immobilized on a macroporous epoxy resin - Mang_2023_Biotechnol.Appl.Biochem__
Author(s) : Mang R , Zhou Y , Du X , Zhou H , Zhu M
Ref : Biotechnol Appl Biochem , : , 2023
Abstract : Diisooctyl 2,5-furandicarboxylate (DEF), an ester derivative of 2,5-furandicarboxylic acid (FDCA, a bio-based platform chemical), resembles the physical and chemical properties of phthalates. Due to its excellent biodegradability, DEF is considered a safer alternative to the hazardous phthalate plasticizers. Although FDCA esters are currently mainly produced by chemical synthesis, the enzymatic synthesis of DEF is a green, promising alternative. The current study investigated the biosynthesis of DEF by Candida antarctica lipase B (CALB) immobilized on macroporous resins. Out of five macroporous resins (NKA-9, LX-1000EP, LX-1000HA, XAD-7HP, and XAD-8) evaluated, the LX-1000EP epoxy resin was identified as the best carrier for CALB, and the XAD-7HP weakly polar resin was identified as the second best. The optimal immobilization conditions were as follows: CALB (500 microL) and LX-1000EP (0.1 g) were incubated in phosphate butter (20 mM, pH 6.0) for 10 h at 35 degreesC. The resulting immobilized CALB (EP-CALB) showed an activity of 639 U/g in the hydrolysis of p-nitrophenyl acetate, with an immobilization efficiency of 87.8% and an activity recovery rate of 56.4%. Using 0.02 g EP-CALB as the catalyst in 10 mL toluene, and the molar ratio of 2,5-dimethyl furanediformate (1 mmol/mL) and isooctyl alcohol (4 mmol/mL) that was 1:4, a DEF conversion rate of 91.3% was achieved after a 24-h incubation at 50 degreesC. EP-CALB had similar thermal stability and organic solvent tolerance compared to Novozym 435, and both were superior to CALB immobilized on the XAD-7HP resin. EP-CALB also exhibited excellent operational stability, with a conversion rate of 52.6% after 10 repeated uses. EP-CALB could be a promising alternative to Novozym 435 in the biomanufacturing of green and safe plasticizers such as DEF.
ESTHER : Mang_2023_Biotechnol.Appl.Biochem__
PubMedSearch : Mang_2023_Biotechnol.Appl.Biochem__
PubMedID: 37264706

Title : Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats - Mei_2023_J.Integr.Neurosci_22_76
Author(s) : Mei D , Wang F , Yuan B , Lai M , Zhou Y , Cui W , Liu H , Zhou W
Ref : J Integr Neurosci , 22 :76 , 2023
Abstract : PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.
ESTHER : Mei_2023_J.Integr.Neurosci_22_76
PubMedSearch : Mei_2023_J.Integr.Neurosci_22_76
PubMedID: 37258429

Title : Glutathione and Esterase Dual-Responsive Smart Nano-drug Delivery System Capable of Breaking the Redox Balance for Enhanced Tumor Therapy - Shen_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Shen P , Zhang X , Ding N , Zhou Y , Wu C , Xing C , Zeng L , Du L , Yuan J , Kang Y
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : Conventional chemotherapy usually fails to achieve its intended effect because of the poor water solubility, poor tumor selectivity, and low tumor accumulation of chemotherapy drugs. The systemic toxicity of chemotherapy agents is also a problem that cannot be ignored. It is expected that smart nano-drug delivery systems that are able to respond to tumor microenvironments will provide better therapeutic outcomes with decreased side effects of chemotherapeutics. Nano-drug delivery systems capable of breaking the redox balance can also increase the sensitivity of tumor cells to chemotherapeutics. In this study, using polymer-containing disulfide bonds, ester bonds, and d-alpha-tocopherol polyethylene glycol succinate (TPGS), which can amplify reactive oxygen species (ROS) in tumor cells, we have successfully prepared a smart glutathione (GSH) and esterase dual-responsive nano-drug delivery system (DTX@PAMBE-SS-TPGS NPs) with the ability to deplete GSH as well as amplify ROS and effectively release an encapsulated chemotherapy drug (DTX) in tumor cells. The potential of DTX@PAMBE-SS-TPGS NPs for enhanced antitumor effects was thoroughly evaluated using in vitro as well as in vivo experiments. Our research offers a promising strategy for maximizing the efficacy of tumor therapy.
ESTHER : Shen_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Shen_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 37083309

Title : Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis - Wu_2023_Kidney.Int.Rep_8_2428
Author(s) : Wu H , Xu H , Lei S , Yang Z , Yang S , Du J , Zhou Y , Liu Y , Yang Y , Hu Z
Ref : Kidney Int Rep , 8 :2428 , 2023
Abstract : INTRODUCTION: Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. METHODS: Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. RESULTS: Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the sigma3/sigma3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with alpha-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. CONCLUSION: LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.
ESTHER : Wu_2023_Kidney.Int.Rep_8_2428
PubMedSearch : Wu_2023_Kidney.Int.Rep_8_2428
PubMedID: 38025240
Gene_locus related to this paper: human-LPL

Title : Reticular Synthesis of Highly Crystalline Three-Dimensional Mesoporous Covalent-Organic Frameworks for Lipase Inclusion - Liu_2023_J.Am.Chem.Soc__
Author(s) : Liu H , Zhou Y , Guo J , Feng R , Hu G , Pang J , Chen Y , Terasaki O , Bu XH
Ref : Journal of the American Chemical Society , : , 2023
Abstract : The synthesis and application of three-dimensional (3D) mesoporous covalent-organic frameworks (COFs) are still to be developed. Herein, two mesoporous 3D COFs with an stp topology were synthesized in a highly crystalline form with aniline as the modulator. The chemical composition of these COFs was confirmed by Fourier transform infrared (FT-IR) and (13)C cross-polarization magic angle spinning nuclear magnetic resonance (NMR) spectroscopies. These 3D mesoporous COFs were highly crystalline and exhibited permanent porosity and good chemical stability in both aqueous and organic media. The space group and unit cell parameters of COF HFPTP-TAE were verified by powder X-ray diffraction (PXRD), small-angle X-ray scattering, and three-dimensional electron diffraction (3D ED). The appropriate pore size of the COF HFPTP-TAE facilitated the inclusion of enzyme lipase PS with a loading amount of 0.28 g g(-1). The lipaseHFPTP-TAE ( refers to "include in") composite exhibited high catalytic activity, good thermal stability, and a wide range of solvent tolerance. Specifically, it could catalyze the alcoholysis of aspirin methyl ester (AME) with high catalytic efficiency. Oriented one-dimensional (1D) channel mesopores in HFPTP-TAE accommodated lipase, meanwhile preventing them from aggregation, while windows on the wall of the 1D channel favored molecular diffusion; thus, this COF-enzyme design outperformed its amorphous isomer, two-dimensional (2D) mesoporous COF, 3D mesoporous COF with limited crystallinity, and mesoporous silica as an enzyme host.
ESTHER : Liu_2023_J.Am.Chem.Soc__
PubMedSearch : Liu_2023_J.Am.Chem.Soc__
PubMedID: 37843005

Title : A novel and controllable method for simultaneous preparation of human milk fat substitutes (OPL, OPO and LPL): two-step enzymatic ethanolysis-esterification strategy - Li_2023_Food.Res.Int_163_112168
Author(s) : Li Y , Zhang Y , Zhou Y , Zheng M
Ref : Food Res Int , 163 :112168 , 2023
Abstract : A novel and effective approach based on the two-step ethanolysis-esterification strategy was proposed for the controllable and simultaneous preparation of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL), 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and 1,3-dilinoleoyl-2-palmitoyl-glycerol (LPL) with adjustable proportions. Enzymatic ethanolysis of fractionated palm stearin was carried out to yield 2-monopalmitoylglycerol (79.4s+/-s0.6s%) with over 91.0s% purity at the optimal conditions. The immobilized Candida sp. lipase (CSL) on octyl-functionalized ordered mesoporous silica (OMS-C(8)) was applied to re-esterify 2-monopalmitoylglycerol with oleic acid and linoleic acid for the simultaneous production of OPL, OPO, and LPL. The total content in the final products was 81.5s%, with 91.3s% of palmitic acid (PA) content at the sn-2 position. Besides, OPL/OPO/LPL was conveniently prepared with suitable proportions for worldwide infants by adjusting the ratio of acyl donors. This paper provides a novel and effective two-step ethanolysis-esterification strategy for the development of human milk fat substitutes (HMFS).
ESTHER : Li_2023_Food.Res.Int_163_112168
PubMedSearch : Li_2023_Food.Res.Int_163_112168
PubMedID: 36596114

Title : Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes - Wu_2023_Diabetes.Obes.Metab__
Author(s) : Wu Y , Cheng S , Gu H , Yang K , Xu Z , Meng X , Wang Y , Jiang Y , Li H , Zhou Y
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m(2) at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m(2) or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.
ESTHER : Wu_2023_Diabetes.Obes.Metab__
PubMedSearch : Wu_2023_Diabetes.Obes.Metab__
PubMedID: 37427758

Title : An ultrasensitive and selective near-infrared fluorescent probe for tracking carboxylesterases with large Stokes shift in living cells and mice - Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
Author(s) : Zhang W , Qi C , Wang X , Fu Z , Zhang J , Zhou Y , Wang Y
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 308 :123708 , 2023
Abstract : Carboxylesterases (CEs) play great role in CEs-related diseases and drug metabolism. Selectively monitoring its activity is important to explore its role in CEs-related diseases and drug combination. Herein, a new "turn-on" near-infrared (NIR) fluorescent probe (CHY-1) was reported with large Stokes shift (145 nm) for CEs detection. Dicyanoisophorone-based derivative was chosen as NIR fluorophore and 4-bromobutyrate was the identifying group. What's more, CHY-1 exhibited ultra-sensitivity (LOD - 9.2 x 10(-5) U/mL), high selectivity against Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE) and Chymotrypsin for CEs fluorescence detection under physiological pH and temperature. Furthermore, CHY-1 showed little effect on cell viability at high concentration and featured good optical imaging character for the slight change of CEs activity induced by 5-Fu (5-Fluorouridine, anti-tumor drug) and CEs inhibitor in living cells. Moreover, CHY-1 was also used to detect the activity and distribution of CEs in mice. Taken together, CHY-1 had widely applicable value in the diagnosis of CEs-related diseases and drug combination.
ESTHER : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedSearch : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedID: 38042124

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 : Rutin hydrate relieves neuroinflammation in zebrafish models: Involvement of NF-kB pathway as a central network - Hu_2023_Fish.Shellfish.Immunol_141_109062
Author(s) : Hu Y , Jia K , Zhou Y , Chen L , Wang F , Yi X , Huang Y , Ge Y , Chen X , Liao D , Peng Y , Meng Y , Liu Y , Luo Q , Cheng B , Zhao Y , Lu H , Yuan W
Ref : Fish Shellfish Immunol , 141 :109062 , 2023
Abstract : Neuroinflammation is prevalent in multiple brain diseases and may also lead to dementia, cognitive impairment, and impaired spatial memory function associated with neurodegenerative diseases. A neuroprotective and antioxidant flavonoid, rutin hydrate (RH), was evaluated for the anti-neuroinflammatory activity mediated by copper sulfate (CuSO(4)) solution and lipopolysaccharide (LPS) in zebrafish. The results showed that 100 mg/L RH significantly reduced the ratio of neutrophil mobility in caudal hematopoietic tissue (CHT) region caused by CuSO(4) and the number of neutrophils co-localized with facial peripheral nerves. In the LPS model, RH co-injection significantly diminished neutrophil and macrophage migration. Therefore, RH exhibited a significant rescue effect on both models. In addition, RH treatment remarkably reduced the effects of neuroinflammation on the locomotor ability, expression levels of genes associated with behavioral disorders, and acetylcholinesterase (AChE) activity. Furthermore, network pharmacology techniques were employed to investigate the potential mechanisms, and the associated genes and enzyme activities were validated in order to elucidate the underlying mechanisms. Network pharmacological analysis and zebrafish model indicated that RH regulated the expressions of NF-kappaB pathway-related targets (Toll-like receptor 9 (tlr9), nuclear factor kappa B subunit 1 (nfkb1), RELA proto-oncogene (RelA), nitric oxide synthase 2a, inducible (nos2a), tumour necrosis factor alpha-like (tnfalpha), interleukin 6 (il6), interleukin 1beta (il1beta), chemokine 8 (cxcl8), and macrophage migration inhibitory factor (mif)) as well as six key factors (arachidonic acid 4 alpha-lipoxygenase (alox4a), arachidonate 5-lipoxygenase a (alox5), prion protein a (prnpa), integrin, beta 2 (itgb2), catalase (CAT), and alkaline phosphatase (ALP) enzymes). Through this study, a thorough understanding of the mechanism underlying the therapeutic effects of RH in neuroinflammation has been achieved, thereby establishing a solid foundation for further research on the potential therapeutic applications of RH in neuroinflammatory disorders.
ESTHER : Hu_2023_Fish.Shellfish.Immunol_141_109062
PubMedSearch : Hu_2023_Fish.Shellfish.Immunol_141_109062
PubMedID: 37678480

Title : Molecular insights into the catalytic mechanism of plasticizer degradation by a monoalkyl phthalate hydrolase - Chen_2023_Commun.Chem_6_45
Author(s) : Chen Y , Wang Y , Xu Y , Sun J , Yang L , Feng C , Wang J , Zhou Y , Zhang ZM
Ref : Commun Chem , 6 :45 , 2023
Abstract : Phthalate acid esters (PAEs), a group of xenobiotic compounds used extensively as plasticizers, have attracted increasing concern for adverse effects to human health and the environment. Microbial degradation relying on PAE hydrolases is a promising treatment. However, only a limited number of PAE hydrolases were characterized to date. Here we report the structures of MehpH, a monoalkyl phthalate (MBP) hydrolase that catalyzes the reaction of MBP to phthalic acid and the corresponding alcohol, in apo and ligand-bound form. The structures reveal a positively-charged catalytic center, complementary to the negatively-charged carboxyl group on MBP, and a penetrating tunnel that serves as exit of alcohol. The study provides a first glimpse into the enzyme-substrate binding model for PAE hydrolases, leading strong support to the development of better enzymes in the future.
ESTHER : Chen_2023_Commun.Chem_6_45
PubMedSearch : Chen_2023_Commun.Chem_6_45
PubMedID: 36859434
Gene_locus related to this paper: 9acto-q2mhh5

Title : Effect of substrate composition on physicochemical properties of the medium-long-medium structured triacylglycerol - Tian_2023_J.Sci.Food.Agric__
Author(s) : Tian Y , Zhou Y , Li L , Huang C , Lin L , Li C , Ye Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Nutritional and functional qualities and applications of structured lipids (SL) depend on the composition and molecular structure of fatty acids in the glycerol backbone of triacylglycerol (TAG). However, the relationship between the substrate composition and physicochemical qualities of SL has not been revealed. The investigation aims to disclose the effect of substrate composition on the physicochemical properties of medium-long-medium structured lipids (MLM-SLs) by enzymatic interesterification of Lipozyme TLIM/RMIM. RESULTS: The medium-long chain triacylglycerol (MLCT) yield could reach 70.32% including 28.98% CaLCa (1,3-dioctonyl-2-linoleoyl glyceride) and 24.34% CaOCa (1,3-didecanoyl-2-oleoyl glyceride). The sn-2 unsaturated fatty acids composition mainly depended on long chain triacylglycerol (LCT) in the substrate. The increased carbon chain length and double bond in triacylglycerol decreased its melting and crystallization temperature. The balanced substrate composition of MCT/LCT increased the size and finer crystals. Molecular docking simulation revealed that the MLCT molecule was mainly interacted with the catalytic triplets of Lipozyme TLIM (Arg81-Ser83-Arg84) and the Lipozyme RMIM (Tyr183-Thr226-Arg262) by O...H bond. The oxygen atom of the ester on the MLCT molecule was primarily bound to the hydrogen of hydroxyl and amino groups on the binding sites of Lipozyme TLIM/RMIM. The intermolecular interplay between MLCT and Lipozyme RMIM is stable than Lipozyme TLIM due to the formation of lower binding affinity energy. CONCLUSION: This research clarifies the interaction mechanism between MLCT molecules and lipases, and provides in-deep understanding the relationship between substrate composition, molecular structure and physicochemical property of MLM-SLs. This article is protected by copyright. All rights reserved.
ESTHER : Tian_2023_J.Sci.Food.Agric__
PubMedSearch : Tian_2023_J.Sci.Food.Agric__
PubMedID: 37708388

Title : EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25\/Keap1\/Nrf2 axis - Zhang_2023_Redox.Biol_63_102765
Author(s) : Zhang CY , Zhong WJ , Liu YB , Duan JX , Jiang N , Yang HH , Ma SC , Jin L , Hong JR , Zhou Y , Guan CX
Ref : Redox Biol , 63 :102765 , 2023
Abstract : Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and gammaH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
ESTHER : Zhang_2023_Redox.Biol_63_102765
PubMedSearch : Zhang_2023_Redox.Biol_63_102765
PubMedID: 37269686

Title : Soluble epoxide hydrolase and TRPC3 channels jointly contribute to homocysteine-induced cardiac hypertrophy: Interrelation and regulation by C\/EBPbeta - Zhou_2023_Biochim.Biophys.Acta.Mol.Basis.Dis__166643
Author(s) : Zhou Y , Wang XC , Wei JH , Xue HM , Sun WT , He GW , Yang Q
Ref : Biochimica & Biophysica Acta Mol Basis Dis , :166643 , 2023
Abstract : OBJECTIVES: Studies in certain cardiac hypertrophy models suggested the individual role of soluble epoxide hydrolase (sEH) and canonical transient receptor potential 3 (TRPC3) channels, however, whether they jointly mediate hypertrophic process remains unexplored. Hyperhomocysteinemia promotes cardiac hypertrophy while the involvement of sEH and TRPC3 channels remains unknown. This study aimed to explore the role of, and interrelation between sEH and TRPC3 channels in homocysteine-induced cardiac hypertrophy. METHODS: Rats were fed methionine-enriched diet to induce hyperhomocysteinemia. H9c2 cells and neonatal rat cardiomyocytes were incubated with homocysteine. Cardiac hypertrophy was evaluated by echocardiography, histological examination, immunofluorescence imaging, and expressions of hypertrophic markers. Epoxyeicosatrienoic acids (EETs) were determined by ELISA. TRPC3 current was recorded by patch-clamp. Gene promotor activity was measured using dual-luciferase reporter assay. RESULTS: Inhibition of sEH by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) reduced ventricular mass, lowered the expression of hypertrophic markers, decreased interstitial collagen deposition, and improved cardiac function in hyperhomocysteinemic rats, associated with restoration of EETs levels in myocardium. TPPU or knockdown of sEH suppressed TRPC3 transcription and translation as well as TRPC3 current that were enhanced by homocysteine. Exogenous 11,12-EET inhibited homocysteine-induced TRPC3 expression and cellular hypertrophy. Silencing C/EBPbeta attenuated, while overexpressing C/EBPbeta promoted homocysteine-induced hypertrophy and expressions of sEH and TRPC3, resulting respectively from inhibition or activation of sEH and TRPC3 gene promoters. CONCLUSIONS: sEH and TRPC3 channels jointly contribute to homocysteine-induced cardiac hypertrophy. Homocysteine transcriptionally activates sEH and TRPC3 genes through a common regulatory element C/EBPbeta. sEH activation leads to an upregulation of TRPC3 channels via a 11,12-EET-dependent manner.
ESTHER : Zhou_2023_Biochim.Biophys.Acta.Mol.Basis.Dis__166643
PubMedSearch : Zhou_2023_Biochim.Biophys.Acta.Mol.Basis.Dis__166643
PubMedID: 36669577

Title : Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy - Wang_2023_J.Pharm.Anal_13_776
Author(s) : Wang X , Zhang J , Zheng K , Du Q , Wang G , Huang J , Zhou Y , Li Y , Jin H , He J
Ref : J Pharm Anal , 13 :776 , 2023
Abstract : Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
ESTHER : Wang_2023_J.Pharm.Anal_13_776
PubMedSearch : Wang_2023_J.Pharm.Anal_13_776
PubMedID: 37577390

Title : Conjugated linoleic acids inhibit lipid deposition in subcutaneous adipose tissue and alter lipid profiles in serum of pigs - Wang_2023_J.Anim.Sci__
Author(s) : Wang L , Zhang S , Huang Y , Zhou Y , Shan T
Ref : J Anim Sci , : , 2023
Abstract : Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 +/- 10.39 kg) were randomly divided into 2 treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 days. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of lipolytic gene (hormone sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced the content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially cermides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorgammaexpression and further inhibit adipogenic differentiation in adipose tissues of pigs through suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short chain fatty acids (SCFAs) in the gut (P < 0.05) but the abundance of Cers were negatively related to the production and functions of SCFAs (P < 0.05). CLAs altered the lipids distribution in serum and inhibited adipogenic differentiation through suppressing the function of Cers and further decreasing PPARgammaexpression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.
ESTHER : Wang_2023_J.Anim.Sci__
PubMedSearch : Wang_2023_J.Anim.Sci__
PubMedID: 37646838

Title : Enzyme-mediated Ru@UiO-66@MnO(2) NSs\/thiamine-based ratiometric fluorescence sensor for visual detection of organophosphorus pesticide residues - Tong_2023_Food.Chem_429_136945
Author(s) : Tong F , Yang Z , Wang Z , Liu W , Jiang W , Zhu L , Wang L , Zheng M , Hou R , Zhou Y , Liu Y
Ref : Food Chem , 429 :136945 , 2023
Abstract : In view of the potential hazards of organophosphorus pesticides (OPs), this paper constructed a ratiometric fluorescent probe utilizing a functionalized metal-organic framework to detect OPs. Ru(bpy)(3)Cl(2) was encapsulated inside UiO-66 as a reference signal, and MnO(2) nanosheets (MnO(2) NSs) were grown on the surface to obtain Ru@UiO-66@MnO(2) NSs. Acetylcholinesterase catalyzed the decomposition of acetylcholine into reductive thiocholine, which consumed MnO(2) NSs, thus restoring the Ru@UiO-66 fluorescence. Due to the enzymatic inhibition of OPs and the redox reaction between MnO(2) NSs and thiamine, this probe emitted blue fluorescence in the presence of OPs. The probe achieved linear responses to dichlorvos and chlorpyrifos with LODs of 9.99 x 10(-6) microg mL(-1) and 9.99 x 10(-5) microg mL(-1). The probe exhibited a satisfactory recovery rate for OPs in green tea. Furthermore, a hydrogel detection platform was developed by embedding the probe into sodium alginate. Overall, this work provides a visual approach to detect OPs in agricultural products.
ESTHER : Tong_2023_Food.Chem_429_136945
PubMedSearch : Tong_2023_Food.Chem_429_136945
PubMedID: 37487398

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2023_Ther.Apher.Dial__
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , : , 2023
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2023_Ther.Apher.Dial__
PubMedSearch : Wan_2023_Ther.Apher.Dial__
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Soluble Epoxide Hydrolase Inhibitor TPPU Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain via Suppressing NF-B Signalling in the Spinal Cord of a Rat - Wei_2023_Pain.Res.Manag_2023_9058774
Author(s) : Wei X , Jia L , Zhou Y , Li W , Shan C , Zhang S , Zhao Y
Ref : Pain Res Manag , 2023 :9058774 , 2023
Abstract : OBJECTIVE: Paclitaxel-induced peripheral neuropathy (PIPN) is a debilitating and difficult-to-treat side effect of paclitaxel. Soluble epoxide hydrolase (sEH) can rapidly metabolize the endogenous anti-inflammatory mediators' epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. This study aimed to assess whether the sEH inhibitor N-(1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy) phenyl)-urea (TPPU) plays a critical role in PIPN of rats and provides a new target for treatment. METHODS: A Sprague-Dawley male rat model of PIPN induced by nab-paclitaxel was established. Rats were randomly divided into a control group, nab-paclitaxel group, and nab-paclitaxel + TPPU (sEH inhibitor) group, with 36 rats in each group. The effects of the sEH inhibitor TPPU on behavioural assays, apoptosis, glial activation, axonal injury, microstructure, and permeability of the blood-spinal cord barrier were detected, and the underlying mechanisms were explored by examining the expression of NF-kappaB signalling pathways, inflammatory cytokines, and oxidative stress. RESULTS: The results showed that the mechanical and thermal pain thresholds of rats were decreased after nab-paclitaxel treatment, accompanied by an increased expression of axonal injury-related proteins, enhanced cell apoptosis, aggravated destruction of vascular permeability, intense glial responses, and elevated inflammatory cytokines and oxidative stress in the L4-L6 spinal cord. TPPU restored the mechanical and thermal thresholds, decreased cell apoptosis, alleviated axonal injury and glial responses, and protected vascular permeability by increasing the expression of tight junction proteins. TPPU relieved PIPN by inhibiting the activation of the sEH and NF-kappaB signalling pathways by decreasing the levels of inflammatory cytokines and oxidative stress. CONCLUSION: These findings support a role for sEH in PIPN and suggest that the inhibition of sEH represents a potential new therapeutic target for PIPN.
ESTHER : Wei_2023_Pain.Res.Manag_2023_9058774
PubMedSearch : Wei_2023_Pain.Res.Manag_2023_9058774
PubMedID: 36819745

Title : Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH(2)(Fe) - Zhao_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Zhao D , Liu J , Zhou Y , Zhang L , Zhong Y , Yang Y , Zhao B , Yang M , Wang Y
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH(2)(Fe) nanoparticles with a size of -100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH(2)(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
ESTHER : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 36867458

Title : Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease - Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
Author(s) : Chen H , Mi J , Li S , Liu Z , Yang J , Chen R , Wang Y , Ban Y , Zhou Y , Dong W , Sang Z
Ref : J Enzyme Inhib Med Chem , 38 :2169682 , 2023
Abstract : A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The insvitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes insvitro and plasma. Furthermore, compound 3f could improve AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.
ESTHER : Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
PubMedSearch : Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
PubMedID: 36688444

Title : COX-2\/sEH-mediated macrophage activation is a target for pulmonary protection in mouse models of chronic obstructive pulmonary disease - Duan_2023_Lab.Invest__100319
Author(s) : Duan JX , Guan XX , Cheng W , Deng DD , Chen P , Liu C , Zhou Y , Hammock BD , Yang HH
Ref : Lab Invest , :100319 , 2023
Abstract : Effective inhibition of macrophage activation is critical for resolving inflammation and restoring pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Here, we identified the dual enhanced cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) as a novel regulator of macrophage activation in COPD. Both COX-2 and sEH were found to be increased in patients and mice with COPD, as well as in macrophages exposed to cigarette smoke extract (CSE). Pharmacological reduction of the COX-2 and sEH by PTUPB effectively prevented macrophage activation, down-regulated inflammation-related genes, and reduced lung injury, thereby improving respiratory function in a mouse model of COPD induced by cigarette smoke and lipopolysaccharide. Mechanistically, enhanced COX-2/sEH triggered the activation of the NLRP3 inflammasome, leading to the cleavage of pro-IL-1beta into its active form in macrophages and amplifying inflammatory responses. These findings demonstrate that targeting COX-2/sEH-mediated macrophage activation may be a promising therapeutic strategy for COPD. Importantly, our data support the potential use of the dual COX-2 and sEH inhibitor PTUPB as a therapeutic drug for the treatment of COPD.
ESTHER : Duan_2023_Lab.Invest__100319
PubMedSearch : Duan_2023_Lab.Invest__100319
PubMedID: 38158123

Title : Computational Modeling Study of the Binding of Aging and Non-Aging Inhibitors with Neuropathy Target Esterase - Wu_2023_Molecules_28_
Author(s) : Wu W , Huang J , Han P , Zhang J , Wang Y , Jin F , Zhou Y , Wang P
Ref : Molecules , 28 : , 2023
Abstract : Neuropathy target esterase (NTE) is a serine hydrolase with phospholipase B activity, which is involved in maintaining the homeostasis of phospholipids. It can be inhibited by aging inhibitors such as some organophosphorus (OP) compounds, which leads to delayed neurotoxicity with distal degeneration of axons. However, the detailed binding conformation of aging and non-aging inhibitors with NTE is not known. In this study, new computational models were constructed by using MODELLER 10.3 and AlphaFold2 to further investigate the inhibition mechanism of aging and non-aging compounds using molecular docking. The results show that the non-aging compounds bind the hydrophobic pocket much deeper than aging compounds and form the hydrophobic interaction with Phe1066. Therefore, the unique binding conformation of non-aging compounds may prevent the aging reaction. These important differences of the binding conformations of aging and non-aging inhibitors with NTE may help explain their different inhibition mechanism and the protection of non-aging NTE inhibitors against delayed neuropathy.
ESTHER : Wu_2023_Molecules_28_
PubMedSearch : Wu_2023_Molecules_28_
PubMedID: 38005352 || 38067477

Title : Biochemical characterization and molecular modification of a zearalenone hydrolyzing enzyme Zhd11D from Phialophora attinorum - Wang_2023_Enzyme.Microb.Technol_170_110286
Author(s) : Wang Z , Luo F , Jiang S , Selvaraj JN , Zhou Y , Zhang G
Ref : Enzyme Microb Technol , 170 :110286 , 2023
Abstract : ZEN lactone hydrolase (ZHD) can hydrolyze zearalenone (ZEN) to less or non-toxic product, providing an environment-friendly way for food or feeds-containing ZENs detoxification. Here, a newly identified ZHD from Phialophora attinorum, annotated as Zhd11D, was characterized to exhibit highest activity against ZEN at pH 8.0 and 35 degC with a specific activity of 304.7 U/mg, which was far higher than most of the reported ZHDs. A nonspecific protein engineering method was introduced through fusing a segment of amphiphilic short peptide S1 at the N-terminus of Zhd11D, resulting in both improved activity (1.5-fold) and thermostability (2-fold at 40 degC). Biochemical analysis demonstrated that self-aggregation caused by intermolecular interactions between S1 contributed to the improvement of the enzymatic properties of Zhd11D. Additionally, S1-Zhd11D showed a higher hydrolysis rate of ZEN than Zhd11D in peanut oil.
ESTHER : Wang_2023_Enzyme.Microb.Technol_170_110286
PubMedSearch : Wang_2023_Enzyme.Microb.Technol_170_110286
PubMedID: 37499311

Title : Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase\/monoamine oxidase B inhibitors - Hu_2023_Future.Med.Chem__
Author(s) : Hu Z , Zhou S , Li J , Li X , Zhou Y , Zhu Z , Xu J , Liu J
Ref : Future Med Chem , : , 2023
Abstract : Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC(50) = 0.054 +/- 0.004 microM; MAO-B: IC(50) = 3.25 +/- 0.20 microM), moderate inhibitory effects on self-mediated amyloid-beta (Abeta) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.
ESTHER : Hu_2023_Future.Med.Chem__
PubMedSearch : Hu_2023_Future.Med.Chem__
PubMedID: 37902028

Title : A Multifunctional (-)-Meptazinol-Serotonin Hybrid Ameliorates Oxidative Stress-Associated Apoptotic Neuronal Death and Memory Deficits via Activating the Nrf2\/Antioxidant Enzyme Pathway - Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
Author(s) : Zhao F , Zhao L , Zhou Y , Tan X , Yang Y , Ni W , Zheng W , Chen H , Qiu Y , Li J
Ref : Oxid Med Cell Longev , 2023 :6935947 , 2023
Abstract : The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H(2)O(2)-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H(2)O(2) through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H(2)O(2)-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and gamma-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.
ESTHER : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedSearch : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedID: 36819782

Title : Two birds with one stone: An enzyme-regulated ratiometric fluorescent and photothermal dual-mode probe for organophosphorus pesticide detection - Jiang_2023_Biosens.Bioelectron_224_115074
Author(s) : Jiang W , Yang Z , Tong F , Zhang S , Zhu L , Wang L , Huang L , Liu K , Zheng M , Zhou Y , Hou R , Liu Y
Ref : Biosensors & Bioelectronics , 224 :115074 , 2023
Abstract : In this study, based on the oxidase activity and photothermal effect of manganese dioxide nanosheets (MnO(2) NSs), with thiamine (TH) as the fluorescence response signal and tris (2,2'-bipyridyl) ruthenium (II) hexahydrate as the reference signal, an enzyme-regulated ratiometric fluorescence and photothermal dual-mode probe was constructed for the quantitative detection of organophosphorus pesticide (OPs) residues. OPs reduced the production of the reductive product thiocholine by inhibiting the activity of acetylcholinesterase, thereby regulating the residual amount of MnO(2) NSs. With the increase of OPs concentration, the color of the probe solution gradually transitioned from red to blue, and the temperature gradually increased. Using dichlorvos and chlorpyrifos as pesticide models, the developed probes exhibited sensitive responses to OPs in a wide linear range of 0.1-8000sng/mL. The detection limits of dichlorvos and chlorpyrifos in fluorescence mode were 1.13sxs10(-3)sng/mL and 0.86sng/mL, respectively. The corresponding detection limits in photothermal mode were 1.01sng/mL and 1.02sng/mL, respectively. The proposed probe displayed excellent anti-interference and reliability in the analysis of OPs residues in real samples. The dual-mode probe with self-verification function is expected to provide more accurate and robust detection results than the single-mode probe, and has a wider application prospect.
ESTHER : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedSearch : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedID: 36638562

Title : Biochemical toxicity and transcriptome aberration induced by dinotefuran in Bombyx mori - Xu_2022_Environ.Pollut__119562
Author(s) : Xu S , Hao Z , Li Y , Zhou Y , Shao R , Chen R , Zheng M , Xu Y , Wang H
Ref : Environ Pollut , :119562 , 2022
Abstract : Dinotefuran is a third-generation neonicotinoid pesticide and is increasingly used in agricultural production, which has adverse effects on nontarget organisms. However, the research on the impact of dinotefuran on nontarget organisms is still limited. Here the toxic effects of dinotefuran on an economic lepidopteran model insect, Bombyx mori, were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. Cytochrome P450, glutathione S-transferase, carboxylesterase, and UDP glycosyl-transferase activities were induced in the fat body at early stages after dinotefuran exposure. By contrast, only glutathione S-transferase activity was increased in the midgut. To overcome the lack of sensitivity of the biological assays at the individual organism level, RNA sequencing was performed to measure differential expressions of mRNA from silkworm larvae after dinotefuran exposure. Differential gene expression profiling revealed that various detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with the upregulation of the detoxifying enzyme. The global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved multiple cellular processes, including energy metabolism, oxidative stress, detoxification, and other fundamental physiological processes. Many metabolism processes, such as carbon metabolism, fatty acid biosynthesis, pyruvate metabolism, and the citrate cycle, were partially repressed in the midgut or fat body. Furthermore, dinotefuran significantly activated the MAPK/CREB, CncC/Keap1, PI3K/Akt, and Toll/IMD pathways. The links between physiological, biochemical toxicity and comparative transcriptomic analysis facilitated the systematic understanding of the integrated biological toxicity of dinotefuran. This study provides a holistic view of the toxicity and detoxification metabolism of dinotefuran in silkworm and other organisms.
ESTHER : Xu_2022_Environ.Pollut__119562
PubMedSearch : Xu_2022_Environ.Pollut__119562
PubMedID: 35659910

Title : SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice - Xiang_2022_Cell.Death.Dis_13_638
Author(s) : Xiang L , Wu Q , Sun H , Miao X , Lv Z , Liu H , Chen L , Gu Y , Chen J , Zhou S , Jiang H , Du S , Zhou Y , Dong H , Fan Y , Miao S , Lu Q , Chang L , Wang H , Lu Y , Xu X , Wang W , Huang Z
Ref : Cell Death Dis , 13 :638 , 2022
Abstract : Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD.
ESTHER : Xiang_2022_Cell.Death.Dis_13_638
PubMedSearch : Xiang_2022_Cell.Death.Dis_13_638
PubMedID: 35869039

Title : Identification of Differential Expression Genes between Volume and Pressure Overloaded Hearts Based on Bioinformatics Analysis - Fu_2022_Genes.(Basel)_13_
Author(s) : Fu Y , Zhao D , Zhou Y , Lu J , Kang L , Jiang X , Xu R , Ding Z , Zou Y
Ref : Genes (Basel) , 13 : , 2022
Abstract : Volume overload (VO) and pressure overload (PO) are two common pathophysiological conditions associated with cardiac disease. VO, in particular, often occurs in a number of diseases, and no clinically meaningful molecular marker has yet been established. We intend to find the main differential gene expression using bioinformatics analysis. GSE97363 and GSE52796 are the two gene expression array datasets related with VO and PO, respectively. The LIMMA algorithm was used to identify differentially expressed genes (DEGs) of VO and PO. The DEGs were divided into three groups and subjected to functional enrichment analysis, which comprised GO analysis, KEGG analysis, and the protein-protein interaction (PPI) network. To validate the sequencing data, cardiomyocytes from AR and TAC mouse models were used to extract RNA for qRT-PCR. The three genes with random absolute values of LogFC and indicators of heart failure (natriuretic peptide B, NPPB) were detected: carboxylesterase 1D (CES1D), whirlin (WHRN), and WNK lysine deficient protein kinase 2 (WNK2). The DEGs in VO and PO were determined to be 2761 and 1093, respectively, in this study. Following the intersection, 305 genes were obtained, 255 of which expressed the opposing regulation and 50 of which expressed the same regulation. According to the GO and pathway enrichment studies, DEGs with opposing regulation are mostly common in fatty acid degradation, propanoate metabolism, and other signaling pathways. Finally, we used Cytoscape's three techniques to identify six hub genes by intersecting 255 with the opposite expression and constructing a PPI network. Peroxisome proliferator-activated receptor (PPARalpha), acyl-CoA dehydrogenase medium chain (ACADM), patatin-like phospholipase domain containing 2 (PNPLA2), isocitrate dehydrogenase 3 (IDH3), heat shock protein family D member 1 (HSPD1), and dihydrolipoamide S-acetyltransferase (DLAT) were identified as six potential genes. Furthermore, we predict that the hub genes PPARalpha, ACADM, and PNPLA2 regulate VO myocardial changes via fatty acid metabolism and acyl-Coa dehydrogenase activity, and that these genes could be employed as basic biomarkers for VO diagnosis and treatment.
ESTHER : Fu_2022_Genes.(Basel)_13_
PubMedSearch : Fu_2022_Genes.(Basel)_13_
PubMedID: 35886059

Title : PFOA exposure causes variations of Acot1 among tissues in rats, and Acot1 in serum can be potentially used as a sensitive marker for health monitoring - Zhou_2022_Toxicol.Res.(Camb)_11_872
Author(s) : Zhou Y , Qiao Y , Zhang X , Ma X , Liu H , Wang L
Ref : Toxicol Res (Camb) , 11 :872 , 2022
Abstract : Perfluorooctanoic acid (PFOA) is a type of 8-carbon perfluoroalkyl substances (PFASs) widely used in industrial and domestic products, which now is a persistent organic pollutant (POP) found in the environment. Its structure is similar to fatty acids, which enables it to induce the expression of ACOT genes. To investigate the expression levels of Acot1 in various tissues and organs after exposure to PFOA for 28 days in rats, and to compare the variations of Acot1 expression in different tissues, we sectioned samples and incubated with Acot1 antibody. The results show that the transcription and protein expression levels of Acot1 in the liver and kidney of rats increased significantly. Meanwhile, the transcription and protein expression of Acot1 gene were also detected in testis, muscle, and adipose. The results of immunohistochemistry were also verified by western blot detection, and we detected the transcription of Acot1 gene in these tissues and found that they all increased in varying degrees. In this study, the expression of Acot1 protein in rat serum was detected for the first time, and the expression of Acot1 in rat serum was found to be significantly increased after PFOA exposure. In addition, the expression level of Acot1 in rat organism was found to be higher than that in the control group after 4 days of depuration for 7 days of acute PFOA exposure, and Acot1 protein expression also showed an increase with increasing exposure time, indicating that Acot1 can be used as a sensitive biomarker for health monitoring of PFOA occupational workers or exposed persons.
ESTHER : Zhou_2022_Toxicol.Res.(Camb)_11_872
PubMedSearch : Zhou_2022_Toxicol.Res.(Camb)_11_872
PubMedID: 36337235

Title : The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events - Xi_2022_Biomed.Environ.Sci_35_206
Author(s) : Xi H , Cheng GL , Hu FF , Li SN , Deng X , Zhou Y
Ref : Biomedical & Environmental Sciences , 35 :206 , 2022
Abstract : OBJECTIVE: To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. METHODS: A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. RESULTS: The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. CONCLUSION: Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
ESTHER : Xi_2022_Biomed.Environ.Sci_35_206
PubMedSearch : Xi_2022_Biomed.Environ.Sci_35_206
PubMedID: 35317900

Title : Epoxyeicosatrienoic Acids Inhibit the Activation of Murine Fibroblasts by Blocking the TGF-beta1-Smad2\/3 Signaling in a PPARgamma-Dependent Manner - Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
Author(s) : Tao JH , Liu T , Zhang CY , Zu C , Yang HH , Liu YB , Yang JT , Zhou Y , Guan CX
Ref : Oxid Med Cell Longev , 2022 :7265486 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs), the metabolite of arachidonic acid by cytochrome P450 (CYP), reportedly serve as a vital endogenous protective factor in several chronic diseases. EETs are metabolized by soluble epoxide hydrolase (sEH). We have observed that prophylactic blocking sEH alleviates bleomycin- (BLM-) induced pulmonary fibrosis (PF) in mice. However, the underlying mechanism and therapeutic effects of EETs on PF remain elusive. OBJECTIVE: In this study, we investigated the effect of CYP2J2/EETs on the activation of murine fibroblasts and their mechanisms. RESULTS: we found that administration of the sEH inhibitor (TPPU) 7 days after the BLM injection also reversed the morphology changes and collagen deposition in the lungs of BLM-treated mice, attenuating PF. Fibroblast activation is regarded as a critical role of PF. Therefore, we investigated the effects of EETs on the proliferation and differentiation of murine fibroblasts. Results showed that the overexpression of CYP2J2 reduced the cell proliferation and the expressions of alpha-SMA and PCNA induced by transforming growth factor- (TGF-) beta1 in murine fibroblasts. Then, we found that EETs inhibited the proliferation and differentiation of TGF-beta1-treated-NIH3T3 cells and primary murine fibroblasts. Mechanistically, we found that 14,15-EET disrupted the phosphorylation of Smad2/3 murine fibroblasts by activating PPARgamma, which was completely abolished by a PPARgamma inhibitor GW9662. CONCLUSION: our study shows that EETs inhibit the activation of murine fibroblasts by blocking the TGF-beta1-Smad2/3 signaling in a PPARgamma-dependent manner. Regulating CYP2J2-EET-sEH metabolic pathway may be a potential therapeutic option in PF.
ESTHER : Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
PubMedSearch : Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
PubMedID: 36275905

Title : Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation - Li_2022_Mol.Metab__101597
Author(s) : Li H , Chen R , Zhou Y , Wang H , Sun L , Yang Z , Bai L , Zhang J
Ref : Mol Metab , :101597 , 2022
Abstract : OBJECTIVE: Contextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. METHODS: We applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA-CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. RESULTS: In the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. CONCLUSIONS: Together, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention.
ESTHER : Li_2022_Mol.Metab__101597
PubMedSearch : Li_2022_Mol.Metab__101597
PubMedID: 36096452

Title : LC-MS\/MS assay of fluoropezil and its two major metabolites in human plasma: an application to pharmacokinetic studies - Guo_2022_Bioanalysis_14_817
Author(s) : Guo R , Hu J , Jing J , Liu Y , Li J , Zhou Y , Liu H , Zhou L , Chen X
Ref : Bioanalysis , 14 :817 , 2022
Abstract : Background: LC-MS/MS methods were developed for pharmacokinetic analysis and verified to measure fluoropezil, a new AchE inhibitor for Alzheimer's disease treatment, and its two primary metabolites (N-debenzyl fluoride fluoropezil [M1] and N-oxidized fluoropezil [M11]) in human plasma. Methods & results: Analytes were extracted from 50 microl plasma using protein precipitation and separated by HPLC using a bridged ethyl hybrid column and gradient elution procedure. Analytical detection was performed with a triple quadrupole mass spectrometer and electrospray ionization source in multiple reaction monitoring mode. The LC-MS/MS method was fully validated. The quantification linear ranges were 0.100-50.0 ng/ml (fluoropezil), 0.0500-25.0 ng/ml (M1) and 0.0500-25.0 ng/ml (M11). Conclusion: A sensitive, reliable LC-MS/MS method was established and used successfully to explore the pharmacokinetics of fluoropezil.
ESTHER : Guo_2022_Bioanalysis_14_817
PubMedSearch : Guo_2022_Bioanalysis_14_817
PubMedID: 35735138

Title : Invasive Plants Have Higher Resistance to Native Generalist Herbivores Than Exotic Noninvasive Congeners - Wu_2022_Environ.Entomol__
Author(s) : Wu S , Chen L , Zhou Y , Xiao F , Liu D , Wang Y
Ref : Environ Entomol , : , 2022
Abstract : Research on the invasive plant Phytolacca americana (L.) mostly focuses on its medicinal value and enrichment of heavy metals. However, little is known regarding its impact on native herbivorous insects. In this study, we explored the effects of P. americana and the exotic noninvasive Phytolacca icosandra (L.) on the Spodoptera litura (Fabricius) (native tobacco cutworm) via bioassay, oviposition preference, detoxifying enzyme activity analysis, and phytochemical determination. We found that the oviposition preference index (OPI) of S. litura feeding on P. icosandra was higher than that of P. americana. The developmental duration of S. litura feeding on P. icosandra was shorter than that of P. americana. Additionally, the Acetylcholinesterase (AchE) and Glutathione-S-transferase (GST) activities of S. litura feeding on P. americana were higher than that of S. litura feeding on artificial diets or P. icosandra. The content of lignin and flavonoids in P. americana was relatively high, whereas starch content was relatively low. These findings suggest invasive plants have higher resistance to herbivores, thereby suffering less damage than exotic noninvasive plants.
ESTHER : Wu_2022_Environ.Entomol__
PubMedSearch : Wu_2022_Environ.Entomol__
PubMedID: 36545824

Title : Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120\/ABHD6 - Li_2022_Drug.Des.Devel.Ther_16_3557
Author(s) : Li R , Ye Z , She D , Fang P , Zong G , Hu K , Kong D , Xu W , Li L , Zhou Y , Zhang K , Xue Y
Ref : Drug Des Devel Ther , 16 :3557 , 2022
Abstract : OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.
ESTHER : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedSearch : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedID: 36238196

Title : Preventive Effect of Limosilactobacillus fermentum SCHY34 on Lead Acetate-Induced Neurological Damage in SD Rats - Long_2022_Front.Nutr_9_852012
Author(s) : Long X , Wu H , Zhou Y , Wan Y , Kan X , Gong J , Zhao X
Ref : Front Nutr , 9 :852012 , 2022
Abstract : Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.
ESTHER : Long_2022_Front.Nutr_9_852012
PubMedSearch : Long_2022_Front.Nutr_9_852012
PubMedID: 35571929

Title : Antioxidant, Antibacterial, Enzyme Inhibitory, and Anticancer Activities and Chemical Composition of Alpinia galanga Flower Essential Oil - Tian_2022_Pharmaceuticals.(Basel)_15_
Author(s) : Tian Y , Jia X , Wang Q , Lu T , Deng G , Tian M , Zhou Y
Ref : Pharmaceuticals (Basel) , 15 : , 2022
Abstract : Alpinia galanga is widely cultivated for its essential oil (EO), which has been used in cosmetics and perfumes. Previous studies of A. galanga focussed mostly on the rhizome but seldom on the flower. Therefore, this study was designed to identify the chemical composition of A. galanga flower EO and firstly estimate its antioxidant, antibacterial, enzyme inhibitory, and anticancer activities. According to the results of the gas chromatography with flame ionization or mass selective detection (GC-FID/MS) analysis, the most abundant component of the EO was farnesene (64.3%), followed by farnesyl acetate (3.6%), aceteugenol (3.2%), eugenol (3.1%), E-nerolidol (2.9%), decyl acetate (2.4%), octyl acetate (2.0%), sesquirosefuran (1.9%), (E)-beta-farnesene (1.7%), and germacrene D (1.5%). For the bioactivities, the EO exhibited moderate DPPH and ABTS radical scavenging effects with IC(50) values of 138.62 +/- 3.07 microg/mL and 40.48 +/- 0.49 microg/mL, respectively. Moreover, the EO showed strong-to-moderate antibacterial activities with various diameter of inhibition zone (DIZ) (8.79-14.32 mm), minimal inhibitory concentration (MIC) (3.13-6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25-12.50 mg/mL) values against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris. Interestingly, the EO possessed remarkable alpha-glucosidase inhibition (IC(50) = 0.16 +/- 0.03 mg/mL), which was equivalent to that of the positive control acarbose (IC(50) = 0.15 +/- 0.01 mg/mL) (p > 0.05). It showed moderate tyrosinase inhibition (IC(50) = 0.62 +/- 0.09 mg/mL) and weak inhibitory activity on acetylcholinesterase (AChE) (IC(50) = 2.49 +/- 0.24 mg/mL) and butyrylcholinesterase (BChE) (IC(50) = 10.14 +/- 0.59 mg/mL). Furthermore, the EO exhibited considerable selective cytotoxicity to K562 cells (IC(50) = 41.55 +/- 2.28 microg/mL) and lower cytotoxicity to non-cancerous L929 cells (IC(50) = 120.54 +/- 8.37 microg/mL), and it induced K562 cell apoptosis in a dose-dependent manner. Hence, A. galanga flower EO could be regarded as a bioactive natural product with great application potential in the pharmaceutical field.
ESTHER : Tian_2022_Pharmaceuticals.(Basel)_15_
PubMedSearch : Tian_2022_Pharmaceuticals.(Basel)_15_
PubMedID: 36145290

Title : Associations of PNPLA3 rs738409 Polymorphism with Plasma Lipid Levels: A Systematic Review and Meta-Analysis - Luo_2022_Horm.Metab.Res_54_686
Author(s) : Luo Z , Liu Y , Li H , Zhou Y , Peng Y , Lin X , Fang Y , Wan J , Wei B
Ref : Hormone & Metabolic Research , 54 :686 , 2022
Abstract : Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.
ESTHER : Luo_2022_Horm.Metab.Res_54_686
PubMedSearch : Luo_2022_Horm.Metab.Res_54_686
PubMedID: 36206762

Title : Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals - Yang_2022_ACS.Omega_7_30720
Author(s) : Yang Y , Liu J , Liu L , Zhou Y , Zhang L , Zhong Y , Zhao D , Wang Y
Ref : ACS Omega , 7 :30720 , 2022
Abstract : A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.
ESTHER : Yang_2022_ACS.Omega_7_30720
PubMedSearch : Yang_2022_ACS.Omega_7_30720
PubMedID: 36092617

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 : Structural and Mechanistic Insights into Chain Release of the Polyene PKS Thioesterase Domain - Zhou_2022_ACS.Catal_12_762
Author(s) : Zhou Y , Tao W , Qi Z , Wei J , Shi T , Kang Q , Zheng J , Zhao Y , Bai L
Ref : ACS Catal , 12 :762 , 2022
Abstract : Polyketides serve as rich source of therapeutically relevant drug leads. The manipulation of polyketide synthases (PKSs) for generating derivatives with improved activities usually results in substantially reduced yields. Growing evidence suggests that type I PKS thioesterase (TE) domains are key bottlenecks in the biosynthesis of polyene antibiotics, such as pimaricin and amphotericin, and their unnatural derivatives. Herein, we elucidate the structure of the 26-membered macrolide-complexed TE domain from the pimaricin pathway (Pim TE), which specifies a spacious bifunnel-shaped substrate channel with a highly hydrophobic cleft proximal to the catalytic triad and a hydrophilic loop I region specific for the cyclization of amphiphilic polyene macrolide. Notably, the natural intermediate with C12-COOH is stabilized by a hydrogen-bond network, as well as by interactions between the polyene moiety and the hydrophobic cleft. Moreover, the bottleneck in processing the unnatural intermediate with C12-CH3 is attributed to the unstable and mismatched docking of the curved substrate in the channel. Aided by an in vitro assay with a fully elongated linear polyene intermediate as the substrate, multiple strategies were adopted, herein, to engineer Pim TE, including introducing H-bond donors, enhancing hydrophobic interactions, and modifying the catalytic center. Efficient TE mutations with increased substrate conversion up to 39.2% in vitro were further conducted in vivo, with a titer increase as high as 37.1% for the less toxic decarboxylated pimaricin derivatives with C12-CH3. Our work uncovers the mechanism of TE-catalyzed polyene macrolide formation and highlights TE domains as targets for PKS manipulation for titer increases in engineered unnatural polyketide derivatives.
ESTHER : Zhou_2022_ACS.Catal_12_762
PubMedSearch : Zhou_2022_ACS.Catal_12_762
PubMedID:
Gene_locus related to this paper: 9actn-f1cla7

Title : Contribution of multiple overexpressed carboxylesterase genes to indoxacarb resistance in Spodoptera litura - Shi_2022_Pest.Manag.Sci__
Author(s) : Shi Y , Li W , Zhou Y , Liao X , Shi L
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: As an important family of detoxification enzymes, carboxylesterases (CarEs) play important roles in the development of insecticides resistance in almost all agricultural pests. Previous studies suggested that the enhancement of CarE activity was an important mechanism mediating indoxacarb resistance in Spodoptera litura, and several CarE genes were found to be overexpressed in the indoxacarb-resistant strains. However, the functions of these CarE genes in indoxacarb resistance needs to be further investigated. RESULTS: The synergist triphenyl phosphate (TPP) effectively reduced the resistance of S. litura to indoxacarb, suggesting an involvement of CarEs in indoxacarb resistance. Among seven identified S. litura CarE genes (SlituCOE hereinafter), six were overexpressed in two indoxacarb-resistant strains, but there were no significant differences in gene copy number. Knockdown of SlituCOE009 and SlituCOE050 enhanced indoxacarb sensitivity in both susceptible and resistant strains, whereas knockdown of SlituCOE090, SlituCOE093 and SlituCOE074 enhanced indoxacarb sensitivity only in the resistant strain. Knockdown of the sixth gene SlituCOE073 did not have any effect. Furthermore, knockdown of the five SlituCOE genes simultaneously had a greater effect on increasing indoxacarb sensitivity than silencing them individually. By contrast, overexpression of the five SlituCOE genes individually in Drosophila melanogaster significantly decreased the toxicity of indoxacarb to transgenic fruit flies. Furthermore, modeling and docking analysis indicated that the catalytic pockets of SlituCOE009 and SlituCOE074 were ideally shaped for indoxacarb and DCJW, but the binding affinity for DCJW was stronger than indoxacarb. CONCLUSION: This study reveals that multiple overexpressed CarE genes are involved in indoxacarb resistance in S. litura.
ESTHER : Shi_2022_Pest.Manag.Sci__
PubMedSearch : Shi_2022_Pest.Manag.Sci__
PubMedID: 35066991

Title : COX-2\/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1\/PI3K\/AKT\/mTOR - Zhang_2022_Int.J.Mol.Sci_23_8267
Author(s) : Zhang CY , Tan XH , Yang HH , Jin L , Hong JR , Zhou Y , Huang XT
Ref : Int J Mol Sci , 23 :8267 , 2022
Abstract : We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) in mice. However, the exact mechanism has not been elucidated. Accumulating evidence points to the essential role of cellular senescence in NAFLD. Herein, we investigated whether restoring the balance of sEH/COX-2-mediated ARA metabolism attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor of sEH and COX-2, PTUPB, was used in our study to restore the balance of sEH/COX-2-mediated ARA metabolism. In vivo, NAFLD was induced by a high-fat diet (HFD) using C57BL/6J mice. In vitro, mouse hepatocytes (AML12) and mouse hepatic astrocytes (JS1) were used to investigate the effects of PTUPB on palmitic acid (PA)-induced hepatocyte senescence and its mechanism. PTUPB alleviated liver injury, decreased collagen and lipid accumulation, restored glucose tolerance, and reduced hepatic triglyceride levels in HFD-induced NAFLD mice. Importantly, PTUPB significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice. In vitro, the protein levels of gammaH2AX, p53, p21, COX-2, and sEH were increased in AML12 hepatocytes treated with PA, while Ki67 and PCNA were significantly decreased. PTUPB decreased the lipid content, the number of beta-gal positive cells, and the expression of p53, p21, and gammaH2AX proteins in AML12 cells. Meanwhile, PTUPB reduced the activation of hepatic astrocytes JS1 by slowing the senescence of AML12 cells in a co-culture system. It was further observed that PTUPB enhanced the ratio of autophagy-related protein LC3II/I in AML12 cells, up-regulated the expression of Fundc1 protein, reduced p62 protein, and suppressed hepatocyte senescence. In addition, PTUPB enhanced hepatocyte autophagy by inhibiting the PI3K/AKT/mTOR pathway through Sirt1, contributing to the suppression of senescence. PTUPB inhibits the PI3K/AKT/mTOR pathway through Sirt1, improves autophagy, slows down the senescence of hepatocytes, and alleviates NAFLD.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_8267
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_8267
PubMedID: 35897843

Title : Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense - Hu_2022_J.Org.Chem__
Author(s) : Hu XY , Zhu SJ , Meng XH , Yu HF , Liu X , Zhang LY , Wei Y , Lei CW , Wei X , Zhou Y
Ref : J Org Chem , : , 2022
Abstract : Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (+/-)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.
ESTHER : Hu_2022_J.Org.Chem__
PubMedSearch : Hu_2022_J.Org.Chem__
PubMedID: 36354352

Title : Maternally inherited diabetes and deafness coexists with lipoprotein lipase gene mutation-associated severe hyperlipidemia that was resistant to fenofibrate and atorvastatin, but sensitive to bezafibrate: A case report - Zhang_2022_J.Diabetes.Investig_13_397
Author(s) : Zhang X , Chen Y , Tong N , Shao Q , Zhou Y , Mu T , Yang X , Zhang Y
Ref : J Diabetes Investig , 13 :397 , 2022
Abstract : Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient's hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.
ESTHER : Zhang_2022_J.Diabetes.Investig_13_397
PubMedSearch : Zhang_2022_J.Diabetes.Investig_13_397
PubMedID: 34460997
Gene_locus related to this paper: human-LPL

Title : Physiological mechanism of strigolactone enhancing tolerance to low light stress in cucumber seedlings - Zhou_2022_BMC.Plant.Biol_22_30
Author(s) : Zhou X , Tan Z , Zhou Y , Guo S , Sang T , Wang Y , Shu S
Ref : BMC Plant Biol , 22 :30 , 2022
Abstract : Strigolactone is a newly discovered type of plant hormone that has multiple roles in modulating plant responses to abiotic stress. Herein, we aimed to investigate the effects of exogenous GR24 (a synthetic analogue of strigolactone) on plant growth, photosynthetic characteristics, carbohydrate levels, endogenous strigolactone content and antioxidant metabolism in cucumber seedlings under low light stress. The results showed that the application of 10 microM GR24 can increase the photosynthetic efficiency and plant biomass of low light-stressed cucumber seedlings. GR24 increased the accumulation of carbohydrates and the synthesis of sucrose-related enzyme activities, enhanced antioxidant enzyme activities and antioxidant substance contents, and reduced the levels of H(2)O(2) and MDA in cucumber seedlings under low light stress. These results indicate that exogenous GR24 might alleviate low light stress-induced growth inhibition by regulating the assimilation of carbon and antioxidants and endogenous strigolactone contents, thereby enhancing the tolerance of cucumber seedlings to low light stress.
ESTHER : Zhou_2022_BMC.Plant.Biol_22_30
PubMedSearch : Zhou_2022_BMC.Plant.Biol_22_30
PubMedID: 35027005

Title : COX-2\/sEH Dual Inhibitor PTUPB Attenuates Epithelial-Mesenchymal Transformation of Alveolar Epithelial Cells via Nrf2-Mediated Inhibition of TGF-beta1\/Smad Signaling - Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
Author(s) : Zhang CY , Guan XX , Song ZH , Jiang HL , Liu YB , Chen P , Duan JX , Zhou Y
Ref : Oxid Med Cell Longev , 2022 :5759626 , 2022
Abstract : BACKGROUND: Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT during pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF. METHODS: A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6 J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice. In vitro experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)-beta1-induced EMT. RESULTS: PTUPB treatment reversed the increase of mesenchymal marker molecule alpha-smooth muscle actin (alpha-SMA) and the loss of epithelial marker molecule E-cadherin in lung tissue of PF mice. In vitro, COX-2 and sEH protein levels were increased in TGF-beta1-treated alveolar epithelial cells (AECs). PTUPB decreased the expression of alpha-SMA and restored the expression of E-cadherin in TGF-beta1-treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB attenuated TGF-beta1-Smad2/3 pathway activation in AECs via Nrf2 antioxidant cascade. CONCLUSION: PTUPB inhibits EMT in AECs via Nrf2-mediated inhibition of the TGF-beta1-Smad2/3 pathway, which holds great promise for the clinical treatment of PF.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
PubMedID: 35509835

Title : The sarcopenia index is an effective predictor for malnutrition in patients with liver cirrhosis - Wu_2022_Nutr.Diet__
Author(s) : Wu YK , Li M , Zhang YC , Gao RZ , Su Y , Zhou Y , Zhao KL , Chen C , Wang WX
Ref : Nutr Diet , : , 2022
Abstract : AIM: Reliable and valid predictors of malnutrition in patients with cirrhosis remain scarce, especially easily accessible blood indicators. Thus, this study aimed to investigate the validity of the sarcopenia index (serum creatinine/serum cystatin C x 100) as a tool in assessing the nutritional status of patients with cirrhosis. METHODS: This prospective cohort study included 109 patients with cirrhosis who were hospitalised in Renmin Hospital of Wuhan University from August 2020 to June 2021. Malnutrition was diagnosed by the Global Leadership Initiative on Malnutrition criteria. Multivariable logistic regression was used to examine the relationship between sarcopenia index and malnutrition. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance of sarcopenia index. By contrast, we evaluated the subjective global assessment and traditional nutrition-related indicators. RESULTS: Of the 109 included patients, 71 (65.1%) were diagnosed with malnutrition. The sarcopenia index was significantly lower in malnourished patients (56.39 +/- 15.23) compared with well-nourished patients (74.95 +/- 13.18, p < 0.001). In addition, the sarcopenia index was independently correlated with malnutrition (p < 0.001). The sarcopenia index was a good tool to predict malnutrition (area under curve = 0.833), which performed better than the subjective global assessment (area under curve = 0.782) and cholinesterase (area under curve = 0.812). A low sarcopenia index indicated longer hospital stay and higher risk of 90-day re-hospitalisation. CONCLUSION: Malnutrition is highly prevalent in this population. The sarcopenia index seems to be a good predictor in nutritional assessment of patients with cirrhosis.
ESTHER : Wu_2022_Nutr.Diet__
PubMedSearch : Wu_2022_Nutr.Diet__
PubMedID: 35434892

Title : The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase - Lu_2022_Chirality__
Author(s) : Lu Y , Zhan R , Song B , Zhou Y , Zhu L , Chen H , Chen X
Ref : Chirality , : , 2022
Abstract : Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.(s) ) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam.
ESTHER : Lu_2022_Chirality__
PubMedSearch : Lu_2022_Chirality__
PubMedID: 35713364

Title : Silencing of MsD14 Resulted in Enhanced Forage Biomass through Increasing Shoot Branching in Alfalfa (Medicago sativa L.) - Ma_2022_Plants.(Basel)_11_
Author(s) : Ma L , Zhang Y , Wen H , Liu W , Zhou Y , Wang X
Ref : Plants (Basel) , 11 : , 2022
Abstract : Branching is one of the key determinants of plant architecture that dramatically affects crop yield. As alfalfa is the most important forage crop, understanding the genetic basis of branching in this plant can facilitate breeding for a high biomass yield. In this study, we characterized the strigolactone receptor gene MsD14 in alfalfa and demonstrated that MsD14 was predominantly expressed in flowers, roots, and seedpods. Furthermore, we found that MsD14 expression could significantly respond to strigolactone in alfalfa seedlings, and its protein was located in the nucleus, cytoplasm, and cytomembrane. Most importantly, transformation assays demonstrated that silencing of MsD14 in alfalfa resulted in increased shoot branching and forage biomass. Significantly, MsD14 could physically interact with AtMAX2 and MsMAX2 in the presence of strigolactone, suggesting a similarity between MsD14 and AtD14. Together, our results revealed the conserved D14-MAX2 module in alfalfa branching regulation and provided candidate genes for alfalfa high-yield molecular breeding.
ESTHER : Ma_2022_Plants.(Basel)_11_
PubMedSearch : Ma_2022_Plants.(Basel)_11_
PubMedID: 35406919

Title : High expression of NDRG3 correlates with poor prognosis in gastric cancer patients - Liu_2021_Rev.Esp.Enferm.Dig_113_524
Author(s) : Liu Y , Xia J , Zhou Y , Shao S
Ref : Rev Esp Enferm Dig , 113 :524 , 2021
Abstract : INTRODUCTION: N-myc downstream-regulated gene 3 (NDRG3) is an important member of the NDRG family and is linked with malignant tumors. However, the relationship between NDRG3 and gastric cancer (GC) is vague. MATERIAL AND METHODS: Western blot, qRT-PCR and immunohistochemistry (IHC) detected the expression of NDRG3 in GC cell lines and GC tissues; public databases were used to analyze NDRG3 in GC patients and the association with EBV infection. RESULTS: NDRG3 was up-regulated in GC cell lines and tissues. IHC data suggested that NDRG3 was correlated with histologic grade (p = 0.006) and is associated with patient survival. DISCUSSION: thus, NDRG3 may be a novel predictor of GC prognosis.
ESTHER : Liu_2021_Rev.Esp.Enferm.Dig_113_524
PubMedSearch : Liu_2021_Rev.Esp.Enferm.Dig_113_524
PubMedID: 33562989
Gene_locus related to this paper: human-NDRG3

Title : A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA\/VSD) and tetralogy of Fallot (TOF) - Peng_2021_FEBS.Open.Bio_11_375
Author(s) : Peng J , Wang Q , Meng Z , Wang J , Zhou Y , Zhou S , Song W , Chen S , Chen AF , Sun K
Ref : FEBS Open Bio , 11 :375 , 2021
Abstract : Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N-myc downstream-regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase-9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell-cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF.
ESTHER : Peng_2021_FEBS.Open.Bio_11_375
PubMedSearch : Peng_2021_FEBS.Open.Bio_11_375
PubMedID: 33211401
Gene_locus related to this paper: human-NDRG4

Title : Dimeric Tacrine(10)-hupyridone as a Multitarget-Directed Ligand To Treat Alzheimer's Disease - Xuan_2021_ACS.Chem.Neurosci_12_2462
Author(s) : Xuan Z , Gu X , Yan S , Xie Y , Zhou Y , Zhang H , Jin H , Hu S , Mak MSH , Zhou D , Tsim KWK , Carlier PR , Han Y , Cui W
Ref : ACS Chem Neurosci , 12 :2462 , 2021
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder with multiple pathological features. Therefore, a multitarget-directed ligands (MTDLs) strategy has been developed to treat AD. We have previously designed and synthesized dimeric tacrine(10)-hupyridone (A10E), a novel tacrine derivative with acetylcholinesterase (AChE) inhibition and brain-derived neurotrophic factor (BDNF) activation activity, by linking tacrine and a fragment of huperzine A. However, it was largely unknown whether A10E could act on other AD targets and produce cognitive-enhancing ability in AD animal models. In this study, A10E could prevent cognitive impairments in APP/PS1 transgenic mice and beta-amyloid (Abeta) oligomers-treated mice, with higher potency than tacrine and huperzine A. Moreover, A10E could effectively inhibit Abeta production and deposition, alleviate neuroinflammation, enhance BDNF expression, and elevate cholinergic neurotransmission in vivo. At nanomolar concentrations, A10E could inhibit Abeta oligomers-induced neurotoxicity via the activation of tyrosine kinase receptor B (TrkB)/Akt pathway in SH-SY5Y cells. Furthermore, Abeta oligomerization and fibrillization could be directly disrupted by A10E. Importantly, A10E at high concentrations did not produce obvious hepatotoxicity. Our results indicated that A10E could produce anti-AD neuroprotective effects via the inhibition of Abeta aggregation, the activation of the BDNF/TrkB pathway, the alleviation of neuroinflammation, and the decrease of AChE activity. As MTDLs could produce additional benefits, such as overcoming the deficits of drug combination and enhancing the compliance of AD patients, our results also suggested that A10E might be developed as a promising MTDL lead for the treatment of AD.
ESTHER : Xuan_2021_ACS.Chem.Neurosci_12_2462
PubMedSearch : Xuan_2021_ACS.Chem.Neurosci_12_2462
PubMedID: 34156230

Title : Synthesis and activity of miconazole derivatives as dual BChE\/IDO1 inhibitors for the treatment of Alzheimer's disease - Lu_2021_Future.Med.Chem_13_1105
Author(s) : Lu X , Liu Y , Qin N , Yang H , Qiao Y , Jiang X , Chen Y , Feng F , Liu W , Zhou Y , Sun H
Ref : Future Med Chem , 13 :1105 , 2021
Abstract : Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.
ESTHER : Lu_2021_Future.Med.Chem_13_1105
PubMedSearch : Lu_2021_Future.Med.Chem_13_1105
PubMedID: 33960203

Title : Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis - Yang_2021_Med.Sci.Monit_27_e928523
Author(s) : Yang Z , Cheng H , Zhang Y , Zhou Y
Ref : Med Sci Monit , 27 :e928523 , 2021
Abstract : BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive cancer with heterogeneous outcomes. In this study, we aimed to investigate genomic and prognostic features of ACC. MATERIAL AND METHODS Clinical, pathologic, and transcriptomic data from 2 independent datasets derived from ACC samples (TCGA-ACC dataset, GEO-GSE76021 dataset) were collected. Weighted gene co-expression network analysis (WGCNA) and survival analyses were performed to identify prognostic genes. Pathway analysis was performed for mechanistic analysis. xCell deconvolution was performed for tumor microenvironment analysis. RESULTS In the TCGA-ACC cohort, WGCNA identified a prognostic module of 5408 genes. Differential expression analysis identified 1969 genes that differed in expression level between long-term and short-term survivors. Univariate Cox regression model analysis identified 8393 genes with prognostic value. The intersection of these gene sets included 820 prognostic genes. Similar protocols were performed for the GSE76021 dataset, and 5 candidate genes were identified. Further intersection of these genes finally identified NDRG4 and CKS2 as key prognostic genes. Multivariate Cox regression model analysis validated the prognostic value of NDRG4 (HR=0.61, 95% CI 0.46-0.80) and CKS2 (HR=2.52, 95% CI 1.38-4.60). Moreover, NDRG4 and CKS2 expression predicted survival in patients treated with mitotane (P<0.001). Further mechanism exploration found an association between CKS2 and DNA mismatch repair pathways. Moreover, NDRG4 positively correlated with CD8 T cell infiltration, while CKS2 negatively correlated with it. CONCLUSIONS We identified NDRG4 and CKS2 expression as key prognostic genes in ACC, which may help in risk stratification of ACC. Moreover, a close relationship was found between CKS2 and mismatch repair pathways. Moreover, immune cell infiltration differed according to NDRG4 and CKS2 expression.
ESTHER : Yang_2021_Med.Sci.Monit_27_e928523
PubMedSearch : Yang_2021_Med.Sci.Monit_27_e928523
PubMedID: 33667214
Gene_locus related to this paper: human-NDRG4

Title : Neuroprotective effect of Betalain against AlCl(3)-induced Alzheimer's disease in Sprague Dawley Rats via putative modulation of oxidative stress and nuclear factor kappa B (NF-kappaB) signaling pathway - Shunan_2021_Biomed.Pharmacother_137_111369
Author(s) : Shunan D , Yu M , Guan H , Zhou Y
Ref : Biomed Pharmacother , 137 :111369 , 2021
Abstract : Alzheimer's disease (AD) is the most progressive form of neurodegenerative disease, which severely impairs cognitive function. Oxidative stress is identified to contribute to the mechanisms responsible for the pathogenesis of such neurodegenerative diseases. Aluminum is a potent neurotoxin for inducing oxidative stress associated with neurodegenerative diseases. The treatment for AD is limited; hence more treatment options are the need of the day. Betalain is known for its multitude of medicinal assets, including anti-inflammatory activity. Hence, this study was intended to investigate the possible protective effect of betalain against aluminum chloride (AlCl(3)) induced AD on Sprague Dawley (SD) rats. AlCl(3) (100 mg/kg) was administrated orally to induce the AD in SD rats. The rats were supplemented with low and high betalain doses (10 mg/kg and 20 mg/kg) for four weeks. At the end of the experiment, the rats were subjected to behavioral examination and sacrificed to study the biochemical and histological parameters. The results showed attenuation of memory and learning capacity, suppression of lipid oxidation (MDA) through regulation of antioxidant content (SOD, CAT, and GSH) and inhibition of lactate dehydrogenase (LDH), nitric oxide (NO), acetylcholinesterase (AChE), and transmembrane protein (Na+K+ATPase) activity. In addition, the NF-B associated mRNA expression (TNF-alpha IL-6, Il-1beta, iNOS, COX-2) was decreased, as evidenced in histopathological results. The present investigation established that the betalain treatment ameliorated the AlCl(3) induced AD by modulating NF-kappaB pathway activation.
ESTHER : Shunan_2021_Biomed.Pharmacother_137_111369
PubMedSearch : Shunan_2021_Biomed.Pharmacother_137_111369
PubMedID: 33582452

Title : Heterologous expression and exploration of the enzymatic properties of the carbaryl hydrolase CarH from a newly isolated carbaryl-degrading strain - Ke_2021_Ecotoxicol.Environ.Saf_224_112666
Author(s) : Ke Z , Zhu Q , Jiang W , Zhou Y , Zhang M , Jiang M , Hong Q
Ref : Ecotoxicology & Environmental Safety , 224 :112666 , 2021
Abstract : Carbaryl is the representative of carbamate insecticide. As an acetylcholinesterase inhibitor, it poses potential threat to humans and other non-target organisms. Agrobacterium sp. XWY-2, which could grow with carbaryl as the sole carbon source, was isolated and characterized. The carH gene, encoding a carbaryl hydrolase, was cloned from strain XWY-2 and expressed in Escherichia coli BL21 (DE3). CarH was able to hydrolyze carbamate pesticides including carbaryl, carbofuran, isoprocarb, propoxur and fenobucarb efficiently, while it hydrolyzed oxamyl and aldicarb poorly. The optimal pH of CarH was 8.0 and the optimal temperature was 30 degC. The apparent K(m) and k(cat) values of CarH for carbaryl were 38.01 +/- 2.81 microM and 0.33 +/- 0.01 s(-1), respectively. The point mutation experiment demonstrated that His341, His343, His346, His416 and D437 are the key sites for CarH to hydrolyze carbaryl.
ESTHER : Ke_2021_Ecotoxicol.Environ.Saf_224_112666
PubMedSearch : Ke_2021_Ecotoxicol.Environ.Saf_224_112666
PubMedID: 34416635

Title : Identification of Detoxification Esterase StrH Initiating Strobilurin Fungicides Degradation in Hyphomicrobium sp. DY-1 - Jiang_2021_Appl.Environ.Microbiol__
Author(s) : Jiang W , Gao Q , Zhang L , Liu Y , Zhang M , Ke Z , Zhou Y , Hong Q
Ref : Applied Environmental Microbiology , : , 2021
Abstract : Strobilurin fungicides are widely used in agricultural production due to their broad-spectrum and fungal mitochondrial inhibitory activities. However, their massive application has detained the growth of eukaryotic algae and increased the collateral damage in freshwater systems, notably the harmful cyanobacterial blooms (HCBs). In this study, a strobilurin fungicide-degrading strain Hyphomicrobium sp. DY-1 was isolated and characterized successfully. Moreover, a novel esterase gene strH responsible for the de-esterification of strobilurin fungicides was cloned, and the enzymatic properties of StrH were studied. For trifloxystrobin, StrH displayed the maximum activity at 50 degreesC and pH 7.0. The catalytic efficiency (k (cat)/K (m)) of StrH for different strobilurin fungicides were 196.32+/-2.30 microM(-1).s(-1) (trifloxystrobin), 4.64+/-0.05 microM(-1).s(-1) (picoxystrobin), 2.94+/-0.02 microM(-1).s(-1) (pyraclostrobin), and (2.41+/-0.19)x10(-2) microM(-1).s(-1) (azoxystrobin). StrH catalyzed the de-esterification of a variety of strobilurin fungicides generating the corresponding parent acid to achieve the detoxification of strobilurin fungicides and relieve strobilurin fungicides growth inhibition on Chlorella This research will provide insight into the microbial remediation of strobilurin fungicides-contaminated environments.IMPORTANCEStrobilurin fungicides have been widely acknowledged as an essential group of pesticides worldwide. So far, their residues and toxic effects on aquatic organisms have been reported in different parts of the world. Microbial degradation could eliminate xenobiotics from the environment. Therefore, the degradation of strobilurin fungicides by microorganisms has also been reported. However, little is known about the involvement of enzyme or gene in strobilurin fungicides degradation. In this study, a novel esterase gene strH responsible for the detoxification of strobilurin fungicides was cloned in the newly isolated strain Hyphomicrobium sp. DY-1. This degradation process detoxifies the strobilurin fungicides and relieves their growth inhibition on Chlorella.
ESTHER : Jiang_2021_Appl.Environ.Microbiol__
PubMedSearch : Jiang_2021_Appl.Environ.Microbiol__
PubMedID: 33741617
Gene_locus related to this paper: hypsm-strH

Title : Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies - Guan_2021_Int.J.Mol.Sci_22_
Author(s) : Guan XX , Rao DN , Liu YZ , Zhou Y , Yang HH
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Organ fibrosis often ends in eventual organ failure and leads to high mortality. Although researchers have identified many effector cells and molecular pathways, there are few effective therapies for fibrosis to date and the underlying mechanism needs to be examined and defined further. Epoxyeicosatrienoic acids (EETs) are endogenous lipid metabolites of arachidonic acid (ARA) synthesized by cytochrome P450 (CYP) epoxygenases. EETs are rapidly metabolized primarily via the soluble epoxide hydrolase (sEH) pathway. The sEH pathway produces dihydroxyeicosatrienoic acids (DHETs), which have lower activity. Stabilized or increased EETs levels exert several protective effects, including pro-angiogenesis, anti-inflammation, anti-apoptosis, and anti-senescence. Currently, intensive investigations are being carried out on their anti-fibrotic effects in the kidney, heart, lung, and liver. The present review provides an update on how the stabilized or increased production of EETs is a reasonable theoretical basis for fibrosis treatment.
ESTHER : Guan_2021_Int.J.Mol.Sci_22_
PubMedSearch : Guan_2021_Int.J.Mol.Sci_22_
PubMedID: 34639055

Title : Biochemical and Structural Characterization of a Novel Bacterial Tannase From Lachnospiraceae bacterium in Ruminant Gastrointestinal Tract - Guan_2021_Front.Bioeng.Biotechnol_9_806788
Author(s) : Guan L , Wang K , Gao Y , Li J , Yan S , Ji N , Ren C , Wang J , Zhou Y , Li B , Lu S
Ref : Front Bioeng Biotechnol , 9 :806788 , 2021
Abstract : Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanA(Lb)) was characterized. The recombinant TanA(Lb) exhibited maximal activity at pH 7.0 and 50 degreesC, and it maintained more than 70% relative activity from 30 degreesC to 55 degreesC. The activity of TanA(Lb) was enhanced by Mg(2+) and Ca(2+), and was dramatically reduced by Cu(2+) and Mn(2+). TanA(Lb) is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (k (cat) /Km) of TanA(Lb) toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanA(Lb) contains an insertion loop (residues 341-450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanA(Lb) is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use.
ESTHER : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedSearch : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedID: 34976993
Gene_locus related to this paper: 9firm-TanALb

Title : Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway - Tan_2021_Drug.Des.Devel.Ther_15_1971
Author(s) : Tan Q , Hu J , Zhou Y , Wan Y , Zhang C , Liu X , Long X , Tan F , Zhao X
Ref : Drug Des Devel Ther , 15 :1971 , 2021
Abstract : AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.
ESTHER : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedSearch : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedID: 34007157

Title : Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma - Gong_2021_Bioengineered_12_5241
Author(s) : Gong H , Niu Q , Zhou Y , Wang YX , Xu XF , Hou KZ
Ref : Bioengineered , 12 :5241 , 2021
Abstract : Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in in vivo and in vitro, and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis in vitro and in vivo. Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus in vitro and in vivo. Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.
ESTHER : Gong_2021_Bioengineered_12_5241
PubMedSearch : Gong_2021_Bioengineered_12_5241
PubMedID: 34402722

Title : Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate - Zhou_2021_J.Med.Chem_64_1844
Author(s) : Zhou Y , Fu Y , Yin W , Li J , Wang W , Bai F , Xu S , Gong Q , Peng T , Hong Y , Zhang D , Liu Q , Xu Y , Xu HE , Zhang H , Jiang H , Liu H
Ref : Journal of Medicinal Chemistry , 64 :1844 , 2021
Abstract : The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
ESTHER : Zhou_2021_J.Med.Chem_64_1844
PubMedSearch : Zhou_2021_J.Med.Chem_64_1844
PubMedID: 33570950
Gene_locus related to this paper: human-ACHE

Title : Binding Peptide-Guided Immobilization of Lipases with Significantly Improved Catalytic Performance Using Escherichia coli BL21(DE3) Biofilms as a Platform - Dong_2021_ACS.Appl.Mater.Interfaces__
Author(s) : Dong H , Zhang W , Xuan Q , Zhou Y , Zhou S , Huang J , Wang P
Ref : ACS Appl Mater Interfaces , : , 2021
Abstract : Developing novel immobilization methods to maximize the catalytic performance of enzymes has been a permanent pursuit of scientific researchers. Engineered Escherichia coli biofilms have attracted great concern as surface display platforms for enzyme immobilization. However, current biological conjugation methods, such as the SpyTag/SpyCatcher tagging pair, that immobilize enzymes onto E. coli biofilms seriously hamper enzymatic performance. Through phage display screening of lipase-binding peptides (LBPs) and co-expression of CsgB (nucleation protein of curli nanofibers) and LBP2-modified CsgA (CsgALBP2, major structural subunit of curli nanofibers) proteins, we developed E. coli BL21::deltaCsgA-CsgB-CsgALBP2 (LBP2-functionalized) biofilms as surface display platforms to maximize the catalytic performance of lipase (Lip181). After immobilization onto LBP2-functionalized biofilm materials, Lip181 showed increased thermostability, pH, and storage stability. Surprisingly, the relative activity of immobilized Lip181 increased from 8.43 to 11.33 U/mg through this immobilization strategy. Furthermore, the highest loading of lipase on LBP2-functionalized biofilm materials reached up to 27.90 mg/g of wet biofilm materials, equivalent to 210.49 mg/g of dry biofilm materials, revealing their potential as a surface with high enzyme loading capacity. Additionally, immobilized Lip181 was used to hydrolyze phthalic acid esters, and the hydrolysis rate against dibutyl phthalate was up to 100%. Thus, LBP2-mediated immobilization of lipases was demonstrated to be far more advantageous than the traditional SpyTag/SpyCatcher strategy in maximizing enzymatic performance, thereby providing a better alternative for enzyme immobilization onto E. coli biofilms.
ESTHER : Dong_2021_ACS.Appl.Mater.Interfaces__
PubMedSearch : Dong_2021_ACS.Appl.Mater.Interfaces__
PubMedID: 33499600

Title : Two novel Mutations of the LPL Gene in two Chinese family cases with Familial Chylomicronemia Syndrome - Wang_2021_Clin.Chim.Acta__
Author(s) : Wang M , Zhou Y , He X , Deng C , Liu X , Li J , Zhou L , Li Y , Zhang Y , Liu H , Li L
Ref : Clinica Chimica Acta , : , 2021
Abstract : The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429+1G>T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.
ESTHER : Wang_2021_Clin.Chim.Acta__
PubMedSearch : Wang_2021_Clin.Chim.Acta__
PubMedID: 34324844
Gene_locus related to this paper: human-LPL

Title : Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents - Zhao_2021_Inorg.Chem__
Author(s) : Zhao D , Liu J , Zhang L , Zhou Y , Zhong Y , Yang Y , Huang C , Wang Y
Ref : Inorg Chem , : , 2021
Abstract : Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), -potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.
ESTHER : Zhao_2021_Inorg.Chem__
PubMedSearch : Zhao_2021_Inorg.Chem__
PubMedID: 34969248

Title : Repressed OsMESL expression triggers reactive oxygen species mediated broad-spectrum disease resistance in rice - Hu_2021_Plant.Biotechnol.J__
Author(s) : Hu B , Zhou Y , Zhou Z , Sun B , Zhou F , Yin C , Ma W , Chen H , Lin Y
Ref : Plant Biotechnol J , : , 2021
Abstract : A few reports have indicated that a single gene confer resistance to bacterial blight, sheath blight, and rice blast. In this study, we identified a novel disease resistance mutant gene, methyl esterase-like (osmesl) in rice. Mutant rice with T-DNA insertion displayed significant resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo), sheath blight caused by Rhizoctonia solani and rice blast caused by Magnaporthe oryzae. Additionally, CRISPR-Cas9 knockout mutants and RNAi lines displayed resistance to these pathogens. Complementary T-DNA mutants demonstrated a phenotype similar to the wild type (WT), thereby indicating that osmesl confers resistance to pathogens. Protein interaction experiments revealed that OsMESL affects reactive oxygen species (ROS) accumulation by interacting with thioredoxin OsTrxm in rice. Moreover, qRT-PCR results showed significantly reduced mRNA levels of multiple ROS scavenging-related genes in osmesl mutants. Nitroblue tetrazolium staining showed that the pathogens cause ROS accumulation, and quantitative detection revealed significantly increased levels of H(2) O(2) in the leaves of osmesl mutants and RNAi lines after infection. The abundance of JA, a hormone associated with disease resistance, was significantly more in osmesl mutants than in WT plants. Overall, these results suggested that osmesl enhances disease resistance to Xoo, R. solani and M. oryzae by modulating the ROS balance.
ESTHER : Hu_2021_Plant.Biotechnol.J__
PubMedSearch : Hu_2021_Plant.Biotechnol.J__
PubMedID: 33567155
Gene_locus related to this paper: orysj-q0d4u5

Title : Phytochemical Analysis, Antioxidant, Antibacterial, Cytotoxic, and Enzyme Inhibitory Activities of Hedychium flavum Rhizome - Tian_2020_Front.Pharmacol_11_572659
Author(s) : Tian M , Wu X , Lu T , Zhao X , Wei F , Deng G , Zhou Y
Ref : Front Pharmacol , 11 :572659 , 2020
Abstract : Hedychium flavum Roxb., a medicinal, edible, and ornamental plant, is widely cultivated throughout China, India, and Southeast Asia. The rhizome from this plant has been used for food flavoring and in traditional Chinese medicine to treat diverse diseases, but the detailed constituents and bioactivities are still limited known. Therefore, phytochemical analysis by GC-MS and UHPLC-Q-Orbitrap-MS, and antioxidant, antibacterial, cytotoxic, and enzyme inhibitory activities tests have been conducted in the current study. Based on the GC-MS results, the essential oil (EO) of rhizome was mainly composed of coronarin E (20.3%), beta-pinene (16.8%), E-nerolidol (11.8%), and linalool (8.5%). Among them, coronarin E was reported in H. flavum EO firstly. Furthermore, the spectrophotometric indicated rhizome had high total phenolic content (TPC, 50.08-57.42 mg GAEs/g extract) and total flavonoid content (TFC, 12.45-21.83 mg REs/g extract), no matter in water extract (WE) or in 70% ethanol extract (EE). UHPLC-Q-Orbitrap-MS was applied to further characterize composition, and 86 compounds were putatively identified from WE and EE, including 13 phenolic components. For the bioactivities, both WE and EE showed remarkable antioxidant activity by DPPH and ABTS tests, being superior to the positive control (butylated hydroxytoluene, BTH). EO revealed significant antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris with DIZ (10.34-24.43 mm), MIC (78.13-312.50 mug/mL), and MBC (156.25-625.00 mug/mL). Moreover, EO exhibited a considerable selectivity to human tumor cell K562 (IC(50) = 27.16 mug/mL), and its toxicity was more than 3.5-fold different from that of non-cancerous MRC-5 cell (IC(50) = 95.96 mug/mL) and L929 cell (IC(50) = 129.91 mug/mL). A series of apoptosis analysis demonstrated that EO induced apoptosis against K562 cells in a dose-dependent manner. In enzyme inhibitory effect assays, WE and EE showed strong alpha-glucosidase inhibition activity, being superior to the positive control (acarbose). Besides, the EO, WE, and EE didn't show a promising inhibition on tyrosinase (19.30-32.51 mg KAEs/g sample) and exhibited a weak inhibitory effect on cholinesterase. Based on the current results, H. flavum could be considered as a source of bioactive compounds and has high exploitation potential in the cosmetics, food, and pharmaceutical industries.
ESTHER : Tian_2020_Front.Pharmacol_11_572659
PubMedSearch : Tian_2020_Front.Pharmacol_11_572659
PubMedID: 33041813

Title : Development of a whole-cell biocatalyst for diisobutyl phthalate degradation by functional display of a carboxylesterase on the surface of Escherichia coli - Ding_2020_Microb.Cell.Fact_19_114
Author(s) : Ding J , Zhou Y , Wang C , Peng Z , Mu Y , Tang X , Huang Z
Ref : Microb Cell Fact , 19 :114 , 2020
Abstract : BACKGROUND: Phthalic acid esters (PAEs) are widely used as plasticizers or additives during the industrial manufacturing of plastic products. PAEs have been detected in both aquatic and terrestrial environments due to their overuse. Exposure of PAEs results in human health concerns and environmental pollution. Diisobutyl phthalate is one of the main plasticizers in PAEs. Cell surface display of recombinant proteins has become a powerful tool for biotechnology applications. In this current study, a carboxylesterase was displayed on the surface of Escherichia coli cells, for use as whole-cell biocatalyst in diisobutyl phthalate biodegradation. RESULTS: A carboxylesterase-encoding gene (carEW) identified from Bacillus sp. K91, was fused to the N-terminal of ice nucleation protein (inpn) anchor from Pseudomonas syringae and gfp gene, and the fused protein was then cloned into pET-28a(+) vector and was expressed in Escherichia coli BL21(DE3) cells. The surface localization of INPN-CarEW/or INPN-CarEW-GFP fusion protein was confirmed by SDS-PAGE, western blot, proteinase accessibility assay, and green fluorescence measurement. The catalytic activity of the constructed E. coli surface-displayed cells was determined. The cell-surface-displayed CarEW displayed optimal temperature of 45 degrees C and optimal pH of 9.0, using p-NPC2 as substrate. In addition, the whole cell biocatalyst retained ~ 100% and ~ 200% of its original activity per OD600 over a period of 23 days at 45 degrees C and one month at 4 degrees C, exhibiting the better stability than free CarEW. Furthermore, approximately 1.5 mg/ml of DiBP was degraded by 10 U of surface-displayed CarEW cells in 120 min. CONCLUSIONS: This work provides a promising strategy of cost-efficient biodegradation of diisobutyl phthalate for environmental bioremediation by displaying CarEW on the surface of E. coli cells. This approach might also provide a reference in treatment of other different kinds of environmental pollutants by displaying the enzyme of interest on the cell surface of a harmless microorganism.
ESTHER : Ding_2020_Microb.Cell.Fact_19_114
PubMedSearch : Ding_2020_Microb.Cell.Fact_19_114
PubMedID: 32471417
Gene_locus related to this paper: bacsu-pnbae

Title : Effects of Quercetin on the Growth and Expression of Immune-Pathway-Related Genes in Silkworm (Lepidoptera: Bombycidae) - Shi_2020_J.Insect.Sci_20_
Author(s) : Shi G , Kang Z , Ren F , Zhou Y , Guo P
Ref : J Insect Sci , 20 : , 2020
Abstract : Quercetin is a flavonoid produced as a defense by plants. The effects of 1% quercetin on the growth and development of Bombyx mori were studied. The activities of the enzymes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), carboxy-lesterase (CarEs), and glutathione S-transferase (GST) were all measured at 24, 48, 72, and 96 h after quercetin exposure. The results show that quercetin induces the activities of antioxidant and detoxification enzymes. With longer exposure times, enzyme activity first increased and then decreased. The relative expressions of AMP (defensin, CecA), the Toll pathway (cactus, Spatzle, and Rel), the IMD pathway (Imd, Fadd, and Dorsal), the JAK-STAT pathway (STAT, HOP, and Pi3k60), and the Melanization gene (DDC and PAH) were analyzed using quantitative polymerase chain reaction (qPCR). The results indicated that long-term exposure to quercetin could inhibit the expression of immune-related pathway genes in silkworms. This suggests that it can inhibit the activities of antioxidant and detoxifying enzymes, thus inhibiting the immune system and affecting the growth and development, resulting in an increase in the death rate in silkworm. This study provides the novel conclusion that quercetin accumulation inhibits the immune system of silkworm and increases its death rate, a result that may promote the development and utilization of better biopesticides that avoid environmental pollution.
ESTHER : Shi_2020_J.Insect.Sci_20_
PubMedSearch : Shi_2020_J.Insect.Sci_20_
PubMedID: 33159528

Title : Double-enzymes-mediated fluorescent assay for sensitive determination of organophosphorus pesticides based on the quenching of upconversion nanoparticles by Fe(3) - Lin_2020_Food.Chem_345_128809
Author(s) : Lin X , Yu Q , Yang W , He C , Zhou Y , Duan N , Wu S
Ref : Food Chem , 345 :128809 , 2020
Abstract : Herein, a new double-enzymes-modulated fluorescent assay based on the quenching of upconversion nanoparticles (UCNPs) by Fe(3+) was constructed for sensitive determination of OPs. OPs can inhibit the activity of acetylcholinesterase to reduce the production of choline and further lead to the lack of H(2)O(2) in the presence of choline oxidase. Therefore, Fe(2+) cannot be converted into Fe(3+), resulting in "turn-on" fluorescence of UCNPs. Under optimal conditions, an excellent linear correlation between the inhibition efficiency and the logarithm of the chlorpyrifos concentration was achieved with a detection limit (LOD) of 6.7 ng/mL in the range of 20-2000 ng/mL. The recovery for chlorpyrifos in apples and cucumbers was 89.5-97.1%. The results were consistent with those obtained by GC-MS. Overall, the integration of UCNPs into the double-enzymes-mediated Fe(3+)/Fe(2+) conversion endows this method with desirable rapidity, sensitivity, selectivity, stability, operational simplicity, and strong anti-interference capability, holding great potential in the application of food safety.
ESTHER : Lin_2020_Food.Chem_345_128809
PubMedSearch : Lin_2020_Food.Chem_345_128809
PubMedID: 33338834

Title : Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice - Zhou_2020_Metab.Brain.Dis__
Author(s) : Zhou Y , Wu X , Ye L , Bai Y , Zhang H , Xuan Z , Feng Y , Zhang P , Chen Y , Yan Y , Zhu B , Cui W
Ref : Metabolic Brain Disease , : , 2020
Abstract : Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3beta (pSer9-GSK3beta) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.
ESTHER : Zhou_2020_Metab.Brain.Dis__
PubMedSearch : Zhou_2020_Metab.Brain.Dis__
PubMedID: 31916204

Title : Directed Evolution of Pseudomonas fluorescens Lipase Variants With Improved Thermostability Using Error-Prone PCR - Guan_2020_Front.Bioeng.Biotechnol_8_1034
Author(s) : Guan L , Gao Y , Li J , Wang K , Zhang Z , Yan S , Ji N , Zhou Y , Lu S
Ref : Front Bioeng Biotechnol , 8 :1034 , 2020
Abstract : Lipases catalyze the hydrolysis of fats and oils, and have been widely used in various industrial fields. However, bacterial lipases have a lower thermostability in industrial processes, which was a limiting factor in their industrial application. In this study, we obtained an improve variant of Pseudomonas fluorescens lipase (PFL) with enhanced thermostability using classical error-prone PCR. Wild-type PFL showed an optimal temperature and pH of 50degC and pH 7.5, respectively. Due to the low thermostability of PFL, a library containing over 3000 individual mutants as constructed using error-prone PCR. Screening for thermotolerance yielded the mutants L218P and P184C/M243C with T (m) values of 62.5 and 66.0degC, which was 2.5 and 6degC higher than that of the WT, respectively. The combination of the two mutants (P184C/M243C/L218P) resulted in an approximately additive effect with a T (m) value of 68.0degC. Although the increase of T (m) was not substantial, the mutant also had dramatically increased methanol tolerance. Structural analysis revealed that the introduction of a disulfide bond between P184C and M243C and the substitution of Pro to reduce the flexibility of a loop increased the thermostability of PFL, which provides a theoretical foundation for improving the thermostability and methanol tolerance of lipase family I.1 to resist the harsh conditions of industrial processes.
ESTHER : Guan_2020_Front.Bioeng.Biotechnol_8_1034
PubMedSearch : Guan_2020_Front.Bioeng.Biotechnol_8_1034
PubMedID: 32984290
Gene_locus related to this paper: psefl-lipa

Title : Characterization of EstZY: A new acetylesterase with 7-aminocephalosporanic acid deacetylase activity from Alicyclobacillus tengchongensis - Ding_2020_Int.J.Biol.Macromol_148_333
Author(s) : Ding J , Zhou Y , Zhu H , Deng M , Gao Y , Yang Y , Huang Z
Ref : Int J Biol Macromol , 148 :333 , 2020
Abstract : Deacetyl-7-aminocephalosporanic acid (D-7-ACA) is required for producing of many semisynthetic beta-lactam antibiotics; therefore, enzymes capable of converting 7-aminocephalosporanic acid (7-ACA) to D-7-ACA present a valuable resource to the pharmaceutical industry. In the present study, a putative acetylesterase, EstZY, was identified and characterized from a thermophilic bacterium Alicyclobacillus tengchongensis. Sequence alignment showed that EstZY was an acetylesterase which belonged to carbohydrate esterase family 7 (CE7), with substrate preference for short-chain acyl esters p-NPC(2) to p-NPC(8). Maximum enzyme activity was recorded at pH 9.0 and 50 degreesC, where K(m) and V(max) were calculated as 1.9 +/- 0.23 mM and 258 +/- 18.5 microM min(-)(1), respectively. The residues Ser185, Asp274, and His303 were identified as the putative catalytic triad by homology modelling, site-directed mutagenesis and molecular docking. Moreover, EstZY can remove the acetyl group at C3' position of 7-ACA to form D-7-ACA; this is the first report of a 7-ACA deacetylase from CE7 family in A. tengchongensis and may represent a new enzyme with industrial values.
ESTHER : Ding_2020_Int.J.Biol.Macromol_148_333
PubMedSearch : Ding_2020_Int.J.Biol.Macromol_148_333
PubMedID: 31954783
Gene_locus related to this paper: 9bacl-a0a6g6c491

Title : Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry - Wan_2020_J.Virol_94_
Author(s) : Wan Y , Shang J , Sun S , Tai W , Chen J , Geng Q , He L , Chen Y , Wu J , Shi Z , Zhou Y , Du L , Li F
Ref : J Virol , 94 : , 2020
Abstract : Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.
ESTHER : Wan_2020_J.Virol_94_
PubMedSearch : Wan_2020_J.Virol_94_
PubMedID: 31826992

Title : Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma - Zhang_2020_Front.Oncol_10_559568
Author(s) : Zhang H , Guo W , Zhang F , Li R , Zhou Y , Shao F , Feng X , Tan F , Wang J , Gao S , Gao Y , He J
Ref : Front Oncol , 10 :559568 , 2020
Abstract : Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in LUAD cells. Moreover, we found that knockdown of MGLL suppresses the expression of matrix metalloproteinase 14 (MMP14) in A549 and H322 cells, and in clinical samples, expression of MMP14 is significantly correlated with MGLL expression. Taken together, our results indicate that MGLL plays an oncogenic role in LUAD progression and metastasis and may serve as a potential biomarker for disease prognosis and as a target for the development of personalized therapies.
ESTHER : Zhang_2020_Front.Oncol_10_559568
PubMedSearch : Zhang_2020_Front.Oncol_10_559568
PubMedID: 33363004

Title : The Antimalarial Natural Product Salinipostin A Identifies Essential alpha\/beta Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites - Yoo_2020_Cell.Chem.Biol_27_143
Author(s) : Yoo E , Schulze CJ , Stokes BH , Onguka O , Yeo T , Mok S , Gnadig NF , Zhou Y , Kurita K , Foe IT , Terrell SM , Boucher MJ , Cieplak P , Kumpornsin K , Lee MCS , Linington RG , Long JZ , Uhlemann AC , Weerapana E , Fidock DA , Bogyo M
Ref : Cell Chemical Biology , 27 :143 , 2020
Abstract : Salinipostin A (Sal A) is a potent antiplasmodial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain alpha/beta serine hydrolase domains and several are essential for parasite growth. One of the essential targets displays a high degree of homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism. Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a PRELI domain-containing protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets.
ESTHER : Yoo_2020_Cell.Chem.Biol_27_143
PubMedSearch : Yoo_2020_Cell.Chem.Biol_27_143
PubMedID: 31978322
Gene_locus related to this paper: plaf7-q8ii19 , plafa-a0a143zya4 , plaf7-q8iik5 , plafa-MAL8P1.38 , plafa-PF07.0040 , plafa-PF10.0020 , plafa-PF10.0379 , plafa-PF13.0153

Title : Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies - Zhou_2020_Bioorg.Med.Chem.Lett__127756
Author(s) : Zhou Y , Lu X , Du C , Liu Y , Wang Y , Ho Hong K , Chen Y , Sun H
Ref : Bioorganic & Medicinal Chemistry Lett , :127756 , 2020
Abstract : In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
ESTHER : Zhou_2020_Bioorg.Med.Chem.Lett__127756
PubMedSearch : Zhou_2020_Bioorg.Med.Chem.Lett__127756
PubMedID: 33359445

Title : PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice - Sun_2020_Biochem.Biophys.Res.Commun__
Author(s) : Sun CC , Zhang CY , Duan JX , Guan XX , Yang HH , Jiang HL , Hammock BD , Hwang SH , Zhou Y , Guan CX , Liu SK , Zhang J
Ref : Biochemical & Biophysical Research Communications , : , 2020
Abstract : Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global adult population, and no effective pharmacological treatment has been found. Products of arachidonic acid metabolism have been developed into a novel therapy for metabolic syndrome and diabetes. It has been demonstrated that protective actions of a novel dual cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) inhibitor, PTUPB, on the metabolic abnormalities. Here, we investigated the effects of PTUPB on hepatic steatosis in high-fat diet (HFD)-induced obese mice, as well as in hepatocytes in vitro. We found that PTUPB treatment reduced body weight, liver weight, liver triglyceride and cholesterol content, and the expression of lipolytic/lipogenic and lipid uptake related genes (Acc, Cd36, and Cidec) in HFD mice. In addition, PTUPB treatment arrested fibrotic progression with a decrease of collagen deposition and expression of Col1a1, Col1a3, and alpha-SMA. In vitro, PTUPB decreased palmitic acid-induced lipid deposition and downregulation of lipolytic/lipogenic genes (Acc and Cd36) in hepatocytes. Additionally, we found that PTUPB reduced the production of pro-inflammatory cytokines and suppressed the NLRP3 inflammasome activation in HFD mice and hepatocytes. In conclusion, dual inhibition of COX-2/sEH attenuates hepatic steatosis by inhibiting the NLRP3 inflammasome activation. PTUPB might be a promising potential therapy for liver steatosis associated with obesity.
ESTHER : Sun_2020_Biochem.Biophys.Res.Commun__
PubMedSearch : Sun_2020_Biochem.Biophys.Res.Commun__
PubMedID: 31973813

Title : Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring - Zhou_2020_Dose.Response_18_1559325820938526
Author(s) : Zhou Y , Hu Y , Lu X , Yang H , Li Q , Du C , Chen Y , Hong KH , Sun H
Ref : Dose Response , 18 :1559325820938526 , 2020
Abstract : Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC50 = 1.4 muM). The binding mode prediction and kinetic analysis were performed to obtain detailed information about compound 5. Besides, a preliminary structure-activity relationship investigation of compound 5 was carried out for further development of the series. The present results provided a valuable chemical template with a novel scaffold for the development of selective BChE inhibitors.
ESTHER : Zhou_2020_Dose.Response_18_1559325820938526
PubMedSearch : Zhou_2020_Dose.Response_18_1559325820938526
PubMedID: 32636723

Title : A COX-2\/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation - Yang_2020_Theranostics_10_4749
Author(s) : Yang HH , Duan JX , Liu SK , Xiong JB , Guan XX , Zhong WJ , Sun CC , Zhang CY , Luo XQ , Zhang YF , Chen P , Hammock BD , Hwang SH , Jiang JX , Zhou Y , Guan CX
Ref : Theranostics , 10 :4749 , 2020
Abstract : Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.
ESTHER : Yang_2020_Theranostics_10_4749
PubMedSearch : Yang_2020_Theranostics_10_4749
PubMedID: 32308747

Title : A COX-2\/sEH dual inhibitor PTUPB ameliorates cecal ligation and puncture-induced sepsis in mice via anti-inflammation and anti-oxidative stress - Zhang_2020_Biomed.Pharmacother_126_109907
Author(s) : Zhang YF , Sun CC , Duan JX , Yang HH , Zhang CY , Xiong JB , Zhong WJ , Zu C , Guan XX , Jiang HL , Hammock BD , Hwang SH , Zhou Y , Guan CX
Ref : Biomed Pharmacother , 126 :109907 , 2020
Abstract : Arachidonic acid can be metabolized to prostaglandins and epoxyeicosatrienoic acids (EETs) by cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP), respectively. While protective EETs are degraded by soluble epoxide hydrolase (sEH) very fast. We have reported that dual inhibition of COX-2 and sEH with specific inhibitor PTUPB shows anti-pulmonary fibrosis and renal protection. However, the effect of PTUPB on cecal ligation and puncture (CLP)-induced sepsis remains unclear. The current study aimed to investigate the protective effects of PTUPB against CLP-induced sepsis in mice and the underlying mechanisms. We found that COX-2 expressions were increased, while CYPs expressions were decreased in the liver, lung, and kidney of mice undergone CLP. PTUPB treatment significantly improved the survival rate, reduced the clinical scores and systemic inflammatory response, alleviated liver and kidney dysfunction, and ameliorated the multiple-organ injury of the mice with sepsis. Besides, PTUPB treatment reduced the expression of hypoxia-inducible factor-1alpha in the liver, lung, and kidney of septic mice. Importantly, we found that PTUPB treatment suppressed the activation of NLRP3 inflammasome in the liver and lung of septic mice. Meanwhile, we found that PTUPB attenuated the oxidative stress, which contributed to the activation of NLRP3 inflammasome. Altogether, our data, for the first time, demonstrate that dual inhibition of COX-2 and sEH with PTUPB ameliorates the multiple organ dysfunction in septic mice.
ESTHER : Zhang_2020_Biomed.Pharmacother_126_109907
PubMedSearch : Zhang_2020_Biomed.Pharmacother_126_109907
PubMedID: 32114358

Title : COX-2\/sEH dual inhibitor PTUPB alleviates bleomycin-induced pulmonary fibrosis in mice via inhibiting senescence - Zhang_2020_FEBS.J_287_1666
Author(s) : Zhang CY , Duan JX , Yang HH , Sun CC , Zhong WJ , Tao JH , Guan XX , Jiang HL , Hammock BD , Hwang SH , Zhou Y , Guan CX
Ref : Febs J , 287 :1666 , 2020
Abstract : Pulmonary fibrosis (PF) is a senescence-associated disease with poor prognosis. Currently, there is no effective therapeutic strategy for preventing and treating the disease process. Mounting evidence suggests that arachidonic acid (ARA) metabolites are involved in the pathogenesis of various fibrosis. However, the relationship between the metabolism of ARA and PF is still elusive. In this study, we observed a disorder in the cyclooxygenase-2/cytochrome P450 (COX-2/CYP) metabolism of ARA in the lungs of PF mice induced by bleomycin (BLM). Therefore, we aimed to explore the role of COX-2/CYP-derived ARA metabolic disorders in PF. PTUPB, a dual COX-2 and soluble epoxide hydrolase (sEH) inhibitor, was used to restore the balance of COX-2/CYP metabolism. sEH is an enzyme hydrolyzing epoxyeicosatrienoic acids derived from ARA by CYP. We found that PTUPB alleviated the pathological changes in lung tissue and collagen deposition, as well as reduced senescence marker molecules (p16(Ink4a) and p53-p21(Waf1/Cip1) ) in the lungs of mice treated by BLM. In vitro, we found that PTUPB pretreatment remarkably reduced the expression of senescence-related molecules in the alveolar epithelial cells (AECs) induced by BLM. In conclusion, our study supports the notion that the COX-2/CYP-derived ARA metabolic disorders may be a potential therapeutic target for PF via inhibiting the cellular senescence in AECs.
ESTHER : Zhang_2020_FEBS.J_287_1666
PubMedSearch : Zhang_2020_FEBS.J_287_1666
PubMedID: 31646730

Title : Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function - Tan_2019_J.Cell.Sci_132_
Author(s) : Tan L , Cho KJ , Kattan WE , Garrido CM , Zhou Y , Neupane P , Capon RJ , Hancock JF
Ref : Journal of Cell Science , 132 : , 2019
Abstract : The primary site for KRAS signaling is the inner leaflet of the plasma membrane (PM). We previously reported that oxanthroquinone G01 (G01) inhibited KRAS PM localization and blocked KRAS signaling. In this study, we identified acylpeptide hydrolase (APEH) as a molecular target of G01. APEH formed a stable complex with biotinylated G01, and the enzymatic activity of APEH was inhibited by G01. APEH knockdown caused profound mislocalization of KRAS and reduced clustering of KRAS that remained PM localized. APEH knockdown also disrupted the PM localization of phosphatidylserine (PtdSer), a lipid critical for KRAS PM binding and clustering. The mislocalization of KRAS was fully rescued by ectopic expression of APEH in knockdown cells. APEH knockdown disrupted the endocytic recycling of epidermal growth factor receptor and transferrin receptor, suggesting that abrogation of recycling endosome function was mechanistically linked to the loss of KRAS and PtdSer from the PM. APEH knockdown abrogated RAS-RAF-MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic.
ESTHER : Tan_2019_J.Cell.Sci_132_
PubMedSearch : Tan_2019_J.Cell.Sci_132_
PubMedID: 31266814

Title : Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids - Pan_2019_Bioorg.Med.Chem.Lett_29_2150
Author(s) : Pan T , Xie S , Zhou Y , Hu J , Luo H , Li X , Huang L
Ref : Bioorganic & Medicinal Chemistry Lett , 29 :2150 , 2019
Abstract : A series of tacrine-pyrazolo[3,4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer's disease (AD). Compound 10j, which is tacrine linked with pyrazolo[3,4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125muM. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50 value of 0.449 and 0.271muM, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD.
ESTHER : Pan_2019_Bioorg.Med.Chem.Lett_29_2150
PubMedSearch : Pan_2019_Bioorg.Med.Chem.Lett_29_2150
PubMedID: 31281020

Title : Nanoparticle-mediated approaches for Alzheimer's disease pathogenesis, diagnosis, and therapeutics - Hettiarachchi_2019_J.Control.Release_314_125
Author(s) : Hettiarachchi SD , Zhou Y , Seven E , Lakshmana MK , Kaushik AK , Chand HS , Leblanc RM
Ref : J Control Release , 314 :125 , 2019
Abstract : Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder manifested by memory loss and cognitive impairment. Deposition of the amyloid beta plaques has been identified as the most common AD pathology; however, the excessive accumulation of phosphorylated or total tau proteins, reactive oxygen species, and higher acetylcholinesterase activity are also strongly associated with Alzheimer's dementia. Several therapeutic approaches targeting these pathogenic mechanisms have failed in clinical or preclinical trials, partly due to the limited bioavailability, poor cell, and blood-brain barrier penetration, and low drug half-life of current regimens. The nanoparticles (NPs)-mediated drug delivery systems improve drug solubility and bioavailability, thus renders as superior alternatives. Moreover, NPs-mediated approaches facilitate multiple drug loading and targeted drug delivery, thereby increasing drug efficacy. However, certain NPs can cause acute toxicity damaging cellular and tissue architecture, therefore, NP material should be carefully selected. In this review, we summarize the recent NPs-mediated studies that exploit various pathologic mechanisms of AD by labeling, identifying, and treating the affected brain pathologies. The disadvantages of the select NP-based deliveries and the future aspects will also be discussed.
ESTHER : Hettiarachchi_2019_J.Control.Release_314_125
PubMedSearch : Hettiarachchi_2019_J.Control.Release_314_125
PubMedID: 31647979

Title : Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats - Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
Author(s) : Wu Q , Cao Y , Liu M , Liu F , Brantner AH , Yang Y , Wei Y , Zhou Y , Wang Z , Ma L , Wang F , Pei H , Li H
Ref : Neuropsychiatr Dis Treat , 15 :3167 , 2019
Abstract : Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.
ESTHER : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedSearch : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedID: 31814724

Title : Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of beta-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease - Wang_2019_Front.Aging.Neurosci_11_3
Author(s) : Wang Y , Xia J , Shen M , Zhou Y , Wu Z , Shi Y , Xu J , Hou L , Zhang R , Qiu Z , Xie Q , Chen H , Zhang Y , Wang H
Ref : Front Aging Neurosci , 11 :3 , 2019
Abstract : Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the beta-amyloid (Abeta) aggregation process. In this study, we bilaterally injected Abeta oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Abeta plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFalpha and IL-6) induced by Abeta were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Abeta intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Abeta deposition and the inflammatory response in the brain.
ESTHER : Wang_2019_Front.Aging.Neurosci_11_3
PubMedSearch : Wang_2019_Front.Aging.Neurosci_11_3
PubMedID: 30723404

Title : Visual detection of mixed organophosphorous pesticide using QD-AChE aerogel based microfluidic arrays sensor - Hu_2019_Biosens.Bioelectron_136_112
Author(s) : Hu T , Xu J , Ye Y , Han Y , Li X , Wang Z , Sun D , Zhou Y , Ni Z
Ref : Biosensors & Bioelectronics , 136 :112 , 2019
Abstract : In this paper, we present a simple strategy to fabricate a sensitive fluorescence microfluidic sensor based on quantum dots (QDs) aerogel and acetylcholinesterase enzyme (AChE) for organophosphate pesticides (OPs) detection The detection is based on the change of fluorescence intensity of QDs aerogel, which will be partly quenched as a consequence of the hydrolytic reaction of acetylthiocholine (ATCh) catalyzed by the AChE, and then the fluorescence of QDs aerogel is recovered due to decreasing of the enzymatic activity in the presence of OPs. The QDs-AChE aerogel based microfluidic arrays sensor provided good sensitivity for rapid detection of OPs with a detection limit of 0.38 pM, while the detection range is from 10(-5) to 10(-12)M. Due to the result of random orientations of AChE in the 3D porous aerogel nano-structure, the sensor presents similar calibration curves to difference pesticides, which promises the ability of the sensor to monitor total OPs of mixture. This determination sensor shows a low detection limit, wide linear range, and highly accurate determination of total OPs and carbamate content. Finally, we show the proposed sensor can be used to monitor of simple OPs and mixture in spiked fruit samples. This novel QDs-AChE aerogel sensor has an extremely high sensitivity and large detection range, it is a promising tool for accurate, rapid and cost-effective detection of various OP residues on agricultural products.
ESTHER : Hu_2019_Biosens.Bioelectron_136_112
PubMedSearch : Hu_2019_Biosens.Bioelectron_136_112
PubMedID: 31054518

Title : Identification and characterization of an acetyl esterase from Paenibacillus sp. XW-6-66 and its novel function in 7-aminocephalosporanic acid deacetylation - Ding_2019_Biotechnol.Lett_41_1059
Author(s) : Ding J , Zhou Y , Zhu H , Deng M , Long L , Yang Y , Wu Q , Huang Z
Ref : Biotechnol Lett , 41 :1059 , 2019
Abstract : OBJECTIVES: To obtain a new acetyl esterase from Paenibacillus sp. XW-6-66 and apply the enzyme to 7-aminocephalosporanic acid (7-ACA) deacetylation. RESULTS: The acetyl esterase AesZY was identified from Paenibacillus sp. XW-6-66, and its enzymatic properties were investigated. With the putative catalytic triad Ser114-Asp203-His235, AesZY belongs to the Acetyl esterase (Aes) family which is included in the alpha/beta hydrolase superfamily and contains the consensus Gly-X-Ser-X-Gly motif. The maximum activity of AesZY was detected at pH 8.0 and 40 degrees C. AesZY was stable at different pH values ranging from 5.0 to 12.0, and was tolerant to several metal ions. Furthermore, the deacetylation activity of AesZY toward 7-ACA was approximately 7.5 U/mg, and the Kcat/Km value was 2.04 s(-1) mM(-1). CONCLUSIONS: Our results demonstrate the characterization of a new acetyl esterase belonging to the Aes family with potential biotechnological applications.
ESTHER : Ding_2019_Biotechnol.Lett_41_1059
PubMedSearch : Ding_2019_Biotechnol.Lett_41_1059
PubMedID: 31302814
Gene_locus related to this paper: 9bacl-7ACAaes

Title : Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations - Zhou_2019_Molecules_24_
Author(s) : Zhou Y , Lu X , Yang H , Chen Y , Wang F , Li J , Tang Z , Cheng X , Yang Y , Xu L , Xia Q
Ref : Molecules , 24 : , 2019
Abstract : As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 muM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.
ESTHER : Zhou_2019_Molecules_24_
PubMedSearch : Zhou_2019_Molecules_24_
PubMedID: 31757047

Title : Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments - Zhou_2019_Bioorg.Chem_93_103322
Author(s) : Zhou Y , Sun W , Peng J , Yan H , Zhang L , Liu X , Zuo Z
Ref : Bioorg Chem , 93 :103322 , 2019
Abstract : Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
ESTHER : Zhou_2019_Bioorg.Chem_93_103322
PubMedSearch : Zhou_2019_Bioorg.Chem_93_103322
PubMedID: 31585263

Title : A multifunctional bis-(-)-nor-meptazinol-oxalamide hybrid with metal-chelating property ameliorates Cu(II)-induced spatial learning and memory deficits via preventing neuroinflammation and oxido-nitrosative stress in mice - Tan_2019_J.Trace.Elem.Med.Biol_52_199
Author(s) : Tan X , Zhou Y , Gong P , Guan H , Wu B , Hou L , Feng X , Zheng W , Li J
Ref : J Trace Elem Med Biol , 52 :199 , 2019
Abstract : Excess copper exposure is a risk factor of neurodegeneration related to Alzheimer's disease (AD). Evidence indicates that, besides promoting amyloid beta aggregation, activation of neuroinflammation and oxido-nitrosative stress (two key pathophysiological processes of AD) may also play important roles in Cu(II)-induced neuronal injury. Therefore, the copper-chelating strategy has gained attention in search for new anti-AD drugs. We previously reported a novel multifunctional compound N(1),N(2)-bis(3-(S)-meptazinol-propyl) oxalamide (ZLA), a bis-(-)-nor-meptazinol-oxalamide hybrid with properties of dual binding site acetylcholinesterase (AChE) inhibition and Cu(II)/Zn(II) chelation. The present study was aimed to explore its effect on cognitive deficits caused by intrahippocampal injection of Cu(II) in mice. Results showed that ZLA (2, 5 mg/kg; i.p.) treatment significantly ameliorated the Cu(II)-induced impairment of hippocampus-dependent learning and memory, whereas rivastigmine, an AChE inhibitor showing a similar potency of enzyme inhibition to ZLA, had no obvious effect. Immunohistochemical and Western blot analyses revealed that ZLA attenuated the decrease in hippocampal expression of microtubule-associated protein 2 (MAP2, a dendritic marker) in Cu(II)-challenged mice. Further analysis showed that ZLA suppressed the Cu(II)-evoked microglial activation. Moreover, it inhibited the Cu(II)-evoked production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1beta and expression of inducible nitric oxide synthase in the hippocampus. The Cu(II)-induced oxidative and nitrosative stress in the hippocampus was also attenuated after ZLA treatment. Collectively, these results suggest that ZLA ameliorates the Cu(II)-caused cognitive deficits. Inhibition of neuroinflammation and oxido-nitrosative stress, and thus ameliorating neuronal injury, may be the potential mechanism for the anti-amnesic effect of ZLA.
ESTHER : Tan_2019_J.Trace.Elem.Med.Biol_52_199
PubMedSearch : Tan_2019_J.Trace.Elem.Med.Biol_52_199
PubMedID: 30732883

Title : Acetylcholinesterase modified AuNPs-MoS2-rGO\/PI flexible film biosensor: Towards efficient fabrication and application in paraoxon detection - Jia_2019_Bioelectrochemistry_131_107392
Author(s) : Jia L , Zhou Y , Wu K , Feng Q , Wang C , He P
Ref : Bioelectrochemistry , 131 :107392 , 2019
Abstract : A flexible acetylcholinesterase (AChE) film biosensor, based on a AuNPs-MoS2-reduced graphene oxide/polyimide flexible film (rGO/PI) electrode, has been synthesized for paraoxon detection. In this study, the rGO/PI film acts as the flexible substrate and AuNPs are reduced by monolayer MoS2 under illumination. Transmission electron microscopy revealed that AuNPs are uniformly dispersed on the MoS2-rGO/PI electrode surface with a diameter ~10nm. X-ray photoelectron spectroscopy indicated that a strong binding force exists between reduced AuNPs and monolayer MoS2. The AChE modified AuNPs-MoS2-rGO/PI flexible film biosensor is used to hydrolyze acetylcholine chloride and obtain a large current response at 0.49V by differential pulse voltammetry, demonstrating successful immobilization of AChE. In view of the inhibition of paraoxon on the AChE, under optimal conditions, the AChE/AuNPs-MoS2-rGO/PI film biosensor shows a linear response over a concentration range 0.005-0.150mug/mL, a sensitivity of 4.44 uA/mugmL(-1), a detection limit of 0.0014mug/mL, acceptable reproducibility and stability to paraoxon. The flexible film biosensor has also proved used for detection of paraoxon in real samples.
ESTHER : Jia_2019_Bioelectrochemistry_131_107392
PubMedSearch : Jia_2019_Bioelectrochemistry_131_107392
PubMedID: 31707277

Title : Arylbenzofurans from the Root Bark of Morus alba as Triple Inhibitors of Cholinesterase, beta-Site Amyloid Precursor Protein Cleaving Enzyme 1, and Glycogen Synthase Kinase-3beta: Relevance to Alzheimer's Disease - Paudel_2019_ACS.Omega_4_6283
Author(s) : Paudel P , Seong SH , Zhou Y , Ha MT , Min BS , Jung HA , Choi JS
Ref : ACS Omega , 4 :6283 , 2019
Abstract : Cholinesterase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3beta (GSK-3beta) are the three main enzymes responsible for the early onset of Alzheimer's disease (AD). The main aim of the present study was to delineate and accentuate the triple-inhibitory potential of arylbenzofurans from Morus alba against these enzymes. Overall, the enzyme inhibition assays demonstrated the prominence of mulberrofuran D2 as an inhibitor of AChE, BChE, BACE1, and GSK-3beta enzymes with IC50 values of 4.61, 1.51, 0.73, and 6.36 muM, respectively. Enzyme kinetics revealed different modes of inhibition, and in silico modeling suggested that mulberrofuran D2 inhibited these enzymes with low binding energy through hydrophilic, hydrophobic, and pi-cation interactions in the active site cavities. Similarly, in Abeta-aggregation assays, mulberrofuran D2 inhibited self-induced and AChE-induced Abeta aggregation in a concentration-dependent manner that was superior to reference drugs. These results suggest that arylbenzofurans from M. alba, especially mulberrofuran D2, are triple inhibitors of cholinesterase, BACE1, and GSK-3beta and may represent a novel class of anti-AD drugs.
ESTHER : Paudel_2019_ACS.Omega_4_6283
PubMedSearch : Paudel_2019_ACS.Omega_4_6283
PubMedID: 31459768

Title : Anti-Alzheimer's Disease Activity of Bromophenols from a Red Alga, Symphyocladia latiuscula (Harvey) Yamada - Paudel_2019_ACS.Omega_4_12259
Author(s) : Paudel P , Seong SH , Zhou Y , Park HJ , Jung HA , Choi JS
Ref : ACS Omega , 4 :12259 , 2019
Abstract : Symphyocladia latiuscula (Harvey) Yamada is a red alga with a myriad of bromophenols accompanied by a diverse array of biological activities. The main purpose of the present study was to characterize the anti-Alzheimer's disease activity of bromophenols from S. latiuscula via inhibition of cholinesterases (AChE and BChE), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3beta (GSK-3beta). The results of enzyme inhibition assays demonstrated 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) as potent inhibitors of aforementioned enzymes. Among the tested bromophenols, 3 showed multifold higher inhibition of all of the tested enzymes. Enzyme kinetics revealed different modes of inhibition, and in silico molecular docking simulation demonstrated the importance of the 7-OH group and bromine number for H-bond and halogen-bond interactions, respectively. Similarly, 1-3 at 20 muM concentration showed more than 50% inhibition of self-induced Abeta25-35 aggregation. These results suggest that bromophenols from S. latiuscula, especially highly brominated (3), may represent a novel class of anti-Alzheimer's disease drugs.
ESTHER : Paudel_2019_ACS.Omega_4_12259
PubMedSearch : Paudel_2019_ACS.Omega_4_12259
PubMedID: 31460342

Title : Comparative transcriptome profiling reveals candidate genes related to insecticide resistance of Glyphodes pyloalis - Su_2019_Bull.Entomol.Res__1
Author(s) : Su H , Gao Y , Liu Y , Li X , Liang Y , Dai X , Xu Y , Zhou Y , Wang H
Ref : Bull Entomol Res , :1 , 2019
Abstract : Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a common pest in sericulture and has developed resistance to different insecticides. However, the mechanisms involved in insecticide resistance of G. pyloalis are poorly understood. Here, we present the first whole-transcriptome analysis of differential expression genes in insecticide-resistant and susceptible G. pyloalis. Clustering and enrichment analysis of DEGs revealed several biological pathways and enriched Gene Ontology terms were related to detoxification or insecticide resistance. Genes involved in insecticide metabolic processes, including cytochrome P450, glutathione S-transferases and carboxylesterase, were identified in the larval midgut of G. pyloalis. Among them, CYP324A19, CYP304F17, CYP6AW1, CYP6AB10, GSTs5, and AChE-like were significantly increased after propoxur treatment, while CYP324A19, CCE001c, and AChE-like were significantly induced by phoxim, suggesting that these genes were involved in insecticide metabolism. Furthermore, the sequence variation analysis identified 21 single nucleotide polymorphisms within CYP9A20, CYP6AB47, and CYP6AW1. Our findings reveal many candidate genes related to insecticide resistance of G. pyloalis. These results provide novel insights into insecticide resistance and facilitate the development of insecticides with greater specificity to G. pyloalis.
ESTHER : Su_2019_Bull.Entomol.Res__1
PubMedSearch : Su_2019_Bull.Entomol.Res__1
PubMedID: 31217039

Title : Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV - Jiang_2019_Viruses_11_
Author(s) : Jiang Y , Li J , Teng Y , Sun H , Tian G , He L , Li P , Chen Y , Guo Y , Zhao G , Zhou Y , Sun S
Ref : Viruses , 11 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
ESTHER : Jiang_2019_Viruses_11_
PubMedSearch : Jiang_2019_Viruses_11_
PubMedID: 30634407

Title : Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease - Wang_2019_Eur.J.Med.Chem_168_207
Author(s) : Wang D , Hu M , Li X , Zhang D , Chen C , Fu J , Shao S , Shi G , Zhou Y , Wu S , Zhang T
Ref : Eur Journal of Medicinal Chemistry , 168 :207 , 2019
Abstract : A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the highest ability to block H3R (IC50=0.27muM) and good inhibitory activity against AChE (IC50=0.08muM). Additionally, compound 9b showed obvious neuroprotective effect on SH-SY5Y by preventing copper-induced neuronal damage and potent anti-neuroinflammatory activity by inhibiting the production of inflammatory factors on BV-2cells. A molecular modeling study revealed that 9b acts as a mixed-type inhibitor that interacts simultaneously with H3R and AChE. Moreover, in vivo data revealed that compound 9b did not cause acute toxicity in mice at doses up to 1000mg/kg, and had desirable pharmacokinetic properties, as well as a good blood-brain barrier (BBB) permeability (log BB=1.24+/-0.07). Further studies demonstrated that chronic oral treatment with 9b significantly improved cognitive dysfunction in scopolamine-induced AD mice in the step-down passive avoidance test. Taken together, the present study showed that compound 9b is a promising multifunctional drug candidate for the treatment of Alzheimer's disease.
ESTHER : Wang_2019_Eur.J.Med.Chem_168_207
PubMedSearch : Wang_2019_Eur.J.Med.Chem_168_207
PubMedID: 30822710

Title : Expansion of the scaffold diversity for the development of highly selective butyrylcholinesterase (BChE) inhibitors: Discovery of new hits through the pharmacophore model generation, virtual screening and molecular dynamics simulation - Lu_2019_Bioorg.Chem_85_117
Author(s) : Lu X , Yang H , Li Q , Chen Y , Zhou Y , Feng F , Liu W , Guo Q , Sun H
Ref : Bioorg Chem , 85 :117 , 2018 || 2019
Abstract : Butyrylcholinesterase (BChE) is recently considered as a new target for the treatment of Alzheimer's disease (AD). There is an increasing interest in the development of BChE inhibitors. In the present study, a set of pharmacophore models for BChE was developed and validated. Based on the models, virtual screening was performed on five compound collections, from which seventeen potential hits were retained for biological investigation. In total, eight of these seventeen potential hits showed selective BChE inhibitory activity. Moreover, four compounds displayed IC50 values in sub-micromolar range on eqBChE and three displayed IC50 values <2muM on huBChE. The diverse scaffolds of the active compounds provided good starting point further development of selective BChE inhibitors. As far as we concerned, here we disclose the first selective pharmacophore model targeting BChE. The high rate of the model in the identification of active hits indicates it is a valuable tool for the development of selective BChE inhibitors, which may benefit the treatment of AD.
ESTHER : Lu_2019_Bioorg.Chem_85_117
PubMedSearch : Lu_2019_Bioorg.Chem_85_117
PubMedID: 30605885

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Antagonism of Transcription Factor MYC2 by EDS1\/PAD4 Complexes Bolsters Salicylic Acid Defense in Arabidopsis Effector-Triggered Immunity - Cui_2018_Mol.Plant_11_1053
Author(s) : Cui H , Qiu J , Zhou Y , Bhandari DD , Zhao C , Bautor J , Parker JE
Ref : Mol Plant , 11 :1053 , 2018
Abstract : In plant immunity, pathogen-activated intracellular nucleotide binding/leucine rich repeat (NLR) receptors mobilize disease resistance pathways, but the downstream signaling mechanisms remain obscure. Enhanced disease susceptibility 1 (EDS1) controls transcriptional reprogramming in resistance triggered by Toll-Interleukin1-Receptor domain (TIR)-family NLRs (TNLs). Transcriptional induction of the salicylic acid (SA) hormone defense sector provides one crucial barrier against biotrophic pathogens. Here, we present genetic and molecular evidence that in Arabidopsis an EDS1 complex with its partner PAD4 inhibits MYC2, a master regulator of SA-antagonizing jasmonic acid (JA) hormone pathways. In the TNL immune response, EDS1/PAD4 interference with MYC2 boosts the SA defense sector independently of EDS1-induced SA synthesis, thereby effectively blocking actions of a potent bacterial JA mimic, coronatine (COR). We show that antagonism of MYC2 occurs after COR has been sensed inside the nucleus but before or coincident with MYC2 binding to a target promoter, pANAC019. The stable interaction of PAD4 with MYC2 in planta is competed by EDS1-PAD4 complexes. However, suppression of MYC2-promoted genes requires EDS1 together with PAD4, pointing to an essential EDS1-PAD4 heterodimer activity in MYC2 inhibition. Taken together, these results uncover an immune receptor signaling circuit that intersects with hormone pathway crosstalk to reduce bacterial pathogen growth.
ESTHER : Cui_2018_Mol.Plant_11_1053
PubMedSearch : Cui_2018_Mol.Plant_11_1053
PubMedID: 29842929

Title : Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice - Chen_2018_Front.Cell.Neurosci_12_396
Author(s) : Chen H , Wu X , Gu X , Zhou Y , Ye L , Zhang K , Pan H , Wang J , Wei H , Zhu B , Naman CB , Mak SH , Carlier PR , Cui W , Han YF
Ref : Front Cell Neurosci , 12 :396 , 2018
Abstract : Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD.
ESTHER : Chen_2018_Front.Cell.Neurosci_12_396
PubMedSearch : Chen_2018_Front.Cell.Neurosci_12_396
PubMedID: 30483056

Title : Toxicological analysis of roast duck flavor components - Zhou_2018_Food.Chem.Toxicol_119_438
Author(s) : Zhou Y , Yan B , Zhao S , Zhou X , Xiao Y
Ref : Food & Chemical Toxicology , 119 :438 , 2018
Abstract : The aim of the study was to investigate toxicity of the synthesized roast duck flavor through animal experiment (mice feeding with the flavor for 35 days), and the major toxic compounds (acrylamide and 3,4-benzopyrene) were detected by high performance liquid chromatography. Compared with the control group, the blood biochemical indexes including protein content, bilirubin content, activity of alkaline phosphatase, activity of aspartate transaminase (AST) and alanine transaminase (ALT), cholesterol content, high density lipoprotein (HDL) and low density lipoprotein (LDL) content, triglycerides content, activity of creatine kinase (CK) and CK-MB, activity of cholinesterase (CHE) and lactate dehydrogenase (LDH), total bile acid (TBA) in high dose feeding group were significantly different. And body weight of mice fed by the flavor was decreased distinctly, and the heart weight was also decreased, while the liver weight was increased obviously. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and heart were significantly decreased, while methane dicarboxylic aldehyde (MDA) contents were increased evidently. Acrylamide was detected by high performance liquid-mass spectrum (HPLC-MS), and the content was 5.21 mg/kg 3,4-benzoapryene was calculated by HPLC with fluorescence detector, and the content was 21.13 mug/kg. Thus, the roast duck flavor was considered to be potential toxicity to human being.
ESTHER : Zhou_2018_Food.Chem.Toxicol_119_438
PubMedSearch : Zhou_2018_Food.Chem.Toxicol_119_438
PubMedID: 29208505

Title : Acetylcholinesterase Biosensor Based On Mesoporous Hollow Carbon Spheres\/Core-Shell Magnetic Nanoparticles-Modified Electrode for the Detection of Organophosphorus Pesticides - Luo_2018_Sensors.(Basel)_18_
Author(s) : Luo R , Feng Z , Shen G , Xiu Y , Zhou Y , Niu X , Wang H
Ref : Sensors (Basel) , 18 : , 2018
Abstract : The present study investigated the synthesis of mesoporous hollow carbon spheres (MHCS) and magnetic mesoporous hollow carbon spheres with core-shell structures (Fe(3)O(4)@MHCS). Two acetylcholinesterase sensors (acetylcholinesterase/mesoporous hollow carbon spheres/glassy carbon electrode (AChE/MHCS/GCE) and acetylcholinesterase/core-shell magnetic mesoporous hollow carbon spheres/glassy carbon electrode (AChE/Fe(3)O(4)@MHCS/GCE) based on mesoporous carbon materials were prepared. Under the optimum conditions, using Malathion as the model compound, the developed biosensors showed a wide detection range, low detection limit, good reproducibility, and high stability. The AChE/MHCS/GCE electrochemical sensor response exhibited two good linear ranges at the incubation time of 10 min at the Malathion concentration ranges of 0.01 to 100 ppb and 100 to 600 ppb, with a detection limit of 0.0148 ppb (S/N = 3). The AChE/Fe(3)O(4)@MHCS/GCE electrochemical sensor that was operated with an incubation time of 12 min at the malathion concentration ranges between 0.01(-)50 ppb and 50(-)600 ppb had a detection limit of 0.0182 ppb (S/N = 3). Moreover, the AChE/MHCS/GCE and AChE/Fe(3)O(4)@MHCS/GCE biosensors were effective for the detection of real samples, and were demonstrated to be suitable for the field-testing of organophosphorus pesticide (OP) residues.
ESTHER : Luo_2018_Sensors.(Basel)_18_
PubMedSearch : Luo_2018_Sensors.(Basel)_18_
PubMedID: 30558201

Title : Investigation of multi-target-directed ligands (MTDLs) with butyrylcholinesterase (BuChE) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition: The design, synthesis of miconazole analogues targeting Alzheimer's disease - Lu_2018_Bioorg.Med.Chem_26_1665
Author(s) : Lu X , He SY , Li Q , Yang H , Jiang X , Lin H , Chen Y , Qu W , Feng F , Bian Y , Zhou Y , Sun H
Ref : Bioorganic & Medicinal Chemistry , 26 :1665 , 2018
Abstract : In our endeavor towards the development of potent multi-target ligands for the treatment of Alzheimer's disease, miconazole was identified to show BuChE-IDO1 dual-target inhibitory effects. Morris water maze test indicated that miconazole obviously ameliorated the cognitive function impaired by scopolamine. Furthermore, it showed good safety in primary hepatotoxicity evaluation. Based on these results, we designed, synthesized, and evaluated a series of miconazole derivatives as BuChE-IDO1 dual-target inhibitors. Out of the 12 compounds, 5i and 5j exhibited the best potency in enzymatic evaluation, thus were selected for subsequent behavioral study, in which the two compounds exerted much improved effect than tacrine. Meanwhile, 5i and 5j displayed no apparent hepatotoxicity. The results suggest that miconazole analogue offers an attractive starting point for further development of new BuChE-IDO1 dual-target inhibitors against Alzheimer's disease.
ESTHER : Lu_2018_Bioorg.Med.Chem_26_1665
PubMedSearch : Lu_2018_Bioorg.Med.Chem_26_1665
PubMedID: 29475581

Title : Expression, functional analysis and mutation of a novel neutral zearalenone-degrading enzyme - Wang_2018_Int.J.Biol.Macromol_118_1284
Author(s) : Wang M , Yin L , Hu H , Selvaraj JN , Zhou Y , Zhang G
Ref : Int J Biol Macromol , 118 :1284 , 2018
Abstract : The crops and grains were often contaminated by high level of mycotoxin zearalenone (ZEN). In order to remove ZEN and keep food safe, ZEN-degrading or detoxifying enzymes are urgently needed. Here, a newly identified lactonohydrolase responsible for the detoxification of ZEN, annotated as Zhd518, was expressed and characterized. Zhd518 showed 65% amino acid identity with Zhd101, which was widely studied for its ZEN-degrading ability. A detailed activity measurement method of ZEN-degrading enzyme was provided. Biochemical analysis indicated that the purified recombinant Zhd518 from E. coli exhibited a high activity against ZEN (207.0 U/mg), with the optimal temperature and pH of 40 degreeC and 8.0, respectively. The Zhd518 can degrade ZEN derivatives, and the specific activities against alpha-Zearalenol, beta-Zearalenol, alpha-Zearalanol and beta-Zearalanol were 23.0 U/mg, 64.7 U/mg, 119.8 U/mg and 66.5 U/mg, respectively. The active sites of Zhd518 were predicted by structure modeling and determined by mutation analysis. A point mutant N156H exhibited 3.3-fold activity against alpha-Zearalenol comparing to Zhd518. Zhd518 is the first reported neutral and the second characterized ZEN-degrading enzyme, which provides a new and more excellent candidate for ZEN detoxifying in food and feed industry.
ESTHER : Wang_2018_Int.J.Biol.Macromol_118_1284
PubMedSearch : Wang_2018_Int.J.Biol.Macromol_118_1284
PubMedID: 29949749
Gene_locus related to this paper: 9euro-a0a0d2ilk1

Title : Comparative transcriptomic profiling of peripheral efferent and afferent nerve fibres at different developmental stages in mice - Wang_2018_Sci.Rep_8_11990
Author(s) : Wang H , Zhou Y , Cong M , Zhang L , Gu X , Tang X
Ref : Sci Rep , 8 :11990 , 2018
Abstract : Peripheral nerve injury impairs motor and sensory function in humans, and its functional recovery largely depends on the axonal outgrowth required for the accurate reinnervation of appropriate targets. To better understand how motor and sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray analysis was conducted to examine differential gene expression patterns in peripheral efferent and afferent fibres at different developmental stages in mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analyses revealed common and distinct features of enrichment for differentially expressed genes during motor and sensory nerve fibre development. Ingenuity Pathway Analysis (IPA) further indicated that the key differentially expressed genes were associated with trans-synaptic neurexin-neuroligin signalling components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of this study was to generate a framework of gene networks regulated during motor and sensory neuron differentiation/maturation. These data may provide new clues regarding the underlying cellular and molecular mechanisms that determine the intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our findings may thus facilitate further development of a potential intervention to manipulate the therapeutic efficiency of peripheral nerve repair in the clinic.
ESTHER : Wang_2018_Sci.Rep_8_11990
PubMedSearch : Wang_2018_Sci.Rep_8_11990
PubMedID: 30097601

Title : Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV - Jiang_2018_Emerg.Microbes.Infect_7_77
Author(s) : Jiang Y , Zhao G , Song N , Li P , Chen Y , Guo Y , Li J , Du L , Jiang S , Guo R , Sun S , Zhou Y
Ref : Emerg Microbes Infect , 7 :77 , 2018
Abstract : The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
ESTHER : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedSearch : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedID: 29691378

Title : Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes - Sun_2018_Nat.Genet_50_1289
Author(s) : Sun S , Zhou Y , Chen J , Shi J , Zhao H , Song W , Zhang M , Cui Y , Dong X , Liu H , Ma X , Jiao Y , Wang B , Wei X , Stein JC , Glaubitz JC , Lu F , Yu G , Liang C , Fengler K , Li B , Rafalski A , Schnable PS , Ware DH , Buckler ES , Lai J
Ref : Nat Genet , 50 :1289 , 2018
Abstract : Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.
ESTHER : Sun_2018_Nat.Genet_50_1289
PubMedSearch : Sun_2018_Nat.Genet_50_1289
PubMedID: 30061735
Gene_locus related to this paper: maize-a0a1d6kqc9 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a3l6d913

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract : Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.
ESTHER : Qi_2018_Org.Biomol.Chem_16_9046
PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

Title : ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data - Guo_2017_BMC.Bioinformatics_18_330
Author(s) : Guo D , Luo J , Zhou Y , Xiao H , He K , Yin C , Xu J , Li F
Ref : BMC Bioinformatics , 18 :330 , 2017
Abstract : BACKGROUND: Insecticide resistance is a substantial problem in controlling agricultural and medical pests. Detecting target site mutations is crucial to manage insecticide resistance. Though PCR-based methods have been widely used in this field, they are time-consuming and inefficient, and typically have a high false positive rate. Acetylcholinesterases (Ace) is the neural target of the widely used organophosphate (OP) and carbamate insecticides. However, there is not any software available to detect insecticide resistance associated mutations in RNA-Seq data at present.
RESULTS: A computational pipeline ACE was developed to detect resistance mutations of ace in insect RNA-Seq data. Known ace resistance mutations were collected and used as a reference. We constructed a Web server for ACE, and the standalone software in both Linux and Windows versions is available for download. ACE was used to analyse 971 RNA-Seq data from 136 studies in 7 insect pests. The mutation frequency of each RNA-Seq dataset was calculated. The results indicated that the resistance frequency was 30%-44% in an eastern Ugandan Anopheles population, thus suggesting this resistance-conferring mutation has reached high frequency in these mosquitoes in Uganda. Analyses of RNA-Seq data from the diamondback moth Plutella xylostella indicated that the G227A mutation was positively related with resistance levels to organophosphate or carbamate insecticides. The wasp Nasonia vitripennis had a low frequency of resistant reads (<5%), but the agricultural pests Chilo suppressalis and Bemisia tabaci had a high resistance frequency. All ace reads in the 30 B. tabaci RNA-Seq data were resistant reads, suggesting that insecticide resistance has spread to very high frequency in B. tabaci.
CONCLUSIONS: To the best of our knowledge, the ACE pipeline is the first tool to detect resistance mutations from RNA-Seq data, and it facilitates the full utilization of large-scale genetic data obtained by using next-generation sequencing.
ESTHER : Guo_2017_BMC.Bioinformatics_18_330
PubMedSearch : Guo_2017_BMC.Bioinformatics_18_330
PubMedID: 28693417

Title : Fatal poisoning by terbufos following occupational exposure - Liang_2017_Clin.Toxicol.(Phila)__1
Author(s) : Liang Y , Tong F , Zhang L , Li W , Huang W , Zhou Y
Ref : Clinical Toxicology (Phila) , :1 , 2017
Abstract : CONTEXT: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. CASE: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 x 10-2 mug/ml in the heart blood and 0.17 mug/g in the liver. DISCUSSIONS: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors.
CONCLUSIONS: TBF is a highly toxic OP. Inadequate regulatory control, improper environmental application, and ineffective PPE resulted in a fatal human exposure.
ESTHER : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedSearch : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedID: 28681657

Title : Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants - Tai_2017_J.Virol_91_
Author(s) : Tai W , Wang Y , Fett CA , Zhao G , Li F , Perlman S , Jiang S , Zhou Y , Du L
Ref : J Virol , 91 : , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. IMPORTANCE: MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.
ESTHER : Tai_2017_J.Virol_91_
PubMedSearch : Tai_2017_J.Virol_91_
PubMedID: 27795425

Title : Silencing of juvenile hormone epoxide hydrolase gene (Nljheh) enhances short wing formation in a macropterous strain of the brown planthopper, Nilaparvata lugens - Zhao_2017_J.Insect.Physiol_102_18
Author(s) : Zhao J , Zhou Y , Li X , Cai W , Hua H
Ref : J Insect Physiol , 102 :18 , 2017
Abstract : The rice brown planthopper, Nilaparvata lugens, is an important migratory pest in many rice planting areas of Asia. The typical wing dimorphism of N. lugens gives them flexibility to adapt to different environmental cues. As an important hormone in the insect's endocrine regulation, juvenile hormone (JH) has previously been shown to participate in the wing morph determination of N. lugens. In this paper, we investigated the possible wing morph determination roles of two JH metabolic enzymes, JH esterase (JHE) and JH epoxide hydrolase (JHEH). A 1957-bp full-length cDNA sequence encoding JHEH in N. lugens (NlJHEH) was first cloned from a hemipteran insect. Except for an uncertain transmembrane segment prediction, the deduced 454-amino-acid sequence of Nljheh has all of the conserved domains of JHEHs such as the H(147)GWP(150), Tyr293 and Tyr368 motif corresponding to the oxyanion hole and the residues Asp222, Glu398, and His425 in the catalytic triad. qRT-PCR results showed that both Nljhe and Nljheh had different expression timeframes between a predominantly brachypterous strain (BS) and a macropterous strain (MS) of N. lugens, indicating that these two enzymes may participate in wing dimorphism regulation in brown planthopper. Silencing Nljheh expression by dsRNA injection enhanced short wing formation in the macropterous strain of N. lugens, while the brachypterizing individuals were mainly females. Compared to the dsgfp injection control, silencing Nljhe had no brachypterizing effect. Our results indicated that NlJHEH plays an important role in the wing morph determination of N. lugens.
ESTHER : Zhao_2017_J.Insect.Physiol_102_18
PubMedSearch : Zhao_2017_J.Insect.Physiol_102_18
PubMedID: 28867330

Title : The sea cucumber genome provides insights into morphological evolution and visceral regeneration - Zhang_2017_PLoS.Biol_15_e2003790
Author(s) : Zhang X , Sun L , Yuan J , Sun Y , Gao Y , Zhang L , Li S , Dai H , Hamel JF , Liu C , Yu Y , Liu S , Lin W , Guo K , Jin S , Xu P , Storey KB , Huan P , Zhang T , Zhou Y , Zhang J , Lin C , Li X , Xing L , Huo D , Sun M , Wang L , Mercier A , Li F , Yang H , Xiang J
Ref : PLoS Biol , 15 :e2003790 , 2017
Abstract : Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.
ESTHER : Zhang_2017_PLoS.Biol_15_e2003790
PubMedSearch : Zhang_2017_PLoS.Biol_15_e2003790
PubMedID: 29023486
Gene_locus related to this paper: stija-a0a2g8k9s2 , stija-a0a2g8ka54 , stija-a0a2g8jd52 , stija-a0a2g8l0w8

Title : Control of secondary cell wall patterning involves xylan deacetylation by a GDSL esterase - Zhang_2017_Nat.Plants_3_17017
Author(s) : Zhang B , Zhang L , Li F , Zhang D , Liu X , Wang H , Xu Z , Chu C , Zhou Y
Ref : Nat Plants , 3 :17017 , 2017
Abstract : O-acetylation, a ubiquitous modification of cell wall polymers, has striking impacts on plant growth and biomass utilization and needs to be tightly controlled. However, the mechanisms that underpin the control of cell wall acetylation remain elusive. Here, we show a rice brittle leaf sheath1 (bs1) mutant, which contains a lesion in a Golgi-localized GDSL esterase that deacetylates the prominent hemicellulose xylan. Cell wall composition, detailed xylan structure characterization and enzyme kinetics and activity assays on acetylated sugars and xylooligosaccharides demonstrate that BS1 is an esterase that cleaves acetyl moieties from the xylan backbone at O-2 and O-3 positions of xylopyranosyl residues. BS1 thus plays an important role in the maintenance of proper acetylation level on the xylan backbone, which is crucial for secondary wall formation and patterning. Our findings outline a mechanism for how plants modulate wall acetylation and endow a plethora of uncharacterized GDSL esterases with surmisable activities.
ESTHER : Zhang_2017_Nat.Plants_3_17017
PubMedSearch : Zhang_2017_Nat.Plants_3_17017
PubMedID: 28260782

Title : Combined Oral Administration of GABA and DPP-4 Inhibitor Prevents Beta Cell Damage and Promotes Beta Cell Regeneration in Mice - Liu_2017_Front.Pharmacol_8_362
Author(s) : Liu W , Son DO , Lau HK , Zhou Y , Prud'homme GJ , Jin T , Wang Q
Ref : Front Pharmacol , 8 :362 , 2017
Abstract : gamma-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD). Male C57BL/6J mice were assigned randomly into four groups: non-treatment diabetic control, GABA, sitagliptin, or GABA plus sitagliptin. Oral drug administration was initiated 1 week before STZ injection and maintained for 6 weeks. GABA or sitagliptin administration decreased ambient blood glucose levels and improved the glucose excursion rate. This was associated with elevated plasma insulin and reduced plasma glucagon levels. Importantly, combined use of GABA and sitagliptin significantly enhanced these effects as compared with each of the monotherapies. An additive effect on reducing water consumption was also observed. Immunohistochemical analyses revealed that combined GABA and sitagliptin therapy was superior in increasing beta cell mass, associated with increased small-size islet numbers, Ki67+ and PDX-1+ beta cell counts; and reduced Tunel+ beta cell counts. Thus, beta cell proliferation was increased, whereas apoptosis was reduced. We also noticed a suppressive effect of GABA or sitagliptin on alpha cell mass, which was not significantly altered by combining the two agents. Although either GABA or sitagliptin administration delays the onset of MDSD, our study indicates that combined use of them produces superior therapeutic outcomes. This is likely due to an amelioration of beta cell proliferation and a decrease of beta cell apoptosis.
ESTHER : Liu_2017_Front.Pharmacol_8_362
PubMedSearch : Liu_2017_Front.Pharmacol_8_362
PubMedID: 28676760

Title : Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus - Zhou_2017_Sci.Adv_3_eaao4966
Author(s) : Zhou J , Li C , Zhao G , Chu H , Wang D , Yan HH , Poon VK , Wen L , Wong BH , Zhao X , Chiu MC , Yang D , Wang Y , Au-Yeung RKH , Chan IH , Sun S , Chan JF , To KK , Memish ZA , Corman VM , Drosten C , Hung IF , Zhou Y , Leung SY , Yuen KY
Ref : Sci Adv , 3 :eaao4966 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
ESTHER : Zhou_2017_Sci.Adv_3_eaao4966
PubMedSearch : Zhou_2017_Sci.Adv_3_eaao4966
PubMedID: 29152574

Title : Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients - Zhou_2017_Sci.Rep_7_44660
Author(s) : Zhou Y , Li P , Brantner A , Wang H , Shu X , Yang J , Si N , Han L , Zhao H , Bian B
Ref : Sci Rep , 7 :44660 , 2017
Abstract : Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.
ESTHER : Zhou_2017_Sci.Rep_7_44660
PubMedSearch : Zhou_2017_Sci.Rep_7_44660
PubMedID: 28304399

Title : Individual and binary mixture effects of bisphenol A and lignin-derived bisphenol in Daphnia magna under chronic exposure - Li_2017_Chemosphere_191_779
Author(s) : Li D , Chen H , Bi R , Xie H , Zhou Y , Luo Y , Xie L
Ref : Chemosphere , 191 :779 , 2017
Abstract : In recent years, many new chemicals have been synthesized from biomass with an aim for sustainable development by replacing the existing toxic chemicals with those having similar properties and applications. However, the effects of these new chemicals on aquatic organisms remain relatively unknown. In this study, the effects of bisphenol A (BPA) and lignin-derived bisphenol (LD-BP, a BPA analogue) on Daphnia magna were evaluated. The animals were exposed to BPA, LD-BP, and their binary mixture at concentrations (2-2000 mug L-1) for 21 days. The expression of various biochemical markers and the effects on growth, molting, and reproduction parameters were examined. The results showed that the weight of daphnids significantly increased after exposure to BPA, LD-BP, and the binary mixture relative to that of the control animals. The activity of superoxide dismutase was significantly inhibited by LD-BP and the binary mixture. At the highest exposure concentration of the binary mixture, the activities of acetylcholinesterase and alpha-glucosidase, fecundity, and the number of neonates per brood were significantly altered. Our results showed that the effects of BPA and LD-BP on D. magna were generally comparable, except for the effect on the weight at their environmentally relevant concentrations (e.g., <20 mug L-1). The effects on the reproduction of D. magna could be mainly due to the shift in energy redistribution under BPA and LD-BP exposures. Our results implied that exposures to both BPA and LD-BP could potentially cause deleterious effects at the population level in D. magna.
ESTHER : Li_2017_Chemosphere_191_779
PubMedSearch : Li_2017_Chemosphere_191_779
PubMedID: 29080539

Title : MERS-CoV spike protein: a key target for antivirals - Du_2017_Expert.Opin.Ther.Targets_21_131
Author(s) : Du L , Yang Y , Zhou Y , Lu L , Li F , Jiang S
Ref : Expert Opin Ther Targets , 21 :131 , 2017
Abstract : INTRODUCTION: The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.
ESTHER : Du_2017_Expert.Opin.Ther.Targets_21_131
PubMedSearch : Du_2017_Expert.Opin.Ther.Targets_21_131
PubMedID: 27936982

Title : N-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc - Wang_2017_Cancer.Lett_401_53
Author(s) : Wang Y , Zhou Y , Tao F , Chai S , Xu X , Yang Y , Xu H , Wang K
Ref : Cancer Letters , 401 :53 , 2017
Abstract : Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC. NDRG1 prevented the degradation of c-Myc through Skp2-mediated ubiquitination. NDRG1 directly interacted with Skp2, and decreased phosphorylation of Skp2 through inactivation of CDK2. Finally, we confirmed that NDRG1 was negatively correlated with survival and prognosis. Thus, our findings indicate that NDRG1 is a potential target for eradicating TICs in NSCLC.
ESTHER : Wang_2017_Cancer.Lett_401_53
PubMedSearch : Wang_2017_Cancer.Lett_401_53
PubMedID: 28456659
Gene_locus related to this paper: human-NDRG1

Title : The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism - Liu_2017_Mol.Plant_10_975
Author(s) : Liu X , Liu Y , Huang P , Ma Y , Qing Z , Tang Q , Cao H , Cheng P , Zheng Y , Yuan Z , Zhou Y , Liu J , Tang Z , Zhuo Y , Zhang Y , Yu L , Huang J , Yang P , Peng Q , Zhang J , Jiang W , Zhang Z , Lin K , Ro DK , Chen X , Xiong X , Shang Y , Huang S , Zeng J
Ref : Mol Plant , 10 :975 , 2017
Abstract : The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding (13)C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.
ESTHER : Liu_2017_Mol.Plant_10_975
PubMedSearch : Liu_2017_Mol.Plant_10_975
PubMedID: 28552780
Gene_locus related to this paper: 9magn-a0a200rdw7 , 9magn-a0a200qd12 , 9magn-a0a200pqd0 , 9magn-a0a200q3h1 , 9magn-a0a200r223 , 9magn-a0a200qv20

Title : Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine Macrophage - Dong_2017_Inflammation_40_13
Author(s) : Dong L , Zhou Y , Zhu ZQ , Liu T , Duan JX , Zhang J , Li P , Hammcok BD , Guan CX
Ref : Inflammation , 40 :13 , 2017
Abstract : Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs. LPS was intratracheally injected into mice to induce pulmonary inflammation, after TPPU treatment for 3 h. Histological examination showed TPPU treatment-alleviated LPS-induced pulmonary inflammation. TPPU decreased TREM-1 expression, but not DAP12 or MyD88 expression. Murine peritoneal macrophages were challenged with LPS in vitro. We found that TPPU reduced LPS-induced TREM-1 expression in a dose-dependent manner, but not DAP12 or MyD88 expression. TPPU also decreased downstream signal from TREM-1, reducing pro-inflammatory cytokine TNF-alpha and IL-1beta mRNA expression. Furthermore, TPPU treatment inhibited IkB degradation in vivo and in vitro. Our results indicate that the inhibition of sEH suppresses LPS-induced TREM-1 expression and inflammation via inhibiting NF-kB activation in murine macrophage.
ESTHER : Dong_2017_Inflammation_40_13
PubMedSearch : Dong_2017_Inflammation_40_13
PubMedID: 27696333

Title : Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice - Zhou_2017_Shock_47_638
Author(s) : Zhou Y , Liu T , Duan JX , Li P , Sun GY , Liu YP , Zhang J , Dong L , Lee KSS , Hammock BD , Jiang JX , Guan CX
Ref : Shock , 47 :638 , 2017
Abstract : Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1beta and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1beta and TNF-alpha, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.
ESTHER : Zhou_2017_Shock_47_638
PubMedSearch : Zhou_2017_Shock_47_638
PubMedID: 27753791

Title : A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection - Tai_2016_Virology_499_375
Author(s) : Tai W , Zhao G , Sun S , Guo Y , Wang Y , Tao X , Tseng CK , Li F , Jiang S , Du L , Zhou Y
Ref : Virology , 499 :375 , 2016
Abstract : Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
ESTHER : Tai_2016_Virology_499_375
PubMedSearch : Tai_2016_Virology_499_375
PubMedID: 27750111

Title : Drug Repositioning for Alzheimer's Disease Based on Systematic 'omics' Data Mining - Zhang_2016_PLoS.One_11_e0168812
Author(s) : Zhang M , Schmitt-Ulms G , Sato C , Xi Z , Zhang Y , Zhou Y , St George-Hyslop P , Rogaeva E
Ref : PLoS ONE , 11 :e0168812 , 2016
Abstract : Traditional drug development for Alzheimer's disease (AD) is costly, time consuming and burdened by a very low success rate. An alternative strategy is drug repositioning, redirecting existing drugs for another disease. The large amount of biological data accumulated to date warrants a comprehensive investigation to better understand AD pathogenesis and facilitate the process of anti-AD drug repositioning. Hence, we generated a list of anti-AD protein targets by analyzing the most recent publically available 'omics' data, including genomics, epigenomics, proteomics and metabolomics data. The information related to AD pathogenesis was obtained from the OMIM and PubMed databases. Drug-target data was extracted from the DrugBank and Therapeutic Target Database. We generated a list of 524 AD-related proteins, 18 of which are targets for 75 existing drugs-novel candidates for repurposing as anti-AD treatments. We developed a ranking algorithm to prioritize the anti-AD targets, which revealed CD33 and MIF as the strongest candidates with seven existing drugs. We also found 7 drugs inhibiting a known anti-AD target (acetylcholinesterase) that may be repurposed for treating the cognitive symptoms of AD. The CAD protein and 8 proteins implicated by two 'omics' approaches (ABCA7, APOE, BIN1, PICALM, CELF1, INPP5D, SPON1, and SOD3) might also be promising targets for anti-AD drug development. Our systematic 'omics' mining suggested drugs with novel anti-AD indications, including drugs modulating the immune system or reducing neuroinflammation that are particularly promising for AD intervention. Furthermore, the list of 524 AD-related proteins could be useful not only as potential anti-AD targets but also considered for AD biomarker development.
ESTHER : Zhang_2016_PLoS.One_11_e0168812
PubMedSearch : Zhang_2016_PLoS.One_11_e0168812
PubMedID: 28005991

Title : Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice - Zhou_2016_Cell.Tissue.Res_363_399
Author(s) : Zhou Y , Sun GY , Liu T , Duan JX , Zhou HF , Lee KS , Hammock BD , Fang X , Jiang JX , Guan CX
Ref : Cell Tissue Research , 363 :399 , 2016
Abstract : Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-beta1-induced alpha-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model.
ESTHER : Zhou_2016_Cell.Tissue.Res_363_399
PubMedSearch : Zhou_2016_Cell.Tissue.Res_363_399
PubMedID: 26310139

Title : Full-Length cDNA Cloning, Molecular Characterization and Differential Expression Analysis of Lysophospholipase I from Ovis aries - Liu_2016_Int.J.Mol.Sci_17_
Author(s) : Liu NN , Liu ZS , Hu P , Zhang Y , Lu SY , Li YS , Yang YJ , Zhang DS , Zhou Y , Ren HL
Ref : Int J Mol Sci , 17 : , 2016
Abstract : Lysophospholipase I (LYPLA1) is an important protein with multiple functions. In this study, the full-length cDNA of the LYPLA1 gene from Ovis aries (OaLypla1) was cloned using primers and rapid amplification of cDNA ends (RACE) technology. The full-length OaLypla1 was 2457 bp with a 5'-untranslated region (UTR) of 24 bp, a 3'-UTR of 1740 bp with a poly (A) tail, and an open reading frame (ORF) of 693 bp encoding a protein of 230 amino acid residues with a predicted molecular weight of 24,625.78 Da. Phylogenetic analysis showed that the OaLypla1 protein shared a high amino acid identity with LYPLA1 of Bos taurus. The recombinant OaLypla1 protein was expressed and purified, and its phospholipase activity was identified. Monoclonal antibodies (mAb) against OaLypla1 that bound native OaLypla1 were generated. Real-time PCR analysis revealed that OaLypla1 was constitutively expressed in the liver, spleen, lung, kidney, and white blood cells of sheep, with the highest level in the kidney. Additionally, the mRNA levels of OaLypla1 in the buffy coats of sheep challenged with virulent or avirulent Brucella strains were down-regulated compared to untreated sheep. The results suggest that OaLypla1 may have an important physiological role in the host response to bacteria. The function of OaLypla1 in the host response to bacterial infection requires further study in the future.
ESTHER : Liu_2016_Int.J.Mol.Sci_17_
PubMedSearch : Liu_2016_Int.J.Mol.Sci_17_
PubMedID: 27483239

Title : High-level expression of a ZEN-detoxifying gene by codon optimization and biobrick in Pichia pastoris - Xiang_2016_Microbiol.Res_193_48
Author(s) : Xiang L , Wang Q , Zhou Y , Yin L , Zhang G , Ma Y
Ref : Microbiol Res , 193 :48 , 2016
Abstract : The mycotoxin zearalenone (ZEN) can be degraded by a lactone hydrolase ZHD, which was derived from Gliocladium roseum. Here, based on the native ZHD encoding gene zhd101, a codon optimized zhd gene was synthesized, which was used for high expression of ZHD in Pichia pastoris GS115. Meanwhile, to further improve the expression of recombinant ZHD, the plasmids containing 1 to 4 copies of the zhd expression cassette were constructed, respectively, using the biobrick method. The protein expression in the recombinant P. pastoris X3c, which was transformed with the plasmid containing 3 copies of zhd expression cassette, was the highest. In addition, the enzymatic activity of ZHD against ZEN was defined for the first time based on a standard curve of peak area vs ZEN concentration. The ZEN degradation activity of ZHD from shake flask fermentation was calculated as 22.5U/mL with the specific activity of 4976.5U/mg. Furthermore, the high-density fermentation of P. pastoris X3c strain was also performed in 5L fermenter. The maximum enzyme activity of the supernatant was 150.1U/mL, which were 6.7-fold higher than that of the shake flask fermentation.
ESTHER : Xiang_2016_Microbiol.Res_193_48
PubMedSearch : Xiang_2016_Microbiol.Res_193_48
PubMedID: 27825486
Gene_locus related to this paper: biooc-ZHD101

Title : Immobilization of Lipase from Pseudomonas fluorescens on Porous Polyurea and Its Application in Kinetic Resolution of Racemic 1-Phenylethanol - Han_2016_ACS.Appl.Mater.Interfaces_8_25714
Author(s) : Han H , Zhou Y , Li S , Wang Y , Kong XZ
Ref : ACS Appl Mater Interfaces , 8 :25714 , 2016
Abstract : A porous polyurea (PPU) was prepared through a simple protocol by reacting toluene diisocyanate with water in binary solvent of water-acetone. Its amine group was determined through spectrophotometric absorbance based on its iminization with p-nitrobenzaldehyde amines. PPU was then used as a novel polymer support for enzyme immobilization, through activation by glutaraldehyde followed by immobilization of an enzyme, lipase from Pseudomonas fluorescens (PFL), via covalent bonding with the amine groups of lipase molecules. Influences of glutaraldehyde and enzyme concentration and pH in the process were studied. The results revealed that the activity of the immobilized PFL reached a maximum at GA concentration of 0.17 mol/L and at pH 8. Immobilization rate of 60% or higher for PFL was obtained under optimized condition with an enzyme activity of 283 U/mg. The porous structure of PPU, prior to and after GA activation and PFL immobilization, was characterized. The activity of the immobilized PFL at different temperature and pH and its stability at 40 degrees C as well as its reusability were tested. The immobilized enzyme was finally used as enantioselective catalyst in kinetic resolution of racemic 1-phenylethanol (1-PEOH), and its performance compared with the free PFL. The results demonstrate that the enzyme activity and stability were greatly improved for the immobilized PFL, and highly pure enantiomers from racemic 1-PEOH were effectively achieved using the immobilized PFL. Noticeable deactivation of PFL in the resolution was observed by acetaldehyde in situ formed. In addition, the immobilized PFL was readily recovered from the reaction system for reuse. A total of 73% of the initial activity was retained after 5 repeated reuse cycles. This work provides a novel route to preparation of a polyurea porous material and its enzyme immobilization, leading to a novel type of immobilized enzyme for efficient kinetic resolution of racemic molecules.
ESTHER : Han_2016_ACS.Appl.Mater.Interfaces_8_25714
PubMedSearch : Han_2016_ACS.Appl.Mater.Interfaces_8_25714
PubMedID: 27618157

Title : Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population - Cai_2015_BMC.Cardiovasc.Disord_15_14
Author(s) : Cai A , Li G , Chen J , Li X , Li L , Zhou Y
Ref : BMC Cardiovasc Disord , 15 :14 , 2015
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD).
METHODS: Totally 781 participants were enrolled and performed coronary angiography (CAG) to figure out the number of coronary artery stenosis. According to clinical presentation, electrocardiography, cardiac biomarker, and CAG result, participants were divided into control (excluded CAD), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) groups. Baseline characteristics were recorded. Statistical analyses were performed to evaluate the relationship between Lp-PLA2 level and CAD severity.
RESULTS: Plasma levels of Lp-PLA2 in control, SA, UA and AMI groups were 7.38(3.33-9.26) mug/L, 5.94(2.89-8.55) mug/L, 8.56(5.34-11.95) mug/L and 8.68(5.56-13.27) mug/L respectively (P < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apoprotein A (apoA) and statins, Lp-PLA2 level was still independently associated with CAD severity, with odd ratio (OR) of 1.055 (AMI group versus control group, 95% confidence interval (CI) 1.021-1.090, P < 0.05). Additionally, the relationship between Lp-PLA2 level and the number of stenosis coronary artery was also assessed. Lp-PLA2 levels in control, single-vessel, and multiple-vessels stenosis groups were 7.38(3.33-9.26) mug/L, 7.80 (4.05-10.76) mug/L and 8.29(5.18-11.76) mug/L respectively (P for trend < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, LDL-C and HDL-C, apoA and statins, Lp-PLA2 level remained independently associated with the number of coronary artery stenosis, with OR of 1.053 (multiple-vessels stenosis group versus control group, 95% CI 1.025-1.069, P < 0.05). CONCLUSION: Increased Lp-PLA2 level is independently associated with CAD severity, and Lp-PLA2 level may be used to discriminate those who are at increased risk of cardiovascular events.
ESTHER : Cai_2015_BMC.Cardiovasc.Disord_15_14
PubMedSearch : Cai_2015_BMC.Cardiovasc.Disord_15_14
PubMedID: 25879827

Title : Complete Genome Sequence of Pseudoxanthomonas suwonensis Strain J1, a Cellulose-Degrading Bacterium Isolated from Leaf- and Wood-Enriched Soil - Hou_2015_Genome.Announc_3_e00614
Author(s) : Hou L , Jiang J , Xu Z , Zhou Y , Leung FC
Ref : Genome Announc , 3 : , 2015
Abstract : We report here the complete genome sequence of the cellulose-degrading bacterium Pseudoxanthomonas suwonensis strain J1, isolated from soil enriched with rotten leaves and wood from the Zhong Mountain Scenic Area in Nanjing, China. This complete genome may contribute to further investigation of plant biomass degradation.
ESTHER : Hou_2015_Genome.Announc_3_e00614
PubMedSearch : Hou_2015_Genome.Announc_3_e00614
PubMedID: 26067962
Gene_locus related to this paper: 9gamm-a0a0e3z1c7 , 9gamm-a0a0e3z304

Title : Cholinesterase inhibitors for rarer dementias associated with neurological conditions - Li_2015_Cochrane.Database.Syst.Rev_3_CD009444
Author(s) : Li Y , Hai S , Zhou Y , Dong BR
Ref : Cochrane Database Syst Rev , 3 :CD009444 , 2015
Abstract : BACKGROUND: Rarer dementias include Huntington's disease (HD), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), frontotemporal dementia (FTD), dementia in multiple sclerosis (MS) and progressive supranuclear palsy (PSP). Cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, are considered to be the first-line medicines for Alzheimer's disease and some other dementias, such as dementia in Parkinson's disease. Cholinesterase inhibitors are hypothesised to work by inhibiting the enzyme acetylcholinesterase (AChE) which breaks down the neurotransmitter acetylcholine. Cholinesterase inhibitors may also lead to clinical improvement for rarer dementias associated with neurological conditions. OBJECTIVES: To assess the efficacy and safety of cholinesterase inhibitors for cognitive impairment or dementia associated with neurological conditions. SEARCH
METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, several trial registries and grey literature sources in August 2013. SELECTION CRITERIA: We included randomised, double-blind, controlled trials assessing the efficacy of treatment of rarer dementias associated with neurological conditions with currently marketed cholinesterase inhibitors. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials, and extracted data. We used the standard methodological procedures of the Cochrane Collaboration. MAIN
RESULTS: We included eight RCTs involving 567 participants. Six studies used a simple parallel-group design; the other two consisted of an open-label treatment period followed by a randomised phase. All trials were well concealed for allocation and double-blind, however the sample sizes of most trials were small. All trials used placebo as control. We performed meta-analyses for some outcomes in patients with MS. For all other conditions, results are presented narratively.Two trials included patients with HD; one found that cholinesterase inhibitor use in the short-term had no statistically significant impact on the cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-Cog; 1 study, WMD 1.00, 95% CI -1.66 to 3.66, P = 0.46; low quality evidence), Unified Huntington's Disease Rating Scale (UHDRS) Verbal Fluency Test (1 study, WMD -1.20, 95% CI -7.97 to 5.57, P = 0.73; low quality evidence), UHDRS Symbol Digit Modalities Test (SDMT; 1 study, WMD 2.70, 95% CI -0.95 to 6.35, P = 0.15; low quality evidence) and other psychometric tests. The other study found that cholinesterase inhibitor use in the medium-term improved the results of the verbal fluency test (1 study, WMD 6.43, 95% CI 0.66 to 12.20, P = 0.03; moderate quality evidence) and California Verbal Learning Test - Second Edition (CVLT-II) Recognition Task (1 study, WMD 2.42, 95% CI 0.17 to 4.67, P = 0.04; moderate quality evidence). There was no statistically significant difference between groups on the SDMT (1 study, WMD -0.31, 95% CI -7.77 to 7.15, P = 0.94; moderate quality evidence), CVLT-II trials 1-5 (1 study, WMD -2.09, 95% CI -11.65 to 7.47, P = 0.67; moderate quality evidence), short-delay recall (1 study, WMD 0.35, 95% CI -2.87 to 3.57, P = 0.83; moderate quality evidence), or long-delay recall (1 study, WMD -0.14, 95% CI -3.08 to 2.80, P = 0.93; moderate quality evidence), and other psychometric tests.Four trials included patients with MS; one found no differences between the cholinesterase inhibitors (short-term) and placebo groups on the Wechsler Memory Scales general memory score (1 study, WMD 0.90, 95% CI -0.52 to 2.32, P = 0.22; low quality evidence). The three other trials found that, in the medium-term - cholinesterase inhibitors improved the clinician's impression of cognitive change (2 studies, OR 1.96, 95% CI 1.06 to 3.62, P = 0.03; high quality evidence). However, the treatment effect on other aspects of cognitive change were unclear, measured by the Selective Reminding Test (3 studies, WMD 1.47, 95% CI -0.39 to 3.32, P = 0.12; high quality evidence), patient's self-reported impression of memory change (2 studies, OR 1.67, 95% CI 0.93 to 3.00, P = 0.08; high quality evidence) and cognitive change (1 study, OR 0.95, 95% CI 0.45 to 1.98, P = 0.89; high quality evidence), clinician's impression of memory change (1 study, OR 1.50, 95% CI 0.59 to 3.84, P = 0.39; moderate quality evidence), other psychometric tests, and activities of daily living - patient reported impact of multiple sclerosis activities (1 study, WMD -1.18, 95% CI -3.02 to 0.66, P = 0.21; low quality evidence).One study on patients with CADASIL found a beneficial effect of cholinesterase inhibitors on the Executive interview, and Trail Making Test parts A and B. The impact of cholinesterase inhibitors on the Vascular ADAS-Cog score (1 study, WMD 0.04, 95% CI -1.57 to 1.65, P = 0.96; high quality evidence), the Clinical Dementia Rating Scale Sum of Boxes (1 study, WMD -0.09, 95% CI -0.48 to 0.03, P = 0.65; high quality evidence) Disability Assessment for Dementia scale (1 study, WMD 0.58, 95% CI -2.72 to 3.88, P = 0.73; moderate quality evidence), and other measures was unclearOne study included patients with FTD. This trial consisted of an open-label treatment period followed by a randomised, double-blind, placebo-controlled phase. No data of primary outcomes were reported in this study.In the included studies, the most common side effect was gastrointestinal symptoms. For all conditions, compared to the treatment group, the placebo group experienced significantly less nausea (6 studies, 44/257 vs. 22/246, OR 2.10, 95% CI 1.22 to 3.62, P = 0.007; high quality evidence), diarrhoea (6 studies, 40/257 vs. 13/246, OR 3.26, 95% CI 1.72 to 6.19, P = 0.0003; moderate quality evidence) and vomiting (3 studies, 17/192 vs. 3/182, OR 5.76, 95% CI 1.67 to 19.87, P = 0.006; moderate quality evidence). AUTHORS'
CONCLUSIONS: The sample sizes of most included trials were small, and some of the results were extracted from only one study. There were no poolable data for HD, CADASIL and FTD patients and there were no results for patients with PSP. Current evidence shows that the efficacy on cognitive function and activities of daily living of cholinesterase inhibitors in people with HD, CADASIL, MS, PSP or FTD is unclear, although cholinesterase inhibitors are associated with more gastrointestinal side effects compared with placebo.
ESTHER : Li_2015_Cochrane.Database.Syst.Rev_3_CD009444
PubMedSearch : Li_2015_Cochrane.Database.Syst.Rev_3_CD009444
PubMedID: 25734590

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 : Preventive effect of Wall. ex Lindl. on activated carbon-induced constipation in mice - Wang_2015_Exp.Ther.Med_9_563
Author(s) : Wang R , Sun P , Zhou Y , Zhao X
Ref : Exp Ther Med , 9 :563 , 2015
Abstract : The aim of this study was to investigate the effects of Dendrobium candidum Wall. ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered D. candidum for 9 days. Body weight, defecation status, gastrointestinal (GI) transit and defecation times, in addition to the levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were used to evaluate the preventive effects of D. candidum on constipation. The laxative drug bisacodyl acted as a positive control. The time to the first defecation of a black stool for the normal, control, bisacodyl-treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126, 161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D. candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and 90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with D. candidum compared with those in the untreated control mice (P<0.05). These results demonstrate that D. candidum has preventive effects on constipation in mice, and a greater functional activity was observed when a higher concentration was administered.
ESTHER : Wang_2015_Exp.Ther.Med_9_563
PubMedSearch : Wang_2015_Exp.Ther.Med_9_563
PubMedID: 25574235

Title : Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases - Zhang_2015_Forensic.Sci.Med.Pathol_11_570
Author(s) : Zhang L , Ma J , Li S , Xue R , Jin M , Zhou Y
Ref : Forensic Science Med Pathol , 11 :570 , 2015
Abstract : Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 microg/ml in heart blood, 39 microg/ml in femoral vein blood, 141 microg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.
ESTHER : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedSearch : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedID: 26481789

Title : Preparation and characterization of a novel thermostable lipase from Thermomicrobium roseum - Fang_2021_Catal.Sci.Technol_11_7386
Author(s) : Fang Y , Zhou Y , Xin Y , Shi Y , Guo Z , Li Y , Gu Z , Ding Z , Shi G , Zhang L
Ref : Catal Sci Technol , 11 :7386 , 2015
Abstract : In this study, a hypothetical lipase gene from Thermomicrobium roseum DSM 5159 (GenBank: ACM04789.1) was recombinantly expressed and characterized. The TrLIP gene was inserted into two different plasmids (pTIG and pMA5 constructed by our laboratory) and further expressed in E. coli BL21 and B. subtilis W600 (TrLIPB/E), respectively. After purification, TrLipE/B showed a single band at approx. 38 kDa on 10% reducing SDS-PAGE gels. The successful expression of TrLipE/B was further confirmed by peptide map fingerprinting (PMF) analysis. For both expression systems, the target enzyme revealed marked stability over a wide temperature and pH range. In E. coli BL21, the optimal temperature and pH were 85 C and 8.5, while these were 90 C and 9 in B. subtilis W600. Additionally, the studied TrLipE/B was found to show remarkable tolerance in mixed systems constituted by water and organic solvents. Depending on the different expression systems, TrLipB has better enzymatic properties, in particular, thermostability and organic solvent tolerance. Based on the circular dichroism (CD) analysis, the corresponding helix, beta-sheet, beta-turn and random coil compositions were slightly different between TrLipE (34.8%, 11.2%, 23.4% and 30.6%) and TrLipB (35.9%, 11.1%, 23.3% and 29.7%). The thermostability of TrLipE/B was further verified with nano-DSC analysis. The melting temperature (Tm) and denaturation enthalpy (deltaH) of TrLipE were 97.51 C and 1637 KJ mol-1, 98.53 C and 1463 kJ mol-1 for TrLipB. The substrate specificity and enzymatic kinetics were analyzed as well. The studied TrLipE/B's capability to catalyze p-nitrophenol esters with different carbon chain lengths was verified. Enzymatic transesterification of immobilized TrLipB was confirmed, with a molar conversion rate of 23.32%. This research therefore provides a candidate that could be applied for biocleanser production and organic synthesis, especially under environments requiring high temperature.
ESTHER : Fang_2021_Catal.Sci.Technol_11_7386
PubMedSearch : Fang_2021_Catal.Sci.Technol_11_7386
PubMedID:

Title : Introducing a salt bridge into the lipase of Stenotrophomonas maltophilia results in a very large increase in thermal stability - Wu_2015_Biotechnol.Lett_37_403
Author(s) : Wu JP , Li M , Zhou Y , Yang LR , Xu G
Ref : Biotechnol Lett , 37 :403 , 2015
Abstract : High thermostability of enzymes is a prerequisite for their biotechnological applications. An organic solvent-tolerant and cold-active lipase, from the Stenotrophomonas maltophilia, was unstable above 40 degrees C in previous studies. To increase the enzyme stability, possible hydrogen-bond networks were simulated by the introduction of a salt bridge in a highly flexible region of the protein. Compared with the wild-type lipase, a mutant lipase (G165D and F73R) showed a >900-fold improvement in half-life at 50 degrees C, with the optimal activity-temperature increasing from 35 to 90 degrees C. Therefore, the hydrogen-bond strategy is a powerful approach for improving enzyme stability through the introduction of a salt bridge.
ESTHER : Wu_2015_Biotechnol.Lett_37_403
PubMedSearch : Wu_2015_Biotechnol.Lett_37_403
PubMedID: 25257598

Title : Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus - Zhao_2015_PLoS.One_10_e0145561
Author(s) : Zhao G , Jiang Y , Qiu H , Gao T , Zeng Y , Guo Y , Yu H , Li J , Kou Z , Du L , Tan W , Jiang S , Sun S , Zhou Y
Ref : PLoS ONE , 10 :e0145561 , 2015
Abstract : The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.
ESTHER : Zhao_2015_PLoS.One_10_e0145561
PubMedSearch : Zhao_2015_PLoS.One_10_e0145561
PubMedID: 26701103

Title : Homozygous missense mutation in the LIPH gene causing autosomal recessive hypotrichosis simplex in a Chinese patient -
Author(s) : Liu LH , Wang JW , Chen G , Chang RX , Zhou Y , Tang HY , Zhu J , Wang PG , Yang S , Zhang XJ
Ref : J Dermatol , 41 :105 , 2014
PubMedID: 24354445

Title : The adverse effects of phoxim exposure in the midgut of silkworm, Bombyx mori - Gu_2014_Chemosphere_96_33
Author(s) : Gu Z , Zhou Y , Xie Y , Li F , Ma L , Sun S , Wu Y , Wang B , Wang J , Hong F , Shen W , Li B
Ref : Chemosphere , 96 :33 , 2014
Abstract : The silkworm is an important economic insect. Poisoning of silkworms by organophosphate pesticides causes tremendous loss to the sericulture. In this study, Solexa sequencing technology was performed to profile the gene expression changes in the midgut of silkworms in response to 24h of phoxim exposure and the impact on detoxification, apoptosis and immune defense were addressed. The results showed that 254 genes displayed at least 2.0-fold changes in expression levels, with 148 genes up-regulated and 106 genes down-regulated. Cytochrome P450 played an important role in detoxification. Histopathology examination and transmission electron microscope revealed swollen mitochondria and disappearance of the cristae of mitochondria, which are the important features in insect apoptotic cells. Cytochrome C release from mitochondria into the cytoplasm was confirmed. In addition, the Toll and immune deficiency (IMD) signal pathways were all inhibited using qRT-PCR. Our results could help better understand the impact of phoxim exposure on silkworm.
ESTHER : Gu_2014_Chemosphere_96_33
PubMedSearch : Gu_2014_Chemosphere_96_33
PubMedID: 23899924

Title : The protective effects of Donepezil (DP) against cartilage matrix destruction induced by TNF-alpha - Zhang_2014_Biochem.Biophys.Res.Commun_454_115
Author(s) : Zhang D , Zhou Y
Ref : Biochemical & Biophysical Research Communications , 454 :115 , 2014
Abstract : The extracellular matrix apparatuses containing collagen and proteoglycan (aggrecan) are important factors for maintaining the integrity of cartilage. Collagen type II, the main component of total cartilage, is mainly degraded by matrix metalloproteinase13 (MMP-13), which is an important molecule responsible for joint damage in Osteoarthritis (OA). Donepezil (DP), a potent and selective acetylcholinesterase inhibitor, is a medication approved by the US Food and Drug Administration and used in the alleviation of dementia in Alzheimer's disease (AD). In this study, we found that DP treatment prevented the degradation of collagen type II induced by TNF-alpha. Mechanistically, DP treatment leads to the inhibition of the transcriptional activity of interferon response factor-1 (IRF-1), thereby prevents the induction of MMP-13. These findings suggest the potential therapeutic effects of DP in OA.
ESTHER : Zhang_2014_Biochem.Biophys.Res.Commun_454_115
PubMedSearch : Zhang_2014_Biochem.Biophys.Res.Commun_454_115
PubMedID: 25450366

Title : [Cloning of feruloyl esterase gene from Aspergillus niger h408 and high-efficient expression in Pichia pastoris] - Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
Author(s) : Zhou Y , Liu X , Chen J , Hu H , Hou Y
Ref : Wei Sheng Wu Xue Bao , 54 :876 , 2014
Abstract : OBJECTIVE: To achieve the high-efficiency expression of feruloyl estrase gene (AnfaeA) from Aspergillus niger h408 in Pichia pastoris and characterize the recombinant feruloyl esterase (FAE).
METHODS: Using gene splicing by overlap extension (SOE), we cloned AnfaeA gene from A. niger h408 and subcloned into T vector for sequencing analysis. The expression vector pPIC9K-Anfae was constructed by the ligation of the Anfae A gene into the shuttle vector pPIC9K. The plasmid pPIC9K-Anfae was linearized and then electrotransformed into P. pastoris GS115. The recombinant strain with high level of FAE activity was obtained through plate screening. Effects of pH and temperature on recombinant FAE were determined by ultraviolet (UV) methods.
RESULTS: We have successfully cloned and high-efficiently expressed the AnfaeA gene (GenBank: KF911349) from A. niger h408 in P. pastoris GS115. The sequencing result showed that the length of Anfae A was 783bp. The gene contained an Open Reading Frame encoding 260 amino acids and was similar to feruloyl esterase A from A. niger by homology analysis. The deduced amino acids contained a typical active lid and catalytic triad of lipase. The SDS-PAGE result indicated that molecular weight of the recombinant FAE was about 30 kDa and the activity of the recombinant enzyme was 24.72 U/mL. The specific activity of the recombinant FAE was 40.84 U/mg. Compared with A. niger h408, the recombinant enzyme activity increased about to 1100 times. The optimal temperature and pH for recombinant FAE was 50 degrees C and 5.0, respectively. Recombinant FAE showed nearly 80% of its maximal activity at 60 degrees C and was active in the pH range 4.0-9.0.
CONCLUSIONS: The high-efficient expression of AnfaeA gene in P. pastoris provided a prerequisite for achieving industrial application in feed and paper-making industry. In addition, the results established the experimental basis for further improvement of recombinant feruloyl esterase by directed evolution.
ESTHER : Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
PubMedSearch : Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
PubMedID: 25345018

Title : Determination of tacrine-6-ferulic acid in rat plasma by LC-MS\/MS and its application to pharmacokinetics study - Sun_2014_Biomed.Chromatogr_28_1352
Author(s) : Sun X , Zhang P , Pi R , Zhou Y , Deng X , Xie Z , Liao Q
Ref : Biomedical Chromatography , 28 :1352 , 2014
Abstract : Tacrine, as a drug for treating Alzheimer's disease (AD), has low efficacy owing to its single function and serious side effects. However, tacrine-6-ferulic acid (T6FA), the dimer which added ferulic acid to tacrine, has been found to be a promising multifunctional drug candidate for AD and much more potent and selective on acetylcholinesterase (AChE) than tacrine. The aim of the present work was to develop and validate an LC-MS/MS method with electrospray ionization for the quantification of T6FA in rat plasma using tacrine-3-ferulic acid (T3FA) as internal standard and to examine its application for pharmacokinetic study in rats. Following a single liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved at 25 degrees C on a BDS Hypersil C18 column with a mobile phase composed of 1% formic acid and methonal (30:70, v/v) at a flow rate of 0.2 mL/min. Quantification was achieved by monitoring the selected ions at m/z 474.2 --> 298.1 for T6FA and m/z 432.2 --> 199.0 for T3FA. The method was validated to be rapid, specific, accurate and precise over the concentration range of 0.5-1000.0 ng/mL in rat samples. Furthermore, it was successfully applied for the pharmacokinetic measurement of T6FA with an oral administration at 40 mg/kg to rats. Copyright (c) 2014 John Wiley & Sons, Ltd.
ESTHER : Sun_2014_Biomed.Chromatogr_28_1352
PubMedSearch : Sun_2014_Biomed.Chromatogr_28_1352
PubMedID: 24706520

Title : Plant genetics. Early allopolyploid evolution in the post-Neolithic Brassica napus oilseed genome - Chalhoub_2014_Science_345_950
Author(s) : Chalhoub B , Denoeud F , Liu S , Parkin IA , Tang H , Wang X , Chiquet J , Belcram H , Tong C , Samans B , Correa M , Da Silva C , Just J , Falentin C , Koh CS , Le Clainche I , Bernard M , Bento P , Noel B , Labadie K , Alberti A , Charles M , Arnaud D , Guo H , Daviaud C , Alamery S , Jabbari K , Zhao M , Edger PP , Chelaifa H , Tack D , Lassalle G , Mestiri I , Schnel N , Le Paslier MC , Fan G , Renault V , Bayer PE , Golicz AA , Manoli S , Lee TH , Thi VH , Chalabi S , Hu Q , Fan C , Tollenaere R , Lu Y , Battail C , Shen J , Sidebottom CH , Canaguier A , Chauveau A , Berard A , Deniot G , Guan M , Liu Z , Sun F , Lim YP , Lyons E , Town CD , Bancroft I , Meng J , Ma J , Pires JC , King GJ , Brunel D , Delourme R , Renard M , Aury JM , Adams KL , Batley J , Snowdon RJ , Tost J , Edwards D , Zhou Y , Hua W , Sharpe AG , Paterson AH , Guan C , Wincker P
Ref : Science , 345 :950 , 2014
Abstract : Oilseed rape (Brassica napus L.) was formed ~7500 years ago by hybridization between B. rapa and B. oleracea, followed by chromosome doubling, a process known as allopolyploidy. Together with more ancient polyploidizations, this conferred an aggregate 72x genome multiplication since the origin of angiosperms and high gene content. We examined the B. napus genome and the consequences of its recent duplication. The constituent An and Cn subgenomes are engaged in subtle structural, functional, and epigenetic cross-talk, with abundant homeologous exchanges. Incipient gene loss and expression divergence have begun. Selection in B. napus oilseed types has accelerated the loss of glucosinolate genes, while preserving expansion of oil biosynthesis genes. These processes provide insights into allopolyploid evolution and its relationship with crop domestication and improvement.
ESTHER : Chalhoub_2014_Science_345_950
PubMedSearch : Chalhoub_2014_Science_345_950
PubMedID: 25146293
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brana-a0a078evd3 , brana-a0a078j4f0 , brana-a0a078cta5 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078iyl8 , brana-a0a078dfa9 , brana-a0a078ic91 , brana-a0a078cnf7 , brana-a0a078fh41 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078h0h8 , brana-a0a078jx23 , brana-a0a078ci96 , brana-a0a078cqd7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078ild2 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , braol-a0a0d3ef55 , brarp-m4dcj8 , brana-a0a078fw53 , brana-a0a078itf3 , brana-a0a078jsn1 , brana-a0a078jrt9 , brana-a0a078i6d2 , brana-a0a078jku0 , brana-a0a078fss7 , brana-a0a078i1l0 , brana-a0a078i402

Title : The genome of the hydatid tapeworm Echinococcus granulosus - Zheng_2013_Nat.Genet_45_1168
Author(s) : Zheng H , Zhang W , Zhang L , Zhang Z , Li J , Lu G , Zhu Y , Wang Y , Huang Y , Liu J , Kang H , Chen J , Wang L , Chen A , Yu S , Gao Z , Jin L , Gu W , Wang Z , Zhao L , Shi B , Wen H , Lin R , Jones MK , Brejova B , Vinar T , Zhao G , McManus DP , Chen Z , Zhou Y , Wang S
Ref : Nat Genet , 45 :1168 , 2013
Abstract : Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
ESTHER : Zheng_2013_Nat.Genet_45_1168
PubMedSearch : Zheng_2013_Nat.Genet_45_1168
PubMedID: 24013640
Gene_locus related to this paper: echgr-k4epc5 , echmu-u6hbw4 , echgr-w6ugl0 , echgr-w6u7y4 , echgr-w6vaq5 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , echgr-a0a068wl60

Title : The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes - Swart_2013_PLoS.Biol_11_e1001473
Author(s) : Swart EC , Bracht JR , Magrini V , Minx P , Chen X , Zhou Y , Khurana JS , Goldman AD , Nowacki M , Schotanus K , Jung S , Fulton RS , Ly A , McGrath S , Haub K , Wiggins JL , Storton D , Matese JC , Parsons L , Chang WJ , Bowen MS , Stover NA , Jones TA , Eddy SR , Herrick GA , Doak TG , Wilson RK , Mardis ER , Landweber LF
Ref : PLoS Biol , 11 :e1001473 , 2013
Abstract : The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction ( approximately 5%) of its precursor "silent" germline micronuclear genome by a process of "unscrambling" and fragmentation. The tiny macronuclear "nanochromosomes" typically encode single, protein-coding genes (a small portion, 10%, encode 2-8 genes), have minimal noncoding regions, and are differentially amplified to an average of approximately 2,000 copies. We report the high-quality genome assembly of approximately 16,000 complete nanochromosomes ( approximately 50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean approximately 3.2 kb) and encode approximately 18,500 genes. Alternative DNA fragmentation processes approximately 10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is approximately 4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease.
ESTHER : Swart_2013_PLoS.Biol_11_e1001473
PubMedSearch : Swart_2013_PLoS.Biol_11_e1001473
PubMedID: 23382650
Gene_locus related to this paper: 9spit-j9j7j1 , 9spit-j9hp22 , 9spit-j9ivu0

Title : Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development - Du_2013_J.Virol_87_9939
Author(s) : Du L , Zhao G , Kou Z , Ma C , Sun S , Poon VK , Lu L , Wang L , Debnath AK , Zheng BJ , Zhou Y , Jiang S
Ref : J Virol , 87 :9939 , 2013
Abstract : A novel human Middle East respiratory syndrome coronavirus (MERS-CoV) caused outbreaks of severe acute respiratory syndrome (SARS)-like illness with a high mortality rate, raising concerns of its pandemic potential. Dipeptidyl peptidase-4 (DPP4) was recently identified as its receptor. Here we showed that residues 377 to 662 in the S protein of MERS-CoV specifically bound to DPP4-expressing cells and soluble DPP4 protein and induced significant neutralizing antibody responses, suggesting that this region contains the receptor-binding domain (RBD), which has a potential to be developed as a MERS-CoV vaccine.
ESTHER : Du_2013_J.Virol_87_9939
PubMedSearch : Du_2013_J.Virol_87_9939
PubMedID: 23824801

Title : Identification of selective and potent inhibitors of fibroblast activation protein and prolyl oligopeptidase - Poplawski_2013_J.Med.Chem_56_3467
Author(s) : Poplawski SE , Lai JH , Li Y , Jin Z , Liu Y , Wu W , Wu Y , Zhou Y , Sudmeier JL , Sanford DG , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 56 :3467 , 2013
Abstract : Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for FAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-d-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets.
ESTHER : Poplawski_2013_J.Med.Chem_56_3467
PubMedSearch : Poplawski_2013_J.Med.Chem_56_3467
PubMedID: 23594271

Title : The assessment of environmental pollution along the coast of Beibu Gulf, northern South China Sea: an integrated biomarker approach in the clam Meretrix meretrix - Meng_2013_Mar.Environ.Res_85_64
Author(s) : Meng F , Wang Z , Cheng F , Du X , Fu W , Wang Q , Yi X , Li Y , Zhou Y
Ref : Mar Environ Research , 85 :64 , 2013
Abstract : The clam Meretrix meretrix was used as a biomonitor to implement an environmental monitoring program along the coast of Beibu Gulf in October 2011. This program not only analyzed biomarkers including acetylcholinesterase, glutathione peroxidase, glutathione S-transferase, catalase and superoxide dismutase activities, total glutathione content and lipid peroxidation level in M. meretrix but also adopted a multi-biomarker approach - integrated biomarker response (IBR) to assess the environmental quality in this ecosystem. In addition, the metal (Hg, As, Cu, Pb, Zn, Cd and Cr) and polychlorinated biphenyls (PCBs) content in the surface sediment at the study area were also measured. The results showed that IBR index was able to distinguish a space trend between sampling sites with different degrees of anthropogenic environmental stress. Integrated contamination degree were displayed in the form of star plots and compared to IBR plots. There was a visual consistency between the pollution level and IBR variation. Based on the results, it was proved that the IBR method coupled with chemical analysis was quite useful for the assessment of environmental pollution in the coastal system.
ESTHER : Meng_2013_Mar.Environ.Res_85_64
PubMedSearch : Meng_2013_Mar.Environ.Res_85_64
PubMedID: 23422511

Title : An open-label, nonplacebo-controlled study on Cistanche tubulosa glycoside capsules (Memoregain((R))) for treating moderate Alzheimer's Disease - Guo_2013_Am.J.Alzheimers.Dis.Other.Demen_28_363
Author(s) : Guo Q , Zhou Y , Wang CJ , Huang YM , Lee YT , Su MH , Lu J
Ref : Am J Alzheimers Dis Other Demen , 28 :363 , 2013
Abstract : AIM: Efficacy and safety of Cistanche tubulosa glycoside capsules (CTG capsule, Memoregain((R))) for treating Alzheimer's disease (AD) were studied.
METHODS: A total of 18 patients with AD administered with Memoregain((R)) for 48 weeks were assessed for drug efficacy by Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADLs), Blessed Behavioral Scale, and Clinical Global Impression (CGI) scales.
RESULTS: The MMSE score was 14.78 +/- 2.51 at baseline and 14.06 +/- 4.26 at study completion. While changes in ADAS-cog score before and after 48 weeks of treatment were statistically insignificant, the score improved, deteriorated, and remained unchanged in 10, 7, and 1 patients, respectively. The ADL and CGI scores showed no significant difference from baseline. All adverse reactions were mild. CONCLUSION: After Memoregain((R)) treatment, patients with AD showed no obvious aggravation of cognitive function, independent living ability, and overall conditions but were stable throughout the study. Comparison with other long-term medications with acetylcholinesterase inhibitors suggests that Memoregain((R)) has a potential to be a possible treatment option for mild to moderate AD. Large trials with bigger population are required to confirm.
ESTHER : Guo_2013_Am.J.Alzheimers.Dis.Other.Demen_28_363
PubMedSearch : Guo_2013_Am.J.Alzheimers.Dis.Other.Demen_28_363
PubMedID: 23687177

Title : A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines - Du_2013_PLoS.One_8_e81587
Author(s) : Du L , Kou Z , Ma C , Tao X , Wang L , Zhao G , Chen Y , Yu F , Tseng CT , Zhou Y , Jiang S
Ref : PLoS ONE , 8 :e81587 , 2013
Abstract : An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
ESTHER : Du_2013_PLoS.One_8_e81587
PubMedSearch : Du_2013_PLoS.One_8_e81587
PubMedID: 24324708

Title : The zebrafish reference genome sequence and its relationship to the human genome - Howe_2013_Nature_496_498
Author(s) : Howe K , Clark MD , Torroja CF , Torrance J , Berthelot C , Muffato M , Collins JE , Humphray S , McLaren K , Matthews L , Mclaren S , Sealy I , Caccamo M , Churcher C , Scott C , Barrett JC , Koch R , Rauch GJ , White S , Chow W , Kilian B , Quintais LT , Guerra-Assuncao JA , Zhou Y , Gu Y , Yen J , Vogel JH , Eyre T , Redmond S , Banerjee R , Chi J , Fu B , Langley E , Maguire SF , Laird GK , Lloyd D , Kenyon E , Donaldson S , Sehra H , Almeida-King J , Loveland J , Trevanion S , Jones M , Quail M , Willey D , Hunt A , Burton J , Sims S , McLay K , Plumb B , Davis J , Clee C , Oliver K , Clark R , Riddle C , Elliot D , Threadgold G , Harden G , Ware D , Begum S , Mortimore B , Kerry G , Heath P , Phillimore B , Tracey A , Corby N , Dunn M , Johnson C , Wood J , Clark S , Pelan S , Griffiths G , Smith M , Glithero R , Howden P , Barker N , Lloyd C , Stevens C , Harley J , Holt K , Panagiotidis G , Lovell J , Beasley H , Henderson C , Gordon D , Auger K , Wright D , Collins J , Raisen C , Dyer L , Leung K , Robertson L , Ambridge K , Leongamornlert D , McGuire S , Gilderthorp R , Griffiths C , Manthravadi D , Nichol S , Barker G , Whitehead S , Kay M , Brown J , Murnane C , Gray E , Humphries M , Sycamore N , Barker D , Saunders D , Wallis J , Babbage A , Hammond S , Mashreghi-Mohammadi M , Barr L , Martin S , Wray P , Ellington A , Matthews N , Ellwood M , Woodmansey R , Clark G , Cooper J , Tromans A , Grafham D , Skuce C , Pandian R , Andrews R , Harrison E , Kimberley A , Garnett J , Fosker N , Hall R , Garner P , Kelly D , Bird C , Palmer S , Gehring I , Berger A , Dooley CM , Ersan-Urun Z , Eser C , Geiger H , Geisler M , Karotki L , Kirn A , Konantz J , Konantz M , Oberlander M , Rudolph-Geiger S , Teucke M , Lanz C , Raddatz G , Osoegawa K , Zhu B , Rapp A , Widaa S , Langford C , Yang F , Schuster SC , Carter NP , Harrow J , Ning Z , Herrero J , Searle SM , Enright A , Geisler R , Plasterk RH , Lee C , Westerfield M , de Jong PJ , Zon LI , Postlethwait JH , Nusslein-Volhard C , Hubbard TJ , Roest Crollius H , Rogers J , Stemple DL
Ref : Nature , 496 :498 , 2013
Abstract : Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
ESTHER : Howe_2013_Nature_496_498
PubMedSearch : Howe_2013_Nature_496_498
PubMedID: 23594743
Gene_locus related to this paper: danre-1neur , danre-ABHD10b , danre-a9jrf7 , danre-d2x2g3 , danre-e7ezq9 , danre-e7ff77 , danre-ndr3 , danre-nlgn4a , danre-q1mti5 , danre-q6nyz4 , danre-q6p2u2 , danre-q7t359 , danre-q08c93 , danre-A2BGU9 , danre-f1q676 , danre-e7f0z8 , danre-e7ez27 , danre-e7f2w1 , danre-f1qid7 , danre-a0a0g2kru2 , danre-f1qla7 , danre-a9jr90 , danre-e7f070 , danre-f172a , danre-e7fb35 , danre-a7mbu9 , danre-f1qtr2

Title : Biophysical influence of isocarbophos on bovine serum albumin: spectroscopic probing - Zhang_2012_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_92_283
Author(s) : Zhang HX , Zhou Y , Liu E
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 92 :283 , 2012
Abstract : Isocarbophos (ICP) is a phosphorous pesticide with high toxicity. It has been detected in several kinds of food and therefore can enter human body. In this paper, spectroscopic approaches including three-dimensional fluorescence (3D-FL) spectroscopy, UV-visible absorption spectroscopy and circular dichroism (CD) spectroscopy were employed to explore the binding of ICP to bovine serum albumin (BSA) at simulated physiological conditions. It was found that the fluorescence quenching of BSA was caused by the formation of ICP-BSA complex at ground state and belonged to static quenching mechanism. The binding constants, the number of binding sites, enthalpy change (DeltaH(theta)), Gibbs free energy change (DeltaG(theta)) and entropy change (DeltaS(theta)) were calculated at four different temperatures according to Scatchard model and thermodynamic equations. To identify the binding location, fluorescence probe techniques were used. The results showed that warfarin, an acknowledged site marker for BSA, could be partially replaced by ICP when ICP was added to warfarin-BSA systems, which demonstrated that ICP primarily bound on Sudlow's site I in domain IIA of BSA molecule. The distance r (3.06 nm) between donor (Trp-212) and acceptor (ICP) was obtained based on Forster's non-radiation fluorescence resonance energy transfer (FRET) theory. Furthermore, the CD spectral results indicated that the secondary structure of BSA was changed in presence of ICP. The study is helpful to evaluating the toxicology of ICP and understanding its effects on the function of protein during the blood transportation process.
ESTHER : Zhang_2012_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_92_283
PubMedSearch : Zhang_2012_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_92_283
PubMedID: 22446777

Title : Lipase-mediated synthesis of water-soluble plant stanol derivatives in tert-butanol - He_2012_Bioresour.Technol_114_1
Author(s) : He WS , Li JJ , Pan XX , Zhou Y , Jia CS , Zhang XM , Feng B
Ref : Bioresour Technol , 114 :1 , 2012
Abstract : The effects of solvents with different log P values, and of lipases on the synthesis of water-soluble plant stanol derivatives were investigated. Results showed that conversion in solvents with log P<0.37 was mainly controlled by the hydrophobicity of the solvent and subsequent complete or partial deactivation of the enzyme. The solubility of substrate was the leading factor for the conversion in solvents with log P>0.37. Lipozyme RM IM and tert-butanol was the most suitable biocatalyst and solvent, respectively. The highest yield (>51%) of plant stanyl sorbitol succinate was obtained under the selected conditions: 50 mol/mL plant stanyl hemisuccinate, 1:3 molar ratio of plant stanyl hemisuccinate to d-sorbitol, 80 mg/mL 3 molecular sieves and 100mg/mL Lipozyme RM IM in tert-butanol, 150 r/min and 55 degreeC. Fourier transform infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy were adopted to determine the structure of product, suggesting that water-soluble plant stanol derivatives were successfully synthesized.
ESTHER : He_2012_Bioresour.Technol_114_1
PubMedSearch : He_2012_Bioresour.Technol_114_1
PubMedID: 22464062

Title : Sequencing the genome of Marssonina brunnea reveals fungus-poplar co-evolution - Zhu_2012_BMC.Genomics_13_382
Author(s) : Zhu S , Cao YZ , Jiang C , Tan BY , Wang Z , Feng S , Zhang L , Su XH , Brejova B , Vinar T , Xu M , Wang MX , Zhang SG , Huang MR , Wu R , Zhou Y
Ref : BMC Genomics , 13 :382 , 2012
Abstract : BACKGROUND: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf spot that devastates poplar plantations by defoliating susceptible trees before normal fall leaf drop.
RESULTS: We sequence the genome of M. brunnea with a size of 52 Mb assembled into 89 scaffolds, representing the first sequenced Dermateaceae genome. By inoculating this fungus onto a poplar hybrid clone, we investigate how M. brunnea interacts and co-evolves with its host to colonize poplar leaves. While a handful of virulence genes in M. brunnea, mostly from the LysM family, are detected to up-regulate during infection, the poplar down-regulates its resistance genes, such as nucleotide binding site domains and leucine rich repeats, in response to infection. From 10,027 predicted proteins of M. brunnea in a comparison with those from poplar, we identify four poplar transferases that stimulate the host to resist M. brunnea. These transferas-encoding genes may have driven the co-evolution of M. brunnea and Populus during the process of infection and anti-infection.
CONCLUSIONS: Our results from the draft sequence of the M. brunnea genome provide evidence for genome-genome interactions that play an important role in poplar-pathogen co-evolution. This knowledge could help to design effective strategies for controlling Marssonina leaf spot in poplar.
ESTHER : Zhu_2012_BMC.Genomics_13_382
PubMedSearch : Zhu_2012_BMC.Genomics_13_382
PubMedID: 22876864
Gene_locus related to this paper: marbu-k1wj37 , marbu-k1xt94 , marbu-k1wdc0 , marbu-k1wht2 , marbu-k1wj82 , marbu-k1wkk6 , marbu-k1wnk8 , marbu-k1wpc4 , marbu-k1wrg1 , marbu-k1wsf4 , marbu-k1wtx1 , marbu-k1x087 , marbu-k1x383 , marbu-k1x3g3 , marbu-k1x464 , marbu-k1x8c9 , marbu-k1xi08 , marbu-k1xzh8 , marbu-k1y283 , marbu-k1x918 , marbu-k1wzc0 , marbu-k1xu92 , marbu-k1xws5 , marbu-k1wxv8

Title : 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities - Wu_2012_Bioorg.Med.Chem.Lett_22_5536
Author(s) : Wu W , Liu Y , Milo LJ, Jr. , Shu Y , Zhao P , Li Y , Woznica I , Yu G , Sanford DG , Zhou Y , Poplawski SE , Connolly BA , Sudmeier JL , Bachovchin WW , Lai JH
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :5536 , 2012
Abstract : The boroProline-based dipeptidyl boronic acids were among the first DPP-IV inhibitors identified, and remain the most potent known. We introduced various substitutions at the 4-position of the boroProline ring regioselectively and stereoselectively, and incorporated these aminoboronic acids into a series of 4-substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg-(4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8 and DPP9.
ESTHER : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedSearch : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedID: 22853995

Title : Complete genome sequence of Riemerella anatipestifer reference strain - Wang_2012_J.Bacteriol_194_3270
Author(s) : Wang X , Zhu D , Wang M , Cheng A , Jia R , Zhou Y , Chen Z , Luo Q , Liu F , Wang Y , Chen XY
Ref : Journal of Bacteriology , 194 :3270 , 2012
Abstract : Riemerella anatipestifer is an infectious pathogen causing serositis in ducks. We had the genome of the R. anatipestifer reference strain ATCC 11845 sequenced. The completed draft genome consists of one circular chromosome with 2,164,087 bp. There are 2,101 genes in the draft, and its GC content is 35.01%.
ESTHER : Wang_2012_J.Bacteriol_194_3270
PubMedSearch : Wang_2012_J.Bacteriol_194_3270
PubMedID: 22628503

Title : Evolution of Burkholderia pseudomallei in recurrent melioidosis - Hayden_2012_PLoS.One_7_e36507
Author(s) : Hayden HS , Lim R , Brittnacher MJ , Sims EH , Ramage ER , Fong C , Wu Z , Crist E , Chang J , Zhou Y , Radey M , Rohmer L , Haugen E , Gillett W , Wuthiekanun V , Peacock SJ , Kaul R , Miller SI , Manoil C , Jacobs MA
Ref : PLoS ONE , 7 :e36507 , 2012
Abstract : Burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable of causing severe acute infection with overwhelming septicemia leading to death. A high rate of recurrent disease occurs in adult patients, most often due to recrudescence of the initial infecting strain. Pathogen persistence and evolution during such relapsing infections are not well understood. Bacterial cells present in the primary inoculum and in late infections may differ greatly, as has been observed in chronic disease, or they may be genetically similar. To test these alternative models, we conducted whole-genome comparisons of clonal primary and relapse B. pseudomallei isolates recovered six months to six years apart from four adult Thai patients. We found differences within each of the four pairs, and some, including a 330 Kb deletion, affected substantial portions of the genome. Many of the changes were associated with increased antibiotic resistance. We also found evidence of positive selection for deleterious mutations in a TetR family transcriptional regulator from a set of 107 additional B. pseudomallei strains. As part of the study, we sequenced to base-pair accuracy the genome of B. pseudomallei strain 1026b, the model used for genetic studies of B. pseudomallei pathogenesis and antibiotic resistance. Our findings provide new insights into pathogen evolution during long-term infections and have important implications for the development of intervention strategies to combat recurrent melioidosis.
ESTHER : Hayden_2012_PLoS.One_7_e36507
PubMedSearch : Hayden_2012_PLoS.One_7_e36507
PubMedID: 22615773
Gene_locus related to this paper: burma-a5tq93 , burma-q62mq7

Title : High-Throughput Immunomagnetic Scavenging Technique for Quantitative Analysis of Live VX Nerve Agent in Water, Hamburger, and Soil Matrixes - Knaack_2012_Anal.Chem_84_10052
Author(s) : Knaack JS , Zhou Y , Abney CW , Prezioso SM , Magnuson M , Evans R , Jakubowski EM , Hardy K , Johnson RC
Ref : Analytical Chemistry , 84 :10052 , 2012
Abstract : We have developed a novel immunomagnetic scavenging technique for extracting cholinesterase inhibitors from aqueous matrixes using biological targeting and antibody-based extraction. The technique was characterized using the organophosphorus nerve agent VX. The limit of detection for VX in high-performance liquid chromatography (HPLC)-grade water, defined as the lowest calibrator concentration, was 25 pg/mL in a small, 500 muL sample. The method was characterized over the course of 22 sample sets containing calibrators, blanks, and quality control samples. Method precision, expressed as the mean relative standard deviation, was less than 9.2\% for all calibrators. Quality control sample accuracy was 102\% and 100\% of the mean for VX spiked into HPLC-grade water at concentrations of 2.0 and 0.25 ng/mL, respectively. This method successfully was applied to aqueous extracts from soil, hamburger, and finished tap water spiked with VX. Recovery was 65%, 81%, and 100% from these matrixes, respectively. Biologically based extractions of organophosphorus compounds represent a new technique for sample extraction that provides an increase in extraction specificity and sensitivity.
ESTHER : Knaack_2012_Anal.Chem_84_10052
PubMedSearch : Knaack_2012_Anal.Chem_84_10052
PubMedID: 23126363

Title : A high-throughput diagnostic method for measuring human exposure to organophosphorus nerve agents - Knaack_2012_Anal.Chem_84_9470
Author(s) : Knaack JS , Zhou Y , Abney CW , Jacob JT , Prezioso SM , Hardy K , Lemire SW , Thomas J , Johnson RC
Ref : Analytical Chemistry , 84 :9470 , 2012
Abstract : An automated high-throughput immunomagnetic separation (IMS) method for diagnosing exposure to the organophosphorus nerve agents (OPNAs) sarin (GB), cyclohexylsarin (GF), VX, and Russian VX (RVX) was developed to increase sample processing capacity for emergency response applications. Diagnosis of exposure to OPNAs was based on the formation of OPNA adducts to butyrylcholinesterase (BCHE). Data reported with this method represent a ratio of the agent-specific BCHE adduct concentration, relative to the total BCHE peptide concentration that provides a nonactivity measurement expressed as percent adducted. All magnetic bead transfer steps and washes were performed using instrumentation in a 96-well format allowing for simultaneous extraction of 86 clinical samples plus reference materials. Automating extractions increased sample throughput 50-fold, as compared to a previously reported manual method. The limits of detection, determined using synthetic peptides, were 1 ng/mL for unadducted BCHE and GB-, GF-, VX-, and RVX-adducted BCHE. The automated method was characterized using unexposed serum and serum pools exposed to GB, GF, VX, or RVX. Variation for the measurement of percent adducted was <12% for all characterized quality control serum pools. Twenty-six (26) serum samples from individuals asymptomatic for cholinesterase inhibitor exposure were analyzed using this method, and no background levels of OPNA exposure were observed. Unexposed BCHE serum concentrations measured using this method ranged from 2.8 mug/mL to 10.6 mug/mL, with an average concentration of 6.4 mug/mL.
ESTHER : Knaack_2012_Anal.Chem_84_9470
PubMedSearch : Knaack_2012_Anal.Chem_84_9470
PubMedID: 23083472

Title : Genome sequencing reveals unique mutations in characteristic metabolic pathways and the transfer of virulence genes between V. mimicus and V. cholerae - Wang_2011_PLoS.One_6_e21299
Author(s) : Wang D , Wang H , Zhou Y , Zhang Q , Zhang F , Du P , Wang S , Chen C , Kan B
Ref : PLoS ONE , 6 :e21299 , 2011
Abstract : Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes.
ESTHER : Wang_2011_PLoS.One_6_e21299
PubMedSearch : Wang_2011_PLoS.One_6_e21299
PubMedID: 21731695
Gene_locus related to this paper: vibmi-d0gt41 , vibmi-u4zh77 , vibmi-g0sil5

Title : Highly-sensitive organophosphorous pesticide biosensors based on nanostructured films of acetylcholinesterase and CdTe quantum dots - Zheng_2011_Biosens.Bioelectron_26_3081
Author(s) : Zheng Z , Zhou Y , Li X , Liu S , Tang Z
Ref : Biosensors & Bioelectronics , 26 :3081 , 2011
Abstract : The optical transducer of CdTe semiconductor quantum dots (QDs) has been integrated with acetylcholinesterase enzyme (AChE) by the layer-by-layer (LbL) assembly technique, resulting in a highly sensitive biosensor for detection of organophosphorus pesticides (OPs) in vegetables and fruits based on enzyme inhibition mechanism. The detection limits of the proposed biosensors are as low as 1.05 x 10(-11) M for paraoxon and 4.47 x 10(-12) M for parathion, which are significantly better than those of the conventional GC/MS methods or amperometric biosensors (0.5 nM). These biosensors are used for quick determination of low concentrations of OPs in real vegetable and fruit samples and exhibit satisfactory reproducibility and accuracy. Moreover, the stock stability of the biosensors are very good due to the stabilizing environment for the enzyme in the nanostructures made by LbL technique. Many advantages provided by these biosensors, like fluorescent change recognized by naked eyes and mass production with low cost, will facilitate future development of rapid and high-throughput screening of OPs.
ESTHER : Zheng_2011_Biosens.Bioelectron_26_3081
PubMedSearch : Zheng_2011_Biosens.Bioelectron_26_3081
PubMedID: 21196108

Title : Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine - Zheng_2011_Genome.Biol_12_R116
Author(s) : Zheng P , Xia Y , Xiao G , Xiong C , Hu X , Zhang S , Zheng H , Huang Y , Zhou Y , Wang S , Zhao GP , Liu X , St Leger RJ , Wang C
Ref : Genome Biol , 12 :R116 , 2011
Abstract : BACKGROUND: Species in the ascomycete fungal genus Cordyceps have been proposed to be the teleomorphs of Metarhizium species. The latter have been widely used as insect biocontrol agents. Cordyceps species are highly prized for use in traditional Chinese medicines, but the genes responsible for biosynthesis of bioactive components, insect pathogenicity and the control of sexuality and fruiting have not been determined.
RESULTS: Here, we report the genome sequence of the type species Cordyceps militaris. Phylogenomic analysis suggests that different species in the Cordyceps/Metarhizium genera have evolved into insect pathogens independently of each other, and that their similar large secretomes and gene family expansions are due to convergent evolution. However, relative to other fungi, including Metarhizium spp., many protein families are reduced in C. militaris, which suggests a more restricted ecology. Consistent with its long track record of safe usage as a medicine, the Cordyceps genome does not contain genes for known human mycotoxins. We establish that C. militaris is sexually heterothallic but, very unusually, fruiting can occur without an opposite mating-type partner. Transcriptional profiling indicates that fruiting involves induction of the Zn2Cys6-type transcription factors and MAPK pathway; unlike other fungi, however, the PKA pathway is not activated.
CONCLUSIONS: The data offer a better understanding of Cordyceps biology and will facilitate the exploitation of medicinal compounds produced by the fungus.
ESTHER : Zheng_2011_Genome.Biol_12_R116
PubMedSearch : Zheng_2011_Genome.Biol_12_R116
PubMedID: 22112802
Gene_locus related to this paper: cormm-g3jhe4 , cormm-g3j5w5 , cormm-g3jjs8 , cormm-g3jj84 , cormm-g3j580 , cormm-g3jkl0 , cormi-a0a2h4sj63 , cormm-g3jpf2

Title : Serine protease acylation proceeds with a subtle re-orientation of the histidine ring at the tetrahedral intermediate - Zhou_2011_Chem.Commun.(Camb)_47_1577
Author(s) : Zhou Y , Zhang Y
Ref : Chem Commun (Camb) , 47 :1577 , 2011
Abstract : The acylation mechanism of a prototypical serine protease trypsin and its complete free energy reaction profile have been determined by Born-Oppenheimer ab initio QM/MM molecular dynamics simulations with umbrella sampling.
ESTHER : Zhou_2011_Chem.Commun.(Camb)_47_1577
PubMedSearch : Zhou_2011_Chem.Commun.(Camb)_47_1577
PubMedID: 21116528

Title : Inhibition or deletion of soluble epoxide hydrolase prevents hyperglycemia, promotes insulin secretion, and reduces islet apoptosis - Luo_2010_J.Pharmacol.Exp.Ther_334_430
Author(s) : Luo P , Chang HH , Zhou Y , Zhang S , Hwang SH , Morisseau C , Wang CY , Inscho EW , Hammock BD , Wang MH
Ref : Journal of Pharmacology & Experimental Therapeutics , 334 :430 , 2010
Abstract : Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of endogenous inflammatory and antiapoptotic mediators. However, the roles of sEH in diabetes and the pancreas are unknown. Our aims were to determine whether sEH is involved in the regulation of hyperglycemia in diabetic mice and to investigate the reasons for the regulation of insulin secretion by sEH deletion or inhibition in islets. We used two separate approaches, targeted disruption of Ephx2 gene [sEH knockout (KO)] and a selective inhibitor of sEH [trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB)], to assess the role of sEH in glucose and insulin homeostasis in streptozotocin (STZ) mice. We also examined the effects of sEH KO or t-AUCB on glucose-stimulated insulin secretion (GSIS) and intracellular calcium levels in islets. Hyperglycemia in STZ mice was prevented by both sEH KO and t-AUCB. In addition, STZ mice with sEH KO had improved glucose tolerance. More important, when insulin levels were assessed by hyperglycemic clamp study, sEH KO was found to promote insulin secretion. In addition, sEH KO and t-AUCB treatment augmented islet GSIS. Islets with sEH KO had a greater intracellular calcium influx when challenged with high glucose or KCl in the presence of diazoxide. Moreover, sEH KO reduced islet cell apoptosis in STZ mice. These results show not only that sEH KO and its inhibition prevent hyperglycemia in diabetes, but also that sEH KO enhances islet GSIS through the amplifying pathway and decreases islet cell apoptosis in diabetes.
ESTHER : Luo_2010_J.Pharmacol.Exp.Ther_334_430
PubMedSearch : Luo_2010_J.Pharmacol.Exp.Ther_334_430
PubMedID: 20439437

Title : Catalytic reaction mechanism of acetylcholinesterase determined by Born-Oppenheimer ab initio QM\/MM molecular dynamics simulations - Zhou_2010_J.Phys.Chem.B_114_8817
Author(s) : Zhou Y , Wang S , Zhang Y
Ref : J Phys Chem B , 114 :8817 , 2010
Abstract : Acetylcholinesterase (AChE) is a remarkably efficient serine hydrolase responsible for the termination of impulse signaling at cholinergic synapses. By employing Born-Oppenheimer molecular dynamics simulations with a B3LYP/6-31G(d) QM/MM potential and the umbrella sampling method, we have characterized its complete catalytic reaction mechanism for hydrolyzing neurotransmitter acetylcholine (ACh) and determined its multistep free-energy reaction profiles for the first time. In both acylation and deacylation reaction stages, the first step involves the nucleophilic attack on the carbonyl carbon, with the triad His447 serving as the general base, and leads to a tetrahedral covalent intermediate stabilized by the oxyanion hole. From the intermediate to the product, the orientation of the His447 ring needs to be adjusted very slightly, and then, the proton transfers from His447 to the product, and the break of the scissile bond happens spontaneously. For the three-pronged oxyanion hole, it only makes two hydrogen bonds with the carbonyl oxygen at either the initial reactant or the final product state, but the third hydrogen bond is formed and stable at all transition and intermediate states during the catalytic process. At the intermediate state of the acylation reaction, a short and low-barrier hydrogen bond (LBHB) is found to be formed between two catalytic triad residues His447 and Glu334, and the spontaneous proton transfer between two residues has been observed. However, it is only about 1-2 kcal/mol stronger than the normal hydrogen bond. In comparison with previous theoretical investigations of the AChE catalytic mechanism, our current study clearly demonstrates the power and advantages of employing Born-Oppenheimer ab initio QM/MM MD simulations in characterizing enzyme reaction mechanisms.
ESTHER : Zhou_2010_J.Phys.Chem.B_114_8817
PubMedSearch : Zhou_2010_J.Phys.Chem.B_114_8817
PubMedID: 20550161

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence - Kulasekara_2009_Infect.Immun_77_3713
Author(s) : Kulasekara BR , Jacobs M , Zhou Y , Wu Z , Sims E , Saenphimmachak C , Rohmer L , Ritchie JM , Radey M , McKevitt M , Freeman TL , Hayden H , Haugen E , Gillett W , Fong C , Chang J , Beskhlebnaya V , Waldor MK , Samadpour M , Whittam TS , Kaul R , Brittnacher M , Miller SI
Ref : Infect Immun , 77 :3713 , 2009
Abstract : In addition to causing diarrhea, Escherichia coli O157:H7 infection can lead to hemolytic-uremic syndrome (HUS), a severe disease characterized by hemolysis and renal failure. Differences in HUS frequency among E. coli O157:H7 outbreaks have been noted, but our understanding of bacterial factors that promote HUS is incomplete. In 2006, in an outbreak of E. coli O157:H7 caused by consumption of contaminated spinach, there was a notably high frequency of HUS. We sequenced the genome of the strain responsible (TW14359) with the goal of identifying candidate genetic factors that contribute to an enhanced ability to cause HUS. The TW14359 genome contains 70 kb of DNA segments not present in either of the two reference O157:H7 genomes. We identified seven putative virulence determinants, including two putative type III secretion system effector proteins, candidate genes that could result in increased pathogenicity or, alternatively, adaptation to plants, and an intact anaerobic nitric oxide reductase gene, norV. We surveyed 100 O157:H7 isolates for the presence of these putative virulence determinants. A norV deletion was found in over one-half of the strains surveyed and correlated strikingly with the absence of stx(1). The other putative virulence factors were found in 8 to 35% of the O157:H7 isolates surveyed, and their presence also correlated with the presence of norV and the absence of stx(1), indicating that the presence of norV may serve as a marker of a greater propensity for HUS, similar to the correlation between the absence of stx(1) and a propensity for HUS.
ESTHER : Kulasekara_2009_Infect.Immun_77_3713
PubMedSearch : Kulasekara_2009_Infect.Immun_77_3713
PubMedID: 19564389
Gene_locus related to this paper: eco57-b3a913 , ecoli-Aes , ecoli-rutD , ecoli-bioh , ecoli-C0410 , ecoli-dlhh , ecoli-entf , ecoli-fes , ecoli-MCMK , ecoli-mhpc , ecoli-pldb , ecoli-ptrb , ecoli-yafa , ecoli-yaim , ecoli-ybff , ecoli-ycfp , ecoli-ycjy , ecoli-yeiG , ecoli-YFBB , ecoli-yghX , ecoli-yhet , ecoli-yjfp , ecoli-YNBC , ecoli-ypfh , ecoli-ypt1 , ecoli-yqia , ecoli-Z0347 , ecoli-Z1341 , ecoli-Z1930 , ecoli-YfhR

Title : Baculo-expression and enzymatic characterization of CES7 esterase - Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
Author(s) : Zhang L , Liu Q , Zhou Y , Zhang Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :731 , 2009
Abstract : The male reproductive tracts in different species are characterized by similar patterns of male-dependent overexpression of carboxylesterases. This phenomenon indicates male sex-associated functions of these enzymes for spermatogenesis, sperm maturation, and sperm use. Recently, a novel epididymis-specific gene named Ces7 was cloned and characterized, which belongs to the carboxylesterase family. To study the functions of CES7 in sperm maturation and storage, CES7 recombinant protein was expressed in baculovirus system. The recombinant protein had carboxylesterase activity hydrolyzing cholesterol ester and choline ester. CES7 as carboxylesterase might be involved in ester hydrolysis, sperm maturation, and storage in male reproductive tract.
ESTHER : Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
PubMedSearch : Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
PubMedID: 19727521

Title : The genome of the cucumber, Cucumis sativus L - Huang_2009_Nat.Genet_41_1275
Author(s) : Huang S , Li R , Zhang Z , Li L , Gu X , Fan W , Lucas WJ , Wang X , Xie B , Ni P , Ren Y , Zhu H , Li J , Lin K , Jin W , Fei Z , Li G , Staub J , Kilian A , van der Vossen EA , Wu Y , Guo J , He J , Jia Z , Tian G , Lu Y , Ruan J , Qian W , Wang M , Huang Q , Li B , Xuan Z , Cao J , Asan , Wu Z , Zhang J , Cai Q , Bai Y , Zhao B , Han Y , Li Y , Li X , Wang S , Shi Q , Liu S , Cho WK , Kim JY , Xu Y , Heller-Uszynska K , Miao H , Cheng Z , Zhang S , Wu J , Yang Y , Kang H , Li M , Liang H , Ren X , Shi Z , Wen M , Jian M , Yang H , Zhang G , Yang Z , Chen R , Ma L , Liu H , Zhou Y , Zhao J , Fang X , Fang L , Liu D , Zheng H , Zhang Y , Qin N , Li Z , Yang G , Yang S , Bolund L , Kristiansen K , Li S , Zhang X , Wang J , Sun R , Zhang B , Jiang S , Du Y
Ref : Nat Genet , 41 :1275 , 2009
Abstract : Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.
ESTHER : Huang_2009_Nat.Genet_41_1275
PubMedSearch : Huang_2009_Nat.Genet_41_1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5 , cucsa-a0a0a0lnt6 , cucsa-a0a0a0kpn7 , cucsa-a0a0a0lvt9 , cucsa-a0a0a0kdx8 , cucsa-a0a0a0m228 , cucsa-a0a0a0kz31 , cucsa-a0a0a0k5t5 , cucsa-a0a0a0kfs7 , cucsa-a0a0a0kjj7 , cucsa-a0a0a0kzs7 , cucsa-a0a0a0l0a6 , cucsa-a0a0a0l4w4 , cucsa-a0a0a0lpz0 , cucsa-a0a0a0ls66

Title : Gene cloning, purification, and characterization of a cold-adapted lipase produced by Acinetobacter baumannii BD5 - Park_2009_J.Microbiol.Biotechnol_19_128
Author(s) : Park IH , Kim SH , Lee YS , Lee SC , Zhou Y , Kim CM , Ahn SC , Choi YL
Ref : J Microbiol Biotechnol , 19 :128 , 2009
Abstract : Acinetobacter baumannii BD5 was isolated from waters of Baek-du mountain, and the lipase gene was cloned using a PCR technique. The deduced amino acid sequence of the lipase and lipase chaperone were found to encode proteins of 325 aa and 344 aa with a molecular mass of 35 kDa and 37 kDa, respectively. The lipase gene was cloned and expressed in Escherichia coli BL21 (trxB) as an inclusion body, which was subsequently solubilized by urea, and then purified using Ni-affinity chromatography. After being purified, the lipase was refolded by incubation at 4oC in the presence of a 1:10 molar ratio of lipase:chaperone. The maximal activity of the refolded lipase was observed at a temperature of 35 degrees and pH 8.3 when p-NP caprate (C10) was used as a substrate; however, 28% of the activity observed at 35 degrees was still remaining at 0 degrees . The stability of the purified enzyme at low temperatures indicates that it is a cold-adapted enzyme. The refolded lipase was activated by Ca2+, Mg2+, and Mn2+, whereas Zn2+ and Cu2+ inhibited it. Additionally, 0.1% Tween 20 increased the lipase activity by 33%, but SDS and Triton X-100 inhibited the lipase activity by 40% and 70%, respectively.
ESTHER : Park_2009_J.Microbiol.Biotechnol_19_128
PubMedSearch : Park_2009_J.Microbiol.Biotechnol_19_128
PubMedID: 19307760
Gene_locus related to this paper: acicp-AbiS

Title : Methylobacterium genome sequences: a reference blueprint to investigate microbial metabolism of C1 compounds from natural and industrial sources - Vuilleumier_2009_PLoS.One_4_e5584
Author(s) : Vuilleumier S , Chistoserdova L , Lee MC , Bringel F , Lajus A , Zhou Y , Gourion B , Barbe V , Chang J , Cruveiller S , Dossat C , Gillett W , Gruffaz C , Haugen E , Hourcade E , Levy R , Mangenot S , Muller E , Nadalig T , Pagni M , Penny C , Peyraud R , Robinson DG , Roche D , Rouy Z , Saenampechek C , Salvignol G , Vallenet D , Wu Z , Marx CJ , Vorholt JA , Olson MV , Kaul R , Weissenbach J , Medigue C , Lidstrom ME
Ref : PLoS ONE , 4 :e5584 , 2009
Abstract : BACKGROUND: Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared. METHODOLOGY/PRINCIPAL FINDINGS: The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids, while the 6.12 Mb genome of strain DM4 features a 5.94 Mb chromosome and two plasmids. The chromosomes are highly syntenic and share a large majority of genes, while plasmids are mostly strain-specific, with the exception of a 130 kb region of the strain AM1 megaplasmid which is syntenic to a chromosomal region of strain DM4. Both genomes contain large sets of insertion elements, many of them strain-specific, suggesting an important potential for genomic plasticity. Most of the genomic determinants associated with methylotrophy are nearly identical, with two exceptions that illustrate the metabolic and genomic versatility of Methylobacterium. A 126 kb dichloromethane utilization (dcm) gene cluster is essential for the ability of strain DM4 to use DCM as the sole carbon and energy source for growth and is unique to strain DM4. The methylamine utilization (mau) gene cluster is only found in strain AM1, indicating that strain DM4 employs an alternative system for growth with methylamine. The dcm and mau clusters represent two of the chromosomal genomic islands (AM1: 28; DM4: 17) that were defined. The mau cluster is flanked by mobile elements, but the dcm cluster disrupts a gene annotated as chelatase and for which we propose the name "island integration determinant" (iid). CONCLUSION/SIGNIFICANCE: These two genome sequences provide a platform for intra- and interspecies genomic comparisons in the genus Methylobacterium, and for investigations of the adaptive mechanisms which allow bacterial lineages to acquire methylotrophic lifestyles.
ESTHER : Vuilleumier_2009_PLoS.One_4_e5584
PubMedSearch : Vuilleumier_2009_PLoS.One_4_e5584
PubMedID: 19440302
Gene_locus related to this paper: metc4-b7krz1 , metea-c5asz7 , metea-c5au09 , metea-c5axg7 , metea-c5b1t3 , metea-c5b215 , metea-c5b387 , meted-c7cbs2 , meted-c7ce76 , meted-c7cfe3 , meted-c7cfx5 , meted-c7cg08 , meted-c7cgc9 , meted-c7cge7 , meted-c7chb8 , meted-c7ci36 , meted-c7cln3 , meted-c7cnd9 , metep-a9vxp1 , metep-a9w2b1 , metep-a9w028 , metex-orf5 , metex-Q8RPA1 , metpb-b1zjw5 , metea-c5as87 , metea-c5awv9 , meted-c7cb08 , metea-rutd , meted-rutd

Title : Large-insert genome analysis technology detects structural variation in Pseudomonas aeruginosa clinical strains from cystic fibrosis patients - Hayden_2008_Genomics_91_530
Author(s) : Hayden HS , Gillett W , Saenphimmachak C , Lim R , Zhou Y , Jacobs MA , Chang J , Rohmer L , D'Argenio DA , Palmieri A , Levy R , Haugen E , Wong GK , Brittnacher MJ , Burns JL , Miller SI , Olson MV , Kaul R
Ref : Genomics , 91 :530 , 2008
Abstract : Large-insert genome analysis (LIGAN) is a broadly applicable, high-throughput technology designed to characterize genome-scale structural variation. Fosmid paired-end sequences and DNA fingerprints from a query genome are compared to a reference sequence using the Genomic Variation Analysis (GenVal) suite of software tools to pinpoint locations of insertions, deletions, and rearrangements. Fosmids spanning regions that contain new structural variants can then be sequenced. Clonal pairs of Pseudomonas aeruginosa isolates from four cystic fibrosis patients were used to validate the LIGAN technology. Approximately 1.5 Mb of inserted sequences were identified, including 743 kb containing 615 ORFs that are absent from published P. aeruginosa genomes. Six rearrangement breakpoints and 220 kb of deleted sequences were also identified. Our study expands the "genome universe" of P. aeruginosa and validates a technology that complements emerging, short-read sequencing methods that are better suited to characterizing single-nucleotide polymorphisms than structural variation.
ESTHER : Hayden_2008_Genomics_91_530
PubMedSearch : Hayden_2008_Genomics_91_530
PubMedID: 18445516

Title : Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety - Connolly_2008_J.Med.Chem_51_6005
Author(s) : Connolly BA , Sanford DG , Chiluwal AK , Healey SE , Peters DE , Dimare MT , Wu W , Liu Y , Maw H , Zhou Y , Li Y , Jin Z , Sudmeier JL , Lai JH , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 51 :6005 , 2008
Abstract : Dipeptidyl peptidase IV (DPP-IV; E.C. 3.4.14.5), a serine protease that degrades the incretin hormones GLP-1 and GIP, is now a validated target for the treatment of type 2 diabetes. Dipeptide boronic acids, among the first, and still among the most potent DPP-IV inhibitors known, suffer from a concern over their safety. Here we evaluate the potency, in vivo efficacy, and safety of a selected set of these inhibitors. The adverse effects induced by boronic acid-based DPP-IV inhibitors are essentially limited to what has been observed previously for non-boronic acid inhibitors and attributed to cross-reactivity with DPP8/9. While consistent with the DPP8/9 hypothesis, they are also consistent with cross-reactivity with some other intracellular target. The results further show that the potency of simple dipeptide boronic acid-based inhibitors can be combined with selectivity against DPP8/9 in vivo to produce agents with a relatively wide therapeutic index (>500) in rodents.
ESTHER : Connolly_2008_J.Med.Chem_51_6005
PubMedSearch : Connolly_2008_J.Med.Chem_51_6005
PubMedID: 18783201

Title : DAG lipase activity is necessary for TRP channel regulation in Drosophila photoreceptors - Leung_2008_Neuron_58_884
Author(s) : Leung HT , Tseng-Crank J , Kim E , Mahapatra C , Shino S , Zhou Y , An L , Doerge RW , Pak WL
Ref : Neuron , 58 :884 , 2008
Abstract : In Drosophila, a phospholipase C-mediated signaling cascade links photoexcitation of rhodopsin to the opening of the TRP/TRPL channels. A lipid product of the cascade, diacylglycerol (DAG) and its metabolite(s), polyunsaturated fatty acids (PUFAs), have both been proposed as potential excitatory messengers. A crucial enzyme in the understanding of this process is likely to be DAG lipase (DAGL). However, DAGLs that might fulfill this role have not been previously identified in any organism. In this work, the Drosophila DAGL gene, inaE, has been identified from mutants that are defective in photoreceptor responses to light. The inaE-encoded protein isoforms show high sequence similarity to known mammalian DAG lipases, exhibit DAG lipase activity in vitro, and are highly expressed in photoreceptors. Analyses of norpA inaE double mutants and severe inaE mutants show that normal DAGL activity is required for the generation of physiologically meaningful photoreceptor responses.
ESTHER : Leung_2008_Neuron_58_884
PubMedSearch : Leung_2008_Neuron_58_884
PubMedID: 18579079
Gene_locus related to this paper: drome-CG33174

Title : Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China - Xu_2008_PLoS.One_3_e1450
Author(s) :