Liu H

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Full name : Liu Hong

First name : Hong

Mail : Shanghai Institute of Materia Medica Chinese Academy of Sciences

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Country : China

Email : hliu@simm.ac.cn

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References (213)

Title : Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits - Li_2024_Food.Chem_443_138459
Author(s) : Li D , Li J , Wu C , Liu H , Zhao M , Shi H , Zhang Y , Wang T
Ref : Food Chem , 443 :138459 , 2024
Abstract : Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu(3) alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.
ESTHER : Li_2024_Food.Chem_443_138459
PubMedSearch : Li_2024_Food.Chem_443_138459
PubMedID: 38306911

Title : Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers - Wang_2024_Clin.Pharmacol.Drug.Dev__
Author(s) : Wang X , Liu H , Cui C , Niu X , Li H , Niu S , Yan P , Wu N , Li F , Wu Q , Chen K , Hu B , Liu D
Ref : Clin Pharmacol Drug Dev , : , 2024
Abstract : Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (deltaQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (deltadeltaQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (C(max)) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.
ESTHER : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedSearch : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedID: 38757550

Title : Phthalate biomarkers composition in relation to fatty liver: evidence from epidemiologic and in vivo studies - Chen_2024_Sci.Total.Environ__171607
Author(s) : Chen S , Liu H , Sun Y , Li S , Shi Y , Cheng Z , Zhu H , Sun H
Ref : Sci Total Environ , :171607 , 2024
Abstract : Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.
ESTHER : Chen_2024_Sci.Total.Environ__171607
PubMedSearch : Chen_2024_Sci.Total.Environ__171607
PubMedID: 38461993

Title : Carboxylesterase Activatable Molecular Probe for Personalized Treatment Guidance by Analyte-Induced Molecular Transformation - Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
Author(s) : Li B , Liu H , Zhao M , Zhang X , Huang P , Chen X , Lin J
Ref : Angew Chem Int Ed Engl , :e202404093 , 2024
Abstract : Accurate visualization of tumor microenvironment is of great significance for personalized medicine. Here, we develop a near-infrared (NIR) fluorescence/photoacoustic (FL/PA) dual-mode molecular probe (denoted as NIR-CE) for distinguishing tumors based on carboxylesterase (CE) level by an analyte-induced molecular transformation (AIMT) strategy. The recognition moiety for CE activity is the acetyl unit of NIR-CE, generating the pre-product, NIR-CE-OH, which undergoes spontaneous hydrogen atom exchange between the nitrogen atoms in the indole group and the phenol hydroxyl group, eventually transforming into NIR-CE-H. In cellular experiments and in vivo blind studies, the human hepatoma cells and tumors with high level of CE were successfully distinguished by both NIR FL and PA imaging. Our findings provide a new molecular imaging strategy for personalized treatment guidance.
ESTHER : Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
PubMedSearch : Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
PubMedID: 38727540

Title : SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to beta-cypermethrin with stereoselectivity - Xu_2024_Bull.Entomol.Res__1
Author(s) : Xu L , Liu H , Li B , Li G , Liu R , Li D
Ref : Bull Entomol Res , :1 , 2024
Abstract : Carboxylesterases (CarEs) is an important detoxification enzyme system in phase participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to beta-cypermethrin showed stereoselectivity, with higher metabolic activity to -cypermethrin than the enantiomer alpha-cypermethrin. The metabolite of beta-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that beta-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of beta-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in beta-cypermethrin resistance in S. litura.
ESTHER : Xu_2024_Bull.Entomol.Res__1
PubMedSearch : Xu_2024_Bull.Entomol.Res__1
PubMedID: 38708572
Gene_locus related to this paper: spolt-SlCarE054

Title : A chromosome-scale genome of Rhus chinensis Mill. provides new insights into plant-insect interaction and gallotannins biosynthesis - Ni_2024_Plant.J__
Author(s) : Ni BB , Liu H , Wang ZS , Zhang GY , Sang ZY , Liu JJ , He CY , Zhang JG
Ref : Plant J , : , 2024
Abstract : Rhus chinensis Mill., an economically valuable Anacardiaceae species, is parasitized by the galling aphid Schlechtendalia chinensis, resulting in the formation of the Chinese gallnut (CG). Here, we report a chromosomal-level genome assembly of R. chinensis, with a total size of 389.40 Mb and scaffold N50 of 23.02 Mb. Comparative genomic and transcriptome analysis revealed that the enhanced structure of CG and nutritional metabolism contribute to improving the adaptability of R. chinensis to S. chinensis by supporting CG and galling aphid growth. CG was observed to be abundant in hydrolysable tannins (HT), particularly gallotannin and its isomers. Tandem repeat clusters of dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) and serine carboxypeptidase-like (SCPL) and their homologs involved in HT production were determined as specific to HT-rich species. The functional differentiation of DQD/SDH tandem duplicate genes and the significant contraction in the phenylalanine ammonia-lyase (PAL) gene family contributed to the accumulation of gallic acid and HT while minimizing the production of shikimic acid, flavonoids, and condensed tannins in CG. Furthermore, we identified one UDP glucosyltransferase (UGT84A), three carboxylesterase (CXE), and six SCPL genes from conserved tandem repeat clusters that are involved in gallotannin biosynthesis and hydrolysis in CG. We then constructed a regulatory network of these genes based on co-expression and transcription factor motif analysis. Our findings provide a genomic resource for the exploration of the underlying mechanisms of plant-galling insect interaction and highlight the importance of the functional divergence of tandem duplicate genes in the accumulation of secondary metabolites.
ESTHER : Ni_2024_Plant.J__
PubMedSearch : Ni_2024_Plant.J__
PubMedID: 38271098

Title : Clinical Features of Non-Hodgkin Lymphoma-Associated Hemophagocytic Syndrome: a Retrospective Study - Wu_2024_Clin.Lab_70_
Author(s) : Wu C , Liu H , Chen J
Ref : Clin Lab , 70 : , 2024
Abstract : BACKGROUND: This study aims to improve the understanding of lymphoma-associated hemophagocytic syndrome, and find effective methods to identify and manage this fatal disease. METHODS: Patients diagnosed with non-Hodgkin lymphoma-associated hemophagocytic syndrome from January 2008 to December 2022 in our center were included. Univariate and multivariate analyses were also conducted using the Cox proportional hazards model. RESULTS: Among 26 patients, 22 patients were diagnosed with T/NK cell lymphoma, while 4 patients were diagnosed with diffuse large B cell lymphoma. A total of 16 patients died with a median follow-up of 71 (26, 236) days. Compared with B cell lymphoma-associated hemophagocytic syndrome patients, T/NK cell lymphoma patients are younger, have lower platelet count, fibrinogen concentration, and serum albumin, have higher blood beta2-mi-croglobulin levels and ferritin, are more likely to be infected with Epstein-Barr virus, are more inclined have a simultaneously occurrence of lymphoma and hemophagocytic syndrome. In multivariate analysis, fibrinogen, albumin, cholinesterase, uric acid, triglyceride, and ferritin are significantly associated with overall mortality. CONCLUSIONS: LAHS is a rare disease with poor prognosis. Early anti-inflammatory treatment combined with anti-lymphoma therapy can improve the overall survival time of patients. Prospective multi-center studies with larger sample sizes and longer follow-up periods are needed to further investigate optimal treatment and prognosis.
ESTHER : Wu_2024_Clin.Lab_70_
PubMedSearch : Wu_2024_Clin.Lab_70_
PubMedID: 38623661

Title : Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS - Li_2024_Nat.Chem.Biol__
Author(s) : Li W , Liu Q , Qian Y , Wang C , Kong C , Sun L , Liu H , Zhang Y , Jiang D , Jiang C , Wang S , Xia P
Ref : Nat Chemical Biology , : , 2024
Abstract : Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1beta, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.
ESTHER : Li_2024_Nat.Chem.Biol__
PubMedSearch : Li_2024_Nat.Chem.Biol__
PubMedID: 38413746

Title : Choline metabolism reprogramming mediates an immunosuppressive microenvironment in non-small cell lung cancer (NSCLC) by promoting tumor-associated macrophage functional polarization and endothelial cell proliferation - Xiao_2024_J.Transl.Med_22_442
Author(s) : Xiao B , Li G , Gulizeba H , Liu H , Sima X , Zhou T , Huang Y
Ref : J Transl Med , 22 :442 , 2024
Abstract : INTRODUCTION: Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. METHODS: Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan-Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. RESULTS: Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. CONCLUSION: Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.
ESTHER : Xiao_2024_J.Transl.Med_22_442
PubMedSearch : Xiao_2024_J.Transl.Med_22_442
PubMedID: 38730286

Title : Improved Production of Recombinant Carboxylesterase FumDM by Co-Expressing Molecular Chaperones in Pichia pastoris - Jiang_2023_Toxins.(Basel)_15_
Author(s) : Jiang L , Guan X , Liu H , Chang X , Sun J , Sun C , Zhao C
Ref : Toxins (Basel) , 15 : , 2023
Abstract : Fumonisins (FBs) are mycotoxins that threaten public health and food safety worldwide. Enzymatic degradation of Fumonisin B1 (FB(1)) through decarboxylation has attracted much attention, whereas application of FB(1) carboxylesterase in detoxification requires more effective expression of the recombinant carboxylesterase. In this study, the carboxylesterase FumDM from Sphingopyxis sp. ASAG22 was codon-optimized and co-expressed with five different molecular chaperones (PDI, CPR5, ERO1, HAC1, and Bip) in order to improve the expression level of FumDM in Pichia pastoris (also known as Komagataella phaffii) GS115. The co-expression of different chaperones caused varying degrees of improvement in FumDM activity for FB(1). The enzyme activities of recombinant strains over-expressing PDI and CPR5 reached the highest levels of 259.47 U/mL and 161.34 U/mL, 635% and 357% higher than the original enzyme activity, respectively. Transcriptomic analysis of the two recombinant strains in comparison with the control strain showed that the correct folding of proteins assisted by molecular chaperones played a key role in the improvement of FumDM expression and its enzyme activity. This study demonstrated that co-expression of carboxylesterase FumDM and folding chaperones was an efficient strategy and therefore might inspire new perspectives on the improvement of carboxylesterase for detoxification of FB(1).
ESTHER : Jiang_2023_Toxins.(Basel)_15_
PubMedSearch : Jiang_2023_Toxins.(Basel)_15_
PubMedID: 36828470
Gene_locus related to this paper: sphmc-FumD

Title : High Peroxidase-Mimicking Metal-Organic Frameworks Decorated with Platinum Nanozymes for the Colorimetric Detection of Acetylcholine Chloride and Organophosphorus Pesticides via Enzyme Cascade Reaction - Yi_2023_Inorg.Chem__
Author(s) : Yi Y , Zhou X , Liao D , Hou J , Liu H , Zhu G
Ref : Inorg Chem , : , 2023
Abstract : The sensitive detection of acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) is very important for the protection of human health. Herein, a hybrid material, Pt NPs/Fe-MOF, consisting of a metal-organic framework (MIL-88B-NH(2), Fe-MOF) decorated with platinum nanoparticles (Pt NPs), was prepared first and exhibited remarkably improved and excellent peroxidase-mimicking activity compared to the Fe-MOF material resulting from the synergistic catalysis effect between Fe-MOF and Pt NPs, which can effectively catalyze 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to generate a blue product (oxidized TMB, oxTMB). Interestingly, in the presence of AChE and acetylcholinesterase, the peroxidase-mimicking activity from Pt NPs/Fe-MOF was inhibited obviously, and thus, a colorimetric sensing platform for AChE can be constructed; more importantly, after the addition of OPs, this nanozyme activity can be recovered, inducing the further successful construction of a sensitive colorimetric sensing platform for OPs. The related sensing mechanism and condition optimization were studied, and the as-prepared Pt NPs/Fe-MOF nanozyme-based colorimetric method for AChE and OP detection displayed superior analytical performances with wide linearities and low detection limits. Furthermore, the designed method offers satisfactory real application ability. We expect the as-proposed Pt NPs/Fe-MOF nanozyme-based colorimetric sensing platform for AChE and OPs via the enzyme cascade reaction to show great potential application.
ESTHER : Yi_2023_Inorg.Chem__
PubMedSearch : Yi_2023_Inorg.Chem__
PubMedID: 37583283

Title : Phosphoproteome reveals long-term potentiation deficit following treatment of ultra-low dose soman exposure in mice - Long_2023_J.Hazard.Mater_459_132211
Author(s) : Long Q , Zhang Z , Li Y , Zhong Y , Liu H , Chang L , Ying Y , Zuo T , Wang Y , Xu P
Ref : J Hazard Mater , 459 :132211 , 2023
Abstract : Soman, a warfare nerve agent, poses a significant threat by inducing severe brain damage that often results in death. Nonetheless, our understanding of the biological changes underlying persistent neurocognitive dysfunction caused by low dosage of soman remains limited. This study used mice to examine the effects of different doses of soman over time. Phosphoproteomic analysis of the mouse brain is the first time to be used to detect toxic effects of soman at such low or ultra-low doses, which were undetectable based on measuring the activity of acetylcholinesterase at the whole-animal level. We also found that phosphoproteome alterations could accurately track the soman dose, irrespective of the sampling time. Moreover, phosphoproteome revealed a rapid and adaptive cellular response to soman exposure, with the points of departure 8-38 times lower than that of acetylcholinesterase activity. Impaired long-term potentiation was identified in phosphoproteomic studies, which was further validated by targeted quantitative proteomics, immunohistochemistry, and immunofluorescence analyses, with significantly increased levels of phosphorylation of protein phosphatase 1 in the hippocampus following soman exposure. This increase in phosphorylation inhibits long-term potentiation, ultimately leading to long-term memory dysfunction in mice.
ESTHER : Long_2023_J.Hazard.Mater_459_132211
PubMedSearch : Long_2023_J.Hazard.Mater_459_132211
PubMedID: 37572605

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 : Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension - Guo_2023_Theranostics_13_1826
Author(s) : Guo Y , He Z , Chen Z , Chen F , Wang C , Zhou W , Liu J , Liu H , Shi R
Ref : Theranostics , 13 :1826 , 2023
Abstract : Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.
ESTHER : Guo_2023_Theranostics_13_1826
PubMedSearch : Guo_2023_Theranostics_13_1826
PubMedID: 37064881

Title : Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos - Yang_2023_Toxics_11_353
Author(s) : Yang Q , Deng P , Xing D , Liu H , Shi F , Hu L , Zou X , Nie H , Zuo J , Zhuang Z , Pan M , Chen J , Li G
Ref : Toxics , 11 :353 , 2023
Abstract :
ESTHER : Yang_2023_Toxics_11_353
PubMedSearch : Yang_2023_Toxics_11_353
PubMedID: 37112580

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 feruloyl esterase\/cellulase integrated biological system for high-efficiency and toxic-chemical free isolation of tobacco based cellulose nanofibers - Zhao_2023_Carbohydr.Polym_313_120885
Author(s) : Zhao M , An X , Fan Z , Nie S , Cheng Z , Cao H , Zhang X , Mian MM , Liu H , Liu L
Ref : Carbohydr Polym , 313 :120885 , 2023
Abstract : Tobacco based cellulose nanofiber (TCNF) is a novel nanocellulose that has recently been used to replace undesirable wood pulp fibers in the preparation of reconstructed tobacco sheets (RTS). However, given the strict requirements for controlling toxic chemical content in tobacco products, there is a global interest in developing a green, efficient, and toxic-chemical free approach to isolate TCNF from tobacco stem as a bioresource. In this study, we propose a creative and environmentally friendly method to efficiently and safely isolate TCNF from tobacco stem pulp, which involves integrated biological pretreatment followed by a facile mechanical defibrillation process. Feruloyl esterase is used to pretreat the stem pulp by disrupting the ether and ester bonds between lignin and polysaccharide carbohydrates within the fiber wall, which effectively facilitates cellulase hydrolysis and swelling of the stem pulp fiber, as well as the following mechanical shearing treatment for TCNF isolation. The results demonstrate that TCNF obtained by the comprehensive feruloyl esterase/cellulase/mechanical process exhibit uniform and well-dispersed nanofiber morphology, higher crystallinity, and stronger mechanical properties than those of the control. The addition of 0.5 % TCNF can replace wood pulp by 18 wt% ~ 25 wt% in the production of RTS samples while maintaining their reasonable strength properties.
ESTHER : Zhao_2023_Carbohydr.Polym_313_120885
PubMedSearch : Zhao_2023_Carbohydr.Polym_313_120885
PubMedID: 37182973

Title : Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis - Wei_2023_CNS.Neurosci.Ther__
Author(s) : Wei N , Liu H , Ye W , Xu S , Lu C , Dai A , Hou T , Zeng X , Wu J , Chen J
Ref : CNS Neurosci Ther , : , 2023
Abstract : BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Abeta), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.
ESTHER : Wei_2023_CNS.Neurosci.Ther__
PubMedSearch : Wei_2023_CNS.Neurosci.Ther__
PubMedID: 37088953

Title : Multi-compartmental MOF microreactors derived from Pickering double emulsions for chemo-enzymatic cascade catalysis - Tian_2023_Nat.Commun_14_3226
Author(s) : Tian D , Hao R , Zhang X , Shi H , Wang Y , Liang L , Liu H , Yang H
Ref : Nat Commun , 14 :3226 , 2023
Abstract : Bioinspired multi-compartment architectures are desired in synthetic biology and metabolic engineering, as credited by their cell-like structures and intrinsic ability of assembling catalytic species for spatiotemporal control over cascade reactions like in living systems. Herein, we describe a general Pickering double emulsion-directed interfacial synthesis method for the fabrication of multicompartmental MOF microreactors. This approach employs multiple liquid-liquid interfaces as a controllable platform for the self-completing growth of dense MOF layers, enabling the microreactor with tailor-made inner architectures and selective permeability. Importantly, simultaneous encapsulation of incompatible functionalities, including hydrophilic enzyme and hydrophobic molecular catalyst, can be realized in a single MOF microreactor for operating chemo-enzymatic cascade reactions. As exemplified by the Grubb' catalyst/CALB lipase driven olefin metathesis/ transesterification cascade reaction and glucose oxidase (GOx)/Fe-porphyrin catalyzed oxidation reaction, the multicompartmental microreactor exhibits 2.24-5.81 folds enhancement in cascade reaction efficiency in comparison to the homogeneous counterparts or physical mixture of individual analogues, due to the restrained mutual inactivation and substrate channelling effects. Our study prompts further design of multicompartment systems and the development of artificial cells capable of complex cellular transformations.
ESTHER : Tian_2023_Nat.Commun_14_3226
PubMedSearch : Tian_2023_Nat.Commun_14_3226
PubMedID: 37270555

Title : Identification and analysis of the secretome of plant pathogenic fungi reveals lifestyle adaptation - Jia_2023_Front.Microbiol_14_1171618
Author(s) : Jia M , Gong X , Fan M , Liu H , Zhou H , Gu S , Liu Y , Dong J
Ref : Front Microbiol , 14 :1171618 , 2023
Abstract : The secretory proteome plays an important role in the pathogenesis of phytopathogenic fungi. However, the relationship between the large-scale secretome of phytopathogenic fungi and their lifestyle is not fully understood. In the present study, the secretomes of 150 plant pathogenic fungi were predicted and the characteristics associated with different lifestyles were investigated. In total, 94,974 secreted proteins (SPs) were predicted from these fungi. The number of the SPs ranged from 64 to 1,662. Among these fungi, hemibiotrophic fungi had the highest number (average of 970) and proportion (7.1%) of SPs. Functional annotation showed that hemibiotrophic and necrotroph fungi, differ from biotrophic and symbiotic fungi, contained much more carbohydrate enzymes, especially polysaccharide lyases and carbohydrate esterases. Furthermore, the core and lifestyle-specific SPs orthogroups were identified. Twenty-seven core orthogroups contained 16% of the total SPs and their motif function annotation was represented by serine carboxypeptidase, carboxylesterase and asparaginase. In contrast, 97 lifestyle-specific orthogroups contained only 1% of the total SPs, with diverse functions such as PAN_AP in hemibiotroph-specific and flavin monooxygenases in necrotroph-specific. Moreover, obligate biotrophic fungi had the largest number of effectors (average of 150), followed by hemibiotrophic fungi (average of 120). Among these effectors, 4,155 had known functional annotation and pectin lyase had the highest proportion in the functionally annotated effectors. In addition, 32 sets of RNA-Seq data on pathogen-host interactions were collected and the expression levels of SPs were higher than that of non-SPs, and the expression level of effector genes was higher in biotrophic and hemibiotrophic fungi than in necrotrophic fungi, while secretase genes were highly expressed in necrotrophic fungi. Finally, the secretory activity of five predicted SPs from Setosphearia turcica was experimentally verified. In conclusion, our results provide a foundation for the study of pathogen-host interaction and help us to understand the fungal lifestyle adaptation.
ESTHER : Jia_2023_Front.Microbiol_14_1171618
PubMedSearch : Jia_2023_Front.Microbiol_14_1171618
PubMedID: 37152749

Title : Design, Synthesis, and Proof of Concept of Balanced Dual Inhibitors of Butyrylcholinesterase (BChE) and Histone Deacetylase 6 (HDAC6) for the Treatment of Alzheimer's Disease - Wang_2023_ACS.Chem.Neurosci__
Author(s) : Wang L , Sun T , Wang Z , Liu H , Qiu W , Tang X , Guo H , Yang P , Chen Y , Sun H
Ref : ACS Chem Neurosci , : , 2023
Abstract : Concomitant inhibition of butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) is supposed to be effective in the treatment of Alzheimer's disease (AD). Inspired by our previous efforts in designing BChE inhibitors, herein, selective BChE and HDAC6 dual inhibitors were successfully identified through the fusion of the core pharmacophoric moiety of BChE and HDAC6 inhibitors. After the structure-activity relationship (SAR) studies, two compounds (24g and 29a) were confirmed to have superior inhibitory activity against BChE (the IC(50) against hBChE are 4.0 and 1.8 nM, respectively) and HDAC6 (the IC(50) against HDAC6 are 8.9 and 71.0 nM, respectively). These two compounds showed prominently neuroprotective effects in vitro, potent reactive oxygen species (ROS) scavenging effects, and effective metal ion (Fe(2+) and Cu(2+)) chelation. In addition, they exhibited pronounced inhibition of phosphorylated tau and a moderate immunomodulatory effect, with a lack of neurotoxicity at the cellular level. In vivo studies showed that both 24g and 29a ameliorated the cognitive impairment in an Abeta(1-42)-induced mouse model at a low dosage (2.5 mg/kg). Our data demonstrated that BChE/HDAC6 dual inhibitors could establish the basis for a potential new symptomatic and disease-modifying strategy to treat AD.
ESTHER : Wang_2023_ACS.Chem.Neurosci__
PubMedSearch : Wang_2023_ACS.Chem.Neurosci__
PubMedID: 37561893

Title : Complete Depolymerization of PET Wastes by an Evolved PET Hydrolase from Directed Evolution - Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
Author(s) : Shi L , Liu P , Tan Z , Zhao W , Gao J , Gu Q , Ma H , Liu H , Zhu L
Ref : Angew Chem Int Ed Engl , 62 :e202218390 , 2023
Abstract : PETase displays great potential in PET depolymerization. Directed evolution has been limited to engineer PETase due to the lack of high-throughput screening assay. In this study, a novel fluorescence-based high-throughput screening assay employing a newly designed substrate, bis (2-hydroxyethyl) 2-hydroxyterephthalate (termed BHET-OH), was developed for PET hydrolases. The best variant DepoPETase produced 1407-fold more products towards amorphous PET film at 50 degreesC and showed a 23.3 degreesC higher T(m) value than the PETase WT. DepoPETase enabled complete depolymerization of seven untreated PET wastes and 19.1g PET waste (0.4 % W(enzyme) /W(PET) ) in liter-scale reactor, suggesting that it is a potential candidate for industrial PET depolymerization processes. The molecular dynamic simulations revealed that the distal substitutions stabilized the loops around the active sites and transmitted the stabilization effect to the active sites through enhancing inter-loop interactions network.
ESTHER : Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
PubMedSearch : Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
PubMedID: 36751696
Gene_locus related to this paper: idesa-peth

Title : Acute thermal stress increased enzyme activity and muscle energy distribution of yellowfin tuna - Liu_2023_PLoS.One_18_e0289606
Author(s) : Liu H , Yang R , Fu Z , Yu G , Li M , Dai S , Ma Z , Zong H
Ref : PLoS ONE , 18 :e0289606 , 2023
Abstract : Heat is a powerful stressor for fish living in natural and artificial environments. Understanding the effects of heat stress on the physiological processes of fish is essential for better aquaculture and fisheries management. In this experiment, a heating rod was used to increase the temperature at 2 degreesC/h to study the changes of energy allocation (CEA) and energy metabolity-related enzyme activities, including pepsin, trypsin, amylase, lipase, acid phosphatase, lactate dehydrogenase, alanine aminotransferase, glutamic oxalic aminotransferase and energy reserve (Ea), energy expenditure (ETS), in juvenile yellowfin tuna cells under acute temperature stress. The results showed that the Ea of juvenile yellowfin tuna muscles in response to high temperature (34 degreesC) was significantly lower than that of the control (28 degreesC), and it also increased ETS. At 6 h, CEA decreased slightly in the high-temperature group, but, the difference in CEA between 24 h and 0 h decreased. After heat stress for 6 h, the activities of acid phosphatase (ACP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and glutamic oxalacetic transaminase (AST) increased, indicating that the metabolic rate was accelerated. After heat stress for 24 h, the activity of ALT decreased, indicating that with time elapsed, the activities of some protein metabolizing enzymes increased, and some decreased. In this study, digestive enzymes, trypsin and lipase increased gradually. After heat stress, Ea and Ec change significantly. Yellowfin tuna muscles use lipids in response to sharp temperature increases at high temperatures, red muscles respond to temperature changes by increasing energy in the early stages, but not nearly as much, and white muscles reduce lipids.
ESTHER : Liu_2023_PLoS.One_18_e0289606
PubMedSearch : Liu_2023_PLoS.One_18_e0289606
PubMedID: 37796965

Title : UNC-43\/CaMKII-triggered anterograde signals recruit GABA(A)Rs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs - Hao_2023_Nat.Commun_14_1436
Author(s) : Hao Y , Liu H , Zeng XT , Wang Y , Zeng WX , Qian KY , Li L , Chi MX , Gao S , Hu Z , Tong XJ
Ref : Nat Commun , 14 :1436 , 2023
Abstract : Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABA(A)Rs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABA(A)Rs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABA(A)Rs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1alpha/Neurexin surface delivery. Together, MADD-4B and NRX-1alpha recruit postsynaptic NLG-1/Neuroligin and stabilize GABA(A)Rs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABA(A)Rs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1alpha, which act as anterograde signals to recruit postsynaptic GABA(A)Rs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity.
ESTHER : Hao_2023_Nat.Commun_14_1436
PubMedSearch : Hao_2023_Nat.Commun_14_1436
PubMedID: 36918518

Title : Neurotoxic effects of chloroquine and its main transformation product formed after chlorination - Hu_2023_Sci.Total.Environ__168043
Author(s) : Hu S , Zhao J , Fang S , Guo K , Qi W , Liu H
Ref : Sci Total Environ , :168043 , 2023
Abstract : Pharmaceutical transformation products (TPs) generated during wastewater treatment have become an environmental concern. However, there is limited understanding regarding the TPs produced from pharmaceuticals during wastewater treatment. In this study, chloroquine (CQ), which was extensively used for treating coronavirus disease-19 (COVID-19) infections during the pandemic, was selected for research. We identified and fractionated the main TP produced from CQ during chlorine disinfection and investigated the neurotoxic effects of CQ and its main TP on zebrafish (Danio rerio) embryos. Halogenated TP353 was observed as one of the main TPs produced from CQ during chlorine disinfection. Zebrafish embryos test revealed that TP353 caused higher neurotoxicity in zebrafish larvae, as compared to the CQ, and that was accompanied by significantly decreased expression levels of the genes related to central nervous system development (e.g., gfap, syn2a, and elavl3), inhibited activity of acetylcholinesterase (AChE), reduced GFP fluorescence intensity of motor neuron axons in transgenic larvae (hb9-GFP), and reduced total swimming distance and swimming velocity of larvae during light-dark transition stimulation. The results of this study can potentially be utilized as a theoretical reference for future evaluations of environmental risks associated with CQ and its related TPs. This work presents a methodology for assessing the environmental hazards linked to the discharge of pharmaceutical TPs after wastewater treatment.
ESTHER : Hu_2023_Sci.Total.Environ__168043
PubMedSearch : Hu_2023_Sci.Total.Environ__168043
PubMedID: 37898196

Title : The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling - Luo_2023_J.Transl.Med_21_71
Author(s) : Luo A , Wu Z , Li S , McReynolds CB , Wang D , Liu H , Huang C , He T , Zhang X , Wang Y , Liu C , Hammock BD , Hashimoto K , Yang C
Ref : J Transl Med , 21 :71 , 2023
Abstract : BACKGROUND: Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown. METHODS: According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling. RESULTS: In anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1beta (IL-1beta) and the tumor necrosis factor alpha (TNF-alpha), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU. CONCLUSIONS: sEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling.
ESTHER : Luo_2023_J.Transl.Med_21_71
PubMedSearch : Luo_2023_J.Transl.Med_21_71
PubMedID: 36732752

Title : In-vitro metabolism of LXY18, an orally available, potent blocker of AURKB relocation in mitosis - Li_2023_J.Pharm.Biomed.Anal_232_115415
Author(s) : Li J , Choudhry N , Lv G , Nimishetti N , Reddy MC , Liu H , Allen TD , Zhang J , Yang D
Ref : J Pharm Biomed Anal , 232 :115415 , 2023
Abstract : This study investigated the metabolism of LXY18, a quinolone-based compound that suppresses tumorigenesis by blocking AURKB localization. Metabolite profiling of LXY18 in liver microsomes from six species and human S9 fractions revealed that LXY18 undergoes various conserved metabolic reactions, such as N-hydroxylation, N-oxygenation, O-dealkylation, and hydrolysis, resulting in ten metabolites. These metabolites were produced through a combination of CYP450 enzymes, and non-CYP450 enzymes including CES1, and AO. Two metabolites, M1 and M2 were authenticated by chemically synthesized standards. M1 was the hydrolyzed product catalyzed by CES1 whereas M2 was a mono-N-oxidative derivative catalyzed by a CYP450 enzyme. AO was identified as the enzyme responsible for the formation of M3 with the help of AO-specific inhibitors and LXY18 analogs, 5b and 5c. M1 was the intermediate of LXY18 to produce M7, M8, M9, and M10. LXY18 potently inhibited 2C19 with an IC(50) of 290 nM but had a negligible impact on the other CYP450s, indicating a low risk of drug-drug interaction. Altogether, the study provides valuable insights into the metabolic process of LXY18 and its suitability as a drug candidate. The data generated serves as a significant reference point for conducting further safety assessments and optimizing drug development.
ESTHER : Li_2023_J.Pharm.Biomed.Anal_232_115415
PubMedSearch : Li_2023_J.Pharm.Biomed.Anal_232_115415
PubMedID: 37120975

Title : Design of carboxymethylcellulose-conjugated polymeric prodrug micelles for enhanced in vivo performance of docetaxel - Liu_2023_Int.J.Biol.Macromol__127690
Author(s) : Liu Z , Liu Y , Liu H , Lv R , Liu B , Zhao L , Yin T , Zhang Y , He H , Gou J , Tang X , Yang L , Gao S
Ref : Int J Biol Macromol , :127690 , 2023
Abstract : Docetaxel (DTX) has become one of the most important cytotoxic drugs to treat cancer; nevertheless, its poor hydrophilicity and non-specific distribution of DTX lead to detrimental side effects. In this article, we devised carboxymethylcellulose (CMC)-conjugated polymeric prodrug micelles (mPEG-CMC-DTX PMs) for DTX delivery. The ester-bonded polymeric prodrug, mPEG-CMC-DTX, was synthesized and exhibited the capacity for self-assembling into polymeric micelles. The CMC is profusely substituted and acetylated to promote the coupling rate of DTX. Covalent binding of DTX and CMC through an ester bond can be hydrolyzed to dissociate the bond under the action of esterase in the tumor. The mPEG-CMC-DTX PMs displayed promoted drug loading (>50 %, wt), commendable stability, and sustained release behavior in vitro. The gradual release of the prodrug amplified the selectivity of cytotoxicity between normal cells and tumor cells, mitigating the systemic toxicity of mPEG-CMC-DTX PMs and enabling dose intensification. Notably, mPEG-CMC-DTX PMs demonstrated a superior antitumor efficacy and low systemic toxicity due to the elevated tolerance dosage (even at 40 mg/kg DTX). In summation, mPEG-CMC-DTX PMs harmonized the antitumor efficacy and toxicity of DTX. In essence, innovative perspectives for the rational design of CMC-conjugated polymeric prodrug micelles for the delivery of potently toxic drugs were proffered.
ESTHER : Liu_2023_Int.J.Biol.Macromol__127690
PubMedSearch : Liu_2023_Int.J.Biol.Macromol__127690
PubMedID: 37898254

Title : Acetylcholinesterase-capped mesoporous silica gated switches for selective detection of high-toxicity organophosphate compounds - Zhang_2022_Anal.Chim.Acta_1207_339708
Author(s) : Zhang Y , Li T , Sun X , Liu H , Wang Y , Nie Z
Ref : Anal Chim Acta , 1207 :339708 , 2022
Abstract : Organophosphate (OP) compounds are widely used in agriculture, industry, and even terrorism. It is important to distinguish high-toxicity OP compounds from low-toxicity OP compounds in dealing with chemical accidents. However, there are very few portable and simple detection methods. Mesoporous silica gated switches may provide an effective solution. In this study, a gated switch based on mesoporous silica as an inorganic scaffold loaded with sulforhodamine B and capped with acetylcholinesterase (AChE) was prepared for specific detection of OP compounds. Carbamate derivatives (G1-G6) were designed and synthetized as grafting compounds in consideration of the binding ability with AChE. Through further modification and optimization, grafting compound G6 with phenylpyridine as the substituent showed the best capping capacity, and it achieved excellent blocking of mesoporous silica gated switches for loaded sulforhodamine B. In the presence of high-toxicity OP compounds, low-toxicity OP compounds, AChE substrates and reversible AChE inhibitors respectively, only high-toxicity OP compounds could make the gated switch release loaded sulforhodamine B. The limit of detection for paraoxon-ethyl was 10.6 micro. Furthermore, the preparation process of the gated switch is fast and simple, and the prepared gated switch has good stability and rapid distinguishing ability. The results of this paper provide a new idea for rapidly distinguishing high-toxicity OP compounds from low-toxicity OP compounds and other related compounds on the spot.
ESTHER : Zhang_2022_Anal.Chim.Acta_1207_339708
PubMedSearch : Zhang_2022_Anal.Chim.Acta_1207_339708
PubMedID: 35491047

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 : Catalytic Features and Thermal Adaptation Mechanisms of a Deep Sea Bacterial Cutinase-Type Poly(Ethylene Terephthalate) Hydrolase - Liu_2022_Front.Bioeng.Biotechnol_10_865787
Author(s) : Liu Y , Liu C , Liu H , Zeng Q , Tian X , Long L , Yang J
Ref : Front Bioeng Biotechnol , 10 :865787 , 2022
Abstract : Poly (ethylene terephthalate) (PET) plastic is chemically inert and persistent. Massive quantities of PET waste end up in landfill sites and oceans, posing major global pollution concerns. PET degrading enzymes with high efficiency provide plastic recycling and bioremediation possibilities. Here, we report a novel cutinase, MtCut with distinct catalytic behaviors, derived from the deep sea Nocardiopsaceae family strain. Biochemical analyses showed MtCut efficiently hydrolyzed PET at ambient temperatures and in an exo-type manner. The activity and stability of MtCut were enhanced by the addition of calcium ions. Notably, no hydrolysis products inhibition was observed during PET depolymerization, suggesting MtCut is a better biocatalyst when compared to other PET hydrolases. In addition, structural components associated with thermal adaptation were investigated using molecular dynamic (MD) simulations, and key regions regulating MtCut thermostability were identified. Our biochemical and structural analyses of MtCut deepen the understanding of PET hydrolysis by cutinases, and provide invaluable insights on improvement and performance engineering strategies for PET-degrading biocatalysts.
ESTHER : Liu_2022_Front.Bioeng.Biotechnol_10_865787
PubMedSearch : Liu_2022_Front.Bioeng.Biotechnol_10_865787
PubMedID: 35557867
Gene_locus related to this paper: 9actn-a0a1t4kk94

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 : Steroid glycosides from the roots of Marsdenia tenacissima - Song_2022_Phytochemistry__113506
Author(s) : Song XQ , Tian LL , Ye T , Liu H , Zhang H
Ref : Phytochemistry , :113506 , 2022
Abstract : Eleven undescribed glycosylated C(21) steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.
ESTHER : Song_2022_Phytochemistry__113506
PubMedSearch : Song_2022_Phytochemistry__113506
PubMedID: 36347308

Title : A hemicyanine-based fluorescent probe for simultaneous imaging of Carboxylesterases and Histone deacetylases in hepatocellular carcinoma - Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
Author(s) : Shu Y , Huang C , Liu H , Hu F , Wen H , Liu J , Wang X , Shan C , Li W
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 281 :121529 , 2022
Abstract : Carboxylesterases (CESs) and Histone deacetylases (HDACs) are regarded as important signaling enzymes highly associated with the development and progression of multiple cancers, including hepatocellular carcinoma (HCC). In this work, a near-infrared (NIR) fluorescent probe named Lys-HXPI was designed and synthesized, which linked a hemicyanine dye and 6-acetamidohexanoic acid via an ester bond. Lys-HXPI displayed a remarkable increase with a NIR emission at 720 nm, a low detection limit (<10 nM) for HDAC1, HDAC 6, CES1 and CES2, as well as a high selectivity for the target enzymes over other relevant analytes. Furthermore, Lys-HXPI was used to image endogenous target enzymes in living cells, tumor-bearing nude mice and tissue slices. The ability of Lys-HXPI to simultaneous image CESs and HDACs was demonstrated with RT-qPCR and the confocal imaging in Hep G2 and MDA-MB-231. Taking advantage of NIR emission, the probe was also successfully applied to imaging Hep G2 tumor mice and tissue slices. Lys-HXPI is expected to be useful for the effective detecting of CESs and HDACs in complex biosystems.
ESTHER : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedSearch : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedID: 35797949

Title : Production of Red Pigments by a Newly Isolated Talaromyces aurantiacus Strain with LED Stimulation for Screen Printing - Gong_2022_Indian.J.Microbiol_62_280
Author(s) : Gong X , Luo H , Wu X , Liu H , Sun C , Chen S
Ref : Indian J Microbiol , 62 :280 , 2022
Abstract : Microbial pigments have been widely applied to printing in food, textile, and paper industries as a sustainable alternative to synthetic dyes. Herein, we isolated a novel Talaromyces aurantiacus strain with a strong ability to produce red pigments. We further studied pigment production conditions, stability, screen printing application, and bioactivities. Our results showed that sucrose was a favourable carbon source and the addition of l-histidine significantly enhanced the production of red pigments. Pigment production was strictly photo-regulated with effective wavelengths around 450 nm (blue light). We mixed the red pigments with cellulosic materials and explored their application potentials for screen printing on paper, cotton fabrics, and polymeric carriers. The printing density was significantly improved from 0.3 to 0.7 by overlay printing. T. aurantiacus pigments could be stably stored at pH 5-11, temperature - 10 to 70 degreesC, and redox potential - 200 to 300 mV. Moreover, the stable ranges were extended to pH 1-11 and temperature over 100 degreesC after screen-printed on paper. The red pigments exhibited antioxidant activity towards 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (IC(50) 10.4 mg L(-1) in solution). Our results further indicated the red pigments by T. aurantiacus was environmentally friendly based on acetylcholinesterase activity assay. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-022-01008-x.
ESTHER : Gong_2022_Indian.J.Microbiol_62_280
PubMedSearch : Gong_2022_Indian.J.Microbiol_62_280
PubMedID: 35462713

Title : Rapid Mining of Novel alpha-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS\/MS - Xu_2022_Mar.Drugs_20_
Author(s) : Xu J , Liu Z , Feng Z , Ren Y , Liu H , Wang Y
Ref : Mar Drugs , 20 : , 2022
Abstract : A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10-16) along with four known related compounds (17-20) were obtained directly from the crude extract of strain HO1518. Compounds 10-13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous alpha-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs.
ESTHER : Xu_2022_Mar.Drugs_20_
PubMedSearch : Xu_2022_Mar.Drugs_20_
PubMedID: 35323488

Title : N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer's Disease - Du_2022_J.Med.Chem__
Author(s) : Du C , Wang L , Guan Q , Yang H , Chen T , Liu Y , Li Q , Lyu W , Lu X , Chen Y , Liu H , Feng F , Liu W , Liu Z , Li W , Sun H
Ref : Journal of Medicinal Chemistry , : , 2022
Abstract : Herein, we report a series of selective sub-nanomolar inhibitors against butyrylcholinesterase (BChE). These compounds, bearing a novel N-benzyl benzamide scaffold, inhibited BChE with IC(50) from picomolar to nanomolar. The inhibitory activity was confirmed by the surface plasmon resonance assay, showing a sub-nanomolar K(D) value, which revealed that the compounds exert the inhibitory effect through directly binding to BChE. Several compounds showed neuroprotective effects verified by the oxidative damage model. Furthermore, the safety of S11-1014 and S11-1033 was demonstrated by the in vivo acute toxicity test. In the behavior study, 0.5 mg/kg S11-1014 or S11-1033 exhibited a marked therapeutic effect, which was almost equal to the treatment with 1 mg/kg rivastigmine, against the cognitive impairment induced by Abeta(1-42). The pharmacokinetics studies characterized the metabolic stability of S11-1014. Thus, N-benzyl benzamide inhibitors are promising compounds with drug-like properties for improving cognitive dysfunction, providing a potential strategy for the treatment of Alzheimer's disease.
ESTHER : Du_2022_J.Med.Chem__
PubMedSearch : Du_2022_J.Med.Chem__
PubMedID: 35969197

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 : Characterization of the synergistic inhibitory effect of cyanidin-3-O-glucoside and catechin on pancreatic lipase - Wang_2022_Food.Chem_404_134672
Author(s) : Wang Y , Chen L , Liu H , Xie J , Yin W , Xu Z , Ma H , Wu W , Zheng M , Liu M , Liu J
Ref : Food Chem , 404 :134672 , 2022
Abstract : This study aimed to identify novel pancreatic lipase (PL) inhibitors using affinity ultrafiltration combined with spectroscopy and molecular docking. Cyanidin-3-O-glucoside (C3G; IC(50): 0.268 mg/mL) and catechin (IC(50): 0.280 mg/mL) were shown to be potent PL inhibitors extracted from black rice and adzuki bean coat extracts. Isobologram analysis revealed that the combined use of C3G and catechin at a ratio of 2:3 had a remarkable synergistic effect (IC(50) of the mixture: 0.201 mg/mL). The inhibitory mechanism of C3G-catechin mixture was of mixed type. The C3G-catechin mixture had a great impact on PL secondary structures. Molecular docking analysis further demonstrated that these polyphenols formed hydrophobic interactions and hydrogen bonds with amino acid residues in the binding pocket of PL. Collectively, C3G and catechin were shown to inhibit PL in a synergistic manner and can be potentially used for the development of food supplements for obesity prevention.
ESTHER : Wang_2022_Food.Chem_404_134672
PubMedSearch : Wang_2022_Food.Chem_404_134672
PubMedID: 36323025

Title : Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor: a singlecenter, phase I study in healthy young and elderly Chinese subjects - Qian_2022_ResearchSquare__
Author(s) : Qian H , Yu C , Zhu H , Ding Q , Cai Y , Jing J , Xu X , Guo R , Zhang H , Liu H , Chen X , Liu Y
Ref : ResearchSquare , : , 2022
Abstract : https://www.researchsquare.com/article/rs-1744060/latest.pdf Background Acetylcholinesterase (AChE) inhibitors attempt to reduce the breakdown of acetylcholine levels in the brain of patients with Alzheimers disease (AD) by inhibiting the responsible enzyme AChE in the synaptic cleft. This study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor under development for the treatment of AD in healthy young and elderly Chinese subjects. Methods The study on young subjects were divided into two arms: the multiple ascending-dose (MAD) arm (double-blind, randomized, placebo-controlled, multiple ascending-dose, 2 and 6 mg, N = 24), and the food effect arm (three-period, self-crossover, open-labeled, fasting/standard diet/high-fat diet administration, 4 mg, N = 12). A two-period, self-crossover, open-labeled, single ascending-dose study was designed for elderly subjects (2 and 4 mg, N = 11). Results For young subjects study: In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, area under the concentrationtime curve from zero to t (AUC0-t) orally after a standard diet and high-fat diet slightly increased by about 19% and 29% and the Tmax were delayed by around 1 hour. For elderly subjects study, Tmax were 1.5 and 1.25 hour, t1/2 were 77.1 and 74.2 hour, respectively. After oral administration of DC20 in healthy young and elderly subjects, no serious adverse events occurred, the most common adverse events associated with the study drug were gastrointestinal reactions. Conclusion We predicted the safety risks of DC20 in the clinical treatment of AD, which were well tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects.
ESTHER : Qian_2022_ResearchSquare__
PubMedSearch : Qian_2022_ResearchSquare__
PubMedID:

Title : A symbiotic gut bacterium enhances Aedes albopictus resistance to insecticide - Wang_2022_PLoS.Negl.Trop.Dis_16_e0010208
Author(s) : Wang H , Liu H , Peng H , Wang Y , Zhang C , Guo X , Liu L , Lv W , Cheng P , Gong M
Ref : PLoS Negl Trop Dis , 16 :e0010208 , 2022
Abstract : BACKGROUND: The increasing insecticide resistance of Aedes albopictus puts many countries in Asia and Africa, including China, at great risk of a mosquito-borne virus epidemic. To date, a growing number of researches have focused on the relationship between intestinal symbiotic bacteria and their hosts' resistance to insecticides. This provides a novel aspect to the study of resistant mechanisms. METHODS/FINDINGS: This study reveals significant composition and dynamic changes in the intestinal symbiotic bacteria of Ae. albopictus between the resistant and susceptible strains based on full-length sequencing technology. The relative abundance of Serratia oryzae was significantly higher in the resistance strain than in the susceptible strains; also, the relative abundance of S. oryzae was significantly higher in deltamethrin-induced Ae. albopictus than in their counterpart. These suggested that S. oryzae may be involved in the development of insecticide resistance in Ae. albopictus. To explore the insecticide resistance mechanism, adult mosquitoes were fed with GFP-tagged S. oryzae, which resulted in stable bacterial enrichment in the mosquito gut without affecting the normal physiology, longevity, oviposition, and hatching rates of the host. The resistance measurements were made based on bioassays as per the WHO guidelines. The results showed that the survival rate of S. oryzae-enriched Ae. albopictus was significantly higher than the untreated mosquitoes, indicating the enhanced resistance of S. oryzae-enriched Ae. albopictus. Also, the activities of three metabolic detoxification enzymes in S. oryzae-enriched mosquitoes were increased to varying degrees. Meanwhile, the activity of extracellular enzymes released by S. oryzae was measured, but only carboxylesterase activity was detected. HPLC and UHPLC were respectively used to measure deltamethrin residue concentration and metabolite qualitative analysis, showing that the deltamethrin degradation efficiency of S. oryzae was positively correlated with time and bacterial amount. Deltamethrin was broken down into 1-Oleoyl-2-hydroxy-sn-glycero-3-PE and 2',2'-Dibromo-2'-deoxyguanosine. Transcriptome analysis revealed that 9 cytochrome P450s, 8 GSTs and 7 CarEs genes were significantly upregulated. CONCLUSIONS: S. oryzae can be accumulated into adult Ae. albopictus by artificial feeding, which enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. S. oryzae is vertically transmitted in Ae. albopictus population. Importantly, S. oryzae can degrade deltamethrin in vitro, and use deltamethrin as the sole carbon source for their growths. Therefore, in the future, S. oryzae may also be commercially used to break down the residual insecticides in the farmland and lakes to protect the environment.
ESTHER : Wang_2022_PLoS.Negl.Trop.Dis_16_e0010208
PubMedSearch : Wang_2022_PLoS.Negl.Trop.Dis_16_e0010208
PubMedID: 35245311

Title : Independent association of Lp(a) with platelet reactivity in subjects without statins or antiplatelet agents - Liu_2022_Sci.Rep_12_16609
Author(s) : Liu H , Fu D , Luo Y , Peng D
Ref : Sci Rep , 12 :16609 , 2022
Abstract : The physiological effect of Lp(a) on platelet activity is unclear. Previous studies explored the relationship between Lp(a) and platelet aggregation in patients taking statins and antiplatelet agents, but few was conducted in individuals without the bias of those drugs that either influence Lp(a) or platelet activity. The aim of this study was to assess the relationship between Lp(a) levels and platelet aggregation in subjects not taking statins or antiplatelet drugs. A hospital-based cross-sectional study was conducted to investigate the independent contribution of Lp(a) to platelet activity by controlling the effects of potential confounding factors including lipoprotein-associated phospholipase A2 [Lp-PLA2]. Blood samples were collected from 92 subjects without statins or antiplatelet agents from the Second Xiangya Hospital. The univariate correlation analysis showed a significant correlation between AA-induced average aggregation rate [AAR] and ApoB (r = 0.324, P = 0.002), ApoA1 (r = 0.252, P = 0.015), Lp(a) (r = 0.370, P < 0.001), Lp-PLA2 (r = 0.233, P = 0.025) and platelet counts [PLT] (r = 0.389, P < 0.001). Multivariate regression analysis suggested that Lp(a) contributed independently to AA-induced average aggregation rate (beta = 0.023, P = 0.027) after controlling for the effects of ApoB, Lp-PLA2 and platelet counts. Lp(a) is positively associated with platelet aggregation independent of Lp-PLA2, which may partly account for the atherothrombotic effect of Lp(a).
ESTHER : Liu_2022_Sci.Rep_12_16609
PubMedSearch : Liu_2022_Sci.Rep_12_16609
PubMedID: 36198899

Title : Metabolic engineering of energycane to hyperaccumulate lipids in vegetative biomass - Luo_2022_BMC.Biotechnol_22_24
Author(s) : Luo G , Cao VD , Kannan B , Liu H , Shanklin J , Altpeter F
Ref : BMC Biotechnol , 22 :24 , 2022
Abstract : BACKGROUND: The metabolic engineering of high-biomass crops for lipid production in their vegetative biomass has recently been proposed as a strategy to elevate energy density and lipid yields for biodiesel production. Energycane and sugarcane are highly polyploid, interspecific hybrids between Saccharum officinarum and Saccharum spontaneum that differ in the amount of ancestral contribution to their genomes. This results in greater biomass yield and persistence in energycane, which makes it the preferred target crop for biofuel production. RESULTS: Here, we report on the hyperaccumulation of triacylglycerol (TAG) in energycane following the overexpression of the lipogenic factors Diacylglycerol acyltransferase1-2 (DGAT1-2) and Oleosin1 (OLE1) in combination with RNAi suppression of SUGAR-DEPENDENT1 (SDP1) and Trigalactosyl diacylglycerol1 (TGD1). TAG accumulated up to 1.52% of leaf dry weight (DW,) a rate that was 30-fold that of non-modified energycane, in addition to almost doubling the total fatty acid content in leaves to 4.42% of its DW. Pearson's correlation analysis showed that the accumulation of TAG had the highest correlation with the expression level of ZmDGAT1-2, followed by the level of RNAi suppression for SDP1. CONCLUSIONS: This is the first report on the metabolic engineering of energycane and demonstrates that this resilient, high-biomass crop is an excellent target for the further optimization of the production of lipids from vegetative tissues.
ESTHER : Luo_2022_BMC.Biotechnol_22_24
PubMedSearch : Luo_2022_BMC.Biotechnol_22_24
PubMedID: 36042455

Title : Strigolactone is involved in nitric oxide-enhanced the salt resistance in tomato seedlings - Liu_2022_J.Plant.Res__
Author(s) : Liu H , Li C , Yan M , Zhao Z , Huang P , Wei L , Wu X , Wang C , Liao W
Ref : J Plant Res , : , 2022
Abstract : Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during stress responses. At present, the interaction and mechanism of SLs and NO in tomato salt tolerance remain unclear. In the current study, tomato 'Micro-Tom' was used to study the roles and interactions of SLs and NO in salinity stress tolerance. The results show that 15 microM SLs synthetic analogs GR24 and 10 microM NO donor S-nitrosoglutathione (GSNO) promoted seedling growth under salt stress. TIS108 (an inhibitor of strigolactone synthesis) suppressed the positive roles of NO in tomato growth under salt stress, indicating that endogenous SLs might be involved in NO-induced salt response in tomato seedlings. Meanwhile, under salt stress, GSNO or GR24 treatment induced the increase of endogenous SLs content in tomato seedlings. Moreover, GR24 or GSNO treatment effectively increased the content of chlorophyll, carotenoids and ascorbic acid (ASA), and enhanced the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), glutathione reductase (GR) and cleavage dioxygenase (CCD) enzyme. Additionally, GSNO or GR24 treatment also up-regulated the expression of SLs synthesis genes (SlCCD7, SlCCD8, SlD27 and SlMAX1) and its signal transduction genes (SlD14 and SlMAX2) in tomato seedlings under salt stress. While, a strigolactone synthesis inhibitor TIS108 blocked the increase of endogenous SLs, chlorophyll, carotenoids and ASA content, and antioxidant enzyme, GR, CCD enzyme activity and SLs-related gene expression levels induced by GSNO. Thus, SLs may play an important role in NO-enhanced salinity tolerance in tomato seedlings by increasing photosynthetic pigment content, enhancing antioxidant capacity and improving endogenous SLs synthesis.
ESTHER : Liu_2022_J.Plant.Res__
PubMedSearch : Liu_2022_J.Plant.Res__
PubMedID: 35106650

Title : UHPLC-QTOF\/MS-based comparative metabolomics in pectoralis major of fast- and slow-growing chickens at market ages - Zhang_2022_Food.Sci.Nutr_10_487
Author(s) : Zhang J , Cao J , Geng A , Wang H , Chu Q , Yan Z , Zhang X , Zhang Y , Liu H
Ref : Food Sci Nutr , 10 :487 , 2022
Abstract : The molecular regulatory mechanism underlying meat quality between different chicken genotypes remains elusive. This study aimed to identify the differences in metabolites and pathways in pectoralis major (breast muscle) between a commercial fast-growing chicken genotype (Cobb500) and a slow-growing Chinese native chicken genotype (Beijing-You chickens, BYC) at market ages respectively based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF/MS). Eighteen metabolites were identified as potential biomarkers between BYC and Cobb500 at market ages. Among them, L-cysteine exhibited a higher relative intensity in BYC compared with Cobb500 and was enriched into 10 potential flavor-associated KEGG pathways. In addition, the glycerophospholipid metabolism pathway was found to be associated with chicken meat flavor and the accumulation of sn-glycerol 3-phosphate and acetylcholine was more predominant in BYC than that in Cobb500, which were catalyzed by glycerophosphocholine phosphodiesterase (GPCPD1, EC:3.1.4.2), choline O-acetyltransferase (CHAT, EC:2.3.1.6), and acetylcholinesterase (ACHE, EC:3.1.1.7). Overall, the present study provided some metabolites and pathways for further investigating the roles of the differences in meat flavor quality in breast muscle between Cobb500 and BYC at market ages.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_487
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_487
PubMedID: 35154685

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

Title : Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt\/beta-catenin Signaling Via p-GSK3beta - Yang_2022_Int.J.Biochem.Cell.Biol__106316
Author(s) : Yang P , Li C , Zhou Q , Zhang X , Kou Y , Feng Q , Wang H , Su R , Hasegawa T , Liu H , Li M
Ref : International Journal of Biochemistryistry & Cell Biology , :106316 , 2022
Abstract : Notum, which belongs to the alpha/beta hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/beta-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC.
ESTHER : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedSearch : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedID: 36280040

Title : Enhancing the secretion of a feruloyl esterase in Bacillus subtilis by signal peptide screening and rational design - Liu_2022_Protein.Expr.Purif__106165
Author(s) : Liu P , Guo J , Miao L , Liu H
Ref : Protein Expr Purif , :106165 , 2022
Abstract : Feruloyl esterase is a subclass of alpha/beta hydrolase, which could release ferulic acid from biomass residues for use as an efficient additive in food or pharmaceutical industries. In the present study, a feruloyl esterase with broad substrate specificity was characterised and secreted by Bacillus subtilis WB600. After codon usage optimisation and signal peptide library screening, the secretion amount of feruloyl esterase was enhanced by up to 10.2-fold in comparison with the base strain. The site-specific amino acid substitutions that facilitate protein folding further improved the secretion by about 1.5-fold. The purified rationally designed enzyme exhibited maximal activity against methyl ferulate at pH 6.5 and 65 degreesC. In the solid-state fermentation, the genetically engineered B. subtilis released about 37% of the total alkali-extractable ferulic acid in maize bran. This study provides a promising candidate for ferulic acid production and demonstrates that the secretion of a heterologous enzyme from B. subtilis can be cumulatively improved by changes in protein sequence features.
ESTHER : Liu_2022_Protein.Expr.Purif__106165
PubMedSearch : Liu_2022_Protein.Expr.Purif__106165
PubMedID: 36038098
Gene_locus related to this paper: strcj-estA

Title : Genome-wide identification and functional analysis of long non-coding RNAs in Chilo suppressalis reveal their potential roles in chlorantraniliprole resistance - Huang_2022_Front.Physiol_13_1091232
Author(s) : Huang S , Jing D , Xu L , Luo G , Hu Y , Wu T , Li F , He K , Qin W , Sun Y , Liu H
Ref : Front Physiol , 13 :1091232 , 2022
Abstract : Long non-coding RNAs, referred to as lncRNAs, perform essential functions in some biological processes, including reproduction, metamorphosis, and other critical life functions. Yet, lncRNAs are poorly understood in pesticide resistance, and no reports to date have characterized which lncRNAs are associated with chlorantraniliprole resistance in Chilo suppressalis. Here, RNA-seq was performed on two strains of C. suppressalis exposed to chlorantraniliprole: one is a susceptible strain (S), and the other is a resistant strain (R). In total, 3,470 lncRNAs were identified from 40,573 merged transcripts in six libraries, including 1,879 lincRNAs, 245 intronic lncRNAs, 853 sense lncRNAs, and 493 antisense lncRNAs. Moreover, differential expression analysis revealed 297 and 335 lncRNAs upregulated in S and R strains, respectively. Differentially expressed (DE) lncRNAs are usually assumed to be involved in the chlorantraniliprole resistance in C. suppressalis. As potential targets, adjacent protein-coding genes (within <1000 kb range upstream or downstream of DE lncRNAs), especially detoxification enzyme genes (cytochrome P450s, carboxyl/cholinesterases/esterases, and ATP-binding cassette transporter), were analyzed. Furthermore, the strand-specific RT-PCR was conducted to confirm the transcript orientation of randomly selected 20 DE lincRNAs, and qRT-PCR was carried out to verify the expression status of 8 out of them. MSTRG.25315.3, MSTRG.25315.6, and MSTRG.7482.1 were upregulated in the R strain. Lastly, RNA interference and bioassay analyses indicated overexpressed lincRNA MSTRG.7482.1 was involved in chlorantraniliprole resistance. In conclusion, we represent, for the first time, the genome-wide identification of chlorantraniliprole-resistance-related lncRNAs in C. suppressalis. It elaborates the views underlying the mechanism conferring chlorantraniliprole resistance in lncRNAs.
ESTHER : Huang_2022_Front.Physiol_13_1091232
PubMedSearch : Huang_2022_Front.Physiol_13_1091232
PubMedID: 36699669

Title : Zeaxanthin remodels cytoplasmic lipid droplets via beta3-adrenergic receptor signaling and enhances perilipin 5-mediated lipid droplet-mitochondrion interactions in adipocytes - Xie_2022_Food.Funct__
Author(s) : Xie J , Liu H , Yin W , Ge S , Jin Z , Zheng M , Cai D , Liu M , Liu J
Ref : Food Funct , : , 2022
Abstract : Cytoplasmic lipid droplets (LDs), which are remarkably dynamic, neutral lipid storage organelles, play fundamental roles in lipid metabolism and energy homeostasis. Both the dynamic remodeling of LDs and LD-mitochondrion interactions in adipocytes are effective mechanisms to ameliorate obesity and related comorbidities. Zeaxanthin (ZEA) is a natural carotenoid and has beneficial effects on anti-obesity. However, the underlying mechanisms of ZEA on LD modulation are still unclear. In the present study, ZEA efficiently inhibited LD accumulation and attenuated adipocyte proliferation by arresting the cell cycle. ZEA drove transcriptional alterations to reprogram a lipid oxidative metabolism phenotype in mature 3T3-L1 adipocytes. ZEA significantly decreased the TAG and FA content and modulated the dynamic alterations of LDs by upregulating the expression of lipases and the LD-mitochondrion contact site protein, perilipin 5 (PLIN5), and downregulating the LD fusion protein, fat-specific protein 27 (FSP27). Mechanistically, ZEA stimulated LD remodeling and ameliorated mitochondrial defects caused by large and unilocular LD accumulation by activating beta3-adrenergic receptor (beta3-AR) signaling. Furthermore, the knockdown of PLIN5 impaired the LD-mitochondrion interactions, thereby disrupting the role of ZEA in promoting mitochondrial fatty acid oxidation and respiratory chain operation. Collectively, the present study demonstrates that ZEA induces LD structural and metabolic remodeling by activating beta3-AR signaling and enhances PLIN5-mediated LD-mitochondrion interactions in hypertrophic white adipocytes, thereby enhancing oxidative capacity, and has the potential as a nutritional intervention for the prevention and treatment of obesity and associated metabolic syndrome.
ESTHER : Xie_2022_Food.Funct__
PubMedSearch : Xie_2022_Food.Funct__
PubMedID: 35924967

Title : Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1\/2-CREB-BDNF signaling pathways in PC12 cells - Chen_2022_Metab.Brain.Dis__
Author(s) : Chen C , Bu L , Liu H , Rang Y , Huang H , Xiao X , Ou G , Liu C
Ref : Metabolic Brain Disease , : , 2022
Abstract : 1,4-butanediol (1,4-BD) is a known gamma-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-alpha) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.
ESTHER : Chen_2022_Metab.Brain.Dis__
PubMedSearch : Chen_2022_Metab.Brain.Dis__
PubMedID: 35348994

Title : Phloroglucinols with hAChE and alpha-glucosidase inhibitory activities from the leaves of tropic Rhodomyrtus tomentosa - Yu_2022_Phytochemistry_203_113394
Author(s) : Yu MY , Liu SN , Luo EE , Jin Q , Liu H , Liu HY , Luo XD , Qin XJ
Ref : Phytochemistry , 203 :113394 , 2022
Abstract : Four undescribed phloroglucinol meroterpenoids, rhodotomentodiones A-D, and one undescribed phloroglucinol dimer, rhodotomentodimer A, were obtained and structurally established from tropic Rhodomyrtus tomentosa leaves. Their structures were unambiguously elucidated based on the comprehensive analyses of the NMR and MS spectroscopic data, electronic circular dichroism (ECD) calculation, and single-crystal X-ray diffraction. In particular, rhodotomentodiones A and B represent the first examples of phloroglucinol meroterpenoids featuring a unique gamma-pyranoid moiety. More importantly, rhodotomentodimer A exhibited the most potential human acetylcholinesterase (hAChE) and alpha-glucosidase inhibitory effects with IC(50) values of 7.5 microM and 5.6 microM, respectively. The possible interaction sites of the above potential hAChE and alpha-glucosidase inhibitor were achieved by molecular docking studies. These findings greatly enrich the diversity of natural products from Myrtaceae species, and provide potential candidates for the further development of anti-Alzheimer and antidiabetic diseases.
ESTHER : Yu_2022_Phytochemistry_203_113394
PubMedSearch : Yu_2022_Phytochemistry_203_113394
PubMedID: 36007662

Title : The efficacy of Azotobacter chroococcum in altering maize plant-defense responses to armyworm at elevated CO(2) concentration - Song_2022_Ecotoxicol.Environ.Saf_248_114296
Author(s) : Song Y , Liu J , Fu M , Liu H , Wang W , Wang S , Chen F
Ref : Ecotoxicology & Environmental Safety , 248 :114296 , 2022
Abstract : Elevated atmospheric carbon dioxide (eCO(2)) concentrations can alter the carbon:nitrogen ratio and palatability of host plants for herbivorous insects, but rhizobacteria likely mitigate the alteration and influence physiological adaptation of insects. In this study, we conducted transcriptomic analysis of maize (Zea mays) response to Azotobacter chroococcum (AC) inoculation under eCO(2) conditions in contrast to ambient CO(2) (aCO(2)), and studied the effects of plant-defense change of maize under eCO(2) on the oriental armyworm, Mythimna separata. Results showed that there were 16, 14, 16 and 135 differentially expressed genes that were associated with plant-defense response in maize leaves between aCO(2)-CK and aCO(2)-AC, eCO(2)-CK and eCO(2)-AC, aCO(2)-CK and eCO(2)-CK, aCO(2)-AC and eCO(2)-AC, respectively. Moreover, A. chroococcum inoculation and eCO(2) influenced plant hormone signal transduction of maize. Interestingly, A. chroococcum inoculation significantly decreased the contents of JA (jasmonic acid) and JA-Ile (isoleucine conjugate of JA) in leaves, but eCO(2) markedly increased contents of JA-Ile, JA and SA (salicylic acid). Compared to aCO(2), eCO(2) significantly decreased activity of protective enzyme (catalase), and increased activities of digestive (lipase and protease), protective (peroxidase) and detoxifying enzymes (carboxylesterase, Mixed-functional oxidase and glutathione s-transferase), prolonged developmental time, and decreased survival rate and body weight of larvae (P<0.05). A. chroococcum inoculation significantly increased the activity of protective enzyme (catalase), and decreased the activities of detoxifying enzymes (carboxylesterase, glutathione s-transferase and mixed-functional oxidase), thus increased the growth rate and body weight of larvae in comparison with no-inoculation of A. chroococcum (P<0.05). The indices of M. separata were significantly correlated with the foliar contents of JA, JA-Ile and SA (|r| = 0.44-0.85, P<0.05), indicating that A. chroococcum inoculation altered the physiological adaptation of M. separata under eCO(2) by disturbing defense substances in maize. Our results in understanding effects of A. chroococcum inoculation on maize resistance to herbivorous insects will be valuable for agricultural pest control in the future at eCO(2) conditions.
ESTHER : Song_2022_Ecotoxicol.Environ.Saf_248_114296
PubMedSearch : Song_2022_Ecotoxicol.Environ.Saf_248_114296
PubMedID: 36399994

Title : FAM135B sustains the reservoir of Tip60-ATM assembly to promote DNA damage response - Zhang_2022_Clin.Transl.Med_12_e945
Author(s) : Zhang K , Wu Q , Liu W , Wang Y , Zhao L , Chen J , Liu H , Liu S , Li J , Zhang W , Zhan Q
Ref : Clin Transl Med , 12 :e945 , 2022
Abstract : BACKGROUND: Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat-interactive protein 60-kDa/ataxia-telangiectasia-mutated (TIP60/ATM) axis-mediated DNA damage response (DDR) is vital for maintaining genomic integrity. METHODS: Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co-immunoprecipitation, proximity ligation assay and GST pull-down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. RESULTS: We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of gammaH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non-homologous end-joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre-existing TIP60-ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre-assembled TIP60-ATM complex participates in DDR. CONCLUSIONS: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60-ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment.
ESTHER : Zhang_2022_Clin.Transl.Med_12_e945
PubMedSearch : Zhang_2022_Clin.Transl.Med_12_e945
PubMedID: 35979619
Gene_locus related to this paper: human-FAM135B

Title : Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure-Activity Relationship, Kinetics and Interaction Mechanism - Pan_2022_Front.Nutr_9_892426
Author(s) : Pan J , Zhang Q , Zhang C , Yang W , Liu H , Lv Z , Liu J , Jiao Z
Ref : Front Nutr , 9 :892426 , 2022
Abstract : With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.
ESTHER : Pan_2022_Front.Nutr_9_892426
PubMedSearch : Pan_2022_Front.Nutr_9_892426
PubMedID: 35634373

Title : AND-Logic Strategy for Accurate Analysis of Alzheimer's Disease via Fluorescent Probe Lighted Up by Two Specific Biomarkers - Zhang_2021_Anal.Chem__
Author(s) : Zhang P , Fu C , Liu H , Guo X , Zhang Q , Gao J , Chen W , Yuan W , Ding C
Ref : Analytical Chemistry , : , 2021
Abstract : Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design.
ESTHER : Zhang_2021_Anal.Chem__
PubMedSearch : Zhang_2021_Anal.Chem__
PubMedID: 34353021

Title : Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia - Issotina_2021_Int.Immunopharmacol__108365
Author(s) : Issotina Zibrila A , Li Y , Wang Z , Zhao G , Liu H , Leng J , Ahasan Ali M , Ampofo Osei J , Kang YM , Liu J
Ref : Int Immunopharmacol , :108365 , 2021
Abstract : Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE.
ESTHER : Issotina_2021_Int.Immunopharmacol__108365
PubMedSearch : Issotina_2021_Int.Immunopharmacol__108365
PubMedID: 34815190

Title : The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review - Fan_2021_J.Alzheimers.Dis__
Author(s) : Fan F , Liu H , Shi X , Ai Y , Liu Q , Cheng Y
Ref : J Alzheimers Dis , : , 2021
Abstract : BACKGROUND: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. OBJECTIVE: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients. METHODS: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles. RESULTS: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Abeta agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD. CONCLUSION: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.
ESTHER : Fan_2021_J.Alzheimers.Dis__
PubMedSearch : Fan_2021_J.Alzheimers.Dis__
PubMedID: 34924395

Title : Acylphloroglucinol trimers from Callistemon salignus seeds: Isolation, configurational assignment, hAChE inhibitory effects, and molecular docking studies - Yu_2021_Bioorg.Chem_117_105404
Author(s) : Yu MY , Liu SN , Liu H , Meng QH , Qin XJ , Liu HY
Ref : Bioorg Chem , 117 :105404 , 2021
Abstract : Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC(50) values of 1.22 +/- 0.23, 2.28 +/- 0.19, and 4.96 +/- 0.39 microM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 microM, respectively.
ESTHER : Yu_2021_Bioorg.Chem_117_105404
PubMedSearch : Yu_2021_Bioorg.Chem_117_105404
PubMedID: 34749116

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

Title : A novel transcription factor UvCGBP1 regulates development and virulence of rice false smut fungus Ustilaginoidea virens - Chen_2021_Virulence_12_1563
Author(s) : Chen X , Li P , Liu H , Huang J , Luo C , Li G , Hsiang T , Collinge DB , Zheng L
Ref : Virulence , 12 :1563 , 2021
Abstract : Ustilaginoidea virens, causing rice false smut (RFS) is an economically important ascomycetous fungal pathogen distributed in rice-growing regions worldwide. Here, we identified a novel transcription factor UvCGBP1 (Cutinase G-box binding protein) from this fungus, which is unique to ascomycetes. Deletion of UvCGBP1 affected development and virulence of U. virens. A total of 865 downstream target genes of UvCGBP1 was identified using ChIP-seq and the most significant KEGG enriched functional pathway was the MAPK signaling pathway. Approximately 36% of target genes contain the AGGGG (G-box) motif in their promoter. Among the targets, deletion of UvCGBP1 affected transcriptional and translational levels of UvPmk1 and UvSlt2, both of which were important in virulence. ChIP-qPCR, yeast one-hybrid and EMSA confirmed that UvCGBP1 can bind the promoter of UvPmk1 or UvSlt2. Overexpression of UvPmk1 in the deltaUvCGBP1-33 mutant restored partially its virulence and hyphae growth, indicating that UvCGBP1 could function via the MAPK pathway to regulate fungal virulence. Taken together, this study uncovered a novel regulatory mechanism of fungal virulence linking the MAPK pathway mediated by a G-box binding transcription factor, UvCGBP1.
ESTHER : Chen_2021_Virulence_12_1563
PubMedSearch : Chen_2021_Virulence_12_1563
PubMedID: 34348597

Title : Prednisolone induces osteocytes apoptosis by promoting Notum expression and inhibiting PI3K\/AKT\/GSK3beta\/beta-catenin pathway - Li_2021_J.Mol.Histol__
Author(s) : Li C , Yang P , Liu B , Bu J , Liu H , Guo J , Hasegawa T , Si H , Li M
Ref : J Mol Histol , : , 2021
Abstract : The apoptosis of mature osteocytes is the main factor causing damage to the microstructure of cortical bone in glucocorticoid-induced osteoporosis (GIOP). Our previous research found damaged areas and empty osteocytes lacunae in the tibial cortical bone of GIOP mice. However, the specific mechanism has not been clarified. Recently, a study showed that the quality of the cortical bone significantly increased by knocking out Notum, a gene encoding alpha/beta hydrolase. However, it is not clear whether Notum affects cortical bone remodeling by participating in glucocorticoids (GCs)-induced apoptosis of osteocytes. The present study aimed to explore the correlation between Notum, osteocytes apoptosis, and cortical bone quality in GIOP. Prednisolone acetate was intragastrically administered to mice for two weeks. Histochemical staining was applied to evaluate changes in GIOP and Notum expression. Osteocytes were stimulated with prednisolone, and cell viability was assessed via CCK8. Hoechst 33342/PI staining, flow cytometry, RT-PCR, and western blot were used to detect osteocytes apoptosis, siRNA transfection efficiency, and expressions of pathway related factors. The results showed that the number of empty osteocytes lacunae increased in GIOP mice. TUNEL-stained apoptotic osteocytes and Notum immuno-positive osteocytes were also observed. Furthermore, prednisolone was found to promote Notum expression and osteocytes apoptosis in vitro. Knocking down Notum via siRNA partially restored osteocytes apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK3beta)/beta-catenin pathway. These findings showed GCs-induced osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3beta/beta-catenin pathway. Thus, Notum might be a potential therapeutic target for the treatment of GIOP.
ESTHER : Li_2021_J.Mol.Histol__
PubMedSearch : Li_2021_J.Mol.Histol__
PubMedID: 34297260

Title : Reduced neuropathy target esterase in pre-eclampsia suppresses tube formation of HUVECs via dysregulation of phospholipid metabolism - Li_2021_J.Cell.Physiol_236_4435
Author(s) : Li M , Shen X , Liu H , Yang B , Lu S , Tang M , Ling Y , Li Y , Kuang H
Ref : Journal of Cellular Physiology , 236 :4435 , 2021
Abstract : Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism.
ESTHER : Li_2021_J.Cell.Physiol_236_4435
PubMedSearch : Li_2021_J.Cell.Physiol_236_4435
PubMedID: 33184906

Title : Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss - Liu_2021_Front.Cell.Dev.Biol_9_640867
Author(s) : Liu H , Zhou C , Qi D , Gao Y , Zhu M , Tao T , Sun X , Xiao J
Ref : Front Cell Developmental Biology , 9 :640867 , 2021
Abstract : Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) pathways was inhibited by JZL184 and deletion of MAGL. Our in vivo study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
ESTHER : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedSearch : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedID: 33777947

Title : Improved efficiency of lipase-mediated epoxidation of alpha-pinene using H2O2 in single-phase systems - Su_2021_Mol.Catal_508_111585
Author(s) : Su W , Li Q , Liu Y , Qin Y , Liu H , Tang A
Ref : Molecular Catalysis , 508 :111585 , 2021
Abstract : Taking advantage of the intersolubility of alcohol and water, we developed an efficient single-phase system for chemoenzymatic epoxidation of (-)-alpha-pinene. Different from traditional methods, it included all substrates, such as (-)-alpha-pinene, acyl donors and oxidants, into one phase. Isopropanol was eventually selected as the epoxidation medium to optimize three controllable parameters. Under the optimal conditions of 3.35 mol/L ethyl acetate and 1.1 mol/L H2O2, the conversion and selectivity reached 92.3% and 86.6% in 90 min, respectively, and the initial reaction rate was 13.58x10-4 mmol.min-1.mg-1 with Novozym435 as a catalyst. Trisodium citrate was screened as an acid-trapping reagent to eliminate the negative impact of acetic acid on (-)-alpha-pinene oxide. The enzyme reusability was at least 6 cycles with a relative activity of 57.5% at the sixth cycle.
ESTHER : Su_2021_Mol.Catal_508_111585
PubMedSearch : Su_2021_Mol.Catal_508_111585
PubMedID:

Title : Protein engineering of stable IsPETase for PET plastic degradation by Premuse - Meng_2021_Int.J.Biol.Macromol_180_667
Author(s) : Meng X , Yang L , Liu H , Li Q , Xu G , Zhang Y , Guan F , Zhang W , Wu N , Tian J
Ref : Int J Biol Macromol , 180 :667 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is used widely by human beings, but is very difficult to degrade. Up to now, the PET degradation effect of PETase from Ideonella sakaiensis 201-F6 (IsPETase) variants with low stability and activity was not ideal. In this study, a mutation design tool, Premuse, was developed to integrate the sequence alignment and quantitative selection of the preferred mutations based on natural sequence evolution. Ten single point mutants were selected from 1486 homologous sequences using Premuse, and then two mutations (W159H and F229Y) with improved stability were screened from them. The derived double point mutant, W159H/F229Y, exhibited a strikingly enhanced enzymatic performance. Its T(m) and catalytic efficiency values (k(cat)/K(m)) respectively increased by 10.4 degreesC and 2.0-fold using p-NPP as the substrate compared with wild type. The degradation activity for amorphous PET was increased by almost 40-fold in comparison with wild type at 40 degreesC in 24 h. Additionally, the variant could catalyze biodegradation of PET bottle preform at a mean rate of 23.4 mg(PET)/h/mg(enzyme). This study allowed us to design the mutation more efficiently, and provides a tool for achieving biodegradation of PET pollution under mild natural environments.
ESTHER : Meng_2021_Int.J.Biol.Macromol_180_667
PubMedSearch : Meng_2021_Int.J.Biol.Macromol_180_667
PubMedID: 33753197
Gene_locus related to this paper: idesa-peth

Title : Enhanced Extracellular Production of IsPETase in Escherichia coli via Engineering of the pelB Signal Peptide - Shi_2021_J.Agric.Food.Chem_69_2245
Author(s) : Shi L , Liu H , Gao S , Weng Y , Zhu L
Ref : Journal of Agricultural and Food Chemistry , 69 :2245 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is one of the most commonly used plastics worldwide and its accumulation in the environment is a global problem. PETase from Ideonella sakaiensis 201-F6 was reported to exhibit higher hydrolytic activity and specificity for PET than other enzymes at ambient temperature. Enzymatic degradation of PET using PETase provides an attractive approach for plastic degradation and recycling. In this work, extracellular PETase was achieved by Escherichia coli BL21 using a Sec-dependent translocation signal peptide, pelB, for secretion. Furthermore, engineering of the pelB through random mutagenesis and screening was performed to improve the secretion efficiency of PETase. Evolved pelB enabled higher PETase secretion by up to 1.7-fold. The improved secretion of PETase led to more efficient hydrolysis of the PET model compound, bis (2-hydroxyethyl) terephthalic acid (BHET), PET powder, and PET film. Our study presents the first example of the increasing secretion of PETase by an engineered signal peptide, providing a promising approach to obtain extracellular PETase for efficient enzymatic degradation of PET.
ESTHER : Shi_2021_J.Agric.Food.Chem_69_2245
PubMedSearch : Shi_2021_J.Agric.Food.Chem_69_2245
PubMedID: 33576230
Gene_locus related to this paper: idesa-peth

Title : Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway - Liu_2021_J.Pharm.Sci__
Author(s) : Liu H , Jin Y , Menon R , Laskowich E , Bareford L , de Vilmorin P , Kolwyck D , Yeung B , Yi L
Ref : J Pharm Sci , : , 2021
Abstract : A liquid chromatography-mass spectrometry (LC-MS) method was developed to provide a fingerprint of polysorbate 80 (PS80) subspecies that enables identification of PS80 degradation pathway. The developed method demonstrates unique monoester peak profile of PS80 from different vendors, attributed by differences in relative abundance of the fatty acid monoesters. The LC-MS method was also applied to examine the susceptibility of PS80, at different grades, to auto-oxidation and hydrolysis. PS80 oxidative degradation induced by iron or occurred in open bottle without nitrogen overlay was found to follow the same pathway, but at a much faster rate in the former scenario. The oxidation preferentially occurs at the double bond of fatty acid chains, thus providing explanation on the faster degradation observed in PS80 at Chinese Pharmacopia (ChP) grade than at multi-compendial (MC) grade. In contrast, the difference in susceptibility of MC and ChP grade PS80 against esterase-induced hydrolysis in placebo was not pronounced. The method was also able to provide a fingerprint to identify both PS80 hydrolysis and oxidation in mAb drug product stability samples, but it requires a solid phase extraction step to remove protein prior to the analysis.
ESTHER : Liu_2021_J.Pharm.Sci__
PubMedSearch : Liu_2021_J.Pharm.Sci__
PubMedID: 34416271

Title : A Valuable Product of Microbial Cell Factories: Microbial Lipase - Yao_2021_Front.Microbiol_12_743377
Author(s) : Yao W , Liu K , Liu H , Jiang Y , Wang R , Wang W , Wang T
Ref : Front Microbiol , 12 :743377 , 2021
Abstract : As a powerful factory, microbial cells produce a variety of enzymes, such as lipase. Lipase has a wide range of actions and participates in multiple reactions, and they can catalyze the hydrolysis of triacylglycerol into its component free fatty acids and glycerol backbone. Lipase exists widely in nature, most prominently in plants, animals and microorganisms, among which microorganisms are the most important source of lipase. Microbial lipases have been adapted for numerous industrial applications due to their substrate specificity, heterogeneous patterns of expression and versatility (i.e., capacity to catalyze reactions at the extremes of pH and temperature as well as in the presence of metal ions and organic solvents). Now they have been introduced into applications involving the production and processing of food, pharmaceutics, paper making, detergents, biodiesel fuels, and so on. In this mini-review, we will focus on the most up-to-date research on microbial lipases and their commercial and industrial applications. We will also discuss and predict future applications of these important technologies.
ESTHER : Yao_2021_Front.Microbiol_12_743377
PubMedSearch : Yao_2021_Front.Microbiol_12_743377
PubMedID: 34616387

Title : Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease - Zhang_2021_Bioorg.Chem_116_105387
Author(s) : Zhang P , Wang Z , Mou C , Zou J , Xie Y , Liu Z , Benjamin Naman C , Mao Y , Wei J , Huang X , Dong J , Yang M , Wang N , Jin H , Liu F , Lin D , Liu H , Zhou F , He S , Zhang B , Cui W
Ref : Bioorg Chem , 116 :105387 , 2021
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
ESTHER : Zhang_2021_Bioorg.Chem_116_105387
PubMedSearch : Zhang_2021_Bioorg.Chem_116_105387
PubMedID: 34628225

Title : Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization - Li_2021_Int.J.Biol.Macromol_169_18
Author(s) : Li Z , Wang Y , Liu Z , Jin S , Pan K , Liu H , Liu T , Li X , Zhang C , Luo X , Song Y , Zhao J , Zhang T
Ref : Int J Biol Macromol , 169 :18 , 2021
Abstract : Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive.
ESTHER : Li_2021_Int.J.Biol.Macromol_169_18
PubMedSearch : Li_2021_Int.J.Biol.Macromol_169_18
PubMedID: 33309671
Gene_locus related to this paper: 9sphn-a0a101vlk1

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 : The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure - Wang_2021_Ecotoxicol.Environ.Saf_228_112959
Author(s) : Wang S , Zhao Q , Li G , Wang M , Liu H , Yu X , Chen J , Li P , Dong L , Zhou G , Cui Y , Liu L , Wang A
Ref : Ecotoxicology & Environmental Safety , 228 :112959 , 2021
Abstract : Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedID: 34808511

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 : Algorithm-based coevolution network identification reveals key functional residues of the alpha\/beta hydrolase subfamilies - Wu_2020_FASEB.J_34_1983
Author(s) : Wu Z , Liu H , Xu L , Chen HF , Feng Y
Ref : FASEB Journal , 34 :1983 , 2020
Abstract : Covariant residues identified by computational algorithms have provided new insights into enzyme evolutionary routes. However, the reliability and accuracy of routine statistical coupling analysis (SCA) are unable to satisfy the needs of protein engineering because SCA depends only on sequence information. Here, we set up a new SCA algorithm, SCA.SIM, by integrating structure information and MD simulation data. The more reliable covariant residues with high-quality scores are obtained from sequence alignment weighted by residual movement for eight related subfamilies, belonging to alpha/beta hydrolase family, with Candida antarctica lipase B (CALB). The 38 predicted covariant residues are tested for function by high-throughput quantitative evaluation in combination with activity and thermostability assays of a mutant library and deep sequencing. Based on the landscapes of both activity and thermostability, most mutants play key roles in catalysis, and some mutants gain 2.4- to 6-fold increase in half-life at 50 degrees C and 9- to 12-fold improvement in catalytic efficiency. The activity of double mutants for A225F/T103A is higher than those of A225F and T103A which means that SCA.SIM method might be useful for identifying the allosteric coupling. The SCA.SIM algorithm can be used for protein coevolution and enzyme engineering research.
ESTHER : Wu_2020_FASEB.J_34_1983
PubMedSearch : Wu_2020_FASEB.J_34_1983
PubMedID: 31907985

Title : Rv3091, An Extracellular Patatin-Like Phospholipase in Mycobacterium tuberculosis, Prolongs Intracellular Survival of Recombinant Mycolicibacterium smegmatis by Mediating Phagosomal Escape - Cui_2020_Front.Microbiol_11_2204
Author(s) : Cui Z , Dang G , Song N , Cui Y , Li Z , Zang X , Liu H , Wang Z , Liu S
Ref : Front Microbiol , 11 :2204 , 2020
Abstract : Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A(1), phospholipase A(2), and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.
ESTHER : Cui_2020_Front.Microbiol_11_2204
PubMedSearch : Cui_2020_Front.Microbiol_11_2204
PubMedID: 33042041

Title : Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure - Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
Author(s) : Fu F , Liu H , Lu X , Zhang R , Li L , Gao R , Xie J , Wang H , Pei C
Ref : Rapid Commun Mass Spectrom , :e8721 , 2020
Abstract : RATIONALE: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. METHODS: After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. RESULTS: The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman, and V-type nerve agents) were shown to bind more readily to K414 on the peptide. CONCLUSIONS: This research revealed the new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from nerve agents and providing an important tool for identification of sarin or cyclosarin in terrorist attacks.
ESTHER : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedSearch : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedID: 31899842

Title : Corrigendum to Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta. [Bioorg. Chem. 103 (2020) 104127] -
Author(s) : Liu H , He XZ , Feng MY , Zeng Y , Rauwolf TJ , Shao LD , Ni W , Yan H , Porco JA, Jr. , Hao XJ , Qin XJ , Liu HY
Ref : Bioorg Chem , 108 :104579 , 2020
PubMedID: 33493929

Title : Polymethylated phloroglucinol meroterpenoids from Rhodomyrtus tomentosa and their antibacterial and acetylcholinesterase inhibitory effects - Liu_2020_Chem.Biodivers__
Author(s) : Liu H , Qin XJ , Liu HY , Li P , Bi LS
Ref : Chem Biodivers , : , 2020
Abstract : Rhotomentodiones C-E ( 1 - 3 ), three new polymethylated phloroglucinol meroterpenoids with diverse configurations, were isolated from the twigs and leaves of Rhodomyrtus tomentosa . Their structures and absolute configurations were established mainly by means of comprehensive spectroscopic data and electron circular dichroism (ECD) calculation. Among them, compound 2 exhibited both antibacterial activity with an MIC value of 12.5 mu g/mL against Propionibacterium acnes and AChE inhibitory activity with an IC 50 value of 22.9 mu M.
ESTHER : Liu_2020_Chem.Biodivers__
PubMedSearch : Liu_2020_Chem.Biodivers__
PubMedID: 32761773

Title : Neuregulin-1beta Protects the Rat Diaphragm during Sepsis against Oxidative Stress and Inflammation by Activating the PI3K\/Akt Pathway - Liu_2020_Oxid.Med.Cell.Longev_2020_1720961
Author(s) : Liu H , Weng XJ , Yao JY , Zheng J , Lv X , Zhou XH , Jiang H , Li ST
Ref : Oxid Med Cell Longev , 2020 :1720961 , 2020
Abstract : Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1beta (NRG-1beta) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1beta therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1beta application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1beta treatment. In vitro, the effects of NRG-1beta on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1beta inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1beta. And NRG-1beta activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1beta, while MK-2206 blocked these effects of NRG-1beta. In conclusion, our findings underlined that NRG-1beta could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.
ESTHER : Liu_2020_Oxid.Med.Cell.Longev_2020_1720961
PubMedSearch : Liu_2020_Oxid.Med.Cell.Longev_2020_1720961
PubMedID: 32765805

Title : FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling - Chen_2020_Biol.Open_9_bio048462
Author(s) : Chen Y , Liu P , Shen D , Liu H , Xu L , Wang J , Sun H , Wu H
Ref : Biol Open , 9 : , 2020
Abstract : FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and beta-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling.
ESTHER : Chen_2020_Biol.Open_9_bio048462
PubMedSearch : Chen_2020_Biol.Open_9_bio048462
PubMedID: 31988090
Gene_locus related to this paper: human-f172a

Title : Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats - Ma_2020_Neuroreport_31_819
Author(s) : Ma B , Cai Y , Zhang X , Wang F , Zhuang D , Liu H , Liu Y , Zhou W
Ref : Neuroreport , 31 :819 , 2020
Abstract : Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50microg/kg/infusion) under the fixed ratio 1 schedule for 14days and then drug-seeking was extinguished for 10days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction.
ESTHER : Ma_2020_Neuroreport_31_819
PubMedSearch : Ma_2020_Neuroreport_31_819
PubMedID: 32576772

Title : RMS2 encoding a GDSL lipase mediates lipid homeostasis in anthers to determine rice male fertility - Zhao_2020_Plant.Physiol__
Author(s) : Zhao J , Long T , Wang Y , Tong X , Tang J , Li J , Wang H , Tang L , Li Z , Shu Y , Liu X , Li S , Liu H , Wu Y , Zhang J
Ref : Plant Physiol , : , 2020
Abstract : Plant male gametogenesis is a coordinated effort involving both reproductive tissues and sporophytic tissues, in which lipid metabolism plays an essential role. Although GDSL esterases/lipases have been well known as key enzymes for many plant developmental processes and stress responses, their functions in reproductive development remain unclear. Here, we report the identification of a rice male sterile 2 (rms2) mutant in rice (Oryza sativa), which is completely male sterile due to the defects in tapetum degradation, cuticle formation in sporophytic tissues, and impaired exine and central vacuole development in pollen grains. RMS2 was map-based cloned as an endoplasmic reticulum-localized GDSL lipase gene, which is predominantly transcribed during early anther development. In rms2, a three-nucleotides deletion and one base substitution (TTGT to A) occurred within the GDSL domain, which reduced the lipid hydrolase activity of the resulting protein and led to significant changes in the content of 16 lipid components and numerous other metabolites as revealed by a comparative metabolic analysis. Furthermore, RMS2 is directly targeted by male fertility regulators Undeveloped Tapetum 1 (UDT1) and Persistent Tapetal Cell 1 (PTC1) both in vitro and in vivo, suggesting that RMS2 may serve as a key node in the rice male fertility regulatory network. These findings shed light on the function of GDSLs in reproductive development and provide a promising gene resource for hybrid rice breeding.
ESTHER : Zhao_2020_Plant.Physiol__
PubMedSearch : Zhao_2020_Plant.Physiol__
PubMedID: 32029522

Title : A Review of the Pharmacological Properties of Psoralen - Ren_2020_Front.Pharmacol_11_571535
Author(s) : Ren Y , Song X , Tan L , Guo C , Wang M , Liu H , Cao Z , Li Y , Peng C
Ref : Front Pharmacol , 11 :571535 , 2020
Abstract : Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/beta-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B(AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARgamma), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin 4/5/6/8/12/13 (IL-4/5/6/8/12/13), GATA-3, acetylcholinesterase (AChE), and the hypothalamic-pituitary-adrenal (HPA) axis. Finally, the toxic effects and mechanisms of action of psoralen have also been reviewed.
ESTHER : Ren_2020_Front.Pharmacol_11_571535
PubMedSearch : Ren_2020_Front.Pharmacol_11_571535
PubMedID: 33013413

Title : Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects - Qin_2020_Bioorg.Chem__104519
Author(s) : Qin XJ , Liu H , Li PP , Ni W , He L , Khan A , Hao XJ , Liu HY
Ref : Bioorg Chem , :104519 , 2020
Abstract : Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two beta-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC(50) value of 8.68 M. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.
ESTHER : Qin_2020_Bioorg.Chem__104519
PubMedSearch : Qin_2020_Bioorg.Chem__104519
PubMedID: 33293058

Title : Kinetics and Mechanism of Solvent Influence on the Lipase-Catalyzed 1,3-Diolein Synthesis - Wang_2020_ACS.Omega_5_24708
Author(s) : Wang Z , Dai L , Liu D , Liu H , Du W
Ref : ACS Omega , 5 :24708 , 2020
Abstract : 1,3-Diacylglycerol preparation has roused increasing attention in recent years as the 1,3-diacylglycerol-rich oils can suppress the deposition of visceral fat and prevent the body weight increasing. Lipozyme TL IM-mediated esterification of oleic acid with monoolein was effective for 1,3-diacylglycerol production. During the esterification process, the solvent shows obvious influence on the diolein synthesis as well as the 1,3-diolein production. This work investigated the related kinetics and mechanism of the solvent effect on the esterification and Lipozyme TL IM performance. The results indicated that both the esterification rate constant and the acyl migration rate constant positively correlated with the logP of the solvent, while the site specificity of lipase has negative correlation with solvent logP. The acylation toward the 2-position of 1-monoolein was more sensitive to the solvent logP compared to the 1-position of glycerides. Molecular dynamics simulation revealed that solvents with different logP influenced the structure of Lipozyme TL IM including RMSD, hydrogen bond, and radial distribution function to a large extent, which subsequently led to the catalytic activity and selectivity variation of the lipase.
ESTHER : Wang_2020_ACS.Omega_5_24708
PubMedSearch : Wang_2020_ACS.Omega_5_24708
PubMedID: 33015488

Title : Induced fluorescent enhancement of protein-directed synthesized gold nanoclusters for selective and sensitive detection of flame retardants - Liu_2020_Sci.Total.Environ_713_136488
Author(s) : Liu H , Zhu N , Li M , Huang X , Wu P , Hu Z , Shuai J
Ref : Sci Total Environ , 713 :136488 , 2020
Abstract : Organophosphate flame retardants (OPFRs), typical toxic and hazardous pollutants, are called for new detection approaches to avoid laborious synthetic procedures and large and expensive instruments. Hence, a novel fluorescent probe was constructed for quantitative detection of OPFRs via heightening the fluorescence of acetylcholinesterase synthesized gold nanoclusters (AChE-AuNCs). The as-prepared AChE-AuNCs exhibited high fluorescence emission at about 398 nm with the average particle size of about 1.60 nm. When the AChE-AuNCs was applied to the proposed fluorescent detection, excellent sensitivity with wide linear range (50-1000 ng L(-1)) and low detection limit (30 ng L(-1)) for TClPP with the response time less than 1 h were achieved. The fluorescent probe could be extended to detect other three types of OPFRs (TEP, TPHP, and TBOEP) and the target pollutants could be detectable in the presence of halogenated flame retardants. The mechanism might be mainly contributed by the interaction between OPFRs and AChE-AuNCs restricting internal vibration consumption of their capping ligands. The proposed detection approach could be easily operated and was not involved with other intermediate products. Therefore, AChE-AuNCs could be a promising fluorescent probe for rapid, selective and sensitive detection of OPFRs and even in the practical application.
ESTHER : Liu_2020_Sci.Total.Environ_713_136488
PubMedSearch : Liu_2020_Sci.Total.Environ_713_136488
PubMedID: 31955081

Title : Selenoprotein F knockout leads to glucose and lipid metabolism disorders in mice - Zheng_2020_J.Biol.Inorg.Chem_25_1009
Author(s) : Zheng X , Ren B , Li X , Yan H , Xie Q , Liu H , Zhou J , Tian J , Huang K
Ref : J Biol Inorg Chem , 25 :1009 , 2020
Abstract : Selenoprotein F (Selenof), an endoplasmic reticulum (ER)-resident protein, is considered to be involved in glycoprotein folding and quality control in the ER. However, its function has not yet been thoroughly addressed. In this study, proteomics analysis revealed that Selenof deficiency in mice led to the differential expression of hepatic proteins associated with glucose and lipid metabolism. The phenotype analysis revealed that Selenof knockout mice showed glucose intolerance and insulin reduction, even with a normal diet. Additionally, Selenof knockout exacerbated high-fat diet-induced obesity, hyperglycemia, glucose intolerance, and hepatic steatosis. Furthermore, lipoprotein lipase and carboxylesterase 1D, two glycoproteins involved in lipid metabolism, were significantly decreased in the liver of Selenof knockout mice with a normal or high-fat diet. Collectively, these findings suggested that Selenof deficiency might cause the perturbation of glycoprotein quality control and thus contribute to glucose and lipid metabolism disorders, implying a novel biological function of Selenof.
ESTHER : Zheng_2020_J.Biol.Inorg.Chem_25_1009
PubMedSearch : Zheng_2020_J.Biol.Inorg.Chem_25_1009
PubMedID: 32995962

Title : Metabolism and pharmacological activities of the natural health-benefiting compound diosmin - Zheng_2020_Food.Funct_11_8472
Author(s) : Zheng Y , Zhang R , Shi W , Li L , Liu H , Chen Z , Wu L
Ref : Food Funct , 11 :8472 , 2020
Abstract : Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKbeta, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.
ESTHER : Zheng_2020_Food.Funct_11_8472
PubMedSearch : Zheng_2020_Food.Funct_11_8472
PubMedID: 32966476

Title : Cancer-related fatigue and biochemical parameters among cancer patients with different stages of sarcopenia - Wang_2020_Support.Care.Cancer_28_581
Author(s) : Wang B , Thapa S , Zhou T , Liu H , Li L , Peng G , Yu S
Ref : Support Care Cancer , 28 :581 , 2020
Abstract : PURPOSE: Cancer-related fatigue (CRF) is a pervasive symptom experienced by cancer patients. Sarcopenia has been suggested as a treatment target of CRF. This study aims to assess the differences of CRF and biochemical markers among different stages of sarcopenia which remain poorly delineated. METHODS: A total of 187 patients were included in this cross-sectional study. Based on muscle mass (skeletal muscle index, SMI), muscle strength (handgrip strength), and physical performance (SARC-F score), patients were divided into four groups (non-sarcopenia, pre-sarcopenia, sarcopenia, and severe sarcopenia). Cancer-related fatigue was measured by the Brief Fatigue Inventory (BFI). Biochemical markers were measured by routine blood tests. RESULTS: The BFI score was significantly associated with sarcopenia stage (r=0.500; P<0.001). Cancer patients in severe sarcopenia group suffered from worse CRF than those in non-sarcopenia, pre-sarcopenia, and sarcopenia groups (P<0.001). In the multivariate linear regression model (R(2)=0.542), CRF was significantly correlated with SARC-F score (standardized B=0.519; P<0.001) and high-sensitivity C-reactive protein (standardized B=0.389; P=0.004). Serum albumin and cholinesterase were statistically correlated with both sarcopenia stage and CRF. CONCLUSIONS: The significantly increased occurrence and severity of CRF in cancer patients with sarcopenia suggest that sarcopenia may be a crucial target to improve the management of CRF. Circulating albumin and cholinesterase have the potential to predicting sarcopenia as biomarkers.
ESTHER : Wang_2020_Support.Care.Cancer_28_581
PubMedSearch : Wang_2020_Support.Care.Cancer_28_581
PubMedID: 31102055

Title : Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta - Liu_2020_Bioorg.Chem_103_104127
Author(s) : Liu H , He XZ , Feng MY , Yuan Z , Rauwolf TJ , Shao LD , Ni W , Yan H , Porco JA, Jr. , Hao XJ , Qin XJ , Liu HY
Ref : Bioorg Chem , 103 :104127 , 2020
Abstract : Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC(50) values of 3.22 +/- 0.36, 3.82 +/- 0.22, and 2.55 +/- 0.28 microM, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds.
ESTHER : Liu_2020_Bioorg.Chem_103_104127
PubMedSearch : Liu_2020_Bioorg.Chem_103_104127
PubMedID: 32745755

Title : Inhibition of cell proliferation and migration in nonsmall cell lung cancer cells through the suppression of LYPLA1 - Mohammed_2019_Oncol.Rep_41_973
Author(s) : Mohammed A , Zhang C , Zhang S , Shen Q , Li J , Tang Z , Liu H
Ref : Oncol Rep , 41 :973 , 2019
Abstract : Lysophospholipase1 (LYPLA1) also known as acylprotein thioesterase1 (APT1) belongs to the superfamily of alpha/beta hydrolase. It has been found to have the properties of a homodimer by manifesting depalmitoylation as well as lysophospholipase activity. LYPLAs are under the control of both microRNAs, miR138 and miR424. They were observed to be significantly overexpressed in chronic lymphocytic leukemia cells. To date, LYPLAs are the sole enzymes recognized to activate depalmitoylation. In this study, we provide the expression pattern of LYPLA1 in nonsmall cell lung cancer (NSCLC) using four different NSCLC cell lines. Western blot analysis and RTPCR were performed to detect the protein expression and mRNA expression of LYPLA1 in NSCLC cell lines. We detected the highest LYPLA1 protein expression level in SPCA1 cells followed by A549 cells, and the highest LYPLA1 mRNA expression level was detected in the SPCA1 cells followed by the H1299 cell line. We found that suppression of LYPLA1 expression using smallinterfering RNA significantly inhibited proliferation, migration and invasion of the LYPLA1transfected NSCLC cells. Furthermore, we explored the involvement of LYPLA1 in the regulation of epithelialmesenchymal transition (EMT). The epithelial marker Ecadherin was significantly increased, while mesenchymal markers Ncadherin, vimentin and SNAIL were markedly decreased in the LYPLA1silenced cells. Collectively the results of the present study suggest that the LYPLA1 gene plays a tumorpromotor role in NSCLC cells in vitro.
ESTHER : Mohammed_2019_Oncol.Rep_41_973
PubMedSearch : Mohammed_2019_Oncol.Rep_41_973
PubMedID: 30431103
Gene_locus related to this paper: human-LYPLA1

Title : A Simple 3D-Printed Enzyme Reactor Paper Spray Mass Spectrometry Platform for Detecting BuChE Activity in Human Serum - Yang_2019_Anal.Chem_91_12874
Author(s) : Yang Y , Liu H , Chen Z , Wu T , Jiang Z , Tong L , Tang B
Ref : Analytical Chemistry , 91 :12874 , 2019
Abstract : To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman's method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis.
ESTHER : Yang_2019_Anal.Chem_91_12874
PubMedSearch : Yang_2019_Anal.Chem_91_12874
PubMedID: 31518111

Title : Isolation and Synthesis of Novel Meroterpenoids from Rhodomyrtus tomentosa: Investigation of a Reactive Enetrione Intermediate - Qin_2019_Angew.Chem.Int.Ed.Engl_58_4291
Author(s) : Qin XJ , Rauwolf TJ , Li PP , Liu H , McNeely J , Hua Y , Liu HY , Porco JA, Jr.
Ref : Angew Chem Int Ed Engl , 58 :4291 , 2019
Abstract : Rhodomyrtusials A-C, the first examples of triketone-sesquiterpene meroterpenoids featuring a unique 6/5/5/9/4 fused pentacyclic ring system were isolated from Rhodomyrtus tomentosa, along with several biogenetically-related dihydropyran isomers. Two bis-furans and one dihydropyran isomer showed acetylcholinesterase (AChE) inhibitory activity. Structures of the isolates were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Bioinspired total syntheses of six isolates were achieved in six steps utilizing a reactive enetrione intermediate generated in situ from a readily available hydroxy-endoperoxide precursor.
ESTHER : Qin_2019_Angew.Chem.Int.Ed.Engl_58_4291
PubMedSearch : Qin_2019_Angew.Chem.Int.Ed.Engl_58_4291
PubMedID: 30681258

Title : Rational design of a Yarrowia lipolytica derived lipase for improved thermostability - Zhang_2019_Int.J.Biol.Macromol_137_1190
Author(s) : Zhang H , Sang J , Zhang Y , Sun T , Liu H , Yue R , Zhang J , Wang H , Dai Y , Lu F , Liu F
Ref : Int J Biol Macromol , 137 :1190 , 2019
Abstract : To improve the thermostability of the lipase LIP2 from Yarrowia lipolytica, molecular dynamics (MD) simulations at various temperatures were used to investigate the common fluctuation sites of the protein, which are considered to be thermally weak points. Two of these residues were selected for mutations to improve the enzyme's thermostability, and the variants predicted by MD simulations to have improved thermostability were expressed in Pichia pastoris GS115 for further investigations. According to the proline rule, the high fluctuation site S115 or V213 was replaced with proline residue, the two lipase mutants S115P and V213P were obtained. The mutant V213P exhibited evidently enhanced thermostability with an approximately 70% longer half-life at 50 degrees C than that of the parent LIP2 expressed in P. pastoris. The temperature optimum of V213P was 42 degrees C, which was about 5.0 degrees C higher than that of the parent LIP2, while its specific catalytic activity was comparable to that of the parent and reached 876.5U/mg. The improved thermostability of V213P together with its high catalytic efficiency indicated that the rational design strategy employed here can be efficiently applied for structure optimization of industrially important enzymes.
ESTHER : Zhang_2019_Int.J.Biol.Macromol_137_1190
PubMedSearch : Zhang_2019_Int.J.Biol.Macromol_137_1190
PubMedID: 31299254
Gene_locus related to this paper: yarli-lip2

Title : Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway - Luo_2019_Front.Pharmacol_10_395
Author(s) : Luo H , Xiang Y , Qu X , Liu H , Liu C , Li G , Han L , Qin X
Ref : Front Pharmacol , 10 :395 , 2019
Abstract : Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by impairments of cognitive function as a result of synaptic deficits and neuronal loss, is associated with inflammation. Apelin-13, a predominant neuropeptide with inhibiting effect on inflammation, has beneficial effects on cognition memory and neuronal damage. However, whether apelin-13 can protect neurons to ameliorate cognitive deficits in AD by inhibiting the inflammatory response remains largely unknown. To test this hypothesis, rats were intracerebroventricularly (ICV) injected with streptozotocin (3 mg/kg) alone or in combination with apelin-13 (2 mug). And tyrosine receptor kinase B (TrkB) blocker K252a (200 nM) was administrated 10 min before apelin injection. Furthermore, cognitive performance was assessed by new object recognition (NOR) and Y-maze tests. Protein expression of apelin, APJ, microglial marker (IBA1), astroglia marker (GFAP), interleukin 1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB) in the hippocampus were examined by western blotting or immunohistochemistry. And the gene expression of IBA1, GFAP, IL-1beta, TNF-alpha, and SYP were detected by real-time quantitative polymerase chain reaction (PCR). Inflammatory disorder in the hippocampus was tested by hematoxylin and eosin (H&E) staining. The enzyme-linked immunosorbent assay (ELISA) was used to study the expression level of acetylcholine. And the activity of acetylcholinesterase was detected by Acetylcholinesterase Assay Kit. We observed that apelin/APJ signaling was downregulated in the hippocampus of rats administrated with STZ. Apelin-13 was found to significantly ameliorate STZ-induced AD-like phenotypes including congnitive deficit, cholinergic disfunction and the damage of neuron and synaptic plasticity. Moreover, apelin-13 inhibited microglia and astrocyte activation, reduced IL-1beta and TNF-alpha expression and hippocampal BDNF/TrkB expression deficit in AD rats. Finally, apelin-13-mediated effects were blocked by TrkB receptor antagonist K252a. These results suggest that apelin-13 upregulates BDNF/TrkB pathway against cognitive deficit in a STZ-induced rat model of sporadic AD by attenuating inflammation.
ESTHER : Luo_2019_Front.Pharmacol_10_395
PubMedSearch : Luo_2019_Front.Pharmacol_10_395
PubMedID: 31040784

Title : Seawater acidification increases copper toxicity: A multi-biomarker approach with a key marine invertebrate, the Pacific Oyster Crassostrea gigas - Cao_2019_Aquat.Toxicol_210_167
Author(s) : Cao R , Zhang T , Li X , Zhao Y , Wang Q , Yang D , Qu Y , Liu H , Dong Z , Zhao J
Ref : Aquat Toxicol , 210 :167 , 2019
Abstract : Ocean acidification (OA) has been found to increase the release of free Cu(2+) in seawater. However, only a handful of studies have investigated the influence of OA on Cu accumulation and cellular toxicity in bivalve species. In this study, Pacific oysters, Crassostrea gigas, were exposed to 25 mug/L Cu(2+) at three pH levels (8.1, 7.8 and 7.6) for 14 and 28 days. Physiological and histopathological parameters [(clearance rate (CR), respiration rate (RR), histopathological damage and condition index (CI)), oxidative stress and neurotoxicity biomarkers [superoxide dismutase (SOD) and glutathione transferase (GST) activities, lipid peroxidation (LPO) and acetylcholinesterase (AChE) activity], combined with glycolytic enzyme activities [pyruvate kinase (PK) and hexokinase (HK)] were investigated in C. gigas. The bioconcentration of Cu was increased in soft tissues of Cu-exposed oysters under OA. Our results suggest that both OA and Cu could lead to physiological disturbance, oxidative stress, cellular damage, disturbance in energy metabolism and neurotoxicity in oysters. The inhibited CR, increased glycolytic enzymes activities and decreased CI suggested that the energy metabolism strategy adopted by oysters was not sustainable in the long term. Furthermore, integrated biomarker response (IBR) results found that OA and Cu exposure lead to severe stress to oysters, and co-exposure was the most stressful condition. Results from this study highlight the need to include OA in future environmental assessments of pollutants and hazardous materials to better elucidate the risks of those environmental perturbations.
ESTHER : Cao_2019_Aquat.Toxicol_210_167
PubMedSearch : Cao_2019_Aquat.Toxicol_210_167
PubMedID: 30870663

Title : mir-234 controls neuropeptide release at the Caenorhabditis elegans neuromuscular junction - Snieckute_2019_Mol.Cell.Neurosci_98_70
Author(s) : Snieckute G , Baltaci O , Liu H , Li L , Hu Z , Pocock R
Ref : Molecular & Cellular Neurosciences , 98 :70 , 2019
Abstract : miR-137 is a highly conserved microRNA (miRNA) that is associated with the control of brain function and the etiology of psychiatric disorders including schizophrenia and bipolar disorder. The Caenorhabditis elegans genome encodes a single miR-137 ortholog called mir-234, the function of which is unknown. Here we show that mir-234 is expressed in a subset of sensory, motor and interneurons in C. elegans. Using a mir-234 deletion strain, we systematically examined the development and function of these neurons in addition to global C. elegans behaviors. We were however unable to detect phenotypes associated with loss of mir-234, possibly due to genetic redundancy. To circumvent this issue, we overexpressed mir-234 in mir-234-expressing neurons to uncover possible phenotypes. We found that mir-234-overexpression endows resistance to the acetylcholinesterase inhibitor aldicarb, suggesting modification of neuromuscular junction (NMJ) function. Further analysis revealed that mir-234 controls neuropeptide levels, therefore positing a cause of NMJ dysfunction. Together, our data suggest that mir-234 functions to control the expression of target genes that are important for neuropeptide maturation and/or transport in C. elegans. SIGNIFICANCE STATEMENT: The miR-137 family of miRNAs is linked to the control of brain function in humans. Defective regulation of miR-137 is associated with psychiatric disorders that include schizophrenia and bipolar disorder. Previous studies have revealed that miR-137 is required for the development of dendrites and for controlling the release of fast-acting neurotransmitters. Here, we analyzed the function a miR-137 family member (called mir-234) in the nematode animal model using anatomical, behavioral, electrophysiological and neuropeptide analysis. We reveal for the first time that mir-234/miR-137 is required for the release of slow-acting neuropeptides, which may also be of relevance for controlling human brain function.
ESTHER : Snieckute_2019_Mol.Cell.Neurosci_98_70
PubMedSearch : Snieckute_2019_Mol.Cell.Neurosci_98_70
PubMedID: 31200102

Title : The clinical parameters for the diagnosis of hepatitis B virus related acute-on-chronic liver failure with sepsis - Xue_2019_Sci.Rep_9_2558
Author(s) : Xue R , Zhu Y , Liu H , Meng Q
Ref : Sci Rep , 9 :2558 , 2019
Abstract : It is still unknown that whether sepsis with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) fit into the conventional diagnostic criteria of sepsis. Our aim was to investigate the potential clinical parameters for the diagnosis of HBV-ACLF with sepsis. A retrospective study was conducted in 43 patients with HBV-ACLF and sepsis who underwent orthotopic liver transplantation. All patients were divided into three groups according to the pathological results and laboratory test results. Immunohistochemistry (IHC) staining, hematoxylin-eosin (HE) staining and Gordon Sweet's reticulin staining were performed in this study. Alanine aminotransferase (ALT), aspartale aminotransferase (AST), total bilirubin (TBiL), cholinesterase (CHE), albumin (ALB), prothrombin activity (PTA), blood routine examination were detected. The results being chosen at admission and before transplantation were analyzed. TBiL had a significant increase (563.5 +/- 191.8 umol/L vs. 383.9 +/- 157.6 umol/L, 438.3 +/- 154.7 umol/L, P = 0.031) and ALT significantly decreased (81.6 +/- 66.4 U/L, 754.5 +/- 1084.7 U/L, 120.6 +/- 102.5 U/L, P = 0.005) in sepsis group before liver transplantation. When sepsis appeared in patients with HBV-ACLF, the ratio of PLT to WBC count before liver transplantation was much lower than it at admission (4.6 +/- 2.0 vs. 16.1 +/- 7.2, P = 0.000). In conclusion, the clinical parameters of sepsis in patients with HBV-ACLF should be reset. The ratio of PLT/WBC and (WBCBLT/WBCAA)/ (PLTBLT/PLTAA) could remind us the occurring of sepsis in patients with HBV-ACLF.
ESTHER : Xue_2019_Sci.Rep_9_2558
PubMedSearch : Xue_2019_Sci.Rep_9_2558
PubMedID: 30796255

Title : Identifying the Potential Substrates of the Depalmitoylation Enzyme Acyl-protein Thioesterase 1 - Liu_2019_Curr.Mol.Med_19_364
Author(s) : Liu H , Yan P , Ren J , Wu C , Yuan W , Rao M , Zhang Z , Kong E
Ref : Curr Mol Med , 19 :364 , 2019
Abstract : BACKGROUND: The homeostasis of palmitoylation and depalmitoylation is involved in various cellular processes, the disruption of which induces severe physiological consequences. Acyl-protein thioesterase (APT) and palmitoyl-protein thioesterases (PPT) catalyze the depalmitoylation process. The natural mutation in human PPT1 caused neurodegenerative disease, yet the understanding of APT1 remains to be elucidated. While the deletion of APT1 in mice turned out to be potentially embryonically lethal, the decoding of its function strictly relied on the identification of its substrates. OBJECTIVE: To determine the potential substrates of APT1 by using the generated human APT1 knockout cell line. METHODS: The combined techniques of palmitoyl-protein enrichment and massspectrometry were used to analyze the different proteins. Palmitoyl-proteins both in HEK293T and APT1-KO cells were extracted by resin-assisted capture (RAC) and data independent acquisition (DIA) quantitative method of proteomics for data collection. RESULTS: In total, 382 proteins were identified. The gene ontology classification segregated these proteins into diverse biological pathways e.g. endoplasmic reticulum process and ubiquitin-mediated proteolysis. A few potential substrates were selected for verification; indeed, major proteins were palmitoylated. Importantly, their levels of palmitoylation were clearly changed in APT1-KO cells. Interestingly, the proliferation of APT1-KO cells escalated dramatically as compared to that of the WT cells, which could be rescued by APT1 overexpression. CONCLUSION: Our study provides a large scale of potential substrates of APT1, thus facilitating the understanding of its intervened molecular functions.
ESTHER : Liu_2019_Curr.Mol.Med_19_364
PubMedSearch : Liu_2019_Curr.Mol.Med_19_364
PubMedID: 30914023

Title : Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin - Fu_2019_Toxicology_430_152346
Author(s) : Fu F , Chen J , Zhao P , Lu X , Gao R , Chen D , Liu H , Wang H , Pei C
Ref : Toxicology , 430 :152346 , 2019
Abstract : V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2-(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans.
ESTHER : Fu_2019_Toxicology_430_152346
PubMedSearch : Fu_2019_Toxicology_430_152346
PubMedID: 31857189

Title : A Flexible Acetylcholinesterase-Modified Graphene for Chiral Pesticide Sensor - Zhang_2019_J.Am.Chem.Soc_141_14643
Author(s) : Zhang Y , Liu X , Qiu S , Zhang Q , Tang W , Liu H , Guo Y , Ma Y , Guo X , Liu Y
Ref : Journal of the American Chemical Society , 141 :14643 , 2019
Abstract : Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 mug/L and 0.32 mug/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission.
ESTHER : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedSearch : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedID: 31448915

Title : Genome-wide association studies reveal genetic loci associated with plasma cholinesterase activity in ducks - Xu_2019_Anim.Genet_50_287
Author(s) : Xu Y , Liu H , Jiang Y , Fan W , Hu J , Zhang Y , Guo Z , Xie M , Huang W , Liu X , Zhou Z , Hou S
Ref : Anim Genet , 50 :287 , 2019
Abstract : Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck x mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.
ESTHER : Xu_2019_Anim.Genet_50_287
PubMedSearch : Xu_2019_Anim.Genet_50_287
PubMedID: 30994195
Gene_locus related to this paper: anapl-BCHE

Title : Shen-Yuan-Dan Capsule Attenuates Atherosclerosis and Foam Cell Formation by Enhancing Autophagy and Inhibiting the PI3K\/Akt\/mTORC1 Signaling Pathway - Zhou_2019_Front.Pharmacol_10_603
Author(s) : Zhou M , Ren P , Zhang Y , Li S , Li M , Li P , Shang J , Liu W , Liu H
Ref : Front Pharmacol , 10 :603 , 2019
Abstract : Background and Aim: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a crucial role in autophagy and inflammation. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a Chinese medicine used for treating angina pectoris, has anti-atherosclerotic and anti-inflammatory effects in mice. However, its effects on autophagy and the PI3K/Akt/mTORC1 signaling pathway remain unclear. This study aimed to explore the effects of SYDC on autophagy and PI3K/Akt/mTORC1 signaling in the apolipoprotein E knockout (ApoE(-/-)) mouse model and in macrophage-derived foam cells to delineate the underlying mechanism. Methods: After 6 weeks of high-fat diet, ApoE(-/-) mice were randomly grouped into control, Lipitor, low-SYDC (SYDC-L), middle-SYDC (SYDC-M), and high-SYDC (SYDC-H) groups (n = 10). The mice were intragastrically administered the respective treatment for 6 weeks. Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (80 microg/ml) for 24 h and then pretreated with SYDC freeze-dried powder for another 24 h. Cells treated with SYDC were co-cultured for 24 h with LY294002, tricirbine, and rapamycin to investigate the effects on the PI3K/Akt/mTORC1 signaling pathway. Results: SYDC ameliorated blood lipid levels, reduced the atherosclerotic index and plaque areas in the aortic root in mice, and inhibited total cholesterol (TC) levels and cholinesterase (ChE)/TC ratios in ox-LDL stimulated macrophages. Moreover, SYDC up-regulated Beclin1 and LC3II/I proteins in mice and in the ox-LDL-stimulated macrophages. Moreover, SYDC inhibited AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 in mice and in ox-LDL-stimulated macrophages. Furthermore, SYDC's inhibitory of ChE/TC ratios in ox-LDL-stimulated macrophages was not changed by selective inhibition of the PI3K/Akt/mTORC1 pathway. Conclusions: Our results highlight that SYDC treatment attenuates foam cell formation by promoting autophagy via inhibiting activation of the PI3K/Akt/mTORC1 signaling pathway. This study provides new insights into the molecular mechanism underlying SYDC's therapeutic potential for treating atherosclerosis.
ESTHER : Zhou_2019_Front.Pharmacol_10_603
PubMedSearch : Zhou_2019_Front.Pharmacol_10_603
PubMedID: 31214032

Title : Structure-activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid - Gao_2018_J.Enzyme.Inhib.Med.Chem_33_519
Author(s) : Gao X , Tang J , Liu H , Liu L , Kang L , Chen W
Ref : J Enzyme Inhib Med Chem , 33 :519 , 2018
Abstract : In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (4d-6g, 10d-12g, 16d-18g and 22d-24g) were designed, synthesized and evaluated for the effect on AChE and BChE in vitro. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound 6g revealed the most potent AChE inhibitory activity (IC50 value: 3.64 micromol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE.
ESTHER : Gao_2018_J.Enzyme.Inhib.Med.Chem_33_519
PubMedSearch : Gao_2018_J.Enzyme.Inhib.Med.Chem_33_519
PubMedID: 29447012

Title : Design, synthesis and evaluation of pterostilbene beta-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment - Zheng_2018_Bioorg.Chem_78_298
Author(s) : Zheng Y , Qiang X , Xu R , Song Q , Tian C , Liu H , Li W , Tan Z , Deng Y
Ref : Bioorg Chem , 78 :298 , 2018
Abstract : A series of pterostilbene beta-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50=24.04muM), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced Abeta1-42 aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Zheng_2018_Bioorg.Chem_78_298
PubMedSearch : Zheng_2018_Bioorg.Chem_78_298
PubMedID: 29625269

Title : Significance of neurexin and neuroligin polymorphisms in regulating risk of Hirschsprung's disease - Li_2018_J.Investig.Med_66_1
Author(s) : Li Y , Liu H , Dong Y
Ref : J Investig Med , 66 :1 , 2018
Abstract : By performing a basic case-control study among a Chinese population, the aims of this study were to explore if single nucleotide polymorphisms (SNPs) within neurexin and neuroligin were associated with susceptibility to Hirschsprung's disease (HD). Eleven SNPs within neurexin and neuroligin were selected in this basic case-control study, and this study recruited 210 children with HD and 187 healthy children. The t-test and Chi(2) test were used to find the difference between case and control in their clinical variables. OR and 95% CI were used to assess the association between HD susceptibility and neurexin/neuroligin polymorphisms/haplotypes. Several SNPs were significantly associated with altered risk of HD in the Chinese Han population, including rs1421589 within NRXN1, rs11795613 and rs4844285 within NLGN3, as well as rs5961397, rs7157669 and rs724373 within NLGX4X (all P<0.05). Further studies presented that the effects of rs1421589 within NRXN1, rs4844285 and rs11795613 within NLGN3, as well as rs5961397 within NLGX4X on HD phenotypes were also statistically significant (all P<0.05). Conclusively, the polymorphisms and haplotypes situated within neurexin and neuroligin were markedly associated with the onset of HD, implying that mutations of neurexin and neuroligin might serve as the treatment target for HD for the Chinese children.
ESTHER : Li_2018_J.Investig.Med_66_1
PubMedSearch : Li_2018_J.Investig.Med_66_1
PubMedID: 29622757

Title : Protein Crystallography and Site-Direct Mutagenesis Analysis of the Poly(ethylene terephthalate) Hydrolase PETase from Ideonella sakaiensis - Liu_2018_Chembiochem_19_1471
Author(s) : Liu B , He L , Wang L , Li T , Li C , Liu H , Luo Y , Bao R
Ref : Chembiochem , 19 :1471 , 2018
Abstract : Unlike traditional recycling strategies, biodegradation is a sustainable solution for disposing of poly(ethylene terephthalate) (PET) waste. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET and is, thus, a prominent candidate for PET degradation. On the basis of biochemical analysis, we propose that a wide substrate-binding pocket is critical for its excellent ability to hydrolyze crystallized PET. Structure-guided site-directed mutagenesis revealed an improvement in PETase catalytic efficiency, providing valuable insight into how the molecular engineering of PETase can optimize its application in biocatalysis.
ESTHER : Liu_2018_Chembiochem_19_1471
PubMedSearch : Liu_2018_Chembiochem_19_1471
PubMedID: 29603535
Gene_locus related to this paper: idesa-peth

Title : Discovery of novel 2,5-dihydroxyterephthalamide derivatives as multifunctional agents for the treatment of Alzheimer's disease - Song_2018_Bioorg.Med.Chem_26_6115
Author(s) : Song Q , Li Y , Cao Z , Liu H , Tian C , Yang Z , Qiang X , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 26 :6115 , 2018
Abstract : A series of 2,5-dihydroxyterephthalamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives exhibited good multifunctional activities. Among them, compound 9d showed the best inhibitory activity against both RatAChE and EeAChE (IC50=0.56muM and 5.12muM, respectively). Moreover, 9d exhibited excellent inhibitory effects on self-induced Abeta1-42 aggregation (IC50=3.05muM) and Cu(2+)-induced Abeta1-42 aggregation (71.7% at 25.0muM), and displayed significant disaggregation ability to self- and Cu(2+)-induced Abeta1-42 aggregation fibrils (75.2% and 77.2% at 25.0muM, respectively). Furthermore, 9d also showed biometal chelating abilities, antioxidant activity, anti-neuroinflammatory activities and appropriate BBB permeability. These multifunctional properties highlight 9d as promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Song_2018_Bioorg.Med.Chem_26_6115
PubMedSearch : Song_2018_Bioorg.Med.Chem_26_6115
PubMedID: 30470598

Title : Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury - Niu_2018_Mol.Med.Rep_18_4516
Author(s) : Niu X , Zheng S , Liu H , Li S
Ref : Mol Med Rep , 18 :4516 , 2018
Abstract : The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a nonproteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead, cadmium, and exerciseinduced oxidative stress. Astrocytes and neuron cells were cocultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factoralpha, interleukin6, caspase3, p53, Bcell lymphoma 2 and Bcl2associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.
ESTHER : Niu_2018_Mol.Med.Rep_18_4516
PubMedSearch : Niu_2018_Mol.Med.Rep_18_4516
PubMedID: 30221665

Title : Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease - Xu_2018_Bioorg.Med.Chem_26_1885
Author(s) : Xu R , Xiao G , Li Y , Liu H , Song Q , Zhang X , Yang Z , Zheng Y , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 26 :1885 , 2018
Abstract : A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50=0.29+/-0.01muM and 0.46+/-0.02muM, respectively), MAO-A (IC50=8.2+/-0.08muM and 7.9+/-0.07muM, respectively) and MAO-B (IC50=20.1+/-0.16muM and 43.8+/-2.0% at 10muM, respectively) inhibitory activities, moderate self-induced Abeta1-42 aggregation inhibitory potency (35.4+/-0.42% and 48.0+/-1.53% at 25muM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD.
ESTHER : Xu_2018_Bioorg.Med.Chem_26_1885
PubMedSearch : Xu_2018_Bioorg.Med.Chem_26_1885
PubMedID: 29500132

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 : Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors - Wu_2018_Medchemcomm_9_149
Author(s) : Wu G , Gao Y , Kang D , Huang B , Huo Z , Liu H , Poongavanam V , Zhan P , Liu X
Ref : Medchemcomm , 9 :149 , 2018
Abstract : We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against Electrophorus electricus acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 muM and 3.61 muM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.
ESTHER : Wu_2018_Medchemcomm_9_149
PubMedSearch : Wu_2018_Medchemcomm_9_149
PubMedID: 30108908

Title : Eucalyptusdimers A-C, Dimeric Phloroglucinol-Phellandrene Meroterpenoids from Eucalyptus robusta - Qin_2018_Org.Lett_20_5066
Author(s) : Qin XJ , Feng MY , Liu H , Ni W , Rauwolf T , Porco JA, Jr. , Yan H , He L , Liu HY
Ref : Org Lett , 20 :5066 , 2018
Abstract : Eucalyptusdimers A-C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (+/-)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects.
ESTHER : Qin_2018_Org.Lett_20_5066
PubMedSearch : Qin_2018_Org.Lett_20_5066
PubMedID: 30088934

Title : The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans Neuromuscular Junction - Sharma_2018_J.Neurosci_38_7072
Author(s) : Sharma P , Li L , Liu H , Tikiyani V , Hu Z , Babu K
Ref : Journal of Neuroscience , 38 :7072 , 2018
Abstract : Communications across chemical synapses are primarily mediated by neurotransmitters and their postsynaptic receptors. There are diverse molecular systems to localize and regulate the receptors at the synapse. Here, we identify HPO-30, a member of the claudin superfamily of membrane proteins, as a positive regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes at the NMJ and shows genetic and physical association with the LAChR subunits LEV-8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the hermaphrodite C. elegans, we demonstrate that HPO-30 functions through Neuroligin at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this work suggests a novel function for a tight junction protein in maintaining normal receptor levels at the NMJ.SIGNIFICANCE STATEMENT Claudins are a large superfamily of membrane proteins. Their role in maintaining the functional integrity of tight junctions has been widely explored. Our experiments suggest a critical role for the claudin-like protein, HPO-30, in maintaining synaptic levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the acetylcholine-mediated conductance in adult Caenorhabditis elegans; however, they play a significant functional role in worm locomotion. This study provides a new perspective in the study of LAChR physiology.
ESTHER : Sharma_2018_J.Neurosci_38_7072
PubMedSearch : Sharma_2018_J.Neurosci_38_7072
PubMedID: 29950505

Title : The Cation-pi Interaction Enables a Halo-Tag Fluorogenic Probe for Fast No-Wash Live Cell Imaging and Gel-Free Protein Quantification - Liu_2017_Biochemistry_56_1585
Author(s) : Liu Y , Miao K , Dunham NP , Liu H , Fares M , Boal AK , Li X , Zhang X
Ref : Biochemistry , 56 :1585 , 2017
Abstract : The design of fluorogenic probes for a Halo tag is highly desirable but challenging. Previous work achieved this goal by controlling the chemical switch of spirolactones upon the covalent conjugation between the Halo tag and probes or by incorporating a "channel dye" into the substrate binding tunnel of the Halo tag. In this work, we have developed a novel class of Halo-tag fluorogenic probes that are derived from solvatochromic fluorophores. The optimal probe, harboring a benzothiadiazole scaffold, exhibits a 1000-fold fluorescence enhancement upon reaction with the Halo tag. Structural, computational, and biochemical studies reveal that the benzene ring of a tryptophan residue engages in a cation-pi interaction with the dimethylamino electron-donating group of the benzothiadiazole fluorophore in its excited state. We further demonstrate using noncanonical fluorinated tryptophan that the cation-pi interaction directly contributes to the fluorogenicity of the benzothiadiazole fluorophore. Mechanistically, this interaction could contribute to the fluorogenicity by promoting the excited-state charge separation and inhibiting the twisting motion of the dimethylamino group, both leading to an enhanced fluorogenicity. Finally, we demonstrate the utility of the probe in no-wash direct imaging of Halo-tagged proteins in live cells. In addition, the fluorogenic nature of the probe enables a gel-free quantification of fusion proteins expressed in mammalian cells, an application that was not possible with previously nonfluorogenic Halo-tag probes. The unique mechanism revealed by this work suggests that incorporation of an excited-state cation-pi interaction could be a feasible strategy for enhancing the optical performance of fluorophores and fluorogenic sensors.
ESTHER : Liu_2017_Biochemistry_56_1585
PubMedSearch : Liu_2017_Biochemistry_56_1585
PubMedID: 28221782
Gene_locus related to this paper: rhoso-halo1

Title : Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma - Yao_2017_Medicine.(Baltimore)_96_e6735
Author(s) : Yao Q , Bao X , Xue R , Liu H , Li J , Dong J , Duan Z , Ren M , Zhao J , Song Q , Yu H , Zhu Y , Lu J , Meng Q
Ref : Medicine (Baltimore) , 96 :e6735 , 2017
Abstract : This study aimed to determine if the immunoscore (IS) staging system would be a potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO), respectively. ImagePro Plus software was used in the calculation of the paraffin-embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV-HCC tissue demonstrated that there were higher density and larger area of lymphocytes in the invasive margins (IM) region than in the center (CT). Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma-glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P = .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis showed that TNM staging was not an independent prognostic factor of DFS and OS. Our results showed ISs did not have a significantly correlation with DFS (P = .35, .19, and .07, respectively), but it was correlated significantly with OS (P = .00, .00, and .00, respectively). There were statistical differences among the OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS staging was closely related to the outcome of patients. It can compensate the TNM tumor classification system in predicting the prognosis of HBV-HCC patients.
ESTHER : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedSearch : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedID: 28445292

Title : Research Advances and Detection Methodologies for Microbe-Derived Acetylcholinesterase Inhibitors: A Systemic Review - Su_2017_Molecules_22_
Author(s) : Su J , Liu H , Guo K , Chen L , Yang M , Chen Q
Ref : Molecules , 22 : , 2017
Abstract : Acetylcholinesterase inhibitors (AChEIs) are an attractive research subject owing to their potential applications in the treatment of neurodegenerative diseases. Fungi and bacteria are major producers of AChEIs. Their active ingredients of fermentation products include alkaloids, terpenoids, phenylpropanoids, and steroids. A variety of in vitro acetylcholinesterase inhibitor assays have been developed and used to measure the activity of acetylcholinesterases, including modified Ellman's method, thin layer chromatography bioautography, and the combined liquid chromatography-mass spectrometry/modified Ellman's method. In this review, we provide an overview of the different detection methodologies, the microbe-derived AChEIs, and their producing strains.
ESTHER : Su_2017_Molecules_22_
PubMedSearch : Su_2017_Molecules_22_
PubMedID: 28125001

Title : Expression of family with sequence similarity 172 member A and nucleotide-binding protein 1 is associated with the poor prognosis of colorectal carcinoma - Liu_2017_Oncol.Lett_14_3587
Author(s) : Liu W , Wang S , Qian K , Zhang J , Zhang Z , Liu H
Ref : Oncol Lett , 14 :3587 , 2017
Abstract : In our previous studies, a functionally unknown gene, family with sequence similarity 172, member A (FAM172A), was identified. High levels of FAM172A suppressed the cell cycle process, arresting HepG2 cells in G1/S and inhibiting cell proliferation. The present study aimed to confirm the expression levels of FAM172A and nucleotide-binding protein 1 (NUBP1) in colorectal cancer (CRC) tissues and normal colorectal tissues. The impact of FAM172A and NUBP1 on the prognosis of patients with CRC was also analyzed. Immunohistochemical staining for FAM172A and NUBP1 was performed on 180 cancerous tissues and 60 normal paraffin-embedded tissues from patients with CRC. In total, 85 and 83% of 180 patients revealed positive expression of FAM172A and NUBP1, respectively. FAM172A expression level was associated with Tumor-Node-Metastasis (TNM) staging (P<0.001), the levels of serum carcinoembryonic antigen (CEA; P=0.023) and carbohydrate antigen 19-9 (CA19-9; P=0.016), lymph node involvement (P=0.004), tissue type (P=0.016), Dukes' staging (P<0.001) and NUBP1 (P=0.026). Furthermore, the expression level of NUBP1 was also markedly associated with the levels of serum CEA (P=0.006) and CA19-9 (P=0.001), TNM staging (P<0.001), lymph node involvement (P=0.005), histological typing (P=0.024) and Dukes' stage (P<0.001). Results of the univariate analysis demonstrated that there was a negative correlation between the expression level of FAM172A and overall survival (OS) and relapse-free survival (RFS) (P=0.013 and P=0.012, respectively), and there was also a negative correlation between NUBP1 expression level and OS and RFS (P<0.001 and P<0.001, respectively). With regards to OS and RFS, multivariate analysis revealed that expression levels of FAM172A and NUBP1 and tumor stage may be independent prognostic factors Thus, the present study suggested that FAM172A and NUBP1 may be prognostic makers for CRC.
ESTHER : Liu_2017_Oncol.Lett_14_3587
PubMedSearch : Liu_2017_Oncol.Lett_14_3587
PubMedID: 28927116

Title : Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease - Sang_2017_Eur.J.Med.Chem_135_307
Author(s) : Sang Z , Qiang X , Li Y , Xu R , Cao Z , Song Q , Wang T , Zhang X , Liu H , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 135 :307 , 2017
Abstract : A series of scutellarein-O-acetamidoalkylbenzylamines derivatives were designed based on a multitarget-directed ligands strategy for the treatment of Alzheimer's disease. Among these compounds, compound T-22 demonstrated excellent acetylcholinesterase inhibitory, moderate inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils, and also acted as potential antioxidant and biometals chelator. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that T-22 interacted with both the catalytic active site and peripheral anionic site of AChE. Moreover, compound T-22 showed a good neuroprotective effect against H2O2-induced PC12 cell injury and low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated T-22 significantly reversed scopolamine-induced memory deficit in mice. Taken together, the data showed that T-22 was an interesting multifunctional lead compound worthy of further study for AD.
ESTHER : Sang_2017_Eur.J.Med.Chem_135_307
PubMedSearch : Sang_2017_Eur.J.Med.Chem_135_307
PubMedID: 28458136

Title : Association of plasma dipeptidyl peptidase-4 activity with non-alcoholic fatty liver disease in nondiabetic Chinese population - Zheng_2017_Metabolism_73_125
Author(s) : Zheng T , Chen B , Yang L , Hu X , Zhang X , Liu H , Qin L
Ref : Metabolism , 73 :125 , 2017
Abstract : OBJECTIVE: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a "multi-hits hypothesis" involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the"multi-hits". Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population. DESIGN AND METHODS: We performed a cross-sectional study using data from 1105 subjects (36-79years) in Guilin between 2015 and 2016. Plasma DPP4 activity, homeostatic model assessment of insulin resistance (HOMA-IR), oxidative stress parameters, and inflammatory markers were measured in all participants. NAFLD and its severity were diagnosed by ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS: Participants in the highest quartile of DPP4 activity had higher HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6, CRP, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase compared with those in the lowest quartile (all P<0.05). Plasma DPP4 activity gradually increased across the groups according to the ultrasonographic severity of steatosis (P<0.001 for the trend). In the highest DPP4 quartile, NAFLD risk was higher (odds ratio 1.88; 95% CI 1.04-3.37) than in the lowest quartile after adjustment for confounders. The risk for NAFLD increased more with higher levels of DPP4 activity, HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6 and CRP. CONCLUSIONS: Plasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4.
ESTHER : Zheng_2017_Metabolism_73_125
PubMedSearch : Zheng_2017_Metabolism_73_125
PubMedID: 28637594

Title : The Role of Oxidative Stress in Decreased Acetylcholinesterase Activity at the Neuromuscular Junction of the Diaphragm during Sepsis - Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
Author(s) : Liu H , Wu J , Yao JY , Wang H , Li ST
Ref : Oxid Med Cell Longev , 2017 :9718615 , 2017
Abstract : Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid-grade septic group than in the low-grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid-grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.
ESTHER : Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
PubMedSearch : Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
PubMedID: 29230271

Title : miR27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker - Liu_2017_Oncol.Rep_37_3554
Author(s) : Liu W , Qian K , Wei X , Deng H , Zhao B , Chen Q , Zhang J , Liu H
Ref : Oncol Rep , 37 :3554 , 2017
Abstract : Accumulating evidence shows that mircroRNAs (miRNAs) play a crucial role in the development of colorectal cancer. In our previous study, FAM172A was demonstrated to be a novel tumor suppressor gene in CRC. Therefore, the aim of the present study was to identify whether the miR27a could be a diagnostic and prognostic marker and the regulatory relationships between miR27a and FAM172A. We demonstrated high levels of miR27a expression in tissues of patients with CRC as well as in CRC cell lines. There was a positive correlation between the levels of miR27a and the poor overall survival of patients with CRC. Furthermore, elevated levels of miR27a expression were associated with TNM stage and distant metastasis. Increased expression or inhibition of miR27a promoted or inhibited the metastasis of CRC cell lines, respectively. Moreover, we showed that miR27a directly targets the 3'-untranslated region of FAM172A mRNA by using a dual-luciferase assay. Increased or decreased expression of FAM172A expression was observed when miR27a expression was inhibited or elevated in the CRC cells, respectively. In summary, our study showed that miR27a expression is a diagnostic and prognostic marker and correlates with overall survival of patients with CRC. Therefore, it may be a therapeutic approach for preventing metastasis of CRC to inhibit expression of miR27a or increase expression of FAM172A.
ESTHER : Liu_2017_Oncol.Rep_37_3554
PubMedSearch : Liu_2017_Oncol.Rep_37_3554
PubMedID: 28440497
Gene_locus related to this paper: human-f172a

Title : Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation - Xu_2017_Brain.Behav_7_e00793
Author(s) : Xu X , Hu Z , Zhang L , Liu H , Cheng Y , Xia K , Zhang X
Ref : Brain Behav , 7 :e00793 , 2017
Abstract : INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing.
METHODS: In this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK293 cells expressing wild-type and mutant neuroligin.
RESULTS: We found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1-neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms. CONCLUSION: Our data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
ESTHER : Xu_2017_Brain.Behav_7_e00793
PubMedSearch : Xu_2017_Brain.Behav_7_e00793
PubMedID: 28948087
Gene_locus related to this paper: human-NLGN4X

Title : Palladium-copper nanowires-based biosensor for the ultrasensitive detection of organophosphate pesticides - Song_2017_Anal.Chim.Acta_982_168
Author(s) : Song D , Li Y , Lu X , Sun M , Liu H , Yu G , Gao F
Ref : Anal Chim Acta , 982 :168 , 2017
Abstract : A highly sensitive acetylcholinesterase (AChE) electrochemical biosensor for the quantitative determination of organophosphate pesticides (OPs) in vegetables and fruits based on palladium-copper nanowires (Pd-Cu NWs) was reported. AChE immobilized on the modified electrode could catalyze hydrolysis of acetylthiocholine chloride (ATCl), generating an irreversible oxidation peak. When exposed to the OPs, the activity of the AChE was inhibited and the current significantly decreased. The detection mechanism is based on the inhibition of AChE. The Pd-Cu NWs not only provide a large active surface area (0.268 +/- 0.01) cm2 for the immobilization of AChE, which was approximately 3.8 times higher than the bare glass carbon electrode, but also exhibit excellent electro-catalytic activity and remarkable electron mobility. The biosensor modified with Pd-Cu NWs displayed a good affinity to ATCl and catalyzed hydrolysis of ATCl, with a low Michaelis-Menten constant (KM) of 50.56 muM. Under optimized conditions, the AChE-Cs/Pd-Cu NWs/GCE biosensor detected malathion with wide linear ranges of 5-1000 ppt and 500-3000 ppb, and the low detection limit was 1.5 ppt (4.5 pM). In addition, the OPs biosensor has been applied to the analysis of malathion in commercial vegetable and fruit samples, with excellent recoveries in the range of 98.5%-113.5%. This work provides a simple, sensitive and effective platform for biosensors and exhibits future potential in practical application for the OPs assay.
ESTHER : Song_2017_Anal.Chim.Acta_982_168
PubMedSearch : Song_2017_Anal.Chim.Acta_982_168
PubMedID: 28734356

Title : Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (NSCLC) - Tang_2017_Int.J.Cancer_140_1620
Author(s) : Tang Z , Li J , Shen Q , Feng J , Liu H , Wang W , Xu L , Shi G , Ye X , Ge M , Zhou X , Ni S
Ref : International Journal of Cancer , 140 :1620 , 2017
Abstract : Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT). The epithelial markers E-cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis-associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA-IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non-cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5-year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.
ESTHER : Tang_2017_Int.J.Cancer_140_1620
PubMedSearch : Tang_2017_Int.J.Cancer_140_1620
PubMedID: 27943262

Title : Retrograde Synaptic Inhibition Is Mediated by alpha-Neurexin Binding to the alpha2delta Subunits of N-Type Calcium Channels - Tong_2017_Neuron_95_326
Author(s) : Tong XJ , Lopez-Soto EJ , Li L , Liu H , Nedelcu D , Lipscombe D , Hu Z , Kaplan JM
Ref : Neuron , 95 :326 , 2017
Abstract : The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/alpha2delta), decreasing UNC-36 abundance at pre-synaptic elements. Retrograde inhibition is mediated by a soluble form of NRX-1's ectodomain, which is released from the post-synaptic membrane by the SUP-17/ADAM10 protease. Mammalian Neurexin-1alpha binds alpha2delta-3 and decreases CaV2.2 current in transfected cells, whereas Neurexin-1alpha has no effect on CaV2.2 reconstituted with alpha2delta-1 and alpha2delta-2. Collectively, these results suggest that alpha-Neurexin binding to alpha2delta is a conserved mechanism for regulating synaptic transmission.
ESTHER : Tong_2017_Neuron_95_326
PubMedSearch : Tong_2017_Neuron_95_326
PubMedID: 28669545

Title : Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome - Zhang_2017_Lipids.Health.Dis_16_57
Author(s) : Zhang R , Song Q , Liu H , Bai H , Zhang Y , Liu Q , Guan L , Fan P
Ref : Lipids Health Dis , 16 :57 , 2017
Abstract : BACKGROUND: The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.
METHODS: A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.
RESULTS: No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.
CONCLUSIONS: There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 --> H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.
ESTHER : Zhang_2017_Lipids.Health.Dis_16_57
PubMedSearch : Zhang_2017_Lipids.Health.Dis_16_57
PubMedID: 28320416

Title : Accurately determining esterase activity via the isosbestic point of p-nitrophenol - Peng_2016_BioRes_11_10099
Author(s) : Peng Y , Fu S , Liu H , Lucia LA
Ref : BioRes , 11 :10099 , 2016
Abstract : Esterase is an important enzyme for ester hydrolysis or synthesis. Its activity, however, has not been accurately ascertained due to a lack of accurate protocols. In this study, the isosbestic point of p-nitrophenol was found and used as the marker for its activity. The methodology avoided decomposition of the substrate, chromophore agents, and pH changes. The esterase activity was determined accurately and rapidly in a complex solution. In this protocol system, organic solvents were used for dissolving substrates, which influenced activity determination to some extent. Among the solvents tested, methanol exerted the least inhibitory influence. The results indicated that this modified method has potential to be applied for esterase activity determination on a large scale and in real time.
ESTHER : Peng_2016_BioRes_11_10099
PubMedSearch : Peng_2016_BioRes_11_10099
PubMedID:

Title : FAM172A modulates apoptosis and proliferation of colon cancer cells via STAT1 binding to its promoter - Qian_2016_Oncol.Rep_35_1273
Author(s) : Qian K , Zhang J , Lu J , Liu W , Yao X , Chen Q , Lu S , Xiang G , Liu H
Ref : Oncol Rep , 35 :1273 , 2016
Abstract : In our previous study, low expression of FAM172A protein was found in colon cancer tissues. This research was planned to explore the functions of FAM172A gene and examine the mechanisms of its transcriptional regulation. Firstly, flow cytometry showed that FAM172A inhibited proliferation and promoted apoptosis and differentiation of colon cancer cells. Then through continuous truncation, we identified the minimal functional promoter region of FAM172A. Subsequently, we found that STAT1, as a transcription factor, could bind to the minimal FAM172A promoter, as evaluated using Chromatin immunoprecipitation (ChIP) and Electrophoreticmobility shift assay (EMSA). The results of Western blot analysis and qRT-PCR indicated that STAT1 was able to upregulate the expression of FAM172A. Our results showed that FAM172A could suppress proliferation of colon cancer cells, and STAT1 could bind to the minimum promoter region of FAM172A and upregulated the expression of FAM172A. These results may provide advanced insights into the functions of FAM172A and its regulatory mechanisms.
ESTHER : Qian_2016_Oncol.Rep_35_1273
PubMedSearch : Qian_2016_Oncol.Rep_35_1273
PubMedID: 26676844
Gene_locus related to this paper: human-f172a

Title : FAM172A is a tumor suppressor in colorectal carcinoma - Cui_2016_Tumour.Biol_37_6501
Author(s) : Cui C , Ye L , Huang Z , Huang S , Liu H , Yu J
Ref : Tumour Biol , 37 :6501 , 2016
Abstract : The present study was designed to elucidate the regulatory role of a novel protein FAM172A in carcinogenesis of colorectal carcinoma (CRC). Investigation of clinical samples using Western blotting showed that expression of FAM172A is significantly lower in cancerous tissues than in adjacent tissues. Furthermore, we constructed in vitro model for continuous overexpression and silencing of FAM172A with a retroviral vector system. FAM172A suppressed the proliferative and invasive potentials of LOVO cells as shown in MTT test, transwell migration assay, wound healing assay, 3D-culture morphologic study, and xenograft experiment. RT-PCR and Western blotting showed that FAM172A overexpression inhibited expressions of Cyclin D1, CDK2, MMP-2, MMP-9, PERK, elF2alpha, ATF6, XBP1, and GRP78, while FAM172A silencing induced their expressions. FAM172A might regulate ERS through PERK-elF2alpha, ATF6-XBP1-GRP78 signal pathway. The results implicated that FAM172A functioned as a tumor suppressor in colorectal carcinoma.
ESTHER : Cui_2016_Tumour.Biol_37_6501
PubMedSearch : Cui_2016_Tumour.Biol_37_6501
PubMedID: 26637224
Gene_locus related to this paper: human-f172a

Title : Novel ferulic amide derivatives with tertiary amine side chain as acetylcholinesterase and butyrylcholinesterase inhibitors: The influence of carbon spacer length, alkylamine and aromatic group - Liu_2016_Eur.J.Med.Chem_126_810
Author(s) : Liu H , Liu L , Gao X , Liu Y , Xu W , He W , Jiang H , Tang J , Fan H , Xia X
Ref : Eur Journal of Medicinal Chemistry , 126 :810 , 2016
Abstract : Based on our recent investigations on chalcone derivatives as AChE inhibitors, a series of ferulic acid (FA) tertiary amine derivatives similar to chalcone compounds were designed and synthesized. The results of bioactivity evaluation revealed that most of new synthesized compounds had comparable or more potent AChE inhibitory activity than the control drug Rivastigmine. The alteration of carbon chain linking tertiary amine groups and ferulic acid scaffold markedly influenced the inhibition activity against AChE. Among them the inhibitory activity of compound 6d (IC50: 0.71 +/- 0.09 mumol/L) and 6e (IC50: 1.11 +/- 0.17 mumol/L) was equal to 15-fold and 9-fold than that of Rivastigmine against AChE (IC50: 10.54 +/- 0.86 mumol/L), respectively. Moreover, compound 6d shows the highest selectivity for AChE over butyrylcholinesterase(BuChE) (ratio: 18.3). The kinetic study suggested that compound 6d revealed a mixed-type inhibition against AChE. The result of molecular docking showed that compound 6d combines to AChE with three amino acid sites(Trp84, Tyr334 and Trp279), while combines to BuChE with two amino acid sites (Tyr67 and Gly66) in enzyme domains, respectively. Compound 6d might act as a potential agent for the treatment of Alzheimer's diseases (AD).
ESTHER : Liu_2016_Eur.J.Med.Chem_126_810
PubMedSearch : Liu_2016_Eur.J.Med.Chem_126_810
PubMedID: 27951489

Title : Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora - Zhang_2016_Sci.Rep_6_23122
Author(s) : Zhang L , Zhou Z , Guo Q , Fokkens L , Miskei M , Pocsi I , Zhang W , Chen M , Wang L , Sun Y , Donzelli BG , Gibson DM , Nelson DR , Luo JG , Rep M , Liu H , Yang S , Wang J , Krasnoff SB , Xu Y , Molnar I , Lin M
Ref : Sci Rep , 6 :23122 , 2016
Abstract : Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle.
ESTHER : Zhang_2016_Sci.Rep_6_23122
PubMedSearch : Zhang_2016_Sci.Rep_6_23122
PubMedID: 26975455
Gene_locus related to this paper: 9hypo-a0a151ga75 , 9hypo-a0a151gbh5 , 9hypo-a0a151gd50 , 9hypo-a0a151ggb9 , 9hypo-a0a151gjd5 , 9hypo-a0a151gtv2 , 9hypo-a0a151gxh2 , 9hypo-a0a151gaw8 , 9hypo-a0a151gia2

Title : Genomic Analysis Reveals Multi-Drug Resistance Clusters in Group B Streptococcus CC17 Hypervirulent Isolates Causing Neonatal Invasive Disease in Southern Mainland China - Campisi_2016_Front.Microbiol_7_1265
Author(s) : Campisi E , Rosini R , Ji W , Guidotti S , Rojas-Lopez M , Geng G , Deng Q , Zhong H , Wang W , Liu H , Nan C , Margarit I , Rinaudo CD
Ref : Front Microbiol , 7 :1265 , 2016
Abstract : Neonatal invasive disease caused by group B Streptococcus (GBS) represents a significant public health care concern globally. However, data related to disease burden, serotype distribution, and molecular epidemiology in China and other Asian countries are very few and specifically relative to confined regions. The aim of this study was to investigate the genetic characteristics of GBS isolates recovered from neonates with invasive disease during 2013-2014 at Guangzhou and Changsha hospitals in southern mainland China. We assessed the capsular polysaccharide type, pilus islands (PIs) distribution and hvgA gene presence in a panel of 26 neonatal clinical isolates, of which 8 were recovered from Early Onset Disease and 18 from Late Onset Disease (LOD). Among 26 isolates examined, five serotypes were identified. Type III was the most represented (15 cases), particularly among LOD strains (n = 11), followed by types Ib (n = 5), V (n = 3), Ia (n = 2) and II (n = 1). We performed whole-genome sequencing analysis and antimicrobial susceptibility testing on the 14 serotype III isolates belonging to the hypervirulent Clonal Complex 17 (serotype III-CC17). The presence of PI-2b alone was associated with 13 out of 14 serotype III-CC17 strains. Genome analysis led us to identify two multi-drug resistance gene clusters harbored in two new versions of integrative and conjugative elements (ICEs), carrying five or eight antibiotic resistance genes, respectively. These ICEs replaced the 16 kb-locus that normally contains the PI-1 operon. All isolates harboring the identified ICEs showed multiple resistances to aminoglycoside, macrolide, and tetracycline antibiotic classes. In conclusion, we report the first whole-genome sequence analysis of 14 GBS serotype III-CC17 strains isolated in China, representing the most prevalent lineage causing neonatal invasive disease. The acquisition of newly identified ICEs conferring multiple antibiotic resistance could in part explain the spread of this specific clone among Chinese neonatal isolates and underlines the need for a constant epidemiological surveillance.
ESTHER : Campisi_2016_Front.Microbiol_7_1265
PubMedSearch : Campisi_2016_Front.Microbiol_7_1265
PubMedID: 27574519

Title : Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual-enzyme-simultaneous-assay - Liu_2015_Anal.Sci_31_421
Author(s) : Liu H , Yuan M , Yang X , Hu X , Liao J , Dang J , Xie Y , Pu J , Li Y , Zhan CG , Liao F
Ref : Anal Sci , 31 :421 , 2015
Abstract : Spectrophotometric-dual-enzyme-simultaneous-assay (SDESA) for enzyme-linked-immunosorbent-assay (ELISA) of two components in one well is a patented platform when a special pair of labels is accessible. With microplate readers, alkaline phosphatase on 4-nitro-1-naphthylphosphate (4NNPP) served as label A; Pseudomonas aeruginosa arylsulfatase (PAAS) and acetylcholinesterase (AChE) on their substrates derived from 4-nitrophenol/analogue served as candidate label B, and were compared for SDESA with an engineered alkaline phosphatase of Eschrichia coli (ECAP). For SDESA, the interference from overlapped absorbance was corrected based on linear additivity of absorbance to derive initial rates reflected by absorbance change at 450 nm for ECAP and at 405 nm for PAAS or AChE, after the correction of spontaneous hydrolysis. For SDESA with ECAP, AChE already had sufficient activity in an optimized buffer; PAAS was more favorable for substrate stability and product absorbance except for lower activity. Therefore, PAAS engineered for sufficient activity plus alkaline phosphatase is absorbing for ELISA via SDESA.
ESTHER : Liu_2015_Anal.Sci_31_421
PubMedSearch : Liu_2015_Anal.Sci_31_421
PubMedID: 25958872

Title : Surrogate markers of the kidney and liver in the assessment of gestational diabetes mellitus and fetal outcome - Liu_2015_J.Clin.Diagn.Res_9_OC14
Author(s) : Liu H , Shao-Gang M , Liang C , Feng B , Wei X
Ref : J Clin Diagn Res , 9 :OC14 , 2015
Abstract : INTRODUCTION: To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as gamma-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. MATERIALS AND
METHODS: Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated.
RESULTS: Levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and gamma- glutamyl transferase (p < 0.05) in the gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of gamma-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p < 0.05). The diagnosis curve demonstrated that gamma-glutamyl transferase had a significant advantage over other markers (p < 0.001) but no significance compared with pre-albumin (p = 0.096). None of the detected markers showed predictive value for fetal outcome. CONCLUSION: Serum levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C and pre-albumin were correlated with gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as gamma-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.
ESTHER : Liu_2015_J.Clin.Diagn.Res_9_OC14
PubMedSearch : Liu_2015_J.Clin.Diagn.Res_9_OC14
PubMedID: 25738017

Title : Molecular cloning and characterization of a new and highly thermostable esterase from Geobacillus sp. JM6 - Zhu_2015_J.Basic.Microbiol_55_1219
Author(s) : Zhu Y , Zheng W , Ni H , Liu H , Xiao A , Cai H
Ref : J Basic Microbiol , 55 :1219 , 2015
Abstract : A new lipolytic enzyme gene was cloned from a thermophile Geobacillus sp. JM6. The gene contained 750 bp and encoded a 249-amino acid protein. The recombinant enzyme was expressed and purified from Escherichia coli BL21 (DE3) with a molecular mass of 33.6 kDa. Enzyme assays using p-nitrophenyl esters with different acyl chain lengths as the substrates confirmed its esterase activity, yielding the highest activity with p-nitrophenyl butyrate. When p-nitrophenyl butyrate was used as a substrate, the optimum reaction temperature and pH for the enzyme were 60 degrees C and pH 7.5, respectively. Geobacillus sp. JM6 esterase showed excellent thermostability with 68% residual activity after incubation at 100 degrees C for 18 h. A theoretical structural model of strain JM6 esterase was developed with a monoacylglycerol lipase from Bacillus sp. H-257 as a template. The predicted core structure exhibits an alpha/beta hydrolase fold, and a putative catalytic triad (Ser97, Asp196, and His226) was identified. Inhibition assays with PMSF indicated that serine residue is involved in the catalytic activity of strain JM6 esterase. The recombinant esterase showed a relatively good tolerance to the detected detergents and denaturants, such as SDS, Chaps, Tween 20, Tween 80, Triton X-100, sodium deoxycholate, urea, and guanidine hydrochloride.
ESTHER : Zhu_2015_J.Basic.Microbiol_55_1219
PubMedSearch : Zhu_2015_J.Basic.Microbiol_55_1219
PubMedID: 26175347
Gene_locus related to this paper: 9baci-a0a0b5kth6

Title : Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives - Liu_2015_J.Enzyme.Inhib.Med.Chem__1
Author(s) : Liu H , Fan H , Gao X , Huang X , Liu X , Liu L , Zhou C , Tang J , Wang Q , Liu W
Ref : J Enzyme Inhib Med Chem , :1 , 2015
Abstract : In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 mumol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.
ESTHER : Liu_2015_J.Enzyme.Inhib.Med.Chem__1
PubMedSearch : Liu_2015_J.Enzyme.Inhib.Med.Chem__1
PubMedID: 26186269

Title : Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors - Ji_2014_Eur.J.Med.Chem_86_242
Author(s) : Ji X , Xia C , Wang J , Su M , Zhang L , Dong T , Li Z , Wan X , Li J , Zhao L , Gao Z , Jiang H , Liu H
Ref : Eur Journal of Medicinal Chemistry , 86 :242 , 2014
Abstract : Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 muM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 muM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9.
ESTHER : Ji_2014_Eur.J.Med.Chem_86_242
PubMedSearch : Ji_2014_Eur.J.Med.Chem_86_242
PubMedID: 25164763

Title : Effects of Fraxinellone on the Midgut Enzyme Activities of the 5th Instar Larvae of Oriental Armyworm, Mythimna separata Walker - Lv_2014_Toxins.(Basel)_6_2708
Author(s) : Lv M , Wu W , Liu H
Ref : Toxins (Basel) , 6 :2708 , 2014
Abstract : Isolated from Dictamnus dasycarpus Turcz., fraxinellone exhibited multiple bioactivities against insects. In the present paper, the changes of digestive enzymes and detoxification enzymes of Mythimna separata Walker (5th instar larvae), treated with fraxinellone, were investigated. Compared with those of the control, the alpha-amylase activity of the fraxinellone-treated 5th instar larvae was inhibited, whereas the level of their protease activity was increased. Based upon further studies on the specific proteases, the levels of the active alkaline trypsin-like enzyme (BApNA as the substrate) and the chymotrypsin-like enzyme (BTEE as the substrate) activities of the treated larvae were declined; however, the level of activity of the weak alkaline trypsin-like enzyme (TAME as the substrate) of the treated ones was increased. Meanwhile, the activities of two detoxification enzymes, such as carboxylesterase (CarE) and glutathione S-transferase (GST), of the treated larvae were increased to some extent, but the activities of NADPH-P450 reductase and O-demethylase of the treated ones declined. Therefore, protease (especially the weak alkaline trypsin-like enzyme), CarE and GST played important roles in the metabolism of fraxinellone in the midgut of Mythimna separata (M. separata).
ESTHER : Lv_2014_Toxins.(Basel)_6_2708
PubMedSearch : Lv_2014_Toxins.(Basel)_6_2708
PubMedID: 25216084

Title : Separation and purification of bioactive botrallin and TMC-264 by a combination of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp. Ponipodef12 - Mao_2014_World.J.Microbiol.Biotechnol_30_2533
Author(s) : Mao Z , Luo R , Luo H , Tian J , Liu H , Yue Y , Wang M , Peng Y , Zhou L
Ref : World J Microbiol Biotechnol , 30 :2533 , 2014
Abstract : Two dibenzo-alpha-pyrones, botrallin (1) and TMC-264 (2) were preparatively separated from crude ethyl acetate extract of the endophytic fungus Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. using a combination of high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with 74.73 % of purity and TMC-264 (2) with 82.29 % of purity were obtained through HSCCC by employing a solvent system containing n-hexane-ethyl acetate-methanol-water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2) to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity on acetylcholinesterase.
ESTHER : Mao_2014_World.J.Microbiol.Biotechnol_30_2533
PubMedSearch : Mao_2014_World.J.Microbiol.Biotechnol_30_2533
PubMedID: 24898177

Title : A Fluorogenic Probe with Aggregation-Induced Emission Characteristics for Carboxylesterase Assay through Formation of Supramolecular Microfibers - Wang_2014_Chem.Asian.J_9_784
Author(s) : Wang X , Liu H , Li J , Ding K , Lv Z , Yang Y , Chen H , Li X
Ref : Chem Asian J , 9 :784 , 2014
Abstract : Herein, we report a novel fluorescent "light-up" probe useful for carboxylesterase assay that is based on a tetraphenylethylene derivative containing carboxylic ester groups. The specific cleavage of the carboxylic ester bonds by carboxylesterase results in the generation of a relatively hydrophobic moiety that self-assembles into supramolecular microfibers, thus giving rise to "turn-on" fluorescent signals. A high sensitivity towards carboxylesterase was achieved with a detection limit as low as 29 pM, which is much lower than the corresponding assays based on other fluorescent approaches.
ESTHER : Wang_2014_Chem.Asian.J_9_784
PubMedSearch : Wang_2014_Chem.Asian.J_9_784
PubMedID: 24403215

Title : Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors - Ji_2014_Eur.J.Med.Chem_75C_111
Author(s) : Ji X , Su M , Wang J , Deng G , Deng S , Li Z , Tang C , Li J , Zhao L , Jiang H , Liu H
Ref : Eur Journal of Medicinal Chemistry , 75C :111 , 2014
Abstract : A series of novel hetero-aromatic moieties substituted alpha-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 muM). Moreover, compounds 6h (IC50 = 0.004 muM) and 6n (IC50 = 0.01 muM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h).
ESTHER : Ji_2014_Eur.J.Med.Chem_75C_111
PubMedSearch : Ji_2014_Eur.J.Med.Chem_75C_111
PubMedID: 24531224

Title : SET-mediated NDRG1 inhibition is involved in acquisition of epithelial-to-mesenchymal transition phenotype and cisplatin resistance in human lung cancer cell - Liu_2014_Cell.Signal_26_2710
Author(s) : Liu H , Gu Y , Yin J , Zheng G , Wang C , Zhang Z , Deng M , Liu J , Jia X , He Z
Ref : Cell Signal , 26 :2710 , 2014
Abstract : Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) have been shown to play roles in resistance to chemotherapy. Here, we utilized a proteomics-based method and identified a significant downregulation of the metastasis suppressor NDRG1 in drug resistant lung cancer cells. We showed that downregulation of DNRG1 constitutes a mechanism for acquisition of EMT phenotype and endows lung cancer cells with an increased resistance to cisplatin. We also identified a signal cascade, namely, SET--- PP2A---| c-myc---| NDRG1, in which upregulation of SET is critical for inhibition of NDRG1. We also found that blockade of SET (or reactivation of PP2A) by FTY720 reverted EMT, restored drug sensitivity, and inhibited invasiveness and growth of lung tumor xenografts. Together, our results indicated a functional link between SET-mediated NDRG1 regulation and acquisition of EMT phenotype and drug resistance, and provided an evidence that blockade of SET-driven EMT can overcome drug resistance and inhibit tumor progression.
ESTHER : Liu_2014_Cell.Signal_26_2710
PubMedSearch : Liu_2014_Cell.Signal_26_2710
PubMedID: 25152373

Title : Associations of Lipoprotein Lipase Gene rs326 with Changes of Lipid Profiles after a High-Carbohydrate and Low-Fat Diet in Healthy Chinese Han Youth - Zhu_2014_Int.J.Environ.Res.Public.Health_11_4544
Author(s) : Zhu XC , Lin J , Wang Q , Liu H , Qiu L , Fang DZ
Ref : Int J Environ Research Public Health , 11 :4544 , 2014
Abstract : To investigate the effects of a high-carbohydrate and low-fat (HC/LF) diet on plasma lipids and apolipoproteins (Apos) of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL) rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Apo B-100 and Apo A-I were analyzed at baseline and before and after the HC/LF diet. The results show that, when compared with before the HC/LF diet, only the male G carriers experienced increased HDL-C (p = 0.008) and Apo A-I (p = 0.005) after the HC/LF diet. Decreased TC in both males and females and increased TG in females were found regardless of the genotype after the HC/LF diet. LDL-C decreased in all the subjects although the decrease was not significant in the female G carriers. These results demonstrate that the G allele of LPL rs326 associates with the elevated levels of HDL-C and Apo A-I after the HC/LF diet in males of the healthy Chinese Han Youth.
ESTHER : Zhu_2014_Int.J.Environ.Res.Public.Health_11_4544
PubMedSearch : Zhu_2014_Int.J.Environ.Res.Public.Health_11_4544
PubMedID: 24762672

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Rice OsPAD4 functions differently from Arabidopsis AtPAD4 in host-pathogen interactions - Ke_2014_Plant.J_78_619
Author(s) : Ke Y , Liu H , Li X , Xiao J , Wang S
Ref : Plant J , 78 :619 , 2014
Abstract : The extensively studied Arabidopsis phytoalexin deficient 4 (AtPAD4) gene plays an important role in Arabidopsis disease resistance; however, the function of its sequence ortholog in rice is unknown. Here, we show that rice OsPAD4 appears not to be the functional ortholog of AtPAD4 in host-pathogen interactions, and that the OsPAD4 encodes a plasma membrane protein but that AtPAD4 encodes a cytoplasmic and nuclear protein. Suppression of OsPAD4 by RNA interference (RNAi) increased rice susceptibility to the biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo), which causes bacteria blight disease in local tissue. OsPAD4-RNAi plants also show compromised wound-induced systemic resistance to Xoo. The increased susceptibility to Xoo was associated with reduced accumulation of jasmonic acid (JA) and phytoalexin momilactone A (MOA). Exogenous application of JA complemented the phenotype of OsPAD4-RNAi plants in response to Xoo. The following results suggest that OsPAD4 functions differently than AtPAD4 in response to pathogen infection. First, OsPAD4 plays an important role in wound-induced systemic resistance, whereas AtPAD4 mediates systemic acquired resistance. Second, OsPAD4-involved defense signaling against Xoo is JA-dependent, but AtPAD4-involved defense signaling against biotrophic pathogens is salicylic acid-dependent. Finally, OsPAD4 is required for the accumulation of terpenoid-type phytoalexin MOA in rice-bacterium interactions, but AtPAD4-mediated resistance is associated with the accumulation of indole-type phytoalexin camalexin.
ESTHER : Ke_2014_Plant.J_78_619
PubMedSearch : Ke_2014_Plant.J_78_619
PubMedID: 24617729
Gene_locus related to this paper: orysa-q53lh1

Title : EPHX1 A139G polymorphism and lung cancer risk: a meta-analysis - Liu_2013_Tumour.Biol_34_155
Author(s) : Liu H , Li HY , Chen HJ , Huang YJ , Zhang S , Wang J
Ref : Tumour Biol , 34 :155 , 2013
Abstract : Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and the detoxification of polycyclic aromatic hydrocarbons and aromatic amines. Polymorphisms at exon 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. Many studies have investigated the association between EPHX1 A139G polymorphism and lung cancer risk, but the impact of EPHX1 A139G polymorphism on lung cancer risk is not clear owing to the apparent inconsistence among those studies. This study aimed to identify the association between EPHX1 A139G polymorphism and lung cancer risk by performing a meta-analysis. We used the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to explore the association. Finally, 26 studies with a total of 14,494 subjects were included into this meta-analysis. Meta-analyses of total studies showed the EPHX1 A139G polymorphism was associated with lung cancer risk under three genetic models (OR (G versus A) = 1.17, 95 % CI 1.04-1.31, P (OR) = 0.01; OR (AG versus AA) = 1.21, 95 % CI 1.06-1.37, P (OR) = 0.004; OR (AG + GG versus AA) = 1.22, 95 % CI 1.06-1.39, P (OR) = 0.005). Sensitivity analyses and subgroup analyses further identified the significant association between the EPHX1 A139G polymorphism and lung cancer risk. No evidence of publication bias was observed. Meta-analyses of available data supported the concept of EPHX1 A139G polymorphism as a genetic susceptibility factor for lung cancer.
ESTHER : Liu_2013_Tumour.Biol_34_155
PubMedSearch : Liu_2013_Tumour.Biol_34_155
PubMedID: 23055191

Title : Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease - Zhang_2013_Mol.Biol.Rep_40_2969
Author(s) : Zhang Q , Wang J , Li A , Liu H , Zhang W , Cui X , Wang K
Ref : Mol Biol Rep , 40 :2969 , 2013
Abstract : To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR.
ESTHER : Zhang_2013_Mol.Biol.Rep_40_2969
PubMedSearch : Zhang_2013_Mol.Biol.Rep_40_2969
PubMedID: 23264101

Title : The evolution and pathogenic mechanisms of the rice sheath blight pathogen - Zheng_2013_Nat.Commun_4_1424
Author(s) : Zheng A , Lin R , Zhang D , Qin P , Xu L , Ai P , Ding L , Wang Y , Chen Y , Liu Y , Sun Z , Feng H , Liang X , Fu R , Tang C , Li Q , Zhang J , Xie Z , Deng Q , Li S , Wang S , Zhu J , Wang L , Liu H , Li P
Ref : Nat Commun , 4 :1424 , 2013
Abstract : Rhizoctonia solani is a major fungal pathogen of rice (Oryza sativa L.) that causes great yield losses in all rice-growing regions of the world. Here we report the draft genome sequence of the rice sheath blight disease pathogen, R. solani AG1 IA, assembled using next-generation Illumina Genome Analyser sequencing technologies. The genome encodes a large and diverse set of secreted proteins, enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, which probably reflect an exclusive necrotrophic lifestyle. We find few repetitive elements, a closer relationship to Agaricomycotina among Basidiomycetes, and expand protein domains and families. Among the 25 candidate pathogen effectors identified according to their functionality and evolution, we validate 3 that trigger crop defence responses; hence we reveal the exclusive expression patterns of the pathogenic determinants during host infection.
ESTHER : Zheng_2013_Nat.Commun_4_1424
PubMedSearch : Zheng_2013_Nat.Commun_4_1424
PubMedID: 23361014
Gene_locus related to this paper: thaca-l8wvp3 , thaca-l8wv47 , thaca-l8wp17 , thaca-l8x532

Title : GLP-1-dependent and independent effects and molecular mechanisms of a dipeptidyl peptidase 4 inhibitor in vascular endothelial cells - Hu_2013_Mol.Biol.Rep_40_2273
Author(s) : Hu Y , Liu H , Simpson RW , Dear AE
Ref : Mol Biol Rep , 40 :2273 , 2013
Abstract : The potential atheroprotective effects of glucagon-like peptide-1 (GLP-1), long-acting GLP-1 analogues and inhibitors of the enzyme dipeptidyl peptidase 4 (DPP-4) are currently the subject of intense research. Recent evidence suggests the effects of DPP-IV inhibitors, may, in-part, be mediated by GLP-1 independent molecular mechanisms. In this report we demonstrate that treatment of human vascular endothelial cells with the DPP-IV inhibitor sitagliptin inhibited tumour necrosis factor alpha (TNFalpha) induction of plasminogen activator inhibitor type-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein expression and that this effect was observed to be both GLP-1-dependent and independent. Importantly we identify a molecular mechanism involving sitagliptin-mediated attenuation of TNFalpha-mediated induction of NFkappaB and orphan nuclear receptor NUR77 mRNA expression, also able to be reproduced, in part, independent of GLP-1. Taken together these observations may serve to provide a molecular explanation, involving transcriptional regulation of gene expression, for recent in vivo studies suggesting DPP-IV inhibitors may have novel, GLP-1 independent, effects in acting to attenuate endothelial cell dysfunction and atherogenesis.
ESTHER : Hu_2013_Mol.Biol.Rep_40_2273
PubMedSearch : Hu_2013_Mol.Biol.Rep_40_2273
PubMedID: 23187735

Title : The interaction between OsMADS57 and OsTB1 modulates rice tillering via DWARF14 - Guo_2013_Nat.Commun_4_1566
Author(s) : Guo S , Xu Y , Liu H , Mao Z , Zhang C , Ma Y , Zhang Q , Meng Z , Chong K
Ref : Nat Commun , 4 :1566 , 2013
Abstract : Rice tillering is a multigenic trait that influences grain yield, but its regulation molecular module is poorly understood. Here we report that OsMADS57 interacts with OsTB1 (TEOSINTE BRANCHED1) and targets D14 (Dwarf14) to control the outgrowth of axillary buds in rice. An activation-tagged mutant osmads57-1 and OsMADS57-overexpression lines showed increased tillers, whereas OsMADS57 antisense lines had fewer tillers. OsMIR444a-overexpressing lines exhibited suppressed OsMADS57 expression and tillering. Furthermore, osmads57-1 was insensitive to strigolactone treatment to inhibit axillary bud outgrowth, and OsMADS57's function in tillering was dependent on D14. D14 expression was downregulated in osmads57-1, but upregulated in antisense and OsMIR444a-overexpressing lines. OsMADS57 bound to the CArG motif [C(A/T)TTAAAAAG] in the promoter and directly suppressed D14 expression. Interaction of OsMADS57 with OsTB1 reduced OsMADS57 inhibition of D14 transcription. Therefore, OsMIR444a-regulated OsMADS57, together with OsTB1, target D14 to control tillering. This regulation mechanism could have important application in rice molecular breeding programs focused on high grain yield.
ESTHER : Guo_2013_Nat.Commun_4_1566
PubMedSearch : Guo_2013_Nat.Commun_4_1566
PubMedID: 23463009

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

Title : The AEROPATH project targeting Pseudomonas aeruginosa: crystallographic studies for assessment of potential targets in early-stage drug discovery. - Moynie_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_25
Author(s) : Moynie L , Schnell R , McMahon SA , Sandalova T , Boulkerou WA , Schmidberger JW , Alphey M , Cukier C , Duthie F , Kopec J , Liu H , Jacewicz A , Hunter WN , Naismith JH , Schneider G
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 69 :25 , 2013
Abstract : Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns.
ESTHER : Moynie_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_25
PubMedSearch : Moynie_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_25
PubMedID: 23295481
Gene_locus related to this paper: pseae-PA2086

Title : Altered quantities and in vivo activities of cholinesterase from Daphnia magna in sub-lethal exposure to organophosphorus insecticides - Liu_2012_Ecotoxicol.Environ.Saf_80_118
Author(s) : Liu H , Yuan B , Li S
Ref : Ecotoxicology & Environmental Safety , 80 :118 , 2012
Abstract : For investigating relationship between activity of cholinesterase (ChE) and ambient concentration of anticholinesterases, Daphnia magna had been exposed for 21 day to sub-lethal concentrations, i.e. 1/6 EC(50), 1/36 EC(50), and 1/216 EC(50), of either triazophos or chlorpyrifos. Samples were taken at different points of time for measuring total activity and immunoreactive content of ChE and actual concentrations of the anticholinesterases. A type of antigen formerly developed by immunizing mice with purified ChE was utilized in this study to establish an indirect non-competitive ELISA for measuring immunoreactive content of ChE in Daphnia. Studies showed that for apparent activity, i.e. activity that was scaled with total protein, the insecticides caused 5.2-6.9 percent inhibition and 17.0-17.7 percent inductions during the 21 d exposure, whereas for inherent activity, i.e. activity that was scaled with immunoreactive protein, no induction was detected during the exposure. Accompanied by up to 65.9 percent and 68.0 percent promotion in terms of the immunoreactive content, up to 42.8 percent and 44.6 percent inhibition in terms of the inherent activity was indicated, respectively, for triazophos and chlopyrifos. Judged by measured concentrations, the inherent activity recovered faster than the rate of dissipation of the anticholinesterases. Result of the study suggested that the inherent activity was more sensitive than the apparent one in predicting sub-lethal and/or long-term stress of anticholinesterases. It also suggested that apart from promotion in terms of content of the ChE, the Daphnia developed capacities to block bio-concentration of anticholinesterases, and these capacities would make it liable to underestimate ambient concentration of anticholinesterases along with the time of exposure.
ESTHER : Liu_2012_Ecotoxicol.Environ.Saf_80_118
PubMedSearch : Liu_2012_Ecotoxicol.Environ.Saf_80_118
PubMedID: 22436861

Title : A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides - Zhu_2012_Nat.Commun_3_1112
Author(s) : Zhu Z , Zhang S , Liu H , Shen H , Lin X , Yang F , Zhou YJ , Jin G , Ye M , Zou H , Zhao ZK
Ref : Nat Commun , 3 :1112 , 2012
Abstract : Triacylglycerols are among the most attractive alternative raw materials for biofuel development. Current oil plant-based technologies are limited in terms of triacylglycerol production capacity and rate. These limitations may be circumvented by biotransformation of carbohydrates into lipids; however, our understanding of microbial oleaginicity remains limited. Here we present the results of a multi-omic analysis of Rhodosporidium toruloides, a robust triacylglycerol-producing fungus. The assembly of genome and transcriptome sequencing data reveals a genome of 20.2 Mb containing 8,171 protein-coding genes, the majority of which have multiple introns. Genes including a novel fatty acid synthase are predicted to participate in metabolic pathways absent in non-oleaginous yeasts. Transcriptomic and proteomic data suggest that lipid accumulation under nitrogen-limited conditions correlates with the induction of lipogenesis, nitrogenous compound recycling, macromolecule metabolism and autophagy. The multi-omic map of R. toruloides therefore provides a valuable resource for efforts to rationally engineer lipid-production pathways.
ESTHER : Zhu_2012_Nat.Commun_3_1112
PubMedSearch : Zhu_2012_Nat.Commun_3_1112
PubMedID: 23047670
Gene_locus related to this paper: rhot1-m7wd80 , rhot1-m7x154 , rhot1-m7xfd0 , rhot1-m7wh41 , rhot1-m7x3p3 , rhot1-m7x835 , rhoto-a0a061bfj5

Title : Distinct subsets of Syt-IV\/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity - Dean_2012_J.Neurosci_32_5398
Author(s) : Dean C , Liu H , Staudt T , Stahlberg MA , Vingill S , Buckers J , Kamin D , Engelhardt J , Jackson MB , Hell SW , Chapman ER
Ref : Journal of Neuroscience , 32 :5398 , 2012
Abstract : BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation, a phenomenon that underlies learning and memory. However, whether BDNF acts in a diffuse manner or is targeted to specific neuronal subcompartments or synaptic sites to affect circuit function remains unknown. Here, using photoactivation of BDNF or syt-IV (a regulator of exocytosis present on BDNF-containing vesicles) in transfected rat hippocampal neurons, we discovered that distinct subsets of BDNF vesicles are targeted to axons versus dendrites and are not shared between these compartments. Moreover, syt-IV- and BDNF-harboring vesicles are recruited to both presynaptic and postsynaptic sites in response to increased neuronal activity. Finally, using syt-IV knockout mouse neurons, we found that syt-IV is necessary for both presynaptic and postsynaptic scaling of synaptic strength in response to changes in network activity. These findings demonstrate that BDNF-containing vesicles can be targeted to specific sites in neurons and suggest that syt-IV-regulated BDNF secretion is subject to spatial control to regulate synaptic function in a site-specific manner.
ESTHER : Dean_2012_J.Neurosci_32_5398
PubMedSearch : Dean_2012_J.Neurosci_32_5398
PubMedID: 22514304

Title : Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment - Li_2012_Mol.Med.Rep_6_1450
Author(s) : Li Q , Chen M , Liu H , Yang L , Yang G
Ref : Mol Med Rep , 6 :1450 , 2012
Abstract : The aim of this study was to investigate the pathological changes in a rat model of Alzheimer's disease (AD) and the effect of donepezil hydrochloride (HCl) treatment. The rat model of AD was established by the bilateral injection of amyloid beta1-40 (Abeta1-40) into the hippocampus. Changes in spatial learning and memory functions were examined using the Morris water maze test and changes in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined using chemical colorimetry. Moreover, the changes in acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) expression were analyzed using immunohistochemical staining. The mRNA expression levels of the amyloid precursor protein (APP) and beta-secreted enzyme 1 (BACE1) were evaluated using RT-PCR. The effects of donepezil HCl on the aforementioned indices were also observed. The rat memories of the platform quadrants in the blank, sham and donepezil HCl groups were improved compared with those of the rats in the model group. The ratio of swim distance in the fourth platform quadrant (l4) to the total swim distance (l total) for the model group rats (l4/l total) was significantly decreased compared with that for the blank and sham group rats. Following donepezil HCl treatment, the ratio of l4/l total significantly increased. AD modeling caused a significant decrease in the CAT and GSH-Px activities in the brain tissues of the rats. The CAT and GSH-Px activities in the AD model rats significantly increased following donepezil HCl treatment. Moreover, donepezil HCl treatment significantly decreased the AChE, APP and BACE1 mRNA expression levels and increased the ChAT expression levels. Therefore, donepezil HCl was able to significantly decrease learning and memory damage in a rat model of AD.
ESTHER : Li_2012_Mol.Med.Rep_6_1450
PubMedSearch : Li_2012_Mol.Med.Rep_6_1450
PubMedID: 23023803

Title : t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-kappaB-p65 - Li_2012_J.Neurooncol_108_385
Author(s) : Li J , Liu H , Xing B , Yu Y , Wang H , Chen G , Gu B , Zhang G , Wei D , Gu P , Li M , Hu W
Ref : J Neurooncol , 108 :385 , 2012
Abstract : Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-kappaB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-kappaB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-kappaB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.
ESTHER : Li_2012_J.Neurooncol_108_385
PubMedSearch : Li_2012_J.Neurooncol_108_385
PubMedID: 22382785

Title : Chromogenic platform based on recombinant Drosophila melanogaster acetylcholinesterase for visible unidirectional assay of organophosphate and carbamate insecticide residues - Han_2012_Anal.Chim.Acta_720_126
Author(s) : Han Z , Chi C , Bai B , Liu G , Rao Q , Peng S , Liu H , Zhao Z , Zhang D , Wu A
Ref : Anal Chim Acta , 720 :126 , 2012
Abstract : In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC(50) values against the tested six insecticides (0.06 mug mL(-1) of carbofuran, 0.28 mug mL(-1) of methomyl, 0.03 mug mL(-1) of dichlorvos, 31.6 mug mL(-1) of methamidophos, 2.0 mug mL(-1) of monocrotophos, 6.3 mug mL(-1) of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10(-3) to 10(1) mug g(-1). Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.
ESTHER : Han_2012_Anal.Chim.Acta_720_126
PubMedSearch : Han_2012_Anal.Chim.Acta_720_126
PubMedID: 22365130

Title : Complete genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28 - Guan_2012_J.Bacteriol_194_6975
Author(s) : Guan P , Ai P , Dai X , Zhang J , Xu L , Zhu J , Li Q , Deng Q , Li S , Wang S , Liu H , Wang L , Li P , Zheng A
Ref : Journal of Bacteriology , 194 :6975 , 2012
Abstract : Bacillus thuringiensis is an important microbial insecticide used in the control of agricultural pests. Here we report the finished, annotated genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28, which can form parasporal crystals consisting of Cry4Cc1, Cry30Fa1, Cry53Ab1, Cry54Aa1, Cry54Ab1, Cry68Aa1, Cry69Aa1, Cry69Aa2, Cry70Ba1, Cyt1Da1, and Cyt2Aa3. It is also highly toxic to lepidopterous and dipterous insects.
ESTHER : Guan_2012_J.Bacteriol_194_6975
PubMedSearch : Guan_2012_J.Bacteriol_194_6975
PubMedID: 23209229

Title : Complete genome sequence of the metabolically versatile halophilic archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) producer - Han_2012_J.Bacteriol_194_4463
Author(s) : Han J , Zhang F , Hou J , Liu X , Li M , Liu H , Cai L , Zhang B , Chen Y , Zhou J , Hu S , Xiang H
Ref : Journal of Bacteriology , 194 :4463 , 2012
Abstract : Haloferax mediterranei, an extremely halophilic archaeon, has shown promise for production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from unrelated cheap carbon sources. Here we report the complete genome (3,904,707 bp) of H. mediterranei CGMCC 1.2087, consisting of one chromosome and three megaplasmids.
ESTHER : Han_2012_J.Bacteriol_194_4463
PubMedSearch : Han_2012_J.Bacteriol_194_4463
PubMedID: 22843593

Title : A GATA transcription factor recruits Hda1 in response to reduced Tor1 signaling to establish a hyphal chromatin state in Candida albicans - Lu_2012_PLoS.Pathog_8_e1002663
Author(s) : Lu Y , Su C , Liu H
Ref : PLoS Pathog , 8 :e1002663 , 2012
Abstract : Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. One critical virulence attribute is its morphogenetic plasticity. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of the cAMP/PKA pathway and promoter recruitment of the histone deacetylase Hda1 under reduced Tor1 signaling. Molecular mechanisms for the temporal connection and the link to Tor1 signaling are not clear. Here, through a forward genetic screen, we report the identification of the GATA family transcription factor Brg1 as the factor that recruits Hda1 to promoters of hypha-specific genes during hyphal elongation. BRG1 expression requires both the removal of Nrg1 and a sub-growth inhibitory level of rapamycin; therefore, it is a sensitive readout of Tor1 signaling. Interestingly, promoters of hypha-specific genes are not accessible to Brg1 in yeast cells. Furthermore, ectopic expression of Brg1 cannot induce hyphae, but can sustain hyphal development. Nucleosome mapping of a hypha-specific promoter shows that Nrg1 binding sites are in nucleosome free regions in yeast cells, whereas Brg1 binding sites are occupied by nucleosomes. Nucleosome disassembly during hyphal initiation exposes the binding sites for both regulators. During hyphal elongation, Brg1-mediated Hda1 recruitment causes nucleosome repositioning and occlusion of Nrg1 binding sites. We suggest that nucleosome repositioning is the underlying mechanism for the yeast-hyphal transition. The hypha-specific regulator Ume6 is a key downstream target of Brg1 and functions after Brg1 as a built-in positive feedback regulator of the hyphal transcriptional program to sustain hyphal development. With the levels of Nrg1 and Brg1 dynamically and sensitively controlled by the two major cellular growth pathways, temporal changes in nucleosome positioning during the yeast-to-hypha transition provide a mechanism for signal integration and cell fate specification. This mechanism is likely used broadly in development.
ESTHER : Lu_2012_PLoS.Pathog_8_e1002663
PubMedSearch : Lu_2012_PLoS.Pathog_8_e1002663
PubMedID: 22536157
Gene_locus related to this paper: canal-hda1

Title : Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats - Liu_2012_Neuropharmacol_62_2515
Author(s) : Liu H , Lai M , Zhou X , Zhu H , Liu Y , Sun A , Ma B , Zhang F , Zhou W
Ref : Neuropharmacology , 62 :2515 , 2012
Abstract : BACKGROUND AND OBJECTIVE: Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues. METHODS: Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking. RESULTS: The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5mg/kg) but not with mecamylamine (3mg/kg) or scopolamine methobromide (1mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior. CONCLUSION: The results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors.
ESTHER : Liu_2012_Neuropharmacol_62_2515
PubMedSearch : Liu_2012_Neuropharmacol_62_2515
PubMedID: 22342742

Title : Complete genome sequence of Haloarcula hispanica, a Model Haloarchaeon for studying genetics, metabolism, and virus-host interaction - Liu_2011_J.Bacteriol_193_6086
Author(s) : Liu H , Wu Z , Li M , Zhang F , Zheng H , Han J , Liu J , Zhou J , Wang S , Xiang H
Ref : Journal of Bacteriology , 193 :6086 , 2011
Abstract : Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid.
ESTHER : Liu_2011_J.Bacteriol_193_6086
PubMedSearch : Liu_2011_J.Bacteriol_193_6086
PubMedID: 21994921
Gene_locus related to this paper: halma-q5uym0

Title : Genome sequence of the halotolerant marine bacterium Myxococcus fulvus HW-1 - Li_2011_J.Bacteriol_193_5015
Author(s) : Li ZF , Li X , Liu H , Liu X , Han K , Wu ZH , Hu W , Li FF , Li YZ
Ref : Journal of Bacteriology , 193 :5015 , 2011
Abstract : Myxococcus fulvus HW-1 (ATCC BAA-855) is a halotolerant marine myxobacterium. This strain exhibits complex social behaviors in the presence of low concentrations of seawater but adopts an asocial living pattern under oceanic conditions. The whole genome of M. fulvus HW-1 will enable us to further investigate the details of its evolution.
ESTHER : Li_2011_J.Bacteriol_193_5015
PubMedSearch : Li_2011_J.Bacteriol_193_5015
PubMedID: 21868801
Gene_locus related to this paper: myxfh-f8c8h2 , myxfh-f8cmh0 , myxfh-f8cps7 , myxxa-Q84FB1 , myxxd-q1d6k0 , myxfh-f8ckt8 , myxfh-f8chw8 , myxfh-f8cq56 , myxfh-f8cj85 , myxfh-f8c7n6 , myxxd-q1d790

Title : Removal of phthalate esters from water using immobilized lipase on chitosan beads - Dulazi_2011_Environ.Technol_32_1443
Author(s) : Dulazi AA , Liu H
Ref : Environ Technol , 32 :1443 , 2011
Abstract : Lipase immobilized on chitosan beads was investigated as a possible efficient and cost-effective method of removing phthalate esters (PAEs) from water, under the hypothesis that the immobilized lipase could degrade PAEs and the amino group of chitosan could adsorb the degraded products. Three immobilization methods, namely crosslinking using glutaraldehyde (GLA), activation with 1-ethyl-3(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC) and a binary method using both GLA and EDC, were compared. The results showed that lipase immobilized by crosslinking with GLA exhibited a higher degradation ability for PAEs with lower molecular weights. It removed 100% of dimethyl phthalate and 93.86% of diethyl phthalate. On the other hand, lipase immobilized by EDC activation exhibited efficient degradation of PAEs with higher molecular weights, such as diethylhexyl phthalate (removal efficiency 100%). However, lipase immobilized by the binary method unexpectedly showed less than 50% removal efficiency for all five PAEs. The PAE solutions treated with different immobilized lipases were characterized using high-performance liquid chromatography, and the mechanism of the removal of PAEs by the lipase immobilized on chitosan beads using different methods is further discussed.
ESTHER : Dulazi_2011_Environ.Technol_32_1443
PubMedSearch : Dulazi_2011_Environ.Technol_32_1443
PubMedID: 22329134

Title : Macrolide antibiotics inhibit mucus secretion and calcium entry in Swine airway submucosal mucous gland cells - Lu_2011_J.Pharmacol.Exp.Ther_336_178
Author(s) : Lu S , Liu H , Farley JM, Sr.
Ref : Journal of Pharmacology & Experimental Therapeutics , 336 :178 , 2011
Abstract : Macrolide antibiotics such as erythromycin (EM) and azithromycin (AZM) are beneficial in the treatment of mucus hypersecretion in inflammatory pulmonary diseases. Several indirect and direct mechanisms of action have been proposed. This study investigates the direct effect of macrolides on secretory function of isolated submucosal mucous gland cells (SMGCs). We hypothesize that macrolides inhibit the calcium influx necessary for evoked mucus secretion. To test this, we quantified mucin protein release using enzyme-linked immunosorbent assay, calcium-activated K(+) (K(Ca)), and calcium-activated Cl(-) (Cl(Ca)) currents. We measured nonselective cation current (NSCC) using whole-cell patch-clamp techniques; intracellular calcium concentration ([Ca(2+)](i)) was measured using fura-2 Ca(2+) imaging. We found that both EM and AZM are agonists at muscarinic receptors. EM (10 muM) evoked a small but significant increase in mucin release but inhibited the mucin release induced by subsequent acetylcholine (ACh) treatment. Both EM and AZM (10 muM) evoked K(Ca) and Cl(Ca) whole-cell currents, which were blocked by atropine. EM and AZM also accelerated the decay of inositol trisphosphate-induced K(Ca) and Cl(Ca) currents without changing the peak current amplitudes. Likewise, internal application of AZM (10 muM) enhanced the decay rate of ACh-induced K(Ca) and Cl(Ca) currents. EM (1-10 muM) and AZM (0.1-10 muM) slowly (over 25-30 min) inhibited thapsigargin (TG)-induced Ca(2+) entry when applied during the plateau phase of Ca(2+) entry but blunted TG-induced Ca(2+) entry by 70% after a 5-min pretreatment before initiating calcium entry. EM blocked TG-induced NSCC. We conclude that macrolide antibiotics are partial agonists at muscarinic receptors but inhibit stimulated mucus release by inhibiting calcium entry in SMGCs.
ESTHER : Lu_2011_J.Pharmacol.Exp.Ther_336_178
PubMedSearch : Lu_2011_J.Pharmacol.Exp.Ther_336_178
PubMedID: 20876748

Title : Characterization and genomic analysis of a highly chromate resistant and reducing bacterial strain Lysinibacillus fusiformis ZC1 - He_2011_J.Hazard.Mater_185_682
Author(s) : He M , Li X , Liu H , Miller SJ , Wang G , Rensing C
Ref : J Hazard Mater , 185 :682 , 2011
Abstract : Lysinibacillus fusiformis ZC1 isolated from chromium (Cr) contaminated wastewater of a metal electroplating factory displayed high chromate [Cr(VI)] resistance with a minimal inhibitory concentration (MIC) of 60mM in R2A medium. L. fusiformis ZC1 showed resistances to multiple metals (Cu, Ni, Co, Hg, Cd and Ag) and a metalloid (As). This bacterium exhibited an extremely rapid Cr(VI) reduction capability. It almost completely reduced 1mM K(2)CrO(4) in 12h. The Cr(VI) reduction ability of L. fusiformis ZC1 was enhanced by sodium acetate and NADH. By whole genome sequence analysis, strain ZC1 was found to contain large numbers of metal(loid) resistance genes. Specifically, a chrA gene encoding a putative chromate transporter conferring chromate resistance was identified. The chromate resistance was constitutive in both phenotypic and gene expression analyses. Furthermore, we found a yieF gene and several genes encoding reductases that were possibly involved in chromate reduction. Expression of adjacent putative chromate reduction related genes, nitR and yieF, was found to be constitutive. The large numbers of NADH-dependent chromate reductase genes may be responsible for the rapid chromate reduction in order to detoxify Cr(VI) and survive in the harsh wastewater environment.
ESTHER : He_2011_J.Hazard.Mater_185_682
PubMedSearch : He_2011_J.Hazard.Mater_185_682
PubMedID: 20952126
Gene_locus related to this paper: 9baci-d7wzf8

Title : The draft genome of the carcinogenic human liver fluke Clonorchis sinensis - Wang_2011_Genome.Biol_12_R107
Author(s) : Wang X , Chen W , Huang Y , Sun J , Men J , Liu H , Luo F , Guo L , Lv X , Deng C , Zhou C , Fan Y , Li X , Huang L , Hu Y , Liang C , Hu X , Xu J , Yu X
Ref : Genome Biol , 12 :R107 , 2011
Abstract : BACKGROUND: Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. RESULTS: We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. CONCLUSIONS: This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control.
ESTHER : Wang_2011_Genome.Biol_12_R107
PubMedSearch : Wang_2011_Genome.Biol_12_R107
PubMedID: 22023798
Gene_locus related to this paper: closi-h2krw6

Title : [Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B] - Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
Author(s) : Sun J , Yu HW , Liu Z , Liu H , Zhang Q , Yao QW , Feng YM , Li J , Meng QH
Ref : Zhonghua Gan Zang Bing Za Zhi , 19 :603 , 2011
Abstract : To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy.
ESTHER : Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
PubMedSearch : Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
PubMedID: 22152318

Title : Elevated adipose triglyceride lipase in newly diagnosed type 2 diabetes mellitus with hypertension - Xu_2011_Am.J.Med.Sci_342_452
Author(s) : Xu S , Yang G , Yang M , Li S , Liu H , Li L
Ref : American Journal of Medicine Sci , 342 :452 , 2011
Abstract : INTRODUCTION: Adipose triglyceride lipase (ATGL) is a recently identified triacylglycerol lipase responsible for adiposity lipolysis. Its pathophysiologic role in humans remains unknown. MATERIAL AND METHODS: In this study, the authors investigated the levels of plasma ATGL among patients with type 2 diabetes mellitus (T2DM), patients with T2DM and hypertension and control subjects. They also assessed the association between plasma ATGL and body composition and metabolic parameters. RESULTS AND CONCLUSIONS: Plasma ATGL levels significantly increased in patients with T2DM and hypertension compared with those with T2DM (78.3 +/- 23.4 versus 65.1 +/- 22.8 mug/L, P < 0.01). No gender differences were found among plasma ATGL levels. Furthermore, they found that the plasma ATGL level was positively correlated with total cholesterol (r = 0.17, P < 0.05) and high-density lipoprotein C (r = 0.16, P < 0.05) in simple regression analysis of pooled data, whereas, in multiple stepwise regression analysis, diastolic blood pressure, total cholesterol and homeostasis model assessment of insulin resistance were independently related factors with plasma ATGL levels (Y = -13.662 + 0.343 x waist + 0.268 x diastolic blood pressure + 0.053 x 2hPin + 0.966 x homeostasis model assessment of insulin resistance). This work indicates the potential link of ATGL with the pathogenesis of insulin resistance and T2DM.
ESTHER : Xu_2011_Am.J.Med.Sci_342_452
PubMedSearch : Xu_2011_Am.J.Med.Sci_342_452
PubMedID: 21709540

Title : Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase - Shen_2011_Mol.Biol.Rep_38_553
Author(s) : Shen LL , Liu H , Peng J , Gan L , Lu L , Zhang Q , Li L , He F , Jiang Y
Ref : Mol Biol Rep , 38 :553 , 2011
Abstract : The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid.
ESTHER : Shen_2011_Mol.Biol.Rep_38_553
PubMedSearch : Shen_2011_Mol.Biol.Rep_38_553
PubMedID: 20373033

Title : Functional characterization of a gene cluster involved in gentisate catabolism in Rhodococcus sp. strain NCIMB 12038 - Liu_2011_Appl.Microbiol.Biotechnol_90_671
Author(s) : Liu TT , Xu Y , Liu H , Luo S , Yin YJ , Liu SJ , Zhou NY
Ref : Applied Microbiology & Biotechnology , 90 :671 , 2011
Abstract : Rhodococcus sp. strain NCIMB 12038 utilizes naphthalene as a sole source of carbon and energy, and degrades naphthalene via salicylate and gentisate. To identify the genes involved in this pathway, we cloned and sequenced a 12-kb DNA fragment containing a gentisate catabolic gene cluster. Among the 13 complete open reading frames deduced from this fragment, three (narIKL) have been shown to encode the enzymes involved in the reactions of gentisate catabolism. NarI is gentisate 1,2-dioxygenase which converts gentisate to maleylpyruvate, NarL is a mycothiol-dependent maleylpyruvate isomerase which catalyzes the isomerization of maleylpyruvate to fumarylpyruvate, and NarK is a fumarylpyruvate hydrolase which hydrolyzes fumarylpyruvate to fumarate and pyruvate. The narX gene, which is divergently transcribed with narIKL, has been shown to encode a functional 3-hydroxybenzoate 6-monooxygenase. This led us to discover that this strain is also capable of utilizing 3-hydroxybenzoate as its sole source of carbon and energy. Both NarL and NarX were purified to homogeneity as His-tagged proteins, and they were determined by gel filtration to exist as a trimer and a monomer, respectively. Our study suggested that the gentisate degradation pathway was shared by both naphthalene and 3-hydroxybenzoate catabolism in this strain.
ESTHER : Liu_2011_Appl.Microbiol.Biotechnol_90_671
PubMedSearch : Liu_2011_Appl.Microbiol.Biotechnol_90_671
PubMedID: 21181154

Title : Enantioselective cytotoxicity of isocarbophos is mediated by oxidative stress-induced JNK activation in human hepatocytes - Liu_2010_Toxicology_276_115
Author(s) : Liu H , Liu J , Xu L , Zhou S , Li L , Liu W
Ref : Toxicology , 276 :115 , 2010
Abstract : Recent studies have shown the enantioselectivity of chiral pesticides in environmental fate, aquatic toxicity, endocrine disruption and cytotoxicity. Thus it is of significance to investigate the molecular mechanisms of chiral pesticides enantioselectivity in cytotoxicity. In the present study, we used Hep G2 cells as in vitro model to assay cytotoxicity of enantiomers of isocarbophos (ICP), a widely used chiral organophosphorus pesticide. The results of cell viability assay and cytoflow assay indicated an obvious enantioselective hepatocyte toxicity of ICP: (-)-ICP was about two times more toxic than (+)-ICP in Hep G2 cells. We found that (-)-ICP, but not (+)-ICP, up-regulated Bax protein expression and down-regulated Bcl-2 expression levels, which resulted in an increase in Bax/Bcl-2 ratio with the apoptosis co-ordination. Although (-)-ICP enantioselectively activated both ERK and JNK, only the specific inhibitor for JNK could completely reverse (-)-ICP-induced apoptosis of Hep G2 cells. It suggests that (-)-ICP-induced hepatocyte toxicity was more dominantly through the sustained activation of JNK pathway, but only partially via ERK cascade. Furthermore, (-)-ICP induced ROS production, while (+)-ICP had no effect on ROS generation. The antioxidant MnTBAP attenuated (-)-ICP-induced activation of JNK and ERK, indicating that the outcome from challenge with (-)-ICP enantiomer depends on the oxidative stress-induced activation of a series of signaling cascades that promote hepatocyte apoptosis. In conclusion, (-)-ICP enantioselectively causes the change of Bax/Bcl-2 ratio, triggers the generation of intracellular ROS and sequentially induces sustainable activation of JNK, which in turn, results in a decrease in cell viability and an increase in cell apoptosis. Our observations provide further insight into enantiomers toxicity pathway which is able to differentiate between enantiomer activities at molecular level.
ESTHER : Liu_2010_Toxicology_276_115
PubMedSearch : Liu_2010_Toxicology_276_115
PubMedID: 20688129

Title : Pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV inhibitor after oral administration in rats - Wang_2010_Xenobiotica_40_707
Author(s) : Wang X , Zhang D , Xu W , Liu H , Wang W
Ref : Xenobiotica , 40 :707 , 2010
Abstract : The pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV (DPP IV) inhibitor, was studied in rats after oral administration for developing it as an antidiabetic agent. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to determine lipoyl vildagliptin in rat plasma. After an overnight fasting, rats were orally given lipoyl vildagliptin. Following a single oral dose of 25, 50, and 100 mg x kg(-1), T(max) values were from 1.25 to 1.84 h, CL/F values were around 100 l h(-1) kg(-1). In the dose range, C(max) values (63.9-296 mug x l(-1)) and AUC(0-infinity)values (260-1214 mug x h x l(-1)) were proportional to the doses. In conclusion, this LC-MS/MS method for the determination of lipoyl vildagliptin in rat plasma was selective and sensitive. In rats, lipoyl vildagliptin displayed linear pharmacokinetics after a single oral dose in the range of 25-100 mg x kg(-1). Lipoyl vildagliptin might have very high CL/F values and V(d)/F values, which indicated that the bioavailability of this drug might be low or lipoyl vildagliptin might distribute extensively or accumulate in tissues in view of its high liposolubility.
ESTHER : Wang_2010_Xenobiotica_40_707
PubMedSearch : Wang_2010_Xenobiotica_40_707
PubMedID: 20735236

Title : Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice - Duan_2010_Biomaterials_31_894
Author(s) : Duan Y , Liu J , Ma L , Li N , Liu H , Wang J , Zheng L , Liu C , Wang X , Zhao X , Yan J , Wang S , Wang H , Zhang X , Hong F
Ref : Biomaterials , 31 :894 , 2010
Abstract : In an effort to examine liver injury, immune response, and other physiological effects in mice caused by intragastric administration of nanoparticulate anatase titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte counts, hematological indices, biochemical parameters of liver functions, and histopathological changes in nanoparticulate titanium dioxide -treated mice. Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed a reduction in body weight, an increase in coefficients of the liver and histopathological changes in the liver. Specifically, in these nanoparticulate titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased, whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red (cell) distribution width, platelets, hematocrit, mean platelet volume of mice were increased. Furthermore, liver functions were also disrupted, as evidenced by the enhanced activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase of the total protein, and the reduction of ratio of albumin to globulin, the total bilirubin, triglycerides, and the total cholesterol levels. These results suggested that the liver function damage observed in mice treated with higher dose nanoparticulate titanium dioxide is likely associated with the damage of haemostasis blood system and immune response. However, low dose nanoparticulate anatase TiO(2) has little influences on haemostasis blood system and immune response in mice.
ESTHER : Duan_2010_Biomaterials_31_894
PubMedSearch : Duan_2010_Biomaterials_31_894
PubMedID: 19857890

Title : Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity - Ma_2010_Biomaterials_31_99
Author(s) : Ma L , Liu J , Li N , Wang J , Duan Y , Yan J , Liu H , Wang H , Hong F
Ref : Biomaterials , 31 :99 , 2010
Abstract : In order to study the mechanisms underlying the effects of TiO(2) nanoparticles on the brain, ICR mice were injected with nanoparticulate anatase TiO(2) (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined the coefficient of the brain, the brain pathological changes and oxidative stress-mediated responses, and the accumulation of nanoparticulate anatase TiO(2) and levels of neurochemicals in the brain. The results showed that high-dose nanoparticulate anatase TiO(2) could induce some neurons to turn into filamentous shapes and others into inflammatory cells. The concentration of nanoparticulate anatase TiO(2) in the brain was increased as increases in nanoparticulate anatase TiO(2) dosages used. The oxidative stress and injury of the brain occurred as nanoparticulate anatase TiO(2) appeared to trigger a cascade of reactions such as lipid peroxidation, the decreases of the total anti-oxidation capacity and activities of antioxidative enzymes, the excessive release of nitric oxide, the reduction of glutamic acid, and the downregulated level of acetylcholinesterase activities. We concluded that TiO(2) nanoparticles injected at the abdominal cavity could be translocated into the brain and in turn caused the brain injury.
ESTHER : Ma_2010_Biomaterials_31_99
PubMedSearch : Ma_2010_Biomaterials_31_99
PubMedID: 19783296

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 : Identification and characterization of full-length cDNAs in channel catfish (Ictalurus punctatus) and blue catfish (Ictalurus furcatus) - Chen_2010_PLoS.One_5_e11546
Author(s) : Chen F , Lee Y , Jiang Y , Wang S , Peatman E , Abernathy J , Liu H , Liu S , Kucuktas H , Ke C , Liu Z
Ref : PLoS ONE , 5 :e11546 , 2010
Abstract : BACKGROUND: Genome annotation projects, gene functional studies, and phylogenetic analyses for a given organism all greatly benefit from access to a validated full-length cDNA resource. While increasingly common in model species, full-length cDNA resources in aquaculture species are scarce. METHODOLOGY AND PRINCIPAL FINDINGS: Through in silico analysis of catfish (Ictalurus spp.) ESTs, a total of 10,037 channel catfish and 7,382 blue catfish cDNA clones were identified as potentially encoding full-length cDNAs. Of this set, a total of 1,169 channel catfish and 933 blue catfish full-length cDNA clones were selected for re-sequencing to provide additional coverage and ensure sequence accuracy. A total of 1,745 unique gene transcripts were identified from the full-length cDNA set, including 1,064 gene transcripts from channel catfish and 681 gene transcripts from blue catfish, with 416 transcripts shared between the two closely related species. Full-length sequence characteristics (ortholog conservation, UTR length, Kozak sequence, and conserved motifs) of the channel and blue catfish were examined in detail. Comparison of gene ontology composition between full-length cDNAs and all catfish ESTs revealed that the full-length cDNA set is representative of the gene diversity encoded in the catfish transcriptome.
CONCLUSIONS: This study describes the first catfish full-length cDNA set constructed from several cDNA libraries. The catfish full-length cDNA sequences, and data gleaned from sequence characteristics analysis, will be a valuable resource for ongoing catfish whole-genome sequencing and future gene-based studies of function and evolution in teleost fishes.
ESTHER : Chen_2010_PLoS.One_5_e11546
PubMedSearch : Chen_2010_PLoS.One_5_e11546
PubMedID: 20634964
Gene_locus related to this paper: ictpu-e3teh0 , ictpu-e3tfr7 , ictpu-a0a2d0pnc6

Title : Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release - Dean_2009_Nat.Neurosci_12_767
Author(s) : Dean C , Liu H , Dunning FM , Chang PY , Jackson MB , Chapman ER
Ref : Nat Neurosci , 12 :767 , 2009
Abstract : Synaptotagmin-IV (syt-IV) is a membrane trafficking protein that influences learning and memory, but its localization and role in synaptic function remain unclear. We found that syt-IV localized to brain-derived neurotrophic factor (BDNF)-containing vesicles in hippocampal neurons. Syt-IV/BDNF-harboring vesicles underwent exocytosis in both axons and dendrites, and syt-IV inhibited BDNF release at both sites. Knockout of syt-IV increased, and overexpression decreased, the rate of synaptic vesicle exocytosis from presynaptic terminals indirectly via changes in postsynaptic release of BDNF. Thus, postsynaptic syt-IV regulates the trans-synaptic action of BDNF to control presynaptic vesicle dynamics. Furthermore, selective loss of presynaptic syt-IV increased spontaneous quantal release, whereas a loss of postsynaptic syt-IV increased quantal amplitude. Finally, syt-IV knockout mice showed enhanced long-term potentiation (LTP), which depended entirely on disinhibition of BDNF release. Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP.
ESTHER : Dean_2009_Nat.Neurosci_12_767
PubMedSearch : Dean_2009_Nat.Neurosci_12_767
PubMedID: 19448629

Title : A draft genome sequence of Pseudomonas syringae pv. tomato T1 reveals a type III effector repertoire significantly divergent from that of Pseudomonas syringae pv. tomato DC3000 - Almeida_2009_Mol.Plant.Microbe.Interact_22_52
Author(s) : Almeida NF , Yan S , Lindeberg M , Studholme DJ , Schneider DJ , Condon B , Liu H , Viana CJ , Warren A , Evans C , Kemen E , Maclean D , Angot A , Martin GB , Jones JD , Collmer A , Setubal JC , Vinatzer BA
Ref : Mol Plant Microbe Interact , 22 :52 , 2009
Abstract : Diverse gene products including phytotoxins, pathogen-associated molecular patterns, and type III secreted effectors influence interactions between Pseudomonas syringae strains and plants, with additional yet uncharacterized factors likely contributing as well. Of particular interest are those interactions governing pathogen-host specificity. Comparative genomics of closely related pathogens with different host specificity represents an excellent approach for identification of genes contributing to host-range determination. A draft genome sequence of Pseudomonas syringae pv. tomato T1, which is pathogenic on tomato but nonpathogenic on Arabidopsis thaliana, was obtained for this purpose and compared with the genome of the closely related A. thaliana and tomato model pathogen P. syringae pv. tomato DC3000. Although the overall genetic content of each of the two genomes appears to be highly similar, the repertoire of effectors was found to diverge significantly. Several P. syringae pv. tomato T1 effectors absent from strain DC3000 were confirmed to be translocated into plants, with the well-studied effector AvrRpt2 representing a likely candidate for host-range determination. However, the presence of avrRpt2 was not found sufficient to explain A. thaliana resistance to P. syringae pv. tomato T1, suggesting that other effectors and possibly type III secretion system-independent factors also play a role in this interaction.
ESTHER : Almeida_2009_Mol.Plant.Microbe.Interact_22_52
PubMedSearch : Almeida_2009_Mol.Plant.Microbe.Interact_22_52
PubMedID: 19061402
Gene_locus related to this paper: pse14-q48ia0 , psesm-e2mn04 , psesm-IRP1 , psesm-METX , psesm-q88a39 , psesm-q881b4 , psesy-ESTA , psesy-IRP4 , psesy-PIP , psesy-PSPTO0421 , psesy-PSPTO0508 , psesy-PSPTO1504 , psesy-PSPTO1559 , psesy-PSPTO1766 , psesy-PSPTO2005 , psesy-PSPTO2134 , psesy-PSPTO2150 , psesy-PSPTO3135 , psesy-PSPTO3138 , psesy-PSPTO3306 , psesy-PSPTO4277 , psesy-PSPTO4519 , psesy-PSPTO4540 , psesy-PSPTO4964 , psesy-PSPTO5299 , psesy-PSPTO5537 , pseub-e2mf08

Title : Genetic and biochemical analyses of chlorobenzene degradation gene clusters in Pandoraea sp. strain MCB032 - Jiang_2009_Arch.Microbiol_191_485
Author(s) : Jiang XW , Liu H , Xu Y , Wang SJ , Leak DJ , Zhou NY
Ref : Arch Microbiol , 191 :485 , 2009
Abstract : Pandoraea sp. strain MCB032 was isolated as an emerging chlorobenzene degrader from a functionally stable bioreactor where species succession had occurred. In this study, two gene clusters encoding chlorobenzene metabolic functions have been cloned. Within the cbs gene cluster, CbsA and CbsB are similar to the chlorobenzene dioxygenase and the cis-chlorobenzene dihydrodiol dehydrogenase in Ralstonia sp. JS705 and shown to transform chlorobenzene to 3-chlorocatechol. The clc gene cluster shows strong similarity to the clc genes of Ralstonia sp. JS705 and encodes chlorocatechol 1,2-dioxygenase (ClcA) and other enzymes, which catalyze the conversion of chlorocatechol to 3-oxoadipate. The Michaelis constants (K (m)) values of ClcA for catechol, 3-methylcatechol and 3-chlorocatechol were determined as 10.0, 8.9 and 3.4 muM, respectively. CbsX, a putative transport protein present in the cbs cluster of strain MCB032 but not in those of other chlorobenzene degraders, shows 76 and 53% identities to two previously identified transport proteins involved in toluene degradation, TbuX from Ralstonia pickettii PKO1 and TodX from Pseudomonas putida F1. The presence of the transport protein in strain MCB032 likely provides a mechanistic explanation for its higher chlorobenzene affinity and may well be the basis for the competitive advantage of this strain in the bioreactor.
ESTHER : Jiang_2009_Arch.Microbiol_191_485
PubMedSearch : Jiang_2009_Arch.Microbiol_191_485
PubMedID: 19365620
Gene_locus related to this paper: 9burk-a7kx00

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 : Biochemical toxicity of nano-anatase TiO2 particles in mice - Liu_2009_Biol.Trace.Elem.Res_129_170
Author(s) : Liu H , Ma L , Zhao J , Liu J , Yan J , Ruan J , Hong F
Ref : Biol Trace Elem Res , 129 :170 , 2009
Abstract : Previous research on the biological and toxic effects of nano-TiO(2) particles on animals only limit to a single dose. However, the toxicity caused by single dose nano-TiO(2) does not truly represent ecological and health effects of nano-TiO(2) retained in the environment. In order to further evaluate the toxicity of nano-TiO(2) particles, nano-anatase TiO(2) (5 nm) was injected into the abdominal cavity of ICR mice everyday for 14 days and the coefficients of organs and serum biochemical parameters were investigated. The results showed that, with increasing doses of nano-anatase TiO(2), the coefficients of liver, kidney, and spleen increased gradually, while the coefficients of lung and brain decreased gradually, and the coefficient of heart had little change. The order of the titanium accumulation in the organs was liver > kidneys > spleen > lung > brain > heart. The serum biochemical parameters with lower dose of nano-anatase TiO(2) showed little difference compared with the control mice, while with higher dose of nano-anatase TiO(2), the indicators of liver function, such as alkaline phosphatase, alanine aminotransferase, leucine acid peptide, pseudocholinesterase, total protein, and albumin level, were enhanced significantly; the indicators of kidney function, such as uric acid and blood urea nitrogen, were decreased; the activities of aspartate aminotransferase, creatine kinase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase, indicator of the myocardium function, were increased. The contents of triglycerides, glucose, and high-density lipoprotein cholesterol were significantly elevated. Taken together, nano-anatase TiO(2) in higher dose caused serious damage to the liver, kidney, and myocardium of mice and disturbed the balance of blood sugar and lipid in mice. The accumulation of titanium in the organs might be closely related to the coefficients of organs and the inflammatory responses of mice.
ESTHER : Liu_2009_Biol.Trace.Elem.Res_129_170
PubMedSearch : Liu_2009_Biol.Trace.Elem.Res_129_170
PubMedID: 19066734

Title : Integrated production for biodiesel and 1,3-propanediol with lipase-catalyzed transesterification and fermentation - Xu_2009_Biotechnol.Lett_31_1335
Author(s) : Xu Y , Liu H , Du W , Sun Y , Ou X , Liu D
Ref : Biotechnol Lett , 31 :1335 , 2009
Abstract : Biodiesel, a renewable alternative to fossil energy, has shown great prospects for global proliferation in the past decade. Lipase catalyzed transesterification for biodiesel production, as a biological process with many advantages has drawn increasing attention. As a by-product, glycerol accounts for about 10% w/w of biodiesel during the process of biodiesel production. As a result, the conversion of glycerol has become a common problem which has to be resolved if considering large amount of biodiesel production. Glycerol can be fermented into 1,3-propanediol, a high value added chemical with a promising future in the polymers, for example, polytrimethylene terephthalate, and also fermentation approaches for 1,3-propanediol production which have drawn more and more attention due to advantages such as relatively low investment, mild reaction conditions and using renewable sources as the starting materials. Based on the latest technology advancements in lipase-mediated transformation for biodiesel production, the aerobic fermentation technology and genetic engineering for 1,3-propanediol production, and the integrated production of 1,3-propanediol from crude glycerol could be a promising way to improve the profit of the whole process during biodiesel production.
ESTHER : Xu_2009_Biotechnol.Lett_31_1335
PubMedSearch : Xu_2009_Biotechnol.Lett_31_1335
PubMedID: 19466559

Title : Postsynaptic Neuroligin1 regulates presynaptic maturation - Wittenmayer_2009_Proc.Natl.Acad.Sci.U.S.A_106_13564
Author(s) : Wittenmayer N , Korber C , Liu H , Kremer T , Varoqueaux F , Chapman ER , Brose N , Kuner T , Dresbach T
Ref : Proc Natl Acad Sci U S A , 106 :13564 , 2009
Abstract : Presynaptic nerve terminals pass through distinct stages of maturation after their initial assembly. Here we show that the postsynaptic cell adhesion molecule Neuroligin1 regulates key steps of presynaptic maturation. Presynaptic terminals from Neuroligin1-knockout mice remain structurally and functionally immature with respect to active zone stability and synaptic vesicle pool size, as analyzed in cultured hippocampal neurons. Conversely, overexpression of Neuroligin1 in immature neurons, that is within the first 5 days after plating, induced the formation of presynaptic boutons that had hallmarks of mature boutons. In particular, Neuroligin1 enhanced the size of the pool of recycling synaptic vesicles, the rate of synaptic vesicle exocytosis, the fraction of boutons responding to depolarization, as well as the responsiveness of the presynaptic release machinery to phorbol ester stimulation. Moreover, Neuroligin1 induced the formation of active zones that remained stable in the absence of F-actin, another hallmark of advanced maturation. Acquisition of F-actin independence of the active zone marker Bassoon during culture development or induced via overexpression of Neuroligin1 was activity-dependent. The extracellular domain of Neuroligin1 was sufficient to induce assembly of functional presynaptic terminals, while the intracellular domain was required for terminal maturation. These data show that induction of presynaptic terminal assembly and maturation involve mechanistically distinct actions of Neuroligins, and that Neuroligin1 is essential for presynaptic terminal maturation.
ESTHER : Wittenmayer_2009_Proc.Natl.Acad.Sci.U.S.A_106_13564
PubMedSearch : Wittenmayer_2009_Proc.Natl.Acad.Sci.U.S.A_106_13564
PubMedID: 19628693

Title : The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo - Li_2009_Cytokine_45_12
Author(s) : Li L , Yang G , Shi S , Yang M , Liu H , Boden G
Ref : Cytokine , 45 :12 , 2009
Abstract : Inflammatory cytokines have been linked to obesity-related insulin resistance. To investigate the effect of TNF-alpha, an inflammatory cytokine, on insulin action, C57BL/6J mice were treated with TNF-alpha for 7 days after which we examined the in vivo effects of TNF-alpha on glucose tolerance and insulin sensitivity with IV glucose tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, we analyzed the in vivo effect of TNF-alpha on several metabolism-related genes and adipocytokines implicated in the development of insulin resistance. TNF-alpha treatment resulted in markedly increased fasting blood glucose, insulin and free fatty acids (FFA) levels and reduced glucose tolerance. During the clamps, the rates insulin-stimulated whole body (G(Rd)) and skeletal muscle glucose uptake (MGU) and insulin's ability to suppress hepatic glucose production (HGP) were decreased in TNF-alpha treated animals, indicating insulin resistance. In addition, both PPARgamma and ATGL mRNA expression in adipose tissues as well as ATGL protein levels in plasma were downregulated. Moreover, adipose mRNA expression and plasma protein levels of adiponectin and visfatin were significantly down-regulated. We conclude that the alterations of PPARgamma, ATGL, adiponectin and visfatin may contribute to the development of insulin resistance mediated by TNF-alpha.
ESTHER : Li_2009_Cytokine_45_12
PubMedSearch : Li_2009_Cytokine_45_12
PubMedID: 19026557

Title : Complete genome sequence of the mosquitocidal bacterium Bacillus sphaericus C3-41 and comparison with those of closely related Bacillus species - Hu_2008_J.Bacteriol_190_2892
Author(s) : Hu X , Fan W , Han B , Liu H , Zheng D , Li Q , Dong W , Yan J , Gao M , Berry C , Yuan Z
Ref : Journal of Bacteriology , 190 :2892 , 2008
Abstract : Bacillus sphaericus strain C3-41 is an aerobic, mesophilic, spore-forming bacterium that has been used with great success in mosquito control programs worldwide. Genome sequencing revealed that the complete genome of this entomopathogenic bacterium is composed of a chromosomal replicon of 4,639,821 bp and a plasmid replicon of 177,642 bp, containing 4,786 and 186 potential protein-coding sequences, respectively. Comparison of the genome with other published sequences indicated that the B. sphaericus C3-41 chromosome is most similar to that of Bacillus sp. strain NRRL B-14905, a marine species that, like B. sphaericus, is unable to metabolize polysaccharides. The lack of key enzymes and sugar transport systems in the two bacteria appears to be the main reason for this inability, and the abundance of proteolytic enzymes and transport systems may endow these bacteria with exclusive metabolic pathways for a wide variety of organic compounds and amino acids. The genes shared between B. sphaericus C3-41 and Bacillus sp. strain NRRL B-14905, including mobile genetic elements, membrane-associated proteins, and transport systems, demonstrated that these two species are a biologically and phylogenetically divergent group. Knowledge of the genome sequence of B. sphaericus C3-41 thus increases our understanding of the bacilli and may also offer prospects for future genetic improvement of this important biological control agent.
ESTHER : Hu_2008_J.Bacteriol_190_2892
PubMedSearch : Hu_2008_J.Bacteriol_190_2892
PubMedID: 18296527
Gene_locus related to this paper: 9baci-d7ws01 , bacan-BA0954 , lyssc-b1hnz8 , lyssc-b1hrh2 , lyssc-b1hwa6 , lyssc-b1hxp5 , lyssc-b1hxz3 , lyssc-b1hy20 , lyssc-b1hy58 , lyssc-b1hyp7 , lyssc-b1hzg4 , lyssc-b1hzn7 , lyssc-b1hnt8

Title : A rice serine carboxypeptidase-like gene OsBISCPL1 is involved in regulation of defense responses against biotic and oxidative stress - Liu_2008_Gene_420_57
Author(s) : Liu H , Wang X , Zhang H , Yang Y , Ge X , Song F
Ref : Gene , 420 :57 , 2008
Abstract : Serine carboxypeptidase-like proteins (SCPLs) comprise a large family of protein hydrolyzing enzymes that play roles in multiple cellular processes. During the course of study aimed at elucidating the molecular basis of induced immunity in rice, a gene, OsBISCPL1, encoding a putative SCPL, was isolated and identified. OsBISCPL1 contains a conserved peptidase S10 domain, serine active site and a signal peptide at N-terminus. OsBISCPL1 is expressed ubiquitously in rice, including roots, stems, leaves and spikes. Expression of OsBISCPL1 in leaves was significantly up-regulated after treatments with benzothiadiazole, salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid, and also up-regulated in incompatible interactions between rice and the blast fungus, Magnaporthe grisea. Transgenic Arabidopsis plants with constitutive expression of OsBISCPL1 were generated and disease resistance assays indicated that the OsBISCPL1-overexpressing plants showed an enhanced disease resistance against Pseudomonas syringae pv. tomato and Alternaria brassicicola. Expression levels of defense-related genes, e.g. PR1, PR2, PR5 and PDF1.2, were constitutively up-regulated in transgenic plants as compared with those in wild-type plants. Furthermore, the OsBISCPL1-overexpressing plants also showed an increased tolerance to oxidative stress and up-regulated expression of oxidative stress-related genes. The results suggest that the OsBISCPL1 may be involved in regulation of defense responses against pathogen infection and oxidative stress.
ESTHER : Liu_2008_Gene_420_57
PubMedSearch : Liu_2008_Gene_420_57
PubMedID: 18571878

Title : [Cutinase production from short-chain organic acids by Thermobifida fusca] - He_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_821
Author(s) : He G , Du G , Liu L , Liu H , Huo G , Chen J
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :821 , 2008
Abstract : We studied cutinase production from short-chain organic acids by Thermobifida fusca WSH03-11 to evaluate the possibility of converting municipal sludge to high value-added products. The optimum organic acid (8.0 g/L) and nitrogen source (1.5 g/L) concentrations were determined by the single factor experiments with butyric acid, propionic acid and acetic acid as the carbon sources. When lactic acid was used as the carbon source, the optimum organic acid (3.0 g/L) and nitrogen source (1.0 g/L) concentrations were obtained. Cutinase production by T. fusca WSH03-11 was further improved with butyric acid (by 31.0%), propionic acid (by 13.3%), acetic acid (by 43.8%) and lactic acid (by 73.2%) as carbon source, respectively, with the optimized cutin concentrations. Among these four short-chain organic acids, the average specific consumption rate of acetic acid was the highest, higher than that of propionic acid 1.3-folds, butyric acid 2.0-folds and lactic acid 2.2-folds. The highest cutinase activity reached 52.4 u/mL with butyric acid (8 g/L) as the sole carbon source, higher than that of lactic acid (3 g/L) 1.7-folds, acetic acid (8 g/L) 2.5-folds and propionic acid (8 g/L) 3.2-folds. The yield of cutinase activity on lactic acid (12.70 u/mg) higher than that of butyric acid 1.4-folds, propionic acid 3.0-folds and acetic acid 3.8-folds. T. fusca WSH03-11 consumed acetic acid firstly in mixed acids carbon sources, and the consumption of butyric acid was inhibited. Further studies indicated that the consumption rate of butyrate was decreased by 66.7% in the presence of 0.5 g/L acetic acid in the mixed acids. This was the first report concerning the production of cutinase by T. fusca with mixed organic acids as the carbon sources. The results presented here provided a novel and efficient approach to produce high value-add products from municipal sludge, and also established a foundation for the industrial production of cutinase by T. fusca WSH03-11 with cheap carbon sources from the processing of municipal sludge.
ESTHER : He_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_821
PubMedSearch : He_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_821
PubMedID: 18724703

Title : Glucagon-like peptide-1 attenuates tumour necrosis factor-alpha-mediated induction of plasminogen [corrected] activator inhibitor-1 expression - Liu_2008_J.Endocrinol_196_57
Author(s) : Liu H , Hu Y , Simpson RW , Dear AE
Ref : J Endocrinol , 196 :57 , 2008
Abstract : Glucagon-like peptide-1 (GLP-1) has been proposed as a target for treatment of type 2 diabetes. GLP-1 has also been demonstrated to improve endothelial cell dysfunction in diabetic patients. Elevated plasminogen activator inhibitor type-1 [corrected] (PAI-1) levels have been implicated in endothelial cell dysfunction. The effect of GLP-1 on PAI-1 expression in vascular endothelial cells has not been explored. In a spontaneously transformed human umbilical vein endothelial cell (HUVEC) line, C11-spontaneously transformed HUVEC (STH) and primary HUVEC cells, GLP-1 treatment, in the presence of a dipeptidyl peptidase IV inhibitor, attenuated induction of PAI-1 protein and mRNA expression by tumour necrosis factor-alpha (TNF-alpha). GLP-1 also inhibited the effect of TNF-alpha on a reporter gene construct harbouring the proximal PAI-1 promoter. In addition, GLP-1 attenuated TNF-alpha-mediated induction of Nur77 mRNA and TNF-alpha-mediated binding of nuclear proteins (NPs) to the PAI-1, Nur77, cis-acting response element nerve growth factor induced clone B response element (NBRE). GLP-1 treatment also inhibited TNF-alpha-mediated induction of Akt phosphorylation. Taken together, these observations suggest that GLP-1 inhibits TNF-alpha-mediated PAI-1 induction in vascular endothelial cells, and this effect may involve Akt-mediated signalling events and the modulation of Nur77 expression and NP binding to the PAI-1 NBRE.
ESTHER : Liu_2008_J.Endocrinol_196_57
PubMedSearch : Liu_2008_J.Endocrinol_196_57
PubMedID: 18180317

Title : Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions - Chen_2008_Nat.Struct.Mol.Biol_15_50
Author(s) : Chen X , Liu H , Shim AH , Focia PJ , He X
Ref : Nat Struct Mol Biol , 15 :50 , 2008
Abstract : The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.
ESTHER : Chen_2008_Nat.Struct.Mol.Biol_15_50
PubMedSearch : Chen_2008_Nat.Struct.Mol.Biol_15_50
PubMedID: 18084303
Gene_locus related to this paper: mouse-1neur

Title : Prostaglandin E2 enhances acetylcholine-induced, Ca2+-dependent ionic currents in swine tracheal mucous gland cells - Liu_2007_J.Pharmacol.Exp.Ther_322_501
Author(s) : Liu H , Farley JM, Sr.
Ref : Journal of Pharmacology & Experimental Therapeutics , 322 :501 , 2007
Abstract : Airway submucosal gland cell (SMGC) secretions are under the control of various neurotransmitters and hormones. Interactions between different pathways, such as those mediated by cAMP and Ca(2+), in controlling mucus or electrolyte secretions are not well understood. Prostaglandin E(2) (PGE(2)) or forskolin has been shown to enhance acetylcholine (ACh)-induced short circuit current (I(SC)) in SMGC mucous cell monolayers. We show that PGE(2), by activating cAMP-dependent protein kinase A (PKA), enhanced ACh-induced, Ca(2+)-mediated current and changes in [Ca(2+)](i) in mucous cells. PGE(2) pretreatment sensitized ACh-induced I(SC) (DeltaI(SC)) by activating endoprostanoid (EP(2)) receptors. PKA inhibitors 14-22 amide PKI (PKI) and Rp-diastereomer (Rp) of cAMPs prevented the effect of PGE(2). Removing external Ca(2+) or pretreatment with the Ca(2+) entry blocker, SKF96365 [1-[beta-(3-(4-methoxyphenyl) propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl) propoxy] ethyl] imidazole], shifted the concentration-response relationships for ACh to the right but did not abolish PGE(2)-induced sensitization of the ACh response. An inositol 1,4,5-trisphosphate (IP(3)) receptor antagonist and Ca(2+) entry blocker, 2-aminoethoxydiphenyl borate, abolished the ACh-induced response. Charybdotoxin, but not iberiotoxin (IbTX), inhibited the ACh-induced DeltaI(SC). Clotrimazole, but not IbTX, inhibited the ACh-induced serosal K(+) current. Under whole-cell patch clamp, ACh-induced K(+) and Cl(-) currents were coincident with increases in [Ca(2+)](i) in single mucous cells. PGE(2) or forskolin pretreatment did not induce current or [Ca(2+)](i) changes but enhanced ACh-induced currents, membrane hyperpolarization, and [Ca(2+)](i) changes. Intra-cellular dialysis with the PKA-catalytic subunit enhanced ACh-induced whole-cell current as well. These findings demonstrate that PGE(2), via EP(2) receptors and the cAMP/PKA pathway, activates Ca(2+) entry-independent mechanisms, possibly by increasing IP(3)-mediated Ca(2+) release, resulting in the sensitization of ACh-induced currents.
ESTHER : Liu_2007_J.Pharmacol.Exp.Ther_322_501
PubMedSearch : Liu_2007_J.Pharmacol.Exp.Ther_322_501
PubMedID: 17483294

Title : The effect of diet type on growth and fatty acid composition of the sea urchin larvae, II. Psammechinus miliaris (Gmelin) -
Author(s) : Liu H , Kelly MS , Cook EJ , Black K , Orr H , Zhu JX , Dong SL
Ref : Aquaculture , 264 :263 , 2007
PubMedID:

Title : The effect of diet type on growth and fatty-acid composition of sea urchin larvae, I. Paracentrotus lividus (Lamarck, 1816) (Echinodermata) -
Author(s) : Liu H , Kelly MS , Cook EJ , Black K , Orr H , Zhu JX , Dong SL
Ref : Aquaculture , 264 :247 , 2007
PubMedID:

Title : Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues - Zhou_2007_Neurosci_144_1209
Author(s) : Zhou W , Liu H , Zhang F , Tang S , Zhu H , Lai M , Kalivas PW
Ref : Neuroscience , 144 :1209 , 2007
Abstract : The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.
ESTHER : Zhou_2007_Neurosci_144_1209
PubMedSearch : Zhou_2007_Neurosci_144_1209
PubMedID: 17184925

Title : Antimuscarinic actions of antihistamines on the heart - Liu_2006_J.Biomed.Sci_13_395
Author(s) : Liu H , Zheng Q , Farley JM
Ref : J Biomed Sci , 13 :395 , 2006
Abstract : Antimuscarinic side-effects, which include dry mouth, tachycardia, thickening of mucus possibly sedation, of the antihistamines limited the usefulness of these drugs. The advent of newer agents has reduced the sedative effect of the antihistamine. The data presented here show that one of the newest antihistamines, desloratadine, and a first generation drug, diphenhydramine, are both competitive inhibitors of muscarinic receptor mediated slowing of the heart as measured using a Langendorff preparation. Both agents have apparent sub-micromolar affinities for the muscarinic receptor. Two other agents, cetirizine and fexofenadine, do not interact with muscarinic receptors in the heart at the concentrations used in this study. Structural similarities of the drugs suggest that substitution of a group with a high dipole moment or charge on the side chain nitrogen decreases the binding with muscarinic receptors. We conclude that of the compounds tested fexofenadine and cetirizine have little or no interaction with muscarinic receptors.
ESTHER : Liu_2006_J.Biomed.Sci_13_395
PubMedSearch : Liu_2006_J.Biomed.Sci_13_395
PubMedID: 16453179

Title : Effects of first and second generation antihistamines on muscarinic induced mucus gland cell ion transport - Liu_2005_BMC.Pharmacol_5_8
Author(s) : Liu H , Farley JM
Ref : BMC Pharmacol , 5 :8 , 2005
Abstract : BACKGROUND: The first generation antihistamines, such as diphenhydramine, are fairly potent muscarinic antagonists in addition to being H1 selective antihistamines. The antimuscarinic action is often not desirable since it is in part responsible for the drying of secretions in the airways and the sedative effect. We therefore examined a number of antihistamines for antimuscarinic effects on ion transport by mucus gland cells isolated from the airways of swine. Enzymatically isolated airway mucus gland cells were purified utilizing density gradients and grown in culture on porous inserts (Millicell HA) at an air interface. Cells grown in this manner maintain phenotype and polarity. Transport of ions, as short-circuit current measured under voltage-clamp, was measured in response to acetylcholine (ACh) or histamine applied to the serosal side of the gland cell layers. Concentration-response relationships for ACh or histamine were generated in the presence and absence of various drugs. The potencies against muscarinic receptor activation were estimated using the dose-ratio method of Schild.
RESULTS: Three known muscarinic antagonists were used to validate the system. Atropine had a pA2 of 9.4 +/- 0.1 (n = 9). 4-DAMP and methoctramine had pA2 values of 8.6 +/- 0.1 and 5.6 +/- 0.1, respectively (n = 12, 11) all consistent with inhibition of an M3 subtype muscarinic receptor. The rank order of potency of the antihistamines against the inhibition of M3 receptors was desloratadine = diphenhydramine > hydroxyzine (pA2; 6.4, 6.2, 4.8, respectively). pA2 values for fexofenadine, loratadine and cetirizine were not determined since they had no effect on the cholinergic response at the highest drug concentrations tested (10, 10 and 100 microM, respectively). The pA2 values for the antihistamines against the histamine response could not be calculated, but the estimates of the rank order of potency were estimated to be desloratadine > cetirizine approximate to hydroxyzine > fexofenadine > loratadine > diphenhydramine. CONCLUSION: The rank order of selectivity for histamine receptors over muscarinic receptors was estimated to be cetirizine approximate to fexofenadine > loratadine > desloratadine > or = hydroxyzine > or = diphenhydramine.
ESTHER : Liu_2005_BMC.Pharmacol_5_8
PubMedSearch : Liu_2005_BMC.Pharmacol_5_8
PubMedID: 15790419

Title : Prostanoids secreted by alveolar macrophages enhance ionic currents in swine tracheal submucosal gland cells - Liu_2005_J.Pharmacol.Exp.Ther_315_729
Author(s) : Liu H , Mamoon AM , Farley JM, Sr.
Ref : Journal of Pharmacology & Experimental Therapeutics , 315 :729 , 2005
Abstract : We examined the effect of substances released by swine alveolar macrophages (AMs) on ionic currents in airway submucosal gland cells (SGCs). AMs obtained by lavage were activated by 24-h zymosan exposure (0.1 mg/ml). Supernatant was collected and used to stimulate short-circuit current changes (DeltaI(SC)) in SGC monolayers in Ussing chambers. Dexamethasone (1 microM) or indomethacin (5 muM) during zymosan exposure of AMs reduced or abolished the supernatant-induced DeltaI(SC). Zymosan exposure induced a 5-fold increase in cyclooxygenase (COX)-2 but not COX-1 protein levels in AMs. Prostaglandin E(2) (PGE(2)) concentration in the supernatant from zymosan-activated AMs was 550 +/- 10 nM (n = 3) compared with 28 +/- 3 nM for unstimulated AMs (n = 3). PGE(2), applied serosally, induced DeltaI(SC) with an EC(50) of 15.5 +/- 1.3 nM (n = 4) and 3.6 +/- 1.8 microM (n = 3) when applied apically. Four types of endoprostanoid receptors (EP(1-4)) were detected in SGCs using Western blot. PGE(2)-induced DeltaI(SC) were inhibited by AH6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) but not by SC19220 (8-chloro-dibenzo[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide), suggesting that endoprostanoid (EP)(2) but not EP(1) receptors were activated by PGE(2). Pretreatment of SGCs with supernatant from zymosan-activated AMs, PGE(2), or forskolin enhanced the sensitivity to acetylcholine (ACh)-induced DeltaI(SC). PGE(2)-induced DeltaI(SC) were blocked by charybdotoxin (ChTX), chromanol 293B, or glibenclamide. ACh-induced DeltaI(SC) were only blocked by ChTX or glibenclamide. None of these blockers altered PGE(2) pretreatment-induced sensitization of ACh-induced DeltaI(SC). These results demonstrate that prostanoids released from activated AMs directly increase cystic fibrosis transmembrane conductance regulator and K(+) channel activity. ACh-induced DeltaI(SC) are also enhanced due to enhanced activation of Ca(2+)-activated K(+) channels (K(Ca)).
ESTHER : Liu_2005_J.Pharmacol.Exp.Ther_315_729
PubMedSearch : Liu_2005_J.Pharmacol.Exp.Ther_315_729
PubMedID: 16055675

Title : Chlorpyrifos resistance in mosquito Culex quinquefasciatus - Liu_2005_J.Med.Entomol_42_815
Author(s) : Liu H , Xu Q , Zhang L , Liu N
Ref : Journal of Medical Entomology , 42 :815 , 2005
Abstract : Two mosquito strains of Culex quinquefasciatus Say, MAmCq and HAmCq, were collected from Mobile and Huntsville, AL, respectively, after the control of mosquitoes with insecticides proved difficult. A synergism study showed that resistance to chlorpyrifos in MAmCq and HAmCq was not suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenase- and hydrolase-mediated detoxication does not contribute to chlorpyrifos resistance in either strain. Diethyl maleate (DEM) did not cause any significant change in the level of chlorpyrifos toxicity to HAmCq. However, DEM enhanced toxicity of chlorpyrifos to MAmCq 2.5-fold, indicating that glutathione S-transferase (GST)-mediated detoxication may play a minor role in the resistance of MAmCq. An inhibition study of acetylcholinesterase (AChE) by chlorpyrifos showed that bimolecular rate constants (Ki) of chlorpyrifos for the inhibition of AChE in adults and larvae of the susceptible S-Lab strain were 2.2- and 1.9-fold higher, respectively, than in the HAmCq strain and 3.4- and 3.8-fold higher than in the MAmCq strain. The single mutation, G119S, resulting from a single nucleotide polymorphism (SNP), G to A, in ace-1 acetylcholinesterase gene was present in HAmCq and MAmCq mosquitoes. The frequency of the heterozygote for the G119S mutant allele in the HAmCq and MAmCq mosquito populations was 0.25 and 0.45, respectively, and no individuals in either of these mosquito strains were homozygous for the A allele. It thus seems likely that the presence of heterozygous individuals for the G119S allele in HAmCq and MAmCq populations may be a response to the insensitivity of AChE observed in these two mosquito strains.
ESTHER : Liu_2005_J.Med.Entomol_42_815
PubMedSearch : Liu_2005_J.Med.Entomol_42_815
PubMedID: 16363165

Title : Opposing muscarinic and nicotinic modulation of hypoglossal motor output to genioglossus muscle in rats in vivo - Liu_2005_J.Physiol_565_965
Author(s) : Liu X , Sood S , Liu H , Horner RL
Ref : Journal de Physiologie , 565 :965 , 2005
Abstract : The genioglossus (GG) muscle of the tongue, innervated by the hypoglossal motor nucleus (HMN), helps maintain an open airway for effective breathing. In vitro studies in neonatal rodents have separately characterized muscarinic and nicotinic receptor influences at the HMN but the net effects of combined nicotinic and muscarinic receptor activation and increased endogenous acetylcholine have not been determined in adult animals in vivo. Urethane-anaesthetized, tracheotomized and vagotomised rats were studied. Microdialysis perfusion of acetylcholine into the HMN significantly decreased respiratory-related GG activity (28.5 +/- 11.0% at a threshold dose of 0.1 mm). Application of the cholinergic agonists carbachol and muscarine have similar suppression effects (GG activity was decreased 11.8 +/- 4.3 and 20.5 +/- 5.8%, respectively, at 0.01 microm). Eserine, an acetylcholinesterase inhibitor, also decreased the amplitude of respiratory-related GG activity (36.4 +/- 11.3% at 1.0 microm) indicating that endogenous acetylcholine modulates GG activity. Although these results showed that suppression of GG activity predominates during cholinergic stimulation at the HMN, application of the nicotinic receptor agonist dimethyl-4-phenylpiperazinium iodide significantly increased tonic and respiratory-related GG activity (156 +/- 33% for respiratory activity at 1.0 mm) showing that excitatory responses are also present. Consistent with this, 100 microm carbachol decreased GG activity by 44.2 +/- 7.5% of control, with atropine (10 microm) reducing this suppression to 13.8 +/- 4.0% (P < 0.001). However, the nicotinic receptor antagonist dihydro-beta-erythroidine (100 microm) increased the carbachol-mediated suppression to 69.5 +/- 5.9% (P = 0.011), consistent with a role for nicotinic receptors in limiting the overall suppression of GG activity during cholinergic stimulation. Application of eserine to increase endogenous acetylcholine also showed that inhibitory muscarinic and excitatory nicotinic receptors together determine the net level of GG activity during cholinergic stimulation at the HMN. The results suggest that acetylcholine has mixed effects at the HMN with muscarinic-mediated GG suppression masking nicotinic excitation.
ESTHER : Liu_2005_J.Physiol_565_965
PubMedSearch : Liu_2005_J.Physiol_565_965
PubMedID: 15817635

Title : Immobilization of lipase onto micron-size magnetic beads - Liu_2005_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_822_91
Author(s) : Liu X , Guan Y , Shen R , Liu H
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 822 :91 , 2005
Abstract : A novel and economical magnetic poly(methacrylate-divinylbenzene) microsphere (less than 8 microm in diameter) was synthesized by the modified suspension polymerization of methacrylate and cross-linker divinylbenzene in the presence of magnetic fluid. Then, surface aminolysis was employed to obtain a high content of surface amino groups (0.40-0.55 mmolg(-1) supports). The morphology and properties of these magnetic supports were characterized with scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and a vibrating sample magnetometer. These magnetic supports exhibited superparamagnetism with a high specific saturation magnetization (sigma(s)) of 14.6 emicrog(-1). Candida cylindracea lipase was covalently immobilized on the amino-functionalized magnetic supports with the activity recovery up to 72.4% and enzyme loading of 34.0 mgg(-1) support, remarkably higher than the previous studies. The factors involved in the activity recovery and enzymatic properties of the immobilized lipase prepared were studied in comparison with free lipase, for which olive oil was chosen as the substrate. The results show that the immobilized lipase has good stability and reusability after recovery by magnetic separation within 20s.
ESTHER : Liu_2005_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_822_91
PubMedSearch : Liu_2005_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_822_91
PubMedID: 15998604

Title : Cloning, identification and expression of an entE homologue angE from Vibrio anguillarum serotype O1 - Liu_2004_Arch.Microbiol_181_287
Author(s) : Liu Q , Ma Y , Wu H , Shao M , Liu H , Zhang Y
Ref : Arch Microbiol , 181 :287 , 2004
Abstract : Anguibactin, an important virulent factor in Vibrio anguillarum serotype O1, is synthesized by a nonribosomal peptide synthetases (NRPS) system encoded on a 65-kb virulence plasmid pJM1. angE, as one of the NRPS genes, is responsible for selecting and activating 2,3-dihydroxybenzoic acid (2,3-DHBA), an important precursor in anguibactin synthesis, into 2,3-DHBA-AMP by adenylylation in the presence of ATP. In this work, an entE homologue, angE, was identified on pEIB1 (a pJM1-like plasmid) from virulent V. anguillarum serotype O1 strain MVM425. A recombinant clone carrying the complete angE was able to complement an Escherichia coli entE mutant. The angE-encoded protein was overexpressed in E. coli and purified by a three-step procedure. Purified AngE was then used to establish an in vitro enzymatic reaction in which its enzymatic activity of 1-(5'-monophosphate adenyl) 2,3-dihydroxybenzoic acid ligase (2,3-DHBA-AMP ligase) was proved using HPLC to detect AMP formation in the reaction mixture. Moreover, evidence at the level of both transcription and translation confirmed that angE was actively expressed in vivo in V. anguillarum MVM425, and interestingly, unlike many other iron-uptake-system-related genes, its expression is not induced by a low iron concentration in the surrounding environment.
ESTHER : Liu_2004_Arch.Microbiol_181_287
PubMedSearch : Liu_2004_Arch.Microbiol_181_287
PubMedID: 14758470
Gene_locus related to this paper: viban-sast

Title : [An experimental study on location and clinical application of recurrent laryngeal nerve in vagus nerve] - Liu_2002_Lin.Chuang.Er.Bi.Yan.Hou.Ke.Za.Zhi_16_123
Author(s) : Liu H , Lou W , Dong M
Ref : Lin Chuang Er Bi Yan Hou Ke Za Zhi , 16 :123 , 2002
Abstract : OBJECTIVE: To locate the recurrent laryngeal nerve fascicles in vagus and investigate the effect of latero-terminal neurorrhaphy to repair recurrent laryngeal nerve. METHOD: The method of dissection and acetylcholinesterase histochemical staining of neural fibers were used to locate the recurrent laryngeal nerve fascicles in vagus. Then 60 SD rats were divided into three groups. In experimental group right recurrent laryngeal nerve were incised and anastomosed to recurrent laryngeal nerve fascicles in vagus by means of latero-terminal neurorrhaphy. In control group right recurrent laryngeal were incised and sutured immediately by means of end-to-end nerve anastomosis. In normal group rats were not treated by any elements. One to three months later, 10 rats from each group were examined for vocal cord movement and nerve regeneration by using fibrolaryngscope and nerve electrormyography. RESULT: The recurrent laryngeal nerve fascicles is in the medial-front segment of the vagus and its diameter is about one-fourth as large as the vagus. One months after operation, This effect of latero-terminal neurorrhaphy had significant difference compared with the control group (P < 0.05). Three months after operation, This effect of latero-terminal neurorrhaphy had not significant difference compared with the control group (P > 0.05). CONCLUSION: The location of the recurrent laryngeal nerve fascicles in vagus provids important anatomical guideline for surgery. The latero-teminal neurorrhaphy has a similiar treatment effect compared with end-to-end nerve anastomosis. This microsurgical technique provides a new method for repairing recurrent laryngeal nerve.
ESTHER : Liu_2002_Lin.Chuang.Er.Bi.Yan.Hou.Ke.Za.Zhi_16_123
PubMedSearch : Liu_2002_Lin.Chuang.Er.Bi.Yan.Hou.Ke.Za.Zhi_16_123
PubMedID: 15510665

Title : Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 - Jin_2002_Nucleic.Acids.Res_30_4432
Author(s) : Jin Q , Yuan Z , Xu J , Wang Y , Shen Y , Lu W , Wang J , Liu H , Yang J , Yang F , Zhang X , Zhang J , Yang G , Wu H , Qu D , Dong J , Sun L , Xue Y , Zhao A , Gao Y , Zhu J , Kan B , Ding K , Chen S , Cheng H , Yao Z , He B , Chen R , Ma D , Qiang B , Wen Y , Hou Y , Yu J
Ref : Nucleic Acids Research , 30 :4432 , 2002
Abstract : We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
ESTHER : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedSearch : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedID: 12384590
Gene_locus related to this paper: ecoli-Aes , ecoli-yafa , ecoli-ycfp , ecoli-yqia , ecoli-YfhR , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH

Title : Inactivation of the human brain muscarinic acetylcholine receptor by oxidative damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer's brain is prevented by pyrophosphate analogs, bioflavonoids and other antioxidants - Fawcett_2002_Brain.Res_950_10
Author(s) : Fawcett J , Bordayo E , Jackson K , Liu H , Peterson J , Svitak A , Frey W, 2nd
Ref : Brain Research , 950 :10 , 2002
Abstract : Oxidative stress has been implicated as a contributing factor to neurodegeneration in Alzheimer's disease. An endogenous, low molecular weight (LMW) inhibitor from Alzheimer's brain inactivates the human brain muscarinic acetylcholine receptor (mAChR). The inhibitor prevents agonist and antagonist binding to the mAChR as assessed by radioligand binding studies. The LMW endogenous inhibitor, which has components with molecular weights between 100 and 1000 Da, requires dissolved oxygen and glutathione. Prevention of inactivation of the mAChR with peroxidase suggests that the LMW endogenous inhibitor generates peroxide. Heme, previously shown to be present in the LMW endogenous inhibitor, also inactivates the mAChR in the presence of peroxide. Free radical damage to the muscarinic receptor by the endogenous inhibitor can be prevented through the use of naturally occurring antioxidants including bilirubin, biliverdin, carnosol, myricetin and quericetin. In addition, pyrophosphate, imidodiphosphate, bisphosphonates and related compounds also protect the muscarinic receptor from free radical damage. Inactivation of the mAChR by the LMW endogenous inhibitor is likely to be a factor in the continual decline of Alzheimer's patients, even those taking acetylcholinesterase inhibitors. Natural antioxidants and pyrophosphate analogs may improve the effectiveness of acetylcholinesterase inhibitors and prove useful in the treatment and prevention of Alzheimer's disease since the muscarinic acetylcholine receptor is required for memory, and decreased cholinergic function is a critical deficit in Alzheimer's disease.
ESTHER : Fawcett_2002_Brain.Res_950_10
PubMedSearch : Fawcett_2002_Brain.Res_950_10
PubMedID: 12231224

Title : Femtomole peptide mapping by derivatization, high-performance liquid chromatography, and fluorescence detection - Liu_2001_Anal.Biochem_294_7
Author(s) : Liu H , Krull IS , Cohen SA
Ref : Analytical Biochemistry , 294 :7 , 2001
Abstract : A highly sensitive peptide mapping method using derivatization and fluorescence detection is described. Bovine cytochrome c was digested using a buffer compatible with the derivatization that followed. The derivatization was performed with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. The peptide mapping of the tagged digest was conducted with both HPLC and capillary LC (CLC) systems. A capillary LC-electrospray ionization mass spectrometer (MS) was set up for measuring the molecular weights of the tagged peptides. Optimization was made of the conditions used for digestion, derivatization, and mapping. MS measurements of the tagged peptides suggested that there was only one derivatization product produced from all peptides (except one) and that all the identified peptides were fully tagged. Peptide mapping of the tagged digest reviews a larger number of peptides, covering almost the entire sequence. Peptide mapping of a 20 fmol amount of tagged digest was readily performed with the CLC system. By using derivatization and fluorescence detection, the sensitivity of peptide mapping could be improved 2000 times compared to that observed with uv detection of untagged peptides.
ESTHER : Liu_2001_Anal.Biochem_294_7
PubMedSearch : Liu_2001_Anal.Biochem_294_7
PubMedID: 11412000

Title : Embryonic limb buds derived neurotrophins on the survival of neurons and the growth of axons in culture in vitro - Liu_1998_J.Tongji.Med.Univ_18_212
Author(s) : Liu H , Hong G , Wang F , Chen F
Ref : J Tongji Med Univ , 18 :212 , 1998
Abstract : Bioactive proteins from SD rat limb buds were extracted and purified. Fractions of 22 ku, 34 ku and 95 ku were proved to have neurotrophic activity to neurons, and the combined activity of these three fractions was the highest. So they were combinedly added into the culture medium of sensor neurons in dorsal root ganglia and motor neurons of anterior spinal cord from 2-week-old embryonic rats, and PBS was added as control. Phase-contrast microscopic and electron microscopic observations, and true cholinesterase measurements were performed to evaluate the survival and changes in growth, function, and ultrastructure of these cultured neurons. In the experimental group, it was found that the AchE activity was higher (P < 0.01), ultrastructural changes in mitochondria, Gorgi's complex and other cell organs were milder than those in the control group. The results showed limb buds derived neurotrophins played an important role in maintaining the survival of the neurons and promoting the growth of axons. It was concluded that embryonic limb buds derived neurotrophins had high neurotrophic activities on neurons' survival and axon growth.
ESTHER : Liu_1998_J.Tongji.Med.Univ_18_212
PubMedSearch : Liu_1998_J.Tongji.Med.Univ_18_212
PubMedID: 10806848

Title : Temporal separation in the specification of primary and secondary motoneurons in zebrafish - Beattie_1997_Dev.Biol_187_171
Author(s) : Beattie CE , Hatta K , Halpern ME , Liu H , Eisen JS , Kimmel CB
Ref : Developmental Biology , 187 :171 , 1997
Abstract : In zebrafish there are two populations of motoneurons, primary and secondary, that are temporally separate in their development. To determine if midline cells play a role in the specification of these neurons, we analyzed both secondary and primary motoneurons in mutants lacking floor plate, notochord, or both floor plate and notochord. Our data show that the specification of secondary motoneurons, those most similar to motoneurons in birds and mammals, depends on the presence of either a differentiated floor plate or notochord. In the absence of both of these structures, secondary motoneurons fail to form. In contrast, primary motoneurons, early developing motoneurons found in fish and amphibians, can develop in the absence of both floor plate and notochord. A spatial correspondence is found between secondary motoneurons and sonic hedgehog-expressing floor plate and notochord. In contrast, primary motoneuronal specification depends on the presence of sonic hedgehog in gastrula axial mesoderm, the tissue that will give rise to the notochord. These results suggest that both primary and secondary motoneurons are specified by signals from midline tissues, but at very different stages of embryonic development.
ESTHER : Beattie_1997_Dev.Biol_187_171
PubMedSearch : Beattie_1997_Dev.Biol_187_171
PubMedID: 9242415

Title : Sequence and analysis of a 31 kb segment of the Bacillus subtilis chromosome in the area of the rrnH and rrnG operons. -
Author(s) : Liu H , Haga K , Yasumoto K , Ohashi Y , Yoshikawa H , Takahashi H
Ref : Microbiology , 143 :2763 , 1997
PubMedID: 9274029