Xu W

References (73)

Title : Oligosaccharides from black ginseng innovatively prepared by low temperature steam-heating process ameliorate cognitive impairment in Alzheimer's disease mice via the Keap-1\/Nrf2 pathway - Xu_2024_J.Sci.Food.Agric__
Author(s) : Xu W , Yu P , Shao S , Xie Z , Wu Y , Liu J , Xu T , Cai G , Yang H
Ref : J Sci Food Agric , : , 2024
Abstract : BACKGROUND: Our objective in this study is to evaluate the effectiveness of the oligosaccharides extracted from black ginseng (BG), innovatively prepared by a low-temperature steam-heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS: 8 carbohydrates involving isomaltose and maltotetraose were detected in BG, where the monosaccharide residues including mannose and rhamnose were discovered too. OSBG-treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine (SCO) group. OSBG could decrease acetylcholinesterase (AChE) activity in a tissue-dependent fashion but not in a dose-dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and Kelch-like ECH-associated protein 1 (Keap1), downregulation of malondialdehyde (MDA) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus, Clostridium_XlVb,) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas, compared to the AD mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine-induced intestinal microbiota in mice, providing a homeostasis of gut microbiota and providing evidence for microbiota-regulated therapeutic potentials of it. CONCLUSION: Our results showed for the first time a clear role for OSBG in improving scopolamine-induced memory impairment by inhibiting cholinergic dysfunction in a tissue-dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap-1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in AD patients. This article is protected by copyright. All rights reserved.
ESTHER : Xu_2024_J.Sci.Food.Agric__
PubMedSearch : Xu_2024_J.Sci.Food.Agric__
PubMedID: 38372395

Title : Bifunctional enzyme-mimicking metal-organic frameworks for sensitive acetylcholine analysis - Wen_2024_Talanta_275_126112
Author(s) : Wen Y , Xu W , Wu Y , Tang Y , Liu M , Sha M , Li J , Xiao R , Hu L , Lin Y , Zhu C , Gu W
Ref : Talanta , 275 :126112 , 2024
Abstract : The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk between different enzymes and the complexities and costs associated with detection. In this study, Pt nanoparticles (Pt NPs) were successfully supported on a Zr-based metal-organic framework (MOF-808) to create a composite catalyst named MOF-808/Pt NPs. This composite catalyst effectively mimics the functions of acetylcholinesterase (AChE) and peroxidase (POD). Leveraging this capability, we replaced AChE and POD with MOF-808/Pt NPs and constructed a biosensor for sensitive detection of acetylcholine (ACh). The MOF-808/Pt NPs catalyze the hydrolysis of ACh, resulting in the production of acetic acid. The subsequent reduction in pH value further enhances the POD-like activity of the MOFs, enabling signal amplification through the oxidation of a colorimetric substrate. This biosensor capitalizes on pH variations during the reaction to modulate the different enzyme-like activities of the MOFs, simplifying the detection process and eliminating cross-talk between different enzymes. The developed biosensor holds great promise for clinical diagnostic analysis and offers significant application value in the field.
ESTHER : Wen_2024_Talanta_275_126112
PubMedSearch : Wen_2024_Talanta_275_126112
PubMedID: 38677169

Title : Correlation of LP-PLA2 and MMP-9 with the occurrence of early neurological deterioration in patients with acute ischemic stroke - Yu_2024_Medicine.(Baltimore)_103_e38310
Author(s) : Yu B , Shi G , Yang F , Xu W
Ref : Medicine (Baltimore) , 103 :e38310 , 2024
Abstract : Early neurological deterioration is a common complication of acute ischemic stroke (AIS), which aggravates symptoms, worsens the condition, and counteracts the benefits of clinical treatment. The aim of this paper was to analyze the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metalloproteinase-9 (MMP-9), and the occurrence of early neurological deterioration (END) in patients with AIS and to explore the clinical prediction of END by the combination of the 2 assays for the clinical prediction of END. A total of 500 AIS patients admitted to our hospital from October 2022 to October 2023 were included as study subjects, and the clinical data of all AIS patients were collected and organized to detect the levels of Lp-PLA2 and MMP-9. Categorized into END and non-END groups according to whether END occurred within 7 days of the onset of AIS, and comparing the clinical baseline data and laboratory index levels of the 2 groups. Logistic regression analysis was performed to determine the independent predictors of END, and the predictive effects of Lp-PLA2 and MMP-9 levels on END were assessed by subject work characteristics (ROC) curves. END occurred in 111 (22.2%) of 500 AIS patients. Multivariate logistic regression analysis showed that diabetes (OR 2.717, 95% CI:1.53-4.81, P<.001), baseline NIHSS score (OR 1.65, 95% CI:1.41-1.94, P<.001), Lp-PLA2 (OR 1.07, 95% CI:1.05-1.09, P<.001) and MMP-9 (OR 1.12, 95% CI:1.09-1.16, P<.001) levels were independent influences on the occurrence of END in patients with AIS after correcting for confounders. ROC curve analysis showed that Lp-PLA2, MMP-9, and a combination of both predicted END with an area under the curve was 0.730, 0.763, and 0.831, respectively, and the area under the curve for the combination of both predicting END was significantly higher than that for any of the inflammatory markers alone (P<.05). Both inflammatory markers, Lp-PLA2 and MMP-9, were independent predictors of the development of END in patients with AIS, and the combination of the two had a higher predictive value.
ESTHER : Yu_2024_Medicine.(Baltimore)_103_e38310
PubMedSearch : Yu_2024_Medicine.(Baltimore)_103_e38310
PubMedID: 38788013
Gene_locus related to this paper: human-PLA2G7

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Biomimetic single Al-OH site with high acetylcholinesterase-like activity and self-defense ability for neuroprotection - Xu_2023_Nat.Commun_14_6064
Author(s) : Xu W , Cai X , Wu Y , Wen Y , Su R , Zhang Y , Huang Y , Zheng Q , Hu L , Cui X , Zheng L , Zhang S , Gu W , Song W , Guo S , Zhu C
Ref : Nat Commun , 14 :6064 , 2023
Abstract : Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al(3+) is engineered onto the nodes of metal-organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al(3+) Lewis acid sites with a strong polarization effect unite the highly electronegative -OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage.
ESTHER : Xu_2023_Nat.Commun_14_6064
PubMedSearch : Xu_2023_Nat.Commun_14_6064
PubMedID: 37770453

Title : Influence of Five Drying Methods on Active Compound Contents and Bioactivities of Fresh Flowers from Syringa pubescens Turcz - Xu_2023_Molecules_28_
Author(s) : Xu W , Zhang J , Wu Y , Zhang Z , Wang X , Ma J
Ref : Molecules , 28 : , 2023
Abstract : The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against alpha-amylase, alpha-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC(50) values with 0.118 +/- 0.004 mg/mL for DPPH radical, 1.538 +/- 0.0972 for hydroxyl radical and 0.886 +/- 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H(2)O(2)-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1beta and TNF-alpha expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC(50) values of inhibitory activity on alpha-glucosidase and alpha-amylase from SHD sample were 2.516 +/- 0.024 and 0.734 +/- 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC(50) values of 3.443 +/- 0.060 and 1.732 +/- 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.
ESTHER : Xu_2023_Molecules_28_
PubMedSearch : Xu_2023_Molecules_28_
PubMedID: 38067533

Title : Mechanisms of microRNA-132 in central neurodegenerative diseases: A comprehensive review - Mu_2023_Biomed.Pharmacother_170_116029
Author(s) : Mu C , Gao M , Xu W , Sun X , Chen T , Xu H , Qiu H
Ref : Biomed Pharmacother , 170 :116029 , 2023
Abstract : MicroRNA-132 (miR-132) is a highly conserved molecule that plays a crucial regulatory role in central nervous system (CNS) disorders. The expression levels of miR-132 exhibit variability in various neurological disorders and have been closely linked to disease onset and progression. The expression level of miR-132 in the CNS is regulated by a diverse range of stimuli and signaling pathways, including neuronal migration and integration, dendritic outgrowth, and complexity, synaptogenesis, synaptic plasticity, as well as inflammation and apoptosis activation. The aberrant expression of miR-132 in various central neurodegenerative diseases has garnered widespread attention. Clinical studies have revealed altered miR-132 expression levels in both chronic and acute CNS diseases, positioning miR-132 as a potential biomarker or therapeutic target. An in-depth exploration of miR-132 holds the promise of enhancing our understanding of the mechanisms underlying CNS diseases, thereby offering novel insights and strategies for disease diagnosis and treatment. It is anticipated that this review will assist researchers in recognizing the potential value of miR-132 and in generating innovative ideas for clinical trials related to CNS degenerative diseases.
ESTHER : Mu_2023_Biomed.Pharmacother_170_116029
PubMedSearch : Mu_2023_Biomed.Pharmacother_170_116029
PubMedID: 38128185

Title : Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus - Sun_2022_Andrology__
Author(s) : Sun T , Xu W , Wang J , Wang T , Wang S , Liu K , Liu J
Ref : Andrology , : , 2022
Abstract : BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved.
ESTHER : Sun_2022_Andrology__
PubMedSearch : Sun_2022_Andrology__
PubMedID: 36113503

Title : Traditional Chinese medicine promotes the control and treatment of dementia - Tao_2022_Front.Pharmacol_13_1015966
Author(s) : Tao P , Xu W , Gu S , Shi H , Wang Q , Xu Y
Ref : Front Pharmacol , 13 :1015966 , 2022
Abstract : Dementia is a syndrome that impairs learning and memory. To date, there is no effective therapy for dementia. Current prescription drugs, such as cholinesterase inhibitors, fail to improve the condition of dementia and are often accompanied by severe adverse effects. In recent years, the number of studies into the use of traditional Chinese medicine (TCM) for dementia treatment has increased, revealing a formula that could significantly improve memory and cognitive dysfunctions in animal models. TCM showed fewer adverse effects, lower costs, and improved suitability for long-term use compared with currently prescribed drugs. Due to the complexity of ingredients and variations in bioactivity of herbal medicines, the multi-target nature of the traditional Chinese formula affected the outcome of dementia therapy. Innovations in TCM will create a platform for the development of new drugs for the prevention and treatment of dementia, further strengthening and enhancing the current influence of TCM.
ESTHER : Tao_2022_Front.Pharmacol_13_1015966
PubMedSearch : Tao_2022_Front.Pharmacol_13_1015966
PubMedID: 36304171

Title : Zearalenone lactonase: characteristics, modification, and application - Fang_2022_Appl.Microbiol.Biotechnol_106_6877
Author(s) : Fang Y , Zhang Z , Xu W , Zhang W , Guang C , Mu W
Ref : Applied Microbiology & Biotechnology , 106 :6877 , 2022
Abstract : Zearalenone (ZEN) and its derivatives are one of the most contaminated fungal toxins worldwide, posing a severe threat to food security and human life. Traditional physical and chemical detoxifying methods are unsatisfactory due to incomplete detoxification, nutrient loss, and secondary pollutants. In recent years, bioremediation for eliminating fungal toxins has been gradually investigated. ZEN lactone hydrolase (lactonase) has been widely studied because of its high activity, mild conditions, and non-toxic product property. This review comprehensively represents the gene mining, characterization, molecular modification, and application of microbial-derived ZEN lactonases. It is aimed to elucidate the advantages and challenges of ZEN lactonases in industrial application, which also provides perspectives on obtaining innovative and promising biocatalysts for ZEN degradation. KEY POINTS: A timely and concise review related to enzymatic elimination towards ZEN is shown. The catalytic conditions and mechanism of ZEN lactonase is presented. The modification and application of ZEN lactonase are exhibited also.
ESTHER : Fang_2022_Appl.Microbiol.Biotechnol_106_6877
PubMedSearch : Fang_2022_Appl.Microbiol.Biotechnol_106_6877
PubMedID: 36173450

Title : Isolation and Mechanistic Characterization of a Novel Zearalenone-Degrading Enzyme - Ji_2022_Foods_11_
Author(s) : Ji J , Yu J , Xu W , Zheng Y , Zhang Y , Sun X
Ref : Foods , 11 : , 2022
Abstract : Zearalenone (ZEN) and its derivatives pose a serious threat to global food quality and animal health. The use of enzymes to degrade mycotoxins has become a popular method to counter this threat. In this study, Aspergillus niger ZEN-S-FS10 extracellular enzyme solution with ZEN-degrading effect was separated and purified to prepare the biological enzyme, FSZ, that can degrade ZEN. The degradation rate of FSZ to ZEN was 7580% (pH = 7.0, 28 degreesC). FSZ can function in a temperature range of 2838 degreesC and pH range of 2.07.0 and can also degrade ZEN derivatives (alpha-ZAL, beta-ZOL, and ZAN). According to the enzyme kinetics fitting, ZEN has a high degradation rate. FSZ can degrade ZEN in real samples of corn flour. FSZ can be obtained stably and repeatedly from the original strain. One ZEN degradation product was isolated: FSZP(C18H26O4), with a relative molecular weight of 306.18 g/mol. Amino-acid-sequencing analysis revealed that FSZ is a novel enzyme (homology < 10%). According to the results of molecular docking, ZEN and ZAN can utilize their end-terminal carbonyl groups to bind FSZ residues PHE307, THR55, and GLU129 for a high-degradation rate. However, alpha-ZAL and beta-ZOL instead contain hydroxyl groups that would prevent binding to GLU129; thus, the degradation rate is low for these derivatives.
ESTHER : Ji_2022_Foods_11_
PubMedSearch : Ji_2022_Foods_11_
PubMedID: 36141036

Title : Biodegradation of polyester polyurethane by the marine fungus Cladosporium halotolerans 6UPA1 - Zhang_2022_J.Hazard.Mater_437_129406
Author(s) : Zhang K , Hu J , Yang S , Xu W , Wang Z , Zhuang P , Grossart HP , Luo Z
Ref : J Hazard Mater , 437 :129406 , 2022
Abstract : Lack of degradability and the accumulation of polymeric wastes increase the risk for the health of the environment. Recently, recycling of polymeric waste materials becomes increasingly important as raw materials for polymer synthesis are in short supply due to the rise in price and supply chain disruptions. As an important polymer, polyurethane (PU) is widely used in modern life, therefore, PU biodegradation is desirable to avoid its accumulation in the environment. In this study, we isolated a fungal strain Cladosporium halotolerans from the deep sea which can grow in mineral medium with a polyester PU (Impranil DLN) as a sole carbon source. Further, we demonstrate that it can degrade up to 80% of Impranil PU after 3 days of incubation at 28 degC by breaking the carbonyl groups (1732 cm(-1)) and C-N-H bonds (1532 cm(-1) and 1247 cm(-1)) as confirmed by Fourier-transform infrared (FTIR) spectroscopy analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed polyols and alkanes as PU degradation intermediates, indicating the hydrolysis of ester and urethane bonds. Esterase and urease activities were detected in 7 days-old cultures with PU as a carbon source. Transcriptome analysis showed a number of extracellular protein genes coding for enzymes such as cutinase, lipase, peroxidase and hydrophobic surface binding proteins A (HsbA) were expressed when cultivated on Impranil PU. The yeast two-hybrid assay revealed that the hydrophobic surface binding protein ChHsbA1 directly interacts with inducible esterases, ChLip1 (lipase) and ChCut1 (cutinase). Further, the KEGG pathway for "fatty acid degradation" was significantly enriched in Impranil PU inducible genes, indicating that the fungus may use the degradation intermediates to generate energy via this pathway. Taken together, our data indicates secretion of both esterase and hydrophobic surface binding proteins by C. halotolerans plays an important role in Impranil PU absorption and subsequent degradation. Our study provides a mechanistic insight into Impranil PU biodegradation by deep sea fungi and provides the basis for future development of biotechnological PU recycling.
ESTHER : Zhang_2022_J.Hazard.Mater_437_129406
PubMedSearch : Zhang_2022_J.Hazard.Mater_437_129406
PubMedID: 35753302

Title : Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies - Xie_2022_Front.Nutr_9_929343
Author(s) : Xie D , Hu J , Wu T , Xu W , Meng Q , Cao K , Luo X
Ref : Front Nutr , 9 :929343 , 2022
Abstract : BACKGROUND: Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given the anti-inflammatory and antioxidant activities, supplementation with flavonoids that are abundant in the human diet has been suggested as a potential strategy to protect against nanomaterial-induced toxicities. However, the beneficial effects of flavonoids remain inconclusive. In the present study, we performed a meta-analysis to comprehensively explore the roles and mechanisms of flavonoids for animals intoxicated with nanomaterials. METHODS: A systematic literature search in PubMed, EMBASE, and Cochrane Library databases was performed up to April 2022. STATA 15.0 software was used for meta-analyses. RESULTS: A total of 26 studies were identified. The results showed that flavonoid supplementation could significantly increase the levels of antioxidative enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione-S-transferase), reduce the production of oxidative agents (malonaldehyde) and pro-inflammatory mediators (tumor necrosis factor-alpha, interleukin-6, IL-1beta, C-reactive protein, immunoglobulin G, nitric oxide, vascular endothelial growth factor, and myeloperoxidase), and alleviate cell apoptosis (manifested by decreases in the mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2), DNA damage (reductions in tail length and tail DNA%), and nanomaterial-induced injuries of the liver (reduced alanine aminotransferase and aspartate aminotransferase activities), kidney (reduced urea, blood urea nitrogen, creatinine, and uric acid concentration), testis (increased testosterone, sperm motility, 17beta-hydroxysteroid dehydrogenase type, and reduced sperm abnormalities), and brain (enhanced acetylcholinesterase activities). Most of the results were not changed by subgroup analyses. CONCLUSION: Our findings suggest that appropriate supplementation of flavonoids may be effective to prevent the occupational detriments resulting from nanomaterial exposure.
ESTHER : Xie_2022_Front.Nutr_9_929343
PubMedSearch : Xie_2022_Front.Nutr_9_929343
PubMedID: 35774549

Title : MnO(2)\/DNAzyme-mediated ratiometric fluorescence assay of acetylcholinesterase - Zhang_2022_Analyst__
Author(s) : Zhang XP , Xu W , Wang JH , Shu Y
Ref : Analyst , : , 2022
Abstract : Acetylcholinesterase (AChE) is an essential serine hydrolase associated with neurodegenerative diseases and serves as a biomarker. In this work, a ratiometric fluorescence strategy for the sensitive assay of AChE activity is developed based on the decomposition of MnO(2) by the enzymatic hydrolysis product and DNAzyme-mediated strand cleavage. The sensing system is termed as MnO(2)/DNAzyme. DNAzyme locked by H2 strands is inactive in the absence of AChE. The fluorescence emission of fluorescein amidite (FAM)-labeled DNA (DNA-F) at 518 nm is quenched by neutral red (NR) and the fluorescence of NR at 632 nm is simultaneously enhanced due to fluorescence resonance energy transfer (FRET). The presence of AChE triggers the hydrolysis of the substrate acetylcholine (ATCh) to enzymatic thiocholine (TCh), which reduces MnO(2) nanowires to Mn(2+) and releases the attached H1 strands into the solution. The H1 strands hybridize with H2 strands through the strand displacement reaction. Meanwhile, the activated DNAzyme cleaves the RNA nucleotide of the DNA-F signal probe to release FAM. The fluorescence of FAM at 518 nm is thus recovered, corresponding to a decrement of NR emission at 632 nm owing to the blocking of FRET. The fluorescence ratio of F(518)/F(632) serves as a signal readout for the AChE assay within 5 x 10(-4)-10 U mL(-1), with a limit of detection (LOD) of 2.7 x 10(-4) U mL(-1). The feasibility of this method was demonstrated by the measurement of AChE activity in human blood, which reveals its promising potential in clinical assays.
ESTHER : Zhang_2022_Analyst__
PubMedSearch : Zhang_2022_Analyst__
PubMedID: 36001020

Title : Sertoli cell survival and barrier function are regulated by miR-181c\/d-Pafah1b1 axis during mammalian spermatogenesis - Feng_2022_Cell.Mol.Life.Sci_79_498
Author(s) : Feng Y , Chen D , Wang T , Zhou J , Xu W , Xiong H , Bai R , Wu S , Li J , Li F
Ref : Cell Mol Life Sciences , 79 :498 , 2022
Abstract : Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
ESTHER : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedID: 36008729

Title : Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia - Hu_2022_Front.Med.(Lausanne)_9_944547
Author(s) : Hu Q , Wang Q , Xu W , Huang C , Tao S , Qi X , Zhang Y , Li X , Jiang X , Song J , Li Q , Chen L , Huang Y
Ref : Front Med (Lausanne) , 9 :944547 , 2022
Abstract : BACKGROUND: A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA. METHODS: 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set. RESULTS: 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index >= 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index <= 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%). CONCLUSION: The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.
ESTHER : Hu_2022_Front.Med.(Lausanne)_9_944547
PubMedSearch : Hu_2022_Front.Med.(Lausanne)_9_944547
PubMedID: 35911415

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

Title : Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues - Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
Author(s) : Zhang X , Xu W , Xu R , Wang Z , Wang P , Peng K , Li M , Li J , Tan Y , Wang X , Pei H
Ref : Oxid Med Cell Longev , 2022 :4594956 , 2022
Abstract : Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedID: 35401929

Title : Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection - Yu_2021_Fish.Shellfish.Immunol__
Author(s) : Yu C , Xu W , Li X , Jin J , Zhao X , Wang S , Zhang Z , Wei Y , Chen Q , Li Y
Ref : Fish Shellfish Immunol , : , 2021
Abstract : Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Dierential gene expression analysis revealed 896 signicantly dierently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
ESTHER : Yu_2021_Fish.Shellfish.Immunol__
PubMedSearch : Yu_2021_Fish.Shellfish.Immunol__
PubMedID: 34303835

Title : Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip\/knee replacement: a prospective cohort study - Lin_2020_BMC.Anesthesiol_20_246
Author(s) : Lin X , Tang J , Liu C , Li X , Cao X , Wang B , Dong R , Xu W , Yu X , Wang M , Bi Y
Ref : BMC Anesthesiol , 20 :246 , 2020
Abstract : BACKGROUND: Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. METHODS: Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. RESULTS: POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-alpha and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-alpha were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. CONCLUSION: The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. TRIAL REGISTRATION: This study was registered at Chictr.org.cn (NO. ChiCTR1900023729 ) June 9th, 2019. (Retrospectively registered).
ESTHER : Lin_2020_BMC.Anesthesiol_20_246
PubMedSearch : Lin_2020_BMC.Anesthesiol_20_246
PubMedID: 32988381

Title : Low Mismatch Rate between Double-Stranded RNA and Target mRNA Does Not Affect RNA Interference Efficiency in Colorado Potato Beetle - He_2020_Insects_11_
Author(s) : He W , Xu W , Fu K , Guo W , Zhang J
Ref : Insects , 11 : , 2020
Abstract : RNA interference (RNAi)-based technology has been proven as a novel approach for insect pest control. However, whether insects could evolve resistance to RNAi and the underlying mechanism is largely unknown. The target gene mutations were thought to be one of the potential ways to develop the resistance. Here we predicted the effective siRNA candidates that could be derived from dsRNA against the Colorado potato beetle (CPB) beta-Actin gene (dsACT). By site-directed mutagenesis, we synthesized the dsRNAs with the defect in generation of effective siRNAs (and thus were supposed to have comparable low RNAi efficacy). We showed that, with mismatches to the target gene, all the dsRNA variants caused similar levels of silencing of target gene, mortality and larval growth retardation of CPB. Our results suggest that when the mismatch rate of dsACT and target beta-Actin mRNA is less than 3%, the RNAi efficiency is not impaired in CPB, which might imply the low possibility of RNAi resistance evolving through the sequence mismatches between dsRNA and the target gene.
ESTHER : He_2020_Insects_11_
PubMedSearch : He_2020_Insects_11_
PubMedID: 32708568

Title : Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials - Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
Author(s) : Yu JT , Xu W , Tan CC , Andrieu S , Suckling J , Evangelou E , Pan A , Zhang C , Jia J , Feng L , Kua EH , Wang YJ , Wang HF , Tan MS , Li JQ , Hou XH , Wan Y , Tan L , Mok V , Dong Q , Touchon J , Gauthier S , Aisen PS , Vellas B
Ref : Journal of Neurology Neurosurg Psychiatry , 91 :1201 , 2020
Abstract : BACKGROUND: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. RESULTS: A total of 44676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
ESTHER : Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
PubMedSearch : Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
PubMedID: 32690803

Title : Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach - Huang_2020_J.Med.Chem_63_7052
Author(s) : Huang F , Hu H , Wang K , Peng C , Xu W , Zhang Y , Gao J , Liu Y , Zhou H , Huang R , Li M , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 63 :7052 , 2020
Abstract : Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases.
ESTHER : Huang_2020_J.Med.Chem_63_7052
PubMedSearch : Huang_2020_J.Med.Chem_63_7052
PubMedID: 32459096
Gene_locus related to this paper: human-PLA2G7

Title : Lipase-Catalyzed Reactive Extrusion: Copolymerization of sigma-Caprolactone and w-Pentadecalactone - Li_2020_Macromol.Rapid.Commun_41_e2000417
Author(s) : Li C , Xu W , Lu Y , Gross RA
Ref : Macromol Rapid Commun , 41 :e2000417 , 2020
Abstract : This study assesses the use of immobilized lipase catalyst N435 during reactive extrusion (REX) versus magnetically stirred bulk and solution reaction conditions for the copolymerization of sigma-caprolactone with omega-pentadecalactone (CL/PDL 1:1 molar). N435-catalyzed REX for reaction times from 1 to 3 h results in total %-monomer conversion, M(n) , and D values increase from 92.7% to 98.8%, 36.1 to 51.3 kDa, and 1.85 to 1.96, respectively. Diad fraction analysis by quantitative (13) C NMR reveals that, after just 1 h, rapid N435-catalyzed transesterification reactions occur that give random copolyesters. In contrast, for bulk polymerization with magnetic stirring in round bottom flasks, reaction times from 1 to 3 h result in the following: M(n) increases from 12.4 to 25.6 kDa, D decreases from 2.98 to 1.87, and the randomness index increases from 0.74 and 0.86 as PDL*-PDL diads are dominant. These results highlight that REX avoids problems associated with internal batch mixing that are encountered in bulk polymerizations. In sharp contrast to a previous study of 1:1 molar PDL/delta-valerolactone (VL) copolymerizations by N435-catalyzed REX, VL %-conversion increases to just 40.1% in 1 h whereas CL reaches 94.7%.
ESTHER : Li_2020_Macromol.Rapid.Commun_41_e2000417
PubMedSearch : Li_2020_Macromol.Rapid.Commun_41_e2000417
PubMedID: 33047442
Gene_locus related to this paper: canar-LipB

Title : Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing - Wu_2020_Anal.Chem__
Author(s) : Wu Y , Wu J , Jiao L , Xu W , Wang H , Wei X , Gu W , Ren G , Zhang N , Zhang Q , Huang L , Gu L , Zhu C
Ref : Analytical Chemistry , : , 2020
Abstract : Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the de-velopment of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple mod-el of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were syn-thesized through a salt-template strategy. With the densely distributed active Cu atoms (~5.1 wt%), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxi-dase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organo-phosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.
ESTHER : Wu_2020_Anal.Chem__
PubMedSearch : Wu_2020_Anal.Chem__
PubMedID: 31941278

Title : Tuning Atomically Dispersed Fe Sites in Metal-Organic Frameworks Boosts Peroxidase-Like Activity for Sensitive Biosensing - Xu_2020_Nanomicro.Lett_12_184
Author(s) : Xu W , Kang Y , Jiao L , Wu Y , Yan H , Li J , Gu W , Song W , Zhu C
Ref : Nanomicro Lett , 12 :184 , 2020
Abstract : Although nanozymes have been widely developed, accurate design of highly active sites at the atomic level to mimic the electronic and geometrical structure of enzymes and the exploration of underlying mechanisms still face significant challenges. Herein, two functional groups with opposite electron modulation abilities (nitro and amino) were introduced into the metal-organic frameworks (MIL-101(Fe)) to tune the atomically dispersed metal sites and thus regulate the enzyme-like activity. Notably, the functionalization of nitro can enhance the peroxidase (POD)-like activity of MIL-101(Fe), while the amino is poles apart. Theoretical calculations demonstrate that the introduction of nitro can not only regulate the geometry of adsorbed intermediates but also improve the electronic structure of metal active sites. Benefiting from both geometric and electronic effects, the nitro-functionalized MIL-101(Fe) with a low reaction energy barrier for the HO* formation exhibits a superior POD-like activity. As a concept of the application, a nitro-functionalized MIL-101(Fe)-based biosensor was elaborately applied for the sensitive detection of acetylcholinesterase activity in the range of 0.2-50 mU mL(-1) with a limit of detection of 0.14 mU mL(-1). Moreover, the detection of organophosphorus pesticides was also achieved. This work not only opens up new prospects for the rational design of highly active nanozymes at the atomic scale but also enhances the performance of nanozyme-based biosensors.
ESTHER : Xu_2020_Nanomicro.Lett_12_184
PubMedSearch : Xu_2020_Nanomicro.Lett_12_184
PubMedID: 34138213

Title : The genome evolution and low-phosphorus adaptation in white lupin - Xu_2020_Nat.Commun_11_1069
Author(s) : Xu W , Zhang Q , Yuan W , Xu F , Muhammad Aslam M , Miao R , Li Y , Wang Q , Li X , Zhang X , Zhang K , Xia T , Cheng F
Ref : Nat Commun , 11 :1069 , 2020
Abstract : White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin.
ESTHER : Xu_2020_Nat.Commun_11_1069
PubMedSearch : Xu_2020_Nat.Commun_11_1069
PubMedID: 32103018
Gene_locus related to this paper: lupal-a0a6a5lz53 , lupal-a0a6a5mjk3

Title : Curcumin Alleviates the Side Effects of Cisplatin on Gastric Emptying of Mice by Inhibiting the Signal Changes of Acetylcholine and Interstitial Cells of Cajal - Li_2020_J.Med.Food_23_920
Author(s) : Li H , Xu W , Liu X , Ye J , Li P , Shang F , Yu X
Ref : J Med Food , 23 :920 , 2020
Abstract : Cisplatin is a widely used anticancer drug that has adverse effects on gastrointestinal function. Curcumin is a natural polyphenol extracted from the rhizome of turmeric that has a wide range of biological activities. The present study investigated the effects of cisplatin on gastric emptying in mice and examined whether these can be inhibited by curcumin. We found that pretreatment with curcumin (200mg/kg/day) for 10-30 days partly inhibited the decreases in gastric emptying rate and body weight induced by cisplatin. Furthermore, cisplatin reduced acetylcholine (ACh) concentration and the messenger RNA (mRNA) level of ACh receptor (AChR) as well as acetylcholinesterase activity in the stomach of mice; caused ultrastructural damage to interstitial cells of Cajal (ICC); and altered the expression of c-kit/stem cell factor and the gap junction protein connexin 43 in ICC. Curcumin pretreatment inhibited the effects of cisplatin on ACh indicators and ICC. These results demonstrate that curcumin can protect against cisplatin-induced gastric emptying disorder and thus has therapeutic potential for alleviating this condition in cancer patients receiving cisplatin chemotherapy.
ESTHER : Li_2020_J.Med.Food_23_920
PubMedSearch : Li_2020_J.Med.Food_23_920
PubMedID: 32833554

Title : Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis - Liu_2019_J.Cancer_10_3746
Author(s) : Liu Y , Feng W , Liu W , Kong X , Li L , He J , Wang D , Zhang M , Zhou G , Xu W , Chen W , Gong A , Xu M
Ref : J Cancer , 10 :3746 , 2019
Abstract : Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.
ESTHER : Liu_2019_J.Cancer_10_3746
PubMedSearch : Liu_2019_J.Cancer_10_3746
PubMedID: 31333792
Gene_locus related to this paper: human-ABHD11

Title : Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity - Wu_2019_Small__e1903108
Author(s) : Wu Y , Jiao L , Luo X , Xu W , Wei X , Wang H , Yan H , Gu W , Xu BZ , Du D , Lin Y , Zhu C
Ref : Small , :e1903108 , 2019
Abstract : Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2 (-) * radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.
ESTHER : Wu_2019_Small__e1903108
PubMedSearch : Wu_2019_Small__e1903108
PubMedID: 31482681

Title : Donepezil decreases heart rate in elderly patients with Alzheimer's disease - Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
Author(s) : Pu Z , Xu W , Lin Y , Shen J , Sun Y
Ref : Int J Clinical Pharmacology & Therapeutics , 57 :94 , 2019
Abstract : OBJECTIVE: Donepezil is an acetylcholinesterase inhibitor (AChI) that improves cognitive function in Alzheimer's disease (AD) patients. However, AChIs are usually associated with peripheral adverse reactions. Here, we investigated the cardiac outcomes in elderly AD patients treated with donepezil. MATERIALS AND METHODS: A total of 82 AD patients (age, 75.47 +/- 6.53 years) received 5 mg or 10 mg donepezil (n = 41/group) once daily for 12 weeks. Next, we examined the heart rate (HR), cardiac rhythm, and PR, QRS, and QTc intervals. RESULTS: Compared to the 5-mg donepezil-treated group, the HR was slower in the 10-mg donepezil-treated group at the 4(th), 8(th), and 12(th) weeks of treatment (p = 0.041, 0.026, 0.008, respectively). The PR interval was longer in the 10-mg donepezil-treated group at the 12(th) week of treatment (p = 0.022). Compared to the pretreatment values, the post-treatment HR and PR interval in the 10-mg donepezil-treated group were significantly slower and longer, respectively (p = 0.002, p = 0.005). Further, the HR was significantly correlated to the donepezil dosage (p = 0.014). Similarly, donepezil dosage and treatment interval were significantly correlated (p = 0.048). CONCLUSION: Taken together, our findings suggest that 10 mg donepezil decreased the HR of elderly AD patients without inducing severe cardiac outcomes. Therefore, AD patients receiving donepezil should undergo regular cardiovascular monitoring..
ESTHER : Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
PubMedSearch : Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
PubMedID: 30378536

Title : Polydopamine-Capped Bimetallic AuPt Hydrogels Enable Robust Biosensor for Organophosphorus Pesticide Detection - Wu_2019_Small__e1900632
Author(s) : Wu Y , Jiao L , Xu W , Gu W , Zhu C , Du D , Lin Y
Ref : Small , :e1900632 , 2019
Abstract : Noble metal hydrogels/aerogels with macroscopic nanoassemblies characterized by ultralow density, profuse continuous porosity, and extremely large surface area have gained abundant interest due to not only their tunable physicochemical properties, but also promising applications in catalysis and sensing. Coupling the increased reaction temperature with dopamine-induced effect, herein, a one-step synthetic approach with accelerated gelation kinetics is reported for the synthesis of polydopamine-capped bimetallic AuPt hydrogels. 3D porous nanowire networks with surface functionalization of polydopamine make them a promising biocompatible microenvironment for immobilizing acetylcholinesterase (AChE) and constructing enzyme-based biosensors for sensitive detection of organophosphorus compounds. Taking advantage of their favorable structure and composition, the optimized product exhibits superior electrochemical activity toward thiocholine produced by AChE-catalyzed hydrolysis of acetylthiocholine. Based on the inhibition of organophosphorus pesticide on the enzymatic activity of AChE, the inhibition mode for the detection of paraoxon-ethyl is established, displaying linear regions over the range of 0.5-1000 ng L(-1) with a low detection limit of 0.185 ng L(-1) .
ESTHER : Wu_2019_Small__e1900632
PubMedSearch : Wu_2019_Small__e1900632
PubMedID: 30938485

Title : Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol\/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition - Zhang_2019_J.Pharm.Pharmacol_71_1291
Author(s) : Zhang H , Zhang K , Liang J , Yan W , Wu F , Xu W , Wu Z , Chen Y , Pan R , Wu G
Ref : J Pharm Pharmacol , 71 :1291 , 2019
Abstract : OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis.
ESTHER : Zhang_2019_J.Pharm.Pharmacol_71_1291
PubMedSearch : Zhang_2019_J.Pharm.Pharmacol_71_1291
PubMedID: 31215026

Title : Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone Family of Fungal Alkaloids - Li_2018_J.Am.Chem.Soc_140_2067
Author(s) : Li L , Tang MC , Tang S , Gao S , Soliman S , Hang L , Xu W , Ye T , Watanabe K , Tang Y
Ref : Journal of the American Chemical Society , 140 :2067 , 2018
Abstract : UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of telomerase. The structures of UCS1025A and related natural products are featured by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined the genome of a thermophilic fungus and activated the ucs gene cluster to produce UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS assembly line that activates 2S,3S-methylproline derived from l-isoleucine, followed by Knoevenagel condensation to construct the pyrrolizidine moiety. Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy used by nature to construct heterocyclic alkaloid-like ring systems using assembly line logic.
ESTHER : Li_2018_J.Am.Chem.Soc_140_2067
PubMedSearch : Li_2018_J.Am.Chem.Soc_140_2067
PubMedID: 29373009
Gene_locus related to this paper: acrsp-ucsc

Title : Multi-Target Anti-Alzheimer Activities of Four Prenylated Compounds from Psoralea Fructus - Xu_2018_Molecules_23_614
Author(s) : Xu QX , Hu Y , Li GY , Xu W , Zhang YT , Yang XW
Ref : Molecules , 23 :614 , 2018
Abstract : Alzheimer's disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloid beta-peptide 42, beta-secretase, glycogen synthase kinase 3beta, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment.
ESTHER : Xu_2018_Molecules_23_614
PubMedSearch : Xu_2018_Molecules_23_614
PubMedID: 29518051

Title : ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma - Wang_2018_Hum.Pathol_77_35
Author(s) : Wang F , Wu J , Qiu Z , Ge X , Liu X , Zhang C , Xu W , Hua D , Qi X , Mao Y
Ref : Hum Pathol , 77 :35 , 2018
Abstract : Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. In addition, GLI3 is a major transcription factor in the regulation of hedgehog signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process. Thus, we investigated the relationship between ACOT1 expression and GLI3 in gastric adenocarcinoma. A tissue microarray was constructed from 280 cases of gastric adenocarcinoma. The immunohistochemistry method was performed on tissue sections of 4 microm from each tissue microarray block. We found a significant correlation between ACOT1 expression and poor histologic grade, a lower T category, TNM stage, and increased GLI3 expression. In addition, the survival analysis revealed that the ACOT1-positive group had significantly decreased overall survival rates compared with the ACOT1-negative group. Furthermore, GLI3 expression had a significant positive correlation with ACOT1 expression in gastric adenocarcinoma cells. In summary, these findings demonstrate that increased expression of ACOT1 is correlated with pivotal clinicopathological parameters and poor prognosis in gastric adenocarcinoma through increased expression of the potential tumor-promoting protein GLI3.
ESTHER : Wang_2018_Hum.Pathol_77_35
PubMedSearch : Wang_2018_Hum.Pathol_77_35
PubMedID: 29555575

Title : A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism - Liu_2017_Int.J.Oncol_50_1792
Author(s) : Liu W , Zhang B , Hu Q , Qin Y , Xu W , Shi S , Liang C , Meng Q , Xiang J , Liang D , Ji S , Liu J , Hu P , Liu L , Liu C , Long J , Ni Q , Yu X , Xu J
Ref : Int J Oncol , 50 :1792 , 2017
Abstract : N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1alpha level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1alpha, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.
ESTHER : Liu_2017_Int.J.Oncol_50_1792
PubMedSearch : Liu_2017_Int.J.Oncol_50_1792
PubMedID: 28350132

Title : Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species - Pearce_2017_BMC.Biol_15_63
Author(s) : Pearce SL , Clarke DF , East PD , Elfekih S , Gordon KHJ , Jermiin LS , McGaughran A , Oakeshott JG , Papanicolaou A , Perera OP , Rane RV , Richards S , Tay WT , Walsh TK , Anderson A , Anderson CJ , Asgari S , Board PG , Bretschneider A , Campbell PM , Chertemps T , Christeller JT , Coppin CW , Downes SJ , Duan G , Farnsworth CA , Good RT , Han LB , Han YC , Hatje K , Horne I , Huang YP , Hughes DST , Jacquin-Joly E , James W , Jhangiani S , Kollmar M , Kuwar SS , Li S , Liu NY , Maibeche MT , Miller JR , Montagne N , Perry T , Qu J , Song SV , Sutton GG , Vogel H , Walenz BP , Xu W , Zhang HJ , Zou Z , Batterham P , Edwards OR , Feyereisen R , Gibbs RA , Heckel DG , McGrath A , Robin C , Scherer SE , Worley KC , Wu YD
Ref : BMC Biol , 15 :63 , 2017
Abstract : BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.
ESTHER : Pearce_2017_BMC.Biol_15_63
PubMedSearch : Pearce_2017_BMC.Biol_15_63
PubMedID: 28756777
Gene_locus related to this paper: helam-a0a2w1bn75 , helam-a0a2w1bp69 , helam-a0a2w1bvf3

Title : Two genomes of highly polyphagous lepidopteran pests (Spodoptera frugiperda, Noctuidae) with different host-plant ranges - Gouin_2017_Sci.Rep_7_11816
Author(s) : Gouin A , Bretaudeau A , Nam K , Gimenez S , Aury JM , Duvic B , Hilliou F , Durand N , Montagne N , Darboux I , Kuwar S , Chertemps T , Siaussat D , Bretschneider A , Mone Y , Ahn SJ , Hanniger S , Grenet AG , Neunemann D , Maumus F , Luyten I , Labadie K , Xu W , Koutroumpa F , Escoubas JM , Llopis A , Mabeche-Coisne M , Salasc F , Tomar A , Anderson AR , Khan SA , Dumas P , Orsucci M , Guy J , Belser C , Alberti A , Noel B , Couloux A , Mercier J , Nidelet S , Dubois E , Liu NY , Boulogne I , Mirabeau O , Le Goff G , Gordon K , Oakeshott J , Consoli FL , Volkoff AN , Fescemyer HW , Marden JH , Luthe DS , Herrero S , Heckel DG , Wincker P , Kergoat GJ , Amselem J , Quesneville H , Groot AT , Jacquin-Joly E , Negre N , Lemaitre C , Legeai F , d'Alencon E , Fournier P
Ref : Sci Rep , 7 :11816 , 2017
Abstract : Emergence of polyphagous herbivorous insects entails significant adaptation to recognize, detoxify and digest a variety of host-plants. Despite of its biological and practical importance - since insects eat 20% of crops - no exhaustive analysis of gene repertoires required for adaptations in generalist insect herbivores has previously been performed. The noctuid moth Spodoptera frugiperda ranks as one of the world's worst agricultural pests. This insect is polyphagous while the majority of other lepidopteran herbivores are specialist. It consists of two morphologically indistinguishable strains ("C" and "R") that have different host plant ranges. To describe the evolutionary mechanisms that both enable the emergence of polyphagous herbivory and lead to the shift in the host preference, we analyzed whole genome sequences from laboratory and natural populations of both strains. We observed huge expansions of genes associated with chemosensation and detoxification compared with specialist Lepidoptera. These expansions are largely due to tandem duplication, a possible adaptation mechanism enabling polyphagy. Individuals from natural C and R populations show significant genomic differentiation. We found signatures of positive selection in genes involved in chemoreception, detoxification and digestion, and copy number variation in the two latter gene families, suggesting an adaptive role for structural variation.
ESTHER : Gouin_2017_Sci.Rep_7_11816
PubMedSearch : Gouin_2017_Sci.Rep_7_11816
PubMedID: 28947760

Title : Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization - DeBruine_2017_Genes.Dev_31_916
Author(s) : DeBruine ZJ , Ke J , Harikumar KG , Gu X , Borowsky P , Williams BO , Xu W , Miller LJ , Xu HE , Melcher K
Ref : Genes Dev , 31 :916 , 2017
Abstract : Wnt/beta-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD(4)) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers. Each dimer is stabilized by interactions of one hydrophobic palmitoleic acid tail with two CRD palmitoleoyl-binding grooves oriented end to end, suggesting that the Wnt palmitoleoyl group stimulates CRD-CRD interaction. Using bioluminescence resonance energy transfer (BRET) in live cells, we show that WNT5A stimulates dimerization of membrane-anchored FZD(4) CRDs and oligomerization of full-length FZD(4), which requires the integrity of CRD palmitoleoyl-binding residues. These results suggest that FZD receptors may form signalosomes in response to Wnt binding through the CRDs and that the Wnt palmitoleoyl group is important in promoting these interactions. These results complement our understanding of lipoprotein receptor-related proteins 5 and 6 (LRP5/6), Dishevelled, and Axin signalosome assembly and provide a more complete model for Wnt signalosome assembly both intracellularly and at the membrane.
ESTHER : DeBruine_2017_Genes.Dev_31_916
PubMedSearch : DeBruine_2017_Genes.Dev_31_916
PubMedID: 28546512

Title : Production of New Cladosporin Analogues by Reconstitution of the Polyketide Synthases Responsible for the Biosynthesis of this Antimalarial Agent - Cochrane_2016_Angew.Chem.Int.Ed.Engl_55_664
Author(s) : Cochrane RV , Sanichar R , Lambkin GR , Reiz B , Xu W , Tang Y , Vederas JC
Ref : Angew Chem Int Ed Engl , 55 :664 , 2016
Abstract : The antimalarial agent cladosporin is a nanomolar inhibitor of the Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood- and liver-stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it is biosynthesized by a highly reducing (HR) and a non-reducing (NR) iterative typeI polyketide synthase (PKS) pair. Genome sequencing of the host organism and subsequent heterologous expression of these enzymes in Saccharomyces cerevisiae produced cladosporin, confirming the identity of the putative gene cluster. Incorporation of a pentaketide intermediate analogue indicated a 5+3 assembly by the HR PKS Cla2 and the NR PKS Cla3 during cladosporin biosynthesis. Advanced-intermediate analogues were synthesized and incorporated by Cla3 to furnish new cladosporin analogues. A putative lysyl-tRNA synthetase resistance gene was identified in the cladosporin gene cluster. Analysis of the active site emphasizes key structural features thought to be important in resistance to cladosporin.
ESTHER : Cochrane_2016_Angew.Chem.Int.Ed.Engl_55_664
PubMedSearch : Cochrane_2016_Angew.Chem.Int.Ed.Engl_55_664
PubMedID: 26783060
Gene_locus related to this paper: clacd-cla3

Title : Synthesis and evaluation of donepezil-ferulic acid hybrids as multi-target-directed ligands against Alzheimer's disease - Xu_2016_Medchemcomm_7_990
Author(s) : Xu W , Wang XB , Wang ZM , Wu JJ , Li F , Wang J , Kong LY
Ref : Medchemcomm , 7 :990 , 2016
Abstract : A novel family of donepezilferulic acid hybrids were designed, synthesized and biologically evaluated as multi-target-directed ligands against Alzheimer's disease by fusing a fragment of donepezil and ferulic acid. The in vitro assay indicated that some of these molecules exhibited potent cholinesterase inhibitory activities, outstanding radical scavenging activities and good neuroprotective effects on PC12 cells, and could penetrate into the central nervous system. Compound 5c especially showed moderate acetylcholinesterase inhibitory activity (IC50 values of 0.398 M for electric eel acetylcholinesterase) and butyrylcholinesterase inhibitory activity (IC50 = 0.976 microM for equine serum butyrylcholinesterase). It also showed significant antioxidant activity (1.78 trolox equivalents by the ABTS method, IC50 values of 24.9 microM by the DPPH method). The kinetic study and molecular docking indicated that compound 5c interacted with both the peripheral anionic site and the catalytic binding site of acetylcholinesterase. Overall, these results indicated that compound 5c is a promising drug candidate with balanced properties for the treatment of Alzheimer's disease.
ESTHER : Xu_2016_Medchemcomm_7_990
PubMedSearch : Xu_2016_Medchemcomm_7_990
PubMedID:

Title : Developmental exposure of zebrafish larvae to organophosphate flame retardants causes neurotoxicity - Sun_2016_Neurotoxicol.Teratol_55_16
Author(s) : Sun L , Xu W , Peng T , Chen H , Ren L , Tan H , Xiao D , Qian H , Fu Z
Ref : Neurotoxicology & Teratology , 55 :16 , 2016
Abstract : With the gradual ban on brominated flame retardants (FRs), the application of organophosphate flame retardants (OPFRs) has increased remarkably. Considering the structural similarity between OPFRs and organophosphate pesticides, hypotheses that OPFRs may interfere with neurodevelopment as organophosphate pesticides are reasonable. In this study, the neurotoxicity of three OPFRs, including tri-n-butyl phosphate (TNBP), tris (2-butoxyethyl) phosphate (TBOEP) and tris (2-chloroethyl) phosphate (TCEP), was evaluated in zebrafish larvae and then compared with the neurotoxicity of organophosphate pesticide chlorpyrifos (CPF). The results showed that similar to CPF, exposure to OPFRs for 5days resulted in significant changes in locomotor behavior, either in free swimming or in photomotor response. However, given the transcriptional changes that occur in nervous system genes in response to OPFRs and CPF, as well as the altered enzyme activity of AChE and its mRNA level, the underlying mechanisms for neurotoxicity among these organophosphate chemicals might be varied. In summary, the results confirm the potential neurodevelopmental toxicity of OPFRs and underscore the importance of identifying the mechanistic targets of the OPFRs with specific moieties. Furthermore, as the neurobehavioral responses are well conserved among vertebrates and the exposure of children to OPFRs is significant, a thorough assessment of the risk of OPFRs exposure during early development should be highly emphasized in future studies.
ESTHER : Sun_2016_Neurotoxicol.Teratol_55_16
PubMedSearch : Sun_2016_Neurotoxicol.Teratol_55_16
PubMedID: 27018022

Title : Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes) - Sun_2016_Environ.Toxicol.Chem_35_2931
Author(s) : Sun L , Tan H , Peng T , Wang S , Xu W , Qian H , Jin Y , Fu Z
Ref : Environ Toxicol Chem , 35 :2931 , 2016
Abstract : Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. (c) 2016 SETAC.
ESTHER : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedSearch : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedID: 27146889

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 : Discovery of Potent and Orally Active Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors as a Potential Therapy for Diabetic Macular Edema - Chen_2016_J.Med.Chem_59_2674
Author(s) : Chen X , Wang K , Xu W , Ma Q , Chen M , Du L , Mo M , Wang Y , Shen J
Ref : Journal of Medicinal Chemistry , 59 :2674 , 2016
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a promising therapeutic target for several inflammation-associated diseases. Herein, we describe the discovery of a series of pyrimidone derivatives as Lp-PLA2 inhibitors. Systematic structural modifications led to the identification of several pyrimidone compounds with promising in vitro inhibitory potency and pharmacokinetic properties. Compound 14c, selected for in vivo evaluation, demonstrated decent pharmacokinetic profiles and robust inhibitory potency against Lp-PLA2 in Sprague-Dawley (SD) rats. Furthermore, 14c significantly inhibited retinal thickening in STZ-induced diabetic SD rats as a model of diabetic macular edema (DME) after oral dosing for 4 weeks. Taken together, these results suggested that 14c can serve as a valuable lead in the search for new Lp-PLA2 inhibitors for prevention and/or treatment of DME.
ESTHER : Chen_2016_J.Med.Chem_59_2674
PubMedSearch : Chen_2016_J.Med.Chem_59_2674
PubMedID: 26927682
Gene_locus related to this paper: human-PLA2G7

Title : Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase\/monoamine oxidase inhibitors for the potential application against Alzheimer's disease - Li_2016_J.Enzyme.Inhib.Med.Chem__1
Author(s) : Li F , Wang ZM , Wu JJ , Wang J , Xie SS , Lan JS , Xu W , Kong LY , Wang XB
Ref : J Enzyme Inhib Med Chem , :1 , 2016
Abstract : In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC50, 0.220 muM for eeAChE; 1.23 muM for eqBuChE; 0.454 muM for hAChE) and an acceptable inhibitory activity against monoamine oxidases (IC50, 3.14 muM for MAO-B; 13.4 muM for MAO-A). Moreover, w18 could also be a metal-chelator, and able to cross the blood-brain barrier with low cell toxicity on PC12 cells. Taken together, these results suggested that w18 might be a promising multitargeted compound for AD treatment.
ESTHER : Li_2016_J.Enzyme.Inhib.Med.Chem__1
PubMedSearch : Li_2016_J.Enzyme.Inhib.Med.Chem__1
PubMedID: 27384289

Title : Phenalenone Polyketide Cyclization Catalyzed by Fungal Polyketide Synthase and Flavin-Dependent Monooxygenase - Gao_2016_J.Am.Chem.Soc_138_4249
Author(s) : Gao SS , Duan A , Xu W , Yu P , Hang L , Houk KN , Tang Y
Ref : Journal of the American Chemical Society , 138 :4249 , 2016
Abstract : Phenalenones are polyketide natural products that display diverse structures and biological activities. The core of phenalenones is a peri-fused tricyclic ring system cyclized from a linear polyketide precursor via an unresolved mechanism. Toward understanding the unusual cyclization steps, the phn biosynthetic gene cluster responsible for herqueinone biosynthesis was identified from the genome of Penicillium herquei. A nonreducing polyketide synthase (NR-PKS) PhnA was shown to synthesize the heptaketide backbone and cyclize it into the angular, hemiketal-containing naphtho-gamma-pyrone prephenalenone. The product template (PT) domain of PhnA catalyzes only the C4-C9 aldol condensation, which is unprecedented among known PT domains. The transformation of prephenalenone to phenalenone requires an FAD-dependent monooxygenase (FMO) PhnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone and ring opening of the gamma-pyrone ring simultaneously. Density functional theory calculations provide insights into why the hydroxylated intermediate undergoes an aldol-like phenoxide-ketone cyclization to yield the phenalenone core. This study therefore unveiled new routes and biocatalysts for polyketide cyclization.
ESTHER : Gao_2016_J.Am.Chem.Soc_138_4249
PubMedSearch : Gao_2016_J.Am.Chem.Soc_138_4249
PubMedID: 26978228
Gene_locus related to this paper: penhr-phna

Title : Dietary methionine level influences growth and lipid metabolism via GCN2 pathway in cobia (Rachycentron canadum) - Wang_2016_Aquaculture_454_148
Author(s) : Wang Z , Mai K , Xu W , Zhang Y , Liu Y , Ai Q
Ref : Aquaculture , 454 :148 , 2016
Abstract : This study investigated the effect of dietary methionine level on growth and lipid metabolism via the general control nonderepressible2 kinase (GCN2) pathway in cobia (Rachycentron canadum). Cobia were fed diets with six levels of methionine (0.62%, 0.84%, 1.02%, 1.15%, 1.25% and 1.42% of dry diet) with a constant cystine level (0.42% dry diet). The feeding experiment began in September 2013 and ended in December 2013; during the experiment, cobia were fed ad libitum twice daily (7:00 and 18:00h) for 10weeks. Cobia fed the diet with 1.02% methionine showed elevated weight gain (WG) and feed efficiency ratio (FER) compared with those fed the other diets (P<0.05). The content of liver lipid, total triglyceride, and total cholesterol were first enhanced significantly with increasing dietary methionine level from 0.62% to 1.02%, and then decreased markedly with higher levels of dietary methionine level (1.02% to 1.42%). Crude lipid was markedly elevated when the dietary methionine level was 1.02%, and then plateaued with higher dietary methionine level. The expression of genes associated with hepatic lipid synthesis (sterol regulatory element binding protein-1, peroxisome proliferator activated receptor , fatty acid synthetase, and stearoyl-CoA desaturase-1) were markedly up-regulated in fish fed the diet containing 1.02% methionine, whereas the transcriptional levels of lipolytic genes (peroxisome proliferator activated receptor , carnitine acyl transferase-1, and lipase lipoprotein lipase) were elevated in fish fed the methionine-deficient diet (0.62%; P<0.05). The expression of insulin-like growth factor-I (IGF-I) was suppressed by the methionine-deficient diet, whereas the hepatic mRNA expression levels of genes related to amino acid responses (AAR), i.e., GCN2, activating transcription factor 4 (ATF4), CCAAT enhancer binding protein (C/EBP), and asparagine synthetase (ASNS), were significantly up-regulated. In conclusion, the dietary methionine requirement of cobia was estimated to be 1.04% and 1.15% of dry matter (2.23% and 2.45% dietary protein) on the basis of WG and FER, respectively. Results of this study suggested that methionine deficiency could suppress growth, decrease lipid content, and inhibit expression of IGF-I and some genes related to lipid synthesis in cobia; these changes might be regulated by inducing the expression of genes related to the GCN2 pathway (GCN2, ATF4, C/EBP, and ASNS). Statement of relevance The present study was conducted to investigate the effect of dietary methionine on growth performance, plasma biochemical indexes, lipid content and gene expression involved in lipid metabolism and GCN2 pathway in cobia (Rachycentron canadum). Our findings have showed that methionine deficiency could suppress growth, decrease lipid content and inhibit expressions of IGF-I and some lipid synthesis related genes of cobia, which may be regulated by inducing the mRNA expressions of GCN2 pathway related genes (GCN2, ATF4, C/EBP and ASNS). The results are reliable and of both theoretical and practical importance. The work described has not been submitted elsewhere for publication, in whole or in part, and all the authors listed have approved the manuscript that is enclosed. I have read and have abided by the statement of ethical standards for manuscripts submitted to Aquaculture.
ESTHER : Wang_2016_Aquaculture_454_148
PubMedSearch : Wang_2016_Aquaculture_454_148
PubMedID:

Title : P450-Mediated Coupling of Indole Fragments To Forge Communesin and Unnatural Isomers - Lin_2016_J.Am.Chem.Soc_138_4002
Author(s) : Lin HC , McMahon TC , Patel A , Corsello M , Simon A , Xu W , Zhao M , Houk KN , Garg NK , Tang Y
Ref : Journal of the American Chemical Society , 138 :4002 , 2016
Abstract : Dimeric indole alkaloids are structurally diverse natural products that have attracted significant attention from the synthetic and biosynthetic communities. Here, we describe the characterization of a P450 monooxygenase CnsC from Penicillium that catalyzes the heterodimeric coupling between two different indole moieties, tryptamine and aurantioclavine, to construct vicinal quaternary stereocenters and yield the heptacyclic communesin scaffold. We show, via biochemical characterization, substrate analogues, and computational methods that CnsC catalyzes the C3-C3' carbon-carbon bond formation and controls the regioselectivities of the pair of subsequent aminal bond formations to yield the communesin core. Use of omega-N-methyltryptamine and tryptophol in place of tryptamine led to the enzymatic synthesis of isocommunesin compounds, which have not been isolated to date.
ESTHER : Lin_2016_J.Am.Chem.Soc_138_4002
PubMedSearch : Lin_2016_J.Am.Chem.Soc_138_4002
PubMedID: 26963294
Gene_locus related to this paper: penen-cnsh

Title : Discovery of a Novel Series of Imidazo[1,2-a]pyrimidine Derivatives as Potent and Orally Bioavailable Lipoprotein-Associated Phospholipase A2 Inhibitors - Chen_2015_J.Med.Chem_58_8529
Author(s) : Chen X , Xu W , Wang K , Mo M , Zhang W , Du L , Yuan X , Xu Y , Wang Y , Shen J
Ref : Journal of Medicinal Chemistry , 58 :8529 , 2015
Abstract : Inhibition of lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested to be a promising therapeutic strategy for several inflammation-associated diseases, including atherosclerosis, Alzheimer's disease, and diabetic macular edema. Herein, we report the discovery of a novel series of Lp-PLA2 inhibitors constructed on an imidazo[1,2-a]pyrimidine scaffold through a conformational restriction strategy. Structure-activity relationship (SAR) analysis resulted in the identification of several compounds with high potency in vitro and good metabolic stability in liver S9 fractions. Compounds 7c and 14b selected for further exploration in vivo demonstrated excellent pharmacokinetic profiles and exhibited significant inhibitory efficacy in SD rats upon oral dosing.
ESTHER : Chen_2015_J.Med.Chem_58_8529
PubMedSearch : Chen_2015_J.Med.Chem_58_8529
PubMedID: 26479945
Gene_locus related to this paper: human-PLA2G7

Title : Comparison of 10,11-Dehydrocurvularin Polyketide Synthases from Alternaria cinerariae and Aspergillus terreus Highlights Key Structural Motifs - Cochrane_2015_Chembiochem_16_2479
Author(s) : Cochrane RV , Gao Z , Lambkin GR , Xu W , Winter JM , Marcus SL , Tang Y , Vederas JC
Ref : Chembiochem , 16 :2479 , 2015
Abstract : Iterative typeI polyketide synthases (PKSs) from fungi are multifunctional enzymes that use their active sites repeatedly in a highly ordered sequence to assemble complex natural products. A phytotoxic macrolide with anticancer properties, 10,11-dehydrocurvularin (DHC), is produced by cooperation of a highly reducing (HR) iterative PKS and a non-reducing (NR) iterative PKS. We have identified the DHC gene cluster in Alternaria cinerariae, heterologously expressed the active HR PKS (Dhc3) and NR PKS (Dhc5) in yeast, and compared them to corresponding proteins that make DHC in Aspergillus terreus. Phylogenetic analysis and homology modeling of these enzymes identified variable surfaces and conserved motifs that are implicated in product formation.
ESTHER : Cochrane_2015_Chembiochem_16_2479
PubMedSearch : Cochrane_2015_Chembiochem_16_2479
PubMedID: 26493380
Gene_locus related to this paper: aspte-curs2 , altci-dhc5

Title : Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments - Liang_2015_Mol.Psychiatry_20_850
Author(s) : Liang J , Xu W , Hsu YT , Yee AX , Chen L , Sudhof TC
Ref : Mol Psychiatry , 20 :850 , 2015
Abstract : Abnormal activity in the medial prefrontal cortex (mPFC) is consistently observed in neuropsychiatric disorders, but the mechanisms involved remain unclear. Chronic aberrant excitation and/or inhibition of mPFC neurons were proposed to cause cognitive impairments. However, direct evidence for this hypothesis is lacking because it is technically challenging to control synaptic properties in a chronic and locally restricted, yet specific, manner. Here, we generated conditional knockout (cKO) mice of neuroligin-2 (Nlgn2), a postsynaptic cell-adhesion molecule of inhibitory synapses linked to neuropsychiatric disorders. cKO of Nlgn2 in adult mPFC rendered Nlgn2 protein undetectable after already 2-3 weeks, but induced major reductions in synaptic inhibition after only 6-7 weeks, and caused parallel impairments in anxiety, fear memory and social interaction behaviors. Moreover, cKO of Nlgn2 severely impaired behavioral stimulation of immediate-early gene expression in the mPFC, suggesting that chronic reduction in synaptic inhibition uncoupled the mPFC from experience-dependent inputs. Our results indicate that Nlgn2 is required for continuous maintenance of inhibitory synapses in the adult mPFC, and that chronic impairment of local inhibition disengages the mPFC from its cognitive functions by partially uncoupling the mPFC from experience-induced inputs.
ESTHER : Liang_2015_Mol.Psychiatry_20_850
PubMedSearch : Liang_2015_Mol.Psychiatry_20_850
PubMedID: 25824299

Title : Bioactivities of phytochemicals in Araiostegia yunnanensis (Christ) - Chen_2015_Food.Chem_186_37
Author(s) : Chen L , Xu W , Shao R , Du X
Ref : Food Chem , 186 :37 , 2015
Abstract : The profile and bioactivity of phytochemicals in Araiostegia yunnanensis (Christ) Cop were investigated. The total flavonoids content in A. yunnanensis is about 84.90mg/g. By means of HPLC-DAD-ESI-MS, the main flavonoids in A. yunnanensis were tentatively identified as myricetin 3-O-rhamnosylglucoside, eriodictyol 7-O-rutinoside, quercetin 3-O-rutinoside, luteolin-7-O-apiosylglucoside, quercetin 3-O-rhamnosylgalactoside, and luteolin 7-O-glucoside. The extract (0.268mg/ml total flavonoids) from A. yunnanensis showed very strong superoxide anion radical scavenging potential and reducing power, which are higher than those of rutin (0.25mg/ml). The extract (0.268mg/ml total flavonoids) from A. yunnanensis exhibited similar DPPH scavenging activity with rutin (0.25mg/ml). However, rutin (0.25mg/ml) showed a significantly higher ABTS radical scavenging effect than that of the extract (0.268mg/ml total flavonoids) from A. yunnanensis. The methanol extract from A. yunnanensis showed obviously cytotoxic effects on A549 cells and it had no effect against acetylcholinesterase.
ESTHER : Chen_2015_Food.Chem_186_37
PubMedSearch : Chen_2015_Food.Chem_186_37
PubMedID: 25976789

Title : Elucidation of the concise biosynthetic pathway of the communesin indole alkaloids - Lin_2015_Angew.Chem.Int.Ed.Engl_54_3004
Author(s) : Lin HC , Chiou G , Chooi YH , McMahon TC , Xu W , Garg NK , Tang Y
Ref : Angew Chem Int Ed Engl , 54 :3004 , 2015
Abstract : The communesins are a prominent class of indole alkaloids isolated from Penicillium species. Owing to their daunting structural framework and potential as pharmaceuticals, communesins have inspired numerous synthetic studies. However, the genetic and biochemical basis of communesin biosynthesis has remained unexplored. Herein, we report the identification and characterization of the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We confirmed that communesin is biosynthesized by the coupling of tryptamine and aurantioclavine, two building blocks derived from L-tryptophan. The postmodification steps were mapped by targeted-gene-deletion experiments and the structural elucidation of intermediates and new analogues. Our studies set the stage for the biochemical characterization of communesin biosynthesis. This knowledge will aid our understanding of how nature generates remarkable structural complexity from simple precursors.
ESTHER : Lin_2015_Angew.Chem.Int.Ed.Engl_54_3004
PubMedSearch : Lin_2015_Angew.Chem.Int.Ed.Engl_54_3004
PubMedID: 25571861
Gene_locus related to this paper: penen-cnsh

Title : Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway - Lin_2014_J.Am.Chem.Soc_136_4426
Author(s) : Lin HC , Tsunematsu Y , Dhingra S , Xu W , Fukutomi M , Chooi YH , Cane DE , Calvo AM , Watanabe K , Tang Y
Ref : Journal of the American Chemical Society , 136 :4426 , 2014
Abstract : Fumagillin (1), a meroterpenoid from Aspergillus fumigatus, is known for its antiangiogenic activity due to binding to human methionine aminopeptidase 2. 1 has a highly oxygenated structure containing a penta-substituted cyclohexane that is generated by oxidative cleavage of the bicyclic sesquiterpene beta-trans-bergamotene. The chemical nature, order, and biochemical mechanism of all the oxygenative tailoring reactions has remained enigmatic despite the identification of the biosynthetic gene cluster and the use of targeted-gene deletion experiments. Here, we report the identification and characterization of three oxygenases from the fumagillin biosynthetic pathway, including a multifunctional cytochrome P450 monooxygenase, a hydroxylating nonheme-iron-dependent dioxygenase, and an ABM family monooxygenase for oxidative cleavage of the polyketide moiety. Most significantly, the P450 monooxygenase is shown to catalyze successive hydroxylation, bicyclic ring-opening, and two epoxidations that generate the sesquiterpenoid core skeleton of 1. We also characterized a truncated polyketide synthase with a ketoreductase function that controls the configuration at C-5 of hydroxylated intermediates.
ESTHER : Lin_2014_J.Am.Chem.Soc_136_4426
PubMedSearch : Lin_2014_J.Am.Chem.Soc_136_4426
PubMedID: 24568283
Gene_locus related to this paper: aspfu-fmac

Title : Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry - Sun_2014_J.Appl.Toxicol_34_176
Author(s) : Sun X , Xu W , Zeng Y , Hou Y , Guo L , Zhao X , Sun C
Ref : J Appl Toxicol , 34 :176 , 2014
Abstract : The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg(-1) body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N(7) G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry. Copyright (c) 2012 John Wiley & Sons, Ltd.
ESTHER : Sun_2014_J.Appl.Toxicol_34_176
PubMedSearch : Sun_2014_J.Appl.Toxicol_34_176
PubMedID: 23280859

Title : The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of beta-trans-bergamotene - Lin_2013_J.Am.Chem.Soc_135_4616
Author(s) : Lin HC , Chooi YH , Dhingra S , Xu W , Calvo AM , Tang Y
Ref : Journal of the American Chemical Society , 135 :4616 , 2013
Abstract : Fumagillin 1 is a meroterpenoid from Aspergillus fumigatus that is known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. The genetic and molecular basis for biosynthesis of 1 had been an enigma despite the availability of the A. fumigatus genome sequence. Here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide synthase and acyltransferase involved in biosynthesis of the dioic acid portion of 1. More significantly, we uncovered the elusive beta-trans-bergamotene synthase in A. fumigatus as a membrane-bound terpene cyclase.
ESTHER : Lin_2013_J.Am.Chem.Soc_135_4616
PubMedSearch : Lin_2013_J.Am.Chem.Soc_135_4616
PubMedID: 23488861
Gene_locus related to this paper: aspfu-fmac

Title : LovG: the thioesterase required for dihydromonacolin L release and lovastatin nonaketide synthase turnover in lovastatin biosynthesis -
Author(s) : Xu W , Chooi YH , Choi JW , Li S , Vederas JC , Da Silva NA , Tang Y
Ref : Angew Chem Int Ed Engl , 52 :6472 , 2013
PubMedID: 23653178
Gene_locus related to this paper: asptn-LOVG

Title : Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat - Blackett_2013_J.Clin.Lipidol_7_132
Author(s) : Blackett P , Tryggestad J , Krishnan S , Li S , Xu W , Alaupovic P , Quiroga C , Copeland K
Ref : J Clin Lipidol , 7 :132 , 2013
Abstract : BACKGROUND: The treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis. OBJECTIVE: To report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition.
METHODS: Serial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample.
RESULTS: The affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk. CONCLUSION: The data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis.
ESTHER : Blackett_2013_J.Clin.Lipidol_7_132
PubMedSearch : Blackett_2013_J.Clin.Lipidol_7_132
PubMedID: 23415432

Title : Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation - Zabala_2012_Chem.Biol_19_1049
Author(s) : Zabala AO , Xu W , Chooi YH , Tang Y
Ref : Chemical Biology , 19 :1049 , 2012
Abstract : Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. Although widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we discovered six azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly reducing PKS and a non-reducing PKS. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones.
ESTHER : Zabala_2012_Chem.Biol_19_1049
PubMedSearch : Zabala_2012_Chem.Biol_19_1049
PubMedID: 22921072
Gene_locus related to this paper: aspna-azac

Title : Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium - Patterson_2012_PLoS.One_7_e43592
Author(s) : Patterson SK , Borewicz K , Johnson T , Xu W , Isaacson RE
Ref : PLoS ONE , 7 :e43592 , 2012
Abstract : Salmonella enterica serovar Typhimurium strain 798 has previously been shown to undergo phenotypic phase variation. One of the phenotypes expresses virulence traits such as adhesion, while the other phenotype does not. Phenotypic phase variation appears to correlate with the ability of this strain to cause persistent, asymptomatic infections of swine. A new method to detect cells in either phenotypic phase was developed using Evans Blue-Uranine agar plates. Using this new assay, rates of phenotypic phase variation were obtained. The rate of phase variation from non-adhesive to adhesive phenotype was approximately 10(-4) per cell per generation while phase variation from the adhesive to the non-adhesive phenotype was approximately 10(-6) per cell per generation. Two highly virulent S. Typhimurium strains, SL1344 and ATCC 14028, were also shown to undergo phase variation. However, while the rate from adhesive to non-adhesive phenotype was approximately the same as for strain 798, the non-adhesive to adhesive phenotype shift was 37-fold higher. Differential gene expression was measured using RNA-Seq. Eighty-three genes were more highly expressed by 798 cells in the adhesive phenotype compared to the non-adhesive cells. Most of the up-regulated genes were in virulence genes and in particular all genes in the Salmonella pathogenicity island 1 were up-regulated. When compared to the virulent strain SL1344, expression of the virulence genes was approximately equal to those up-regulated in the adhesive phenotype of strain 798. A comparison of invasive ability demonstrated that strain SL1344 was the most invasive followed by the adhesive phenotype of strain 798, then the non-adhesive phenotype of strain 798. The least invasive strain was ATCC 14028. The genome of strain 798 was sequenced and compared to SL1344. Both strains had very similar genome sequences and gene deletions could not readily explain differences in the rates of phase variation from non-adhesive to the adhesive phenotype.
ESTHER : Patterson_2012_PLoS.One_7_e43592
PubMedSearch : Patterson_2012_PLoS.One_7_e43592
PubMedID: 22937065

Title : Metabonomics analysis of urine and plasma from rats given long-term and low-dose dimethoate by ultra-performance liquid chromatography-mass spectrometry - Feng_2012_Chem.Biol.Interact_199_143
Author(s) : Feng Z , Sun X , Yang J , Hao D , Du L , Wang H , Xu W , Zhao X , Sun C
Ref : Chemico-Biological Interactions , 199 :143 , 2012
Abstract : This study assessed the effects of long-term low-dose dimethoate administration to rats by ultra-performance liquid chromatography-mass spectrometry UPLC-MS Dimethoate 0.04 0.12 and 0.36mg/kg body weight/day was administered daily to male Wistar rats through their drinking water for 24weeks Significant changes in serum clinical chemistry were observed in the middle and high-dose groups UPLC-MS revealed evident separate clustering among the different dose groups using global metabolic profiling by supervised partial least squares-discriminant analysis Metabonomic analysis showed alterations in a number of metabolites 12 from urine and 13 from plasma such as l-tyrosine dimethylthiophosphate DMTP dimethyldithiophosphate DMDTP citric acid uric acid suberic acid glycylproline allantoin isovalerylglutamic acid and kinds of lipids The results suggest that long-term low-dose exposure to dimethoate can cause disturbances in liver function antioxidant and nervous systems as well as the metabolisms of lipids glucose fatty acids amino acids and collagen in rats DMTP and DMDTP which had the most significant changes among all other studied biomarkers were considered as early sensitive biomarkers of exposure to dimethoate The other aforementioned proposed toxicity biomarkers in metabonomic analysis may be useful in the risk assessment of the toxic effects of dimethoate Metabonomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of dimethoate induced toxicity In addition the results indicate that metabonomic approach could detect systemic toxic effects at an earlier stage compared to clinical chemistry The combination of metabonomics and clinical chemistry made the toxicity of dimethoate on rats more comprehensive.
ESTHER : Feng_2012_Chem.Biol.Interact_199_143
PubMedSearch : Feng_2012_Chem.Biol.Interact_199_143
PubMedID: 22884955

Title : Formation of cyclic structure at amino-terminus of glucagon-like peptide-1 exhibited a prolonged half-life in vivo - Cao_2012_Diabetes.Res.Clin.Pract_96_362
Author(s) : Cao Z , Li Y , Tang L , Xu W , Liu C , Zhang J , Gong M
Ref : Diabetes Res Clin Pract , 96 :362 , 2012
Abstract : The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the therapy of type 2 diabetes. However, the biological half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The stabilization of GLP-1 is critical for its utility in drug development. In this study, several GLP-1 mutants containing an N-terminal cyclic conformation were prepared in that the existence of cyclic conformation is predicted to increase the stabilization of GLP-1 in vivo. In this study, the binding capacities of the mutants were determined, the stabilities of the mutants were investigated and the physiological functions of the mutants were compared with those of wild-type GLP-1 in animals. The results indicated that the mutant (GLP1N8) remarkably raised the half-life in vivo; it also showed better glucose tolerance and higher HbA(1c) reduction than GLP-1 and exendin-4 in rodents. These results suggest that the GLP-1 analog (GLP1N8) which contains an N-terminal cyclic structure might be utilized as possible potent anti-diabetic drugs in the treatment of type 2 diabetes mellitus.
ESTHER : Cao_2012_Diabetes.Res.Clin.Pract_96_362
PubMedSearch : Cao_2012_Diabetes.Res.Clin.Pract_96_362
PubMedID: 22284602

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 : Expression level of lipoprotein lipase in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors - Xu_2009_Int.J.Lab.Hematol_31_552
Author(s) : Xu W , Li JY , Shen QD , Wu YJ , Yu H , Fan L
Ref : Int J Lab Hematol , 31 :552 , 2009
Abstract : Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in the Western world, however, infrequent in the Eastern. It shows a remarkable heterogeneity, with some patients having an almost normal lifespan, others surviving only several years after diagnosis despite intensive therapy. To investigate lipoprotein lipase (LPL) expression level in Chinese patients with CLL and its correlation with other prognostic factors, including immunoglobulin heavy-chain variable region (IgVH) mutation status, Binet stages, ZAP-70 protein and CD38 expression level, semiquantitative RT-PCR was used to detect LPL expression in peripheral blood samples of 58 Chinese patients with CLL. LPL expression level was significantly correlated with IgVH mutational status (r = 0.348, P = 0.010), Binet stages (r = 0.276, P = 0.036), ZAP-70 protein (r = 0.431, P = 0.001) and CD38 (r = 0.546, P < 0.001). Patients with unmutated IgVH genes had higher expression of LPL than patients with IgVH mutations. The higher expression level of LPL was also associated with higher level of ZAP-70 and CD38, and more aggressive Binet stage. We also analyzed LPL expression in different cytogenetic subgroups. Higher LPL level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22) in contrast to lower level in good risk cytogenetics (deletion in 13q as the sole abnormality) (r = 0.404, P = 0.002). It was showed that LPL expression correlates with IgVH mutational status and other clinical or laboratory prognostic factors, and might be applied for the assessment of prognosis in patients with CLL.
ESTHER : Xu_2009_Int.J.Lab.Hematol_31_552
PubMedSearch : Xu_2009_Int.J.Lab.Hematol_31_552
PubMedID: 18616755

Title : A putative lipase gene EXTRA GLUME1 regulates both empty-glume fate and spikelet development in rice - Li_2009_Plant.J_57_593
Author(s) : Li H , Xue D , Gao Z , Yan M , Xu W , Xing Z , Huang D , Qian Q , Xue Y
Ref : Plant J , 57 :593 , 2009
Abstract : Recent studies have shown that molecular control of inner floral organ identity appears to be largely conserved between monocots and dicots, but little is known regarding the molecular mechanism underlying development of the monocot outer floral organ, a unique floral structure in grasses. In this study, we report the cloning of the rice EXTRA GLUME1 (EG1) gene, a putative lipase gene that specifies empty-glume fate and floral meristem determinacy. In addition to affecting the identity and number of empty glumes, mutations in EG1 caused ectopic floral organs to be formed at each organ whorl or in extra ectopic whorls. Iterative glume-like structures or new floral organ primordia were formed in the presumptive region of the carpel, resulting in an indeterminate floral meristem. EG1 is expressed strongly in inflorescence primordia and weakly in developing floral primordia. We also found that the floral meristem and organ identity gene OsLHS1 showed altered expression with respect to both pattern and levels in the eg1 mutant, and is probably responsible for the pleiotropic floral defects in eg1. As a putative class III lipase that functionally differs from any known plant lipase, EG1 reveals a novel pathway that regulates rice empty-glume fate and spikelet development.
ESTHER : Li_2009_Plant.J_57_593
PubMedSearch : Li_2009_Plant.J_57_593
PubMedID: 18980657

Title : Stability and activity of lipase in subcritical 1,1,1,2-tetrafluoroethane (R134a) - Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
Author(s) : Yu G , Xue Y , Xu W , Zhang J , Xue CH
Ref : J Ind Microbiol Biotechnol , 34 :793 , 2007
Abstract : The stability and activity of commercial immobilized lipase from Candida antarctica (Novozym 435) in subcritical 1,1,1,2-tetrafluoroethane (R134a) was investigated. The esterification of oleic acid with glycerol was studied as a model reaction in subcritical R134a and in solvent-free conditions. The results indicated that subcritical R134a treatment led to significant increase of activity of Novozym 435, and a maximum residual activity of 300% was measured at 4 MPa, 30 degrees C after 7 h incubation. No deactivation of Novozym 435 treated with subcritical R134a under different operation factors (pressure 2-8 MPa, temperature 30-60 degrees C, incubation time 1-12 h, water content 1:1, 1:2, 1:5 enzyme/water, depressurization rate 4 MPa/1 min, 4 MPa/30 min, 4 MPa/90 min) was observed. While the initial reaction rate was high in subcritical R134a, higher conversion was obtained in solvent-free conditions. Though the apparent conversion of the reaction is lower in subcritical R134a, it is more practicable, especially at low enzyme concentrations desired at commercial scales.
ESTHER : Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
PubMedSearch : Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
PubMedID: 17909872

Title : A newly isolated organic solvent tolerant Staphylococcus saprophyticus M36 produced organic solvent-stable lipase - Fang_2006_Curr.Microbiol_53_510
Author(s) : Fang Y , Lu Z , Lv F , Bie X , Liu S , Ding Z , Xu W
Ref : Curr Microbiol , 53 :510 , 2006
Abstract : Thirty-eight high lipase activity strains were isolated from soil, seawater, and Brassica napus. Among them, a novel organic solvent tolerant bacterium (strain M36) was isolated from the seawater in Jiangsu, China. Isolate M36 was able to grow at high concentration of benzene or toluene up to 40% (vol/vol), and later identified as Staphylococcus saprophyticus by biochemical test and 16s ribosomal DNA sequence. No work on Staphylococcus producing lipase with organic solvent tolerance has been reported so far. The lipase of strain M36 whose activity in liquid medium was 42 U mL(-1) at 24-h incubation time was stable in the presence of 25% (vol/vol) p-xylene, benzene, toluene, and hexane.
ESTHER : Fang_2006_Curr.Microbiol_53_510
PubMedSearch : Fang_2006_Curr.Microbiol_53_510
PubMedID: 17089221

Title : Nicotinic acetylcholine receptors in the autonomic control of bladder function - De Biasi_2000_Eur.J.Pharmacol_393_137
Author(s) : De Biasi M , Nigro F , Xu W
Ref : European Journal of Pharmacology , 393 :137 , 2000
Abstract : Micturition is achieved through complex neurological mechanisms involving somatic, autonomic and central components. This article briefly reviews recent findings on the autonomic control of urinary bladder function. Neuronal nicotinic acetylcholine receptors mediate fast synaptic transmission in autonomic ganglia, and activation of nicotinic receptors in parasympathetic bladder neurons produces contraction of the detrusor muscle. Autonomic ganglia contain transcripts for the alpha(3), alpha(4), alpha(5), alpha(7), beta(2) and beta(4) nicotinic subunits, which can assemble to form multiple nicotinic receptor subtypes, but the exact nicotinic receptor subunit composition in bladder ganglia is unknown. Mutant mice lacking the alpha(3) or the beta(2) and the beta(4) nicotinic subunits have enlarged bladders with dribbling urination and develop urinary infection and bladder stones. Bladder strips from alpha(3) null mice do not respond to nicotine but contract when stimulated with a muscarinic agonist or electric field stimulation. Mice lacking the beta(2) subunit have no overt bladder phenotype, and their bladders contract in response to nicotine. Surprisingly, bladder strips from beta(4) mutant mice do not respond to nicotine despite the absence of major bladder dysfunction in vivo. These findings suggest that nicotinic receptors containing the alpha(3) and the beta(4) subunits are necessary for normal bladder function.
ESTHER : De Biasi_2000_Eur.J.Pharmacol_393_137
PubMedSearch : De Biasi_2000_Eur.J.Pharmacol_393_137
PubMedID: 10771006

Title : Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor - Xu_1999_Proc.Natl.Acad.Sci.U.S.A_96_5746
Author(s) : Xu W , Gelber S , Orr-Urtreger A , Armstrong D , Lewis RA , Ou CN , Patrick J , Role LW , De Biasi M , Beaudet AL
Ref : Proc Natl Acad Sci U S A , 96 :5746 , 1999
Abstract : The alpha3 subunit of the neuronal nicotinic acetylcholine receptor is widely expressed in autonomic ganglia and in some parts of the brain. The alpha3 subunit can form heteromultimeric ion channels with other alpha subunits and with beta2 and beta4 subunits, but its function in vivo is poorly understood. We prepared a null mutation for the alpha3 gene by deletion of exon 5 and found that homozygous (-/-) mice lacked detectable mRNA on Northern blotting. The -/- mice survive to birth but have impaired growth and increased mortality before and after weaning. The -/- mice have extreme bladder enlargement, dribbling urination, bladder infection, urinary stones, and widely dilated ocular pupils that do not contract in response to light. Detailed histological studies of -/- mice revealed no significant abnormalities in brain or peripheral tissues except urinary bladder, where inflammation was prominent. Ganglion cells and axons were present in bladder and bowel. Bladder strips from -/- mice failed to contract in response to 0.1 mM nicotine, but did contract in response to electrical field stimulation or carbamoylcholine. The number of acetylcholine-activated single-channel currents was severely reduced in the neurons of superior cervical ganglia in -/- mice with five physiologically distinguishable nicotinic acetylcholine receptor subtypes with different conductance and kinetic properties in wild-type mice, all of which were reduced in -/- mice. The findings in the alpha3-null mice suggest that this subunit is an essential component of the nicotinic receptors mediating normal function of the autonomic nervous system. The phenotype in -/- mice may be similar to the rare human genetic disorder of megacystis-microcolon-intestinal hypoperistalsis syndrome.
ESTHER : Xu_1999_Proc.Natl.Acad.Sci.U.S.A_96_5746
PubMedSearch : Xu_1999_Proc.Natl.Acad.Sci.U.S.A_96_5746
PubMedID: 10318955

Title : Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors - Xu_1999_J.Neurosci_19_9298
Author(s) : Xu W , Orr-Urtreger A , Nigro F , Gelber S , Sutcliffe CB , Armstrong D , Patrick JW , Role LW , Beaudet AL , De Biasi M
Ref : Journal of Neuroscience , 19 :9298 , 1999
Abstract : Transcripts for the beta2 and the beta4 nicotinic acetylcholine receptor (nAChR) subunits are found throughout the CNS and the peripheral nervous system. These two beta subunits can form heteromultimeric channels with any of the alpha2, alpha3, alpha4, or alpha5 subunits in heterologous expression systems. Nonetheless, the subunit composition of native nAChRs and the role of different nAChR subtypes in vivo remain unclear. We prepared null mutations for the beta2 and the beta4 genes and bred beta2-/-beta4-/- mice by mating mice of identical beta2-/-beta4+/- or beta2+/-beta4-/- genotype. The beta2-/- and the beta4-/- single-mutant mice grow to adulthood with no visible phenotypic abnormalities. The beta2-/-beta4-/- double mutants survive to birth but have impaired growth and increased perinatal mortality. They also present enlarged bladders with dribbling urination and develop urinary infection and bladder stones. The ocular pupils are widely dilated and do not constrict in response to light. Histological studies revealed no significant abnormalities of brain or peripheral tissues except for hyperplasia in the bladder mucosa of beta4-/- and beta2-/-beta4-/- mutants. Bladder strips from beta2-/-beta4-/- mice did not respond to nicotine but contracted when stimulated with a muscarinic agonist or electric field stimulation. Bladder strips from beta4 mutants did not respond to nicotine despite the absence of major bladder dysfunction in vivo. Acetylcholine-activated whole-cell currents were absent in superior cervical ganglion neurons from beta2-/-beta4-/- mice and reduced in neurons from beta4-/- mice. Although there is apparent redundancy and a superficially normal phenotype in beta2-/- and beta4-/- mice, physiological studies indicate major deficits in the beta4-/- mice. Our previous description of a similar phenotype in alpha3-/- mice and the current data suggest that the alpha3 and the beta4 subunits are major components in autonomic nAChRs. The phenotype of the beta2-/-beta4-/- and alpha3-/- mice resembles the autosomal recessive megacystis-microcolon-hypoperistalsis syndrome in humans.
ESTHER : Xu_1999_J.Neurosci_19_9298
PubMedSearch : Xu_1999_J.Neurosci_19_9298
PubMedID: 10531434

Title : Effect of interleukin-1 beta on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats - Tsukagoshi_1994_J.Allergy.Clin.Immunol_93_464
Author(s) : Tsukagoshi H , Sakamoto T , Xu W , Barnes PJ , Chung KF
Ref : J Allergy Clin Immunol , 93 :464 , 1994
Abstract : Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p < 0.0005). We conclude that intratracheal administration of IL-1 beta induces the inflammatory changes, which are characterized by an increase in neutrophil counts in BALF, and increased AR to bradykinin, and that active sensitization per se does not potentiate the effect of IL-1 beta on AR to acetylcholine or bradykinin or on airway inflammation.
ESTHER : Tsukagoshi_1994_J.Allergy.Clin.Immunol_93_464
PubMedSearch : Tsukagoshi_1994_J.Allergy.Clin.Immunol_93_464
PubMedID: 8120273