Huang Y

References (163)

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

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : Antisolvent precipitation for the synergistic preparation of ultrafine particles of nobiletin under ultrasonication-homogenization and evaluation of the inhibitory effects of alpha-glucosidase and porcine pancreatic lipase in vitro - Zhang_2024_Ultrason.Sonochem_105_106865
Author(s) : Zhang X , Huang Y , Huang S , Xie W , Huang W , Chen Y , Li Q , Zeng F , Liu X
Ref : Ultrason Sonochem , 105 :106865 , 2024
Abstract : To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.
ESTHER : Zhang_2024_Ultrason.Sonochem_105_106865
PubMedSearch : Zhang_2024_Ultrason.Sonochem_105_106865
PubMedID: 38564909

Title : NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury - Huang_2024_Biol.Direct_19_32
Author(s) : Huang Y , Li X , Wei L , Ma S , Ma L , Zan Y , He X , Tang Y , Ding Y
Ref : Biol Direct , 19 :32 , 2024
Abstract : BACKGROUND: Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism. METHODS: In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe. RESULTS: NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5'UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2. CONCLUSION: NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.
ESTHER : Huang_2024_Biol.Direct_19_32
PubMedSearch : Huang_2024_Biol.Direct_19_32
PubMedID: 38685056

Title : FsCGBP, a Cutinase G-Box Binding Protein, Regulates the Growth, Development, and Virulence of Fusarium sacchari, the Pathogen of Sugarcane Pokkah Boeng Disease - Liang_2024_J.Fungi.(Basel)_10_
Author(s) : Liang H , Li F , Huang Y , Yu Q , Huang Z , Zeng Q , Chen B , Meng J
Ref : J Fungi (Basel) , 10 : , 2024
Abstract : Fusarium sacchari is a causal agent of sugarcane Pokkah boeng, an important fungal disease that causes a considerable reduction in yield and sugar content in susceptible varieties of sugarcane worldwide. Despite its importance, the fungal factors that regulate the virulence of this pathogen remain largely unknown. In our previous study, mapping of an insertional mutant defect in virulence resulted in the identification of a cutinase G-box binding protein gene, designated FsCGBP, that encodes a C2H2-type transcription factor (TF). FsCGBP was shown to localize in the nuclei, and the transcript level of FsCGBP was significantly upregulated during the infection process or in response to abiotic stresses. Deletion or silencing of FsCGBP resulted in a reduction in mycelial growth, conidial production, and virulence and a delay in conidial germination in the F. sacchari. Cutinase genes FsCUT2, FsCUT3, and FsCUT4 and the mitogen-activated protein kinase (MAPK) genes FsHOG1, FsMGV1, and FsGPMK1, which were significantly downregulated in deltaFsCGBP. Except for FsHOG1, all of these genes were found to be transcriptionally activated by FsCGBP using the yeast one-hybrid system in vitro. The deletion of individual cutinase genes did not result in any of the phenotypes exhibited in the deltaFsCGBP mutant, except for cutinase activity. However, disruption of the MAPK pathway upon deletion of FsMGV1 or FsGPMK1 resulted in phenotypes similar to those of the deltaFsCGBP mutant. The above results suggest that FsCGBP functions by regulating the MAPK pathway and cutinase genes, providing new insights into the mechanism of virulence regulation in F. sacchari.
ESTHER : Liang_2024_J.Fungi.(Basel)_10_
PubMedSearch : Liang_2024_J.Fungi.(Basel)_10_
PubMedID: 38667917

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

Title : 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 : Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia - Yang_2023_Front.Pharmacol_14_1236656
Author(s) : Yang SH , Zhu J , Wu WT , Li JM , Tong HL , Huang Y , Gong QF , Gong FP , Zhong LY
Ref : Front Pharmacol , 14 :1236656 , 2023
Abstract : Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.
ESTHER : Yang_2023_Front.Pharmacol_14_1236656
PubMedSearch : Yang_2023_Front.Pharmacol_14_1236656
PubMedID: 37601055

Title : Enzymatic synthesis of branched chain fatty acid-enriched structured triacylglycerols via esterification with glycerol - Huang_2023_Food.Chem_429_136943
Author(s) : Huang Y , Li H , Wang Z , Fu Y , Chen Y , Wang X
Ref : Food Chem , 429 :136943 , 2023
Abstract : While branched-chain fatty acids (BCFA)-enriched triacylglycerols (TAG) has various health benefits, its preparation has not been reported. This study aimed to synthesize high-purity BCFA-enriched structured TAG. First, BCFA was enriched from lanolin through saponification, calcification, and urea complexation. Next, BCFA-enriched TAG was synthesized by enzymatic esterification of BCFA and glycerol. Then, lipases were screened by molecular docking and practical experiments, which suggested that Lipozyme 435 was the best lipase for esterification since it had the lowest binding energy. Structured TAG containing 92.23% BCFA was synthesized under conditions optimized by single-factor experiments. Furthermore, molecular distillation was adapted to remove excess fatty acids and small molecule impurities. Finally, high-purity BCFA-enriched structured lipid containing 70.26% TAG was obtained. Overall, this study successfully developed a method for synthesizing BCFA-enriched structured TAG, which holds great promise for applications in value-added foods.
ESTHER : Huang_2023_Food.Chem_429_136943
PubMedSearch : Huang_2023_Food.Chem_429_136943
PubMedID: 37517224

Title : Case Report: Telitacicept in severe myasthenia gravis: a case study with multiple autoantibodies - Guo_2023_Front.Immunol_14_1270011
Author(s) : Guo Q , Huang Y , Wang F , Fang L
Ref : Front Immunol , 14 :1270011 , 2023
Abstract : Multi-antibody-positive myasthenia gravis (MG) presentations are relatively rare, often found in older patients, and generally predict a poor prognosis. We report a case of a female patient with generalized MG, testing positive for Titin antibodies (Titin-Ab), ryanodine receptor antibodies (RyR-Ab), and acetylcholine receptor antibodies (AChR-Ab), and resistant to acetylcholinesterase inhibitors. Following unsuccessful traditional therapies, she received Telitacicept, leading to significant improvements. This case underscores Telitacicept's potential efficacy for similar patients and offers insights into the clinical characteristics of multi-antibody MG.
ESTHER : Guo_2023_Front.Immunol_14_1270011
PubMedSearch : Guo_2023_Front.Immunol_14_1270011
PubMedID: 38124751

Title : A S-substituted Nile Blue-derived bifunctional near-infrared fluorescent probe for in vivo carboxylesterase imaging-guided photodynamic therapy of hepatocellular carcinoma - Wang_2023_J.Mater.Chem.B__
Author(s) : Wang B , Huang Y , Yang D , Xu J , Zhong X , Zhao S , Liang H
Ref : J Mater Chem B , : , 2023
Abstract : The development of theranostic probes that integrate both diagnostic and therapeutic functions still remains an intractable challenge in precise cancer treatment. Herein, a novel bifunctional near-infrared (NIR) fluorescent probe (CEP1) for carboxylesterase (CE) imaging and photodynamic therapy (PDT) of hepatocellular carcinoma (HCC) has been firstly developed and successfully applied in vitro and in vivo. The probe was constructed by introducing carbamate as both the recognition unit and the fluorescence quenching unit into the fluorophore S-substituted Nile Blue (ENBS) via a self-eliminating spacer with substituted chloride. It can be activated by CE and hydrolyzed into fluorescent ENBS, which recover fluorescence at about 700 nm, and can generate superoxide radical anions under NIR irradiation. Additionally, the probe could effectively distinguish tumor cells from normal cells by CE imaging of live cells. Furthermore, it could achieve CE imaging in vivo and significantly inhibits tumor growth by imaging-guided PDT. Therefore, this study offers a promising and attractive platform for activatable imaging-guided PDT of HCC.
ESTHER : Wang_2023_J.Mater.Chem.B__
PubMedSearch : Wang_2023_J.Mater.Chem.B__
PubMedID: 37427685

Title : Discovery of quinazolin-4(3H)-one derivatives as novel AChE inhibitors with anti-inflammatory activities - Lv_2023_Eur.J.Med.Chem_254_115346
Author(s) : Lv L , Maimaitiming M , Huang Y , Yang J , Chen S , Sun Y , Zhang X , Li X , Xue C , Wang P , Wang CY , Liu Z
Ref : Eur Journal of Medicinal Chemistry , 254 :115346 , 2023
Abstract : A series of quinazolin-4(3H)-one derivatives was designed through scaffold-hopping strategy and synthesized as novel multifunctional anti-AD agents demonstrating both cholinesterase inhibition and anti-inflammatory activities. Their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated, and the enzyme kinetics study as well as detailed binding mode via molecular docking were performed for selected compounds. MR2938 (B12) displayed promising AChE inhibitory activity with an IC(50) value of 5.04 microM and suppressed NO production obviously (IC(50) = 3.29 microM). Besides, it was able to decrease the mRNA levels of pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-6 and CCL2 at 1.25 microM. Further mechanism study suggested that MR2938 suppressed the neuroinflammation through blocking MAPK/JNK and NF-kappaB signaling pathways. All these results indicate that MR2938 is a good starting point to develop multifunctional anti-AD lead compounds.
ESTHER : Lv_2023_Eur.J.Med.Chem_254_115346
PubMedSearch : Lv_2023_Eur.J.Med.Chem_254_115346
PubMedID: 37043994

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

Title : Plants of the genus Mahonia as a Potential Traditional Chinese Medicine for the Prevention and Treatment of Alzheimer's Disease - Yang_2023_Curr.Top.Med.Chem__
Author(s) : Yang S , Shao H , Chen X , Liu Q , Huang S , Huang Y
Ref : Curr Top Med Chem , : , 2023
Abstract : Alzheimer's disease (AD), a prevalent multiple neurodegenerative disease, has gained attention, particularly in the aging population. However, presently available therapies merely focus on alleviating the symptoms of AD and fail to slow disease progression significantly. Traditional Chinese medicine (TCM) has been used to ameliorate symptoms or interfere with the pathogenesis of aging-associated diseases for many years based on disease-modifying in multiple pathological roles with multi-targets, multi-systems and multi-aspects. Mahonia species as a TCM present potential for anti-inflammatory activity, antioxidant activity, anti-acetylcholinesterase activity, and anti-amyloid-beta activity that was briefly discussed in this review. They are regarded as promising drug candidates for AD therapy. The findings in this review support the use of Mahonia species as an alternative therapy source for treating AD.
ESTHER : Yang_2023_Curr.Top.Med.Chem__
PubMedSearch : Yang_2023_Curr.Top.Med.Chem__
PubMedID: 37005525

Title : Extracellular Macrophage Migration Inhibitory Factor (MIF) Downregulates Adipose Hormone-Sensitive Lipase (HSL) and Contributes to Obesity - Chen_2023_Mol.Metab__101834
Author(s) : Chen L , Li L , Cui D , Huang Y , Tong H , Zabihi H , Wang S , Qi Y , Lakowski T , Leng L , Liu S , Wu H , Young LH , Bucala R , Qi D
Ref : Mol Metab , :101834 , 2023
Abstract : Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role of cytokine, macrophage migration inhibitory factor (MIF) in regulating adipose HSL and adipocyte hypertrophy. Extracellular MIF released from adipocytes downregulates HSL in an autocrine fashion, by activating the AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well as mice overexpressing MIF, both had high circulating MIF levels and showed suppression of HSL during the development of obesity. Blocking the extracellular action of MIF by a neutralizing MIF antibody significantly reduced obesity in HFD mice. Interestingly, intracellular MIF binds with Csn5 and JNK, which leads to an opposing effect to inhibit JNK phosphorylation. With global MIF deletion, adipocyte JNK phosphorylation increased, resulting in decreased HSL expression, suggesting that the loss of MIF's intracellular inhibitory action on JNK was dominant in Mif(-/-) mice. Adipose tissue from Mif(-/-) mice also exhibited higher Akt and lower PKA phosphorylation following HFD feeding compared with WT, which may contribute to the downregulation of HSL activation during more severe obesity. Both intracellular and extracellular MIF have opposing effects to regulate HSL, but extracellular actions predominate to downregulate HSL and exacerbate the development of obesity during HFD.
ESTHER : Chen_2023_Mol.Metab__101834
PubMedSearch : Chen_2023_Mol.Metab__101834
PubMedID: 37935315

Title : Biotransformation, metabolic response, and toxicity of UV-234 and UV-326 in larval zebrafish (Danio rerio) - Zhang_2023_Environ.Int_174_107896
Author(s) : Zhang J , Huang Y , Pei Y , Wang Y , Li M , Chen H , Liang X , Martyniuk CJ
Ref : Environ Int , 174 :107896 , 2023
Abstract : Benzotriazole ultraviolet stabilizers (BUVSs) are emerging pollutants that are widely detected in aquatic ecosystems. While structure-dependent effects of BUVSs are reported, the relationship between biotransformation and toxicity outcomes remains unclear. In this study, zebrafish embryos were exposed to two common BUVSs (UV-234 and UV-326) at 1, 10, and 100 microg/L for up to 7 days. Comparison of their uptake and biotransformation revealed that the bioaccumulation capacity of UV-234 was higher than that of UV-326, while UV-326 was more extensively biotransformed with additional conjugation reactions. However, UV-326 showed low metabolism due to inhibited phase II enzymes, which may result in the comparable internal concentrations of both BUVSs in larval zebrafish. Both BUVSs induced oxidative stress while decreased MDA, suggesting the disturbance of lipid metabolism. The subsequent metabolomic profiling revealed that UV-234 and UV-326 exerted different effects on arachidonic acid, lipid, and energy metabolism. However, both BUVSs negatively impacted the cyclic guanosine monophosphate / protein kinase G pathway. This converged metabolic change resulted in comparable toxicity of UV-234 and UV-326, which was confirmed by the induction of downstream apoptosis, neuroinflammation, and abnormal locomotion behavior. These data have important implications for understanding the metabolism, disposition, and toxicology of BUVSs in aquatic organisms.
ESTHER : Zhang_2023_Environ.Int_174_107896
PubMedSearch : Zhang_2023_Environ.Int_174_107896
PubMedID: 36966637

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : Evaluation and clinical implications of interactions between compound Danshen dropping pill and warfarin associated with the epoxide hydrolase gene - Chen_2023_Front.Pharmacol_14_1105702
Author(s) : Chen X , Zuo X , Zhao Y , Huang Y , Lv C
Ref : Front Pharmacol , 14 :1105702 , 2023
Abstract : Introduction: In clinical practice, warfarin is often combined with Compound Danshen dripping pill (CDDP) for the treatment of cardiovascular diseases. However, warfarin has a narrow therapeutic index, wide interindividual variability (genetic and non-genetic factors), and is susceptible to drug-drug interactions. Our previous study indicated that CDDP might interact with warfarin in individuals with the epoxide hydrolase gene (EPHX1; single-nucleotide polymorphism: rs2292566) A/A subtype. We sought to clarify the interaction between CDDP and warfarin associated with EPHX1 in a comprehensive and accurate manner. Methods: Here, EPHX1 A and EPHX1 G cell lines were established. Expression of microsomal epoxide hydrolase (mEH), vitamin K epoxide reductase (VKOR), and vitamin K-dependent clotting factors (FII, FVII, FIX, FX) was measured by western blotting upon incubation with CDDP and warfarin. mEH activity was evaluated by measuring the transformation of epoxyeicosatrienoic acids into dihydroxyeicosatrienoic acids. Then, healthy volunteers (HVs) with the EPHX1 A/A genotype were recruited and administered warfarin and CDDP to investigate the pharmacokinetics and pharmacodynamics of warfarin. Results: CDDP combined with warfarin could decrease expression of mEH and VKOR, and increase protein expression of FII, FVII, FIX, and FX, in EPHX1 A cells. CDDP could slightly influence the pharmacokinetics/pharmacodynamics of warfarin in HVs with the EPHX1 A/A genotype. Discussion: Rational combination of CDDP and warfarin was safe with no risk of bleeding, but the therapeutic management is also needed. The clinical study is posted in the China Clinical Trial Registry (ChiCTR190002434).
ESTHER : Chen_2023_Front.Pharmacol_14_1105702
PubMedSearch : Chen_2023_Front.Pharmacol_14_1105702
PubMedID: 37214448

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

Title : Enzymatic enrichment of acylglycerols rich in n - 3 polyunsaturated fatty acids by selective methanolysis: Optimization and kinetic studies - Jiang_2023_J.Food.Sci__
Author(s) : Jiang C , Wang Z , Huang Y , Wang X , Chang M
Ref : J Food Sci , : , 2023
Abstract : n - 3 Polyunsaturated fatty acids (n - 3 PUFA) have special physiological effect, but their contents in natural oils may not meet the growing demand. Lipase-catalyzed selective methanolysis could be used to produce acylglycerols rich in n - 3 PUFA. To explore the kinetics of enzymatic methanolysis, factors affecting the reaction, including reaction system, water content, substrate molar ratio, temperature, lipase loading, and reaction time, were first investigated in the view of optimizing the reaction. Then the effects of triacylglycerol concentrations and methanol concentrations on initial reaction rate were studied. Finally, the key kinetic parameters of methanolysis were determined subsequently. The results showed that under optimal conditions, the n - 3 PUFA content in acylglycerols increased from 39.88% to 71.41%, and the n - 3 PUFA yield was 73.67%. The reaction followed a Ping-Pong Bi Bi mechanism with inhibition by methanol. The kinetic analysis indicated the lipase could selectively remove saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in acylglycerols. The inhibition constant of methanol to the n - 3 PUFA (K(iM) , 0.30 mmol/L) was lower than that to the SFA and MUFA (219.64 and 79.71 mmol/L). The combined effects of the fatty acid selectivity of Candida antarctica lipase A and methanol inhibition resulted in an enrichment of n - 3 PUFA in acylglycerols. Overall, the methanolysis reaction catalyzed by the lipase A is a prospective enrichment method. PRACTICAL APPLICATION: This study demonstrated that enzymatic selective methanolysis is a prospective enrichment method to produce acylglycerols rich in n - 3 PUFA. This method is highly efficient, environment-friendly, and simple. n - 3 PUFA concentrates have been widely applied in the food, health-care food, and pharmaceutical industries.
ESTHER : Jiang_2023_J.Food.Sci__
PubMedSearch : Jiang_2023_J.Food.Sci__
PubMedID: 37219384

Title : Sphk1 deficiency induces apoptosis and developmental defects and premature death in zebrafish - Huang_2023_Fish.Physiol.Biochem__
Author(s) : Huang L , Han F , Huang Y , Liu J , Liao X , Cao Z , Li W
Ref : Fish Physiol Biochem , : , 2023
Abstract : The sphk1 gene plays a crucial role in cell growth and signal transduction. However, the developmental functions of the sphk1 gene during early vertebrate zebrafish embryo remain not completely understood. In this study, we constructed zebrafish sphk1 mutants through CRISPR/Cas9 to investigate its role in zebrafish embryonic development. Knockout of the sphk1 gene was found to cause abnormal development in zebrafish embryos, such as darkening and atrophy of the head, trunk deformities, pericardial edema, retarded yolk sac development, reduced heart rate, and premature death. The acetylcholinesterase activity was significantly increased after the knockout of sphk1, and some of the neurodevelopmental genes and neurotransmission system-related genes were expressed abnormally. The deletion of sphk1 led to abnormal expression of immune genes, as well as a significant decrease in the number of hematopoietic stem cells and neutrophils. The mRNA levels of cardiac development-related genes were significantly decreased. In addition, cell apoptosis increases in the sphk1 mutants, and the proliferation of head cells decreases. Therefore, our study has shown that the sphk1 is a key gene for zebrafish embryonic survival and regulation of organ development. It deepened our understanding of its physiological function. Our study lays the foundation for investigating the mechanism of the sphk1 gene in early zebrafish embryonic development.
ESTHER : Huang_2023_Fish.Physiol.Biochem__
PubMedSearch : Huang_2023_Fish.Physiol.Biochem__
PubMedID: 37464180

Title : The role of s-palmitoylation in neurological diseases: implication for zDHHC family - Liao_2023_Front.Pharmacol_14_1342830
Author(s) : Liao D , Huang Y , Liu D , Zhang H , Shi X , Li X , Luo P
Ref : Front Pharmacol , 14 :1342830 , 2023
Abstract : S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer's disease), HD (Huntington's disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.
ESTHER : Liao_2023_Front.Pharmacol_14_1342830
PubMedSearch : Liao_2023_Front.Pharmacol_14_1342830
PubMedID: 38293675

Title : Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[(18)F]flubatine PET study - Calakos_2023_Neuropsychopharmacology__
Author(s) : Calakos KC , Hillmer AT , Anderson JM , LeVasseur B , Baldassarri SR , Angarita GA , Matuskey D , Kapinos M , Zheng MQ , Huang Y , Cosgrove KP
Ref : Neuropsychopharmacology , : , 2023
Abstract : The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking. We used positron emission tomography (PET) brain imaging with the beta(2)-subunit containing nicotinic acetylcholine receptor (beta(2)*-nAChR) partial agonist radioligand (-)-[(18)F]flubatine and the acetylcholinesterase inhibitor physostigmine to jointly examine the cholinergic system, smoking status, and cognition. (-)-[(18)F]Flubatine scans and cognitive data were acquired from twenty people who recently stopped smoking cigarettes (aged 38 +/- 11 years; 6 female, 14 male; abstinent 7 +/- 1 days) and 27 people who never smoked cigarettes (aged 29 +/- 8 years; 11 female, 16 male). A subset of fifteen recently abstinent smokers and 21 never smokers received a mid-scan physostigmine challenge to increase acetylcholine levels. Regional volume of distribution (V(T)) was estimated with equilibrium analysis at 'baseline' and post-physostigmine. Participants completed a cognitive battery prior to (-)-[(18)F]flubatine injection and physostigmine administration assessing executive function (Groton Maze Learning test), verbal learning (International Shopping List test), and working memory (One Back test). Physostigmine significantly decreased cortical (-)-[(18)F]flubatine V(T), consistent with increased cortical acetylcholine levels reducing the number of beta(2)*-nAChR sites available for (-)-[(18)F]flubatine binding, at comparable magnitudes across groups (p values < 0.05). A larger magnitude of physostigmine-induced decrease in (-)-[(18)F]flubatine V(T) was significantly associated with worse executive function in people who recently stopped smoking (p values < 0.05). These findings underscore the role of the cholinergic system in early smoking cessation and highlight the importance of neuroscience-informed treatment strategies.
ESTHER : Calakos_2023_Neuropsychopharmacology__
PubMedSearch : Calakos_2023_Neuropsychopharmacology__
PubMedID: 36681758

Title : CuCeTA nanoflowers as an efficient peroxidase candidate for direct colorimetric detection of glyphosate - Jiang_2023_J.Mater.Chem.B__
Author(s) : Jiang C , Zhong H , Zou J , Zhu G , Huang Y
Ref : J Mater Chem B , : , 2023
Abstract : Conventional nanozyme-based pesticide detection often requires the assistance of acetylcholinesterase. In this work, a CuCeTA nanozyme was successfully designed for the direct colorimetric detection of glyphosate. Direct detection can effectively avoid the problems caused by cascading with natural enzymes such as acetylcholinesterase. By assembling tannic acid, copper sulfate pentahydrate and cerium(III) nitrate hexahydrate, CuCeTA nanoflowers were prepared. The obtained CuCeTA possessed excellent peroxidase-like activity that could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB in the presence of hydrogen peroxide. Glyphosate could effectively inhibit the peroxidase-like activity of CuCeTA while other pesticides (fenthion, chlorpyrifos, profenofos, phosmet, bromoxynil and dichlorophen) did not show significant inhibitory effects on the catalytic activity of CuCeTA. In this way, CuCeTA could be used for the colorimetric detection of glyphosate with a low detection limit of 0.025 ppm. Combined with a smartphone and imageJ software, a glyphosate test paper was designed with a detection limit of 3.09 ppm. Fourier transform infrared spectroscopy demonstrated that glyphosate and CuCeTA might be bound by coordination, which could affect the catalytic activity of CuCeTA. Our CuCeTA-based nanozyme system exhibited unique selectivity and sensitivity for glyphosate detection and this work may provide a new strategy for rapid and convenient detection of pesticides.
ESTHER : Jiang_2023_J.Mater.Chem.B__
PubMedSearch : Jiang_2023_J.Mater.Chem.B__
PubMedID: 37750214

Title : Biological Degradation of Plastics and Microplastics: A Recent Perspective on Associated Mechanisms and Influencing Factors - Cai_2023_Microorganisms_11_
Author(s) : Cai Z , Li M , Zhu Z , Wang X , Huang Y , Li T , Gong H , Yan M
Ref : Microorganisms , 11 : , 2023
Abstract : Plastic and microplastic pollution has caused a great deal of ecological problems because of its persistence and potential adverse effects on human health. The degradation of plastics through biological processes is of great significance for ecological health, therefore, the feasibility of plastic degradation by microorganisms has attracted a lot of attention. This study comprises a preliminary discussion on the biodegradation mechanism and the advantages and roles of different bacterial enzymes, such as PET hydrolase and PCL-cutinase, in the degradation of different polymers, such as PET and PCL, respectively. With a particular focus on their modes of action and potential enzymatic mechanisms, this review sums up studies on the biological degradation of plastics and microplastics related to mechanisms and influencing factors, along with their enzymes in enhancing the degradation of synthetic plastics in the process. In addition, biodegradation of plastic is also affected by plastic additives and plasticizers. Plasticizers and additives in the composition of plastics can cause harmful impacts. To further improve the degradation efficiency of polymers, various pretreatments to improve the efficiency of biodegradation, which can cause a significant reduction in toxic plastic pollution, were also preliminarily discussed here. The existing research and data show a large number of microorganisms involved in plastic biodegradation, though their specific mechanisms have not been thoroughly explored yet. Therefore, there is a significant potential for employing various bacterial strains for efficient degradation of plastics to improve human health and safety.
ESTHER : Cai_2023_Microorganisms_11_
PubMedSearch : Cai_2023_Microorganisms_11_
PubMedID: 37512834

Title : Selection and Identification of an ssDNA Aptamer for Fibroblast Activation Protein - Zhang_2023_Molecules_28_
Author(s) : Zhang X , Yang G , Zhao Y , Dai X , Liu W , Qu F , Huang Y
Ref : Molecules , 28 : , 2023
Abstract : As a type II transmembrane serine protease, fibroblast activation protein (FAP) is specifically expressed on the surface of fibroblasts associated with a variety of epithelial-derived malignancies such as pancreatic cancer, breast cancer, and colon cancer. It participates in the processes of tumorigenesis, progression, and immunosuppression. FAP constitutes an important target for tumor treatment; however, the current studies on FAP are mainly related to structural characteristics, enzymatic properties, and biological functions, and aptamers of FAP have not been investigated. In this work, by using recombinant human FAP as the target, five candidate aptamers, which are AptFAP-A1, AptFAP-A2, AptFAP-A3, AptFAP-A4, and AptFAP-A5, were selected by capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX), and their secondary structures were predicted to be mainly stem-loop. Moreover, the CE-laser-induced fluorescence (LIF) method was used to determine the equilibrium dissociation constant K(D) values between the FAP protein and candidate aptamers, and the K(D) value was in the low molar range. Finally, Cy5-labeled aptamers were co-incubated with human pancreatic cancer-associated fibroblasts highly expressing FAP protein, and confocal microscopy imaging showed that aptamer AptFAP-A4 had the highest affinities with the cells. The FAP aptamers screened in this study provide a promising direction for the development of rapid tumor diagnosis and targeted therapy.
ESTHER : Zhang_2023_Molecules_28_
PubMedSearch : Zhang_2023_Molecules_28_
PubMedID: 36838669

Title : Dinotefuran induces oxidative stress and autophagy on Bombyx mori silk gland: Toxic effects and implications for nontarget organisms - Huang_2023_Environ.Pollut_336_122470
Author(s) : Huang Y , Zou S , Zhan P , Hao Z , Lu Q , Jing W , Li Y , Xu Y , Wang H
Ref : Environ Pollut , 336 :122470 , 2023
Abstract : Dinotefuran, a third-generation neonicotinoid insecticide, is widely utilized in agriculture for pest control; however, its environmental consequences and risks to non-target organisms remain largely unknown. Bombyx mori is an economically important insect and a good toxic detector for environmental assessments. In this study, ultrastructure analysis showed that dinotefuran exposure caused an increase in autophagic vesicles in the silk gland. Dinotefuran exposure triggered elevated levels of oxidative stress in silk glands. Reactive oxygen species, oxidized glutathione disulfide, glutathione peroxidase, the activities of UDP glucuronosyl-transferase and carboxylesterase were induced in the middle silk gland, while malondialdehyde, reactive oxygen species, superoxide dismutase oxidized glutathione disulfide were increased in the posterior silk gland. Global transcription patterns revealed the physiological responses were induced by dinotefuran. Dinotefuran exposure substantially induced the expression levels of many genes involved in the mTOR and PI3K - Akt signaling pathways in the middle silk gland, whereas many differentially expressed genes involved in fatty acid and pyrimidine metabolism were found in the posterior silk gland. Additionally, functional, ultrastructural, and transcriptomic analysis indicate that dinotefuran exposure induced an increase of autophagy in the silk gland. This study illuminates the toxicity effects of dinotefuran exposure on silkworms and provides new insights into the underlying molecular toxicity mechanisms of dinotefuran to nontarget organisms.
ESTHER : Huang_2023_Environ.Pollut_336_122470
PubMedSearch : Huang_2023_Environ.Pollut_336_122470
PubMedID: 37657723

Title : Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice - Sun_2023_Int.J.Biol.Macromol__125517
Author(s) : Sun W , Zhu J , Qin G , Huang Y , Cheng S , Chen Z , Zhang Y , Shu Y , Zeng X , Guo R
Ref : Int J Biol Macromol , :125517 , 2023
Abstract : Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreasing the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.
ESTHER : Sun_2023_Int.J.Biol.Macromol__125517
PubMedSearch : Sun_2023_Int.J.Biol.Macromol__125517
PubMedID: 37353132

Title : Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease - Li_2023_EBioMedicine_90_104543
Author(s) : Li Z , Zhang B , Liu Q , Tao Z , Ding L , Guo B , Zhang E , Zhang H , Meng Z , Guo S , Chen Y , Peng J , Li J , Wang C , Huang Y , Xu H , Wu Y
Ref : EBioMedicine , 90 :104543 , 2023
Abstract : BACKGROUND: Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. METHODS: Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. FINDINGS: No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR(1) = 0.60 [95% CI 0.50-0.72], p(1) = 2.07 x 10(-8); OR(2) = 0.57 [95% CI 0.39-0.82], p(2) = 3.00 x 10(-3)). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 x 10(-3)) and strong colocalisation association (PP.H(4) = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. INTERPRETATION: Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. FUNDING: Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).
ESTHER : Li_2023_EBioMedicine_90_104543
PubMedSearch : Li_2023_EBioMedicine_90_104543
PubMedID: 37002989

Title : The effects of carvacrol on development and gene expression profiles in Spodoptera frugiperda - Liu_2023_Pestic.Biochem.Physiol_195_105539
Author(s) : Liu J , Lin Y , Huang Y , Liu L , Cai X , Lin J , Shu B
Ref : Pestic Biochem Physiol , 195 :105539 , 2023
Abstract : The fall armyworm, Spodoptera frugiperda, is a highly polyphagous agricultural pest that is widely distributed around the world and causes severe crop yield loss. Carvacrol showed adverse effects on many pests, such as larval death and growth inhibition. While the effects of carvacrol on S. frugiperda larvae are not yet known. In this study, the effects of carvacrol on S. frugiperda, including larval growth inhibition and mortality induction, were observed. The detoxification and digestive enzyme activities of larvae with 1.0 and 2.0 g/kg carvacrol treatments were analyzed. Carvacrol boosted the enzyme activities of carboxylesterase (CarE) and glutathione S-transferase (GST) while decreasing the activities of alpha-amylase (AMS), lipase (LIP), and trypsin. A total of 3422 differentially expressed genes were identified in the larvae treated with 2.0 g/kg carvacrol, of which the DEGs involved in xenobiotic detoxification, food digestion, and insecticidal targets were further examined. These results suggest that carvacrol could regulate growth and development by affecting the process of food digestion, and exert its toxicity on the larvae through interaction with a variety of insecticidal targets. While the altered expressions of detoxification enzymes might be related to the detoxification and metabolism of carvacrol. Our findings offer a theoretical foundation for the use of carvacrol for S. frugiperda control in the field.
ESTHER : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedSearch : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedID: 37666589

Title : Environmental Adaptability and Organic Pollutant Degradation Capacity of a Novel Rhodococcus Species Derived from Soil in the Uninhabited Area of the Qinghai-Tibet Plateau - Huang_2022_Microorganisms_10_
Author(s) : Huang J , Ai G , Liu N , Huang Y
Ref : Microorganisms , 10 : , 2022
Abstract : The Qinghai-Tibet Plateau (QTP) is known for extreme natural environments and, surprisingly, has been reported to contain widespread organic pollutants. Rhodococcus can survive a variety of extreme environments and degrade many organic contaminants. Here, we isolated a Rhodococcus strain (FXJ9.536 = CGMCC 4.7853) from a soil sample collected in the QTP. Phylogenomic analysis indicated that the strain represents a novel Rhodococcus species, for which the name Rhodococcus tibetensis sp. nov. is proposed. Interestingly, R. tibetensis FXJ9.536 maintained a fast growth rate and degraded 6.2% of p-nitrophenol (4-NP) and 50.0% of malathion even at 10 degreesC. It could degrade 53.6% of 4-NP and 99.9% of malathion at a moderate temperature. The genome of R. tibetensis FXJ9.536 contains 4-hydroxyphenylacetate 3-monoxygenase and carboxylesterase genes, which are likely associated with the degradation of 4-NP and malathion, respectively. Further genomic analysis revealed that the strain might employ multiple strategies to adapt to the harsh QTP environment. These include synthesizing cold shock proteins, compatible solutes, secondary metabolites, and storage compounds, utilizing inorganic compounds as energy and nutrition sources, as well as degrading a range of organic pollutants. Overall, our study reveals the potential of a QTP-derived new actinobacterial species for environmental adaptation and remediation in cold regions.
ESTHER : Huang_2022_Microorganisms_10_
PubMedSearch : Huang_2022_Microorganisms_10_
PubMedID: 36296211

Title : Familial chylomicronemia syndrome caused by compound heterozygous mutation of lipoprotein lipase gene: a case report and review of literature - Huang_2022_Clin.Chim.Acta__
Author(s) : Huang Y , Qin Y , Liao L , Lin F
Ref : Clinica Chimica Acta , : , 2022
Abstract : Familial chylomicronemia syndrome (FCS) caused by mutations of lipoprotein lipase (LPL) gene and other triglyceride-rich lipoprotein genes related with catabolism is an autosomal recessive rare disease. Herein, we report an infant with FCS and review the relevant literature. The proband is a male infant with FCS for which the whole-exome sequencing (WES), sanger sequencing and copy number variation (CNV) based on WES were performed. Compound heterozygous mutations (LPL gene c.1322+1G>C and loss in exons 8 to 10) were found in the LPL gene of the proband, the c.1322+1G>C mutation was inherited from his father with the heterozygous mutation, and the deletion of exons 8-10 due to CNVs was inherited from his mother. Carriers of heterozygous mutation or heterozygous deletion in LPL may have normal plasma lipid or develop FCS. Plasma lipid management of FCS in infancy should focus on the diet and adopt an individualized management.
ESTHER : Huang_2022_Clin.Chim.Acta__
PubMedSearch : Huang_2022_Clin.Chim.Acta__
PubMedID: 36252692
Gene_locus related to this paper: human-LPL

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 : Monoacylglycerol Lipase (MAGL) Inhibition Impedes the Osteosarcoma Progression by Regulating Epithelial Mesenchymal Transition - Gong_2022_Tohoku.J.Exp.Med_256_19
Author(s) : Gong X , Zheng X , Huang Y , Song W , Chen G , Chen T
Ref : Tohoku J Exp Med , 256 :19 , 2022
Abstract : Osteosarcoma is a primary malignancy of mesenchymal origin, and its metastasis and multidrug resistance remain major problems affecting the therapeutic effect. This study aimed to evaluate the efficacy and underlying mechanism of monoacylglycerol lipase (MAGL) on osteosarcoma progression. MAGL expression was downregulated by shMAGL or JZL184 (an MAGL inhibitor) and upregulated through plasmid. RT-PCR and Western blot were utilized to determine the expression of target molecules. CCK-8 assay, transwell assay and ROS assay were performed to investigate the inhibitory effect of MAGL on the growth and metastasis of osteosarcoma cells. The role of JZL184 on tumor growth was examined in cisplatin-resistant MG-63 (MG-63/R) xenograft model. MAGL was highly expressed in osteosarcoma cells and tissues. MAGL knockdown significantly impeded the proliferation, clone formation, invasion and migration of MG-63 cells, whereas opposite result was observed in 143B cells with MAGL overexpression. Likewise, an MAGL inhibitor JZL184 displayed reduced viability, clone formation, invasion and migration of osteosarcoma cells. Western blot of the epithelial mesenchymal transition (EMT)-related proteins indicated that MAGL knockdown or JZL184 could upregulated E-cadherin expression and downregulated vimentin expression. In vitro and in vivo experiments indicated that JZL184 re-sensitized MG-63/R cells to cisplatin. In summary, MAGL regulated osteosarcoma by modulating EMT, and JZL184 might be a promising agent for osteosarcoma patients who are resistant to cisplatin.
ESTHER : Gong_2022_Tohoku.J.Exp.Med_256_19
PubMedSearch : Gong_2022_Tohoku.J.Exp.Med_256_19
PubMedID: 35067491

Title : ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms - Mineur_2022_Mol.Psychiatry_27_4918
Author(s) : Mineur YS , Mose TN , Maibom KL , Pittenger ST , Soares AR , Wu H , Taylor SR , Huang Y , Picciotto MR
Ref : Mol Psychiatry , 27 :4918 , 2022
Abstract : The balance between excitatory and inhibitory (E/I) signaling is important for maintaining homeostatic function in the brain. Indeed, dysregulation of inhibitory GABA interneurons in the amygdala has been implicated in human mood disorders. We hypothesized that acetylcholine (ACh) signaling in the basolateral amygdala (BLA) might alter E/I balance resulting in changes in stress-sensitive behaviors. We therefore measured ACh release as well as activity of calmodulin-dependent protein kinase II (CAMKII)-, parvalbumin (PV)-, somatostatin (SOM)- and vasoactive intestinal protein (VIP)-expressing neurons in the BLA of awake, behaving male mice. ACh levels and activity of both excitatory and inhibitory BLA neurons increased when animals were actively coping, and decreased during passive coping, in the light-dark box, tail suspension and social defeat. Changes in neuronal activity preceded behavioral state transitions, suggesting that BLA activity may drive the shift in coping strategy. In contrast to exposure to escapable stressors, prolonging ACh signaling with a cholinesterase antagonist changed the balance of activity among BLA cell types, significantly increasing activity of VIP neurons and decreasing activity of SOM cells, with little effect on CaMKII or PV neurons. Knockdown of alpha7 or beta2-containing nAChR subtypes in PV and SOM, but not CaMKII or VIP, BLA neurons altered behavioral responses to stressors, suggesting that ACh signaling through nAChRs on GABA neuron subtypes contributes to stress-induced changes in behavior. These studies show that ACh modulates the GABAergic signaling network in the BLA, shifting the balance between SOM, PV, VIP and CaMKII neurons, which are normally activated coordinately during active coping in response to stress. Thus, prolonging ACh signaling, as occurs in response to chronic stress, may contribute to maladaptive behaviors by shifting the balance of inhibitory signaling in the BLA.
ESTHER : Mineur_2022_Mol.Psychiatry_27_4918
PubMedSearch : Mineur_2022_Mol.Psychiatry_27_4918
PubMedID: 36050437

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer - Ran_2022_BMC.Cancer_22_93
Author(s) : Ran H , Ma J , Cai L , Zhou H , Yuan Z , Chen Y , Chang W , Huang Y , Xiao Y
Ref : BMC Cancer , 22 :93 , 2022
Abstract : BACKGROUND: Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. METHODS: A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. RESULTS: The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67-0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56-0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54-0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66-0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59-0.96, p < 0.02). CONCLUSION: Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding.
ESTHER : Ran_2022_BMC.Cancer_22_93
PubMedSearch : Ran_2022_BMC.Cancer_22_93
PubMedID: 35062903

Title : Antibacterial Efficacy and Mechanisms of Curcumin-Based Photodynamic Treatment against Staphylococcus aureus and Its Application in Juices - Yuan_2022_Molecules_27_
Author(s) : Yuan Y , Liu Q , Huang Y , Qi M , Yan H , Li W , Zhuang H
Ref : Molecules , 27 : , 2022
Abstract : Antimicrobial Photodynamic Treatment (aPDT) is a non-thermal sterilization technology, which can inactivate common foodborne pathogens. In the present study, photodynamic inactivation on Staphylococcus aureus (S. aureus) with different concentrations of curcumin and light dose was evaluated and the mechanisms were also investigated. The results showed that curcumin-based aPDT could inactivate S. aureus cells by 6.9 log CFU/mL in phosphate buffered saline (PBS). Moreover, the modified Gompertz model presented a good fit at the inactivation data of S. aureus. Photodynamic treatment caused cell membrane damage as revealed by analyzing scanning electron microscopy (SEM) images. Leakage of intracellular constituents further indicated that cell membrane permeability was changed. Flow cytometry with double staining demonstrated that cell membrane integrity and the activity of nonspecific esterase were destroyed. Compared with the control group, intracellular reactive oxygen species (ROS) levels caused by photodynamic treatment significantly increased. Furthermore, curcumin-based aPDT reduced S. aureus by 5 log CFU/mL in juices. The color of the juices was also tested using a Chromatic meter, and it was found that b* values were the most markedly influenced by photodynamic treatment. Overall, curcumin-based aPDT had strong antibacterial activity against S. aureus. This approach has the potential to remove foodborne pathogens from liquid food.
ESTHER : Yuan_2022_Molecules_27_
PubMedSearch : Yuan_2022_Molecules_27_
PubMedID: 36296729

Title : Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder - Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
Author(s) : Huang S , Huang Y , Lin W , Wang L , Yang Y , Li P , Xiao L , Chen Y , Chu Q , Yuan X
Ref : Oxid Med Cell Longev , 2022 :2586305 , 2022
Abstract : Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and gamma-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.
ESTHER : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedSearch : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedID: 35620578

Title : Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial - Xu_2022_Diabetes.Obes.Metab__
Author(s) : Xu J , Ling H , Geng J , Huang Y , Xie Y , Zheng H , Niu H , Zhang T , Yuan J , Xiao X
Ref : Diabetes Obes Metab , : , 2022
Abstract : AIMS: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl-peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2DM patients with glycated hemoglobin A1c (HbA1c) levels ranging from 7.0-9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108+metformin and placebo+metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square (LS) mean (standard error [SE]) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than that in the placebo group (-0.07% [0.11%]) (P-value <0.001), with a treatment difference of -0.63% (95% confidence interval [CI]: -0.87, -0.39) on full analysis set. A higher proportion of patients achieved an HbA1c >=6.5% (19.7% vs. 8.5%) and HbA1c >=7.0% (50.0% vs. 21.1%) at week 24 in the DBPR108+metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose (2-h PPG) without causing weight gain. The overall frequency of adverse events (AEs) was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycemic control, was superior to metformin monotherapy (placebo), and was safe and well-tolerated in T2DM patients that is inadequately controlled with metformin. This article is protected by copyright. All rights reserved.
ESTHER : Xu_2022_Diabetes.Obes.Metab__
PubMedSearch : Xu_2022_Diabetes.Obes.Metab__
PubMedID: 35791646

Title : Acute thiamethoxam exposure induces hepatotoxicity and neurotoxicity in juvenile Chinese mitten crab (Eriocheir sinensis) - Yang_2022_Ecotoxicol.Environ.Saf_249_114399
Author(s) : Yang Y , Yu Q , Zhang C , Wang X , He L , Huang Y , Li E , Qin J , Chen L
Ref : Ecotoxicology & Environmental Safety , 249 :114399 , 2022
Abstract : The similar nervous system structure between crustaceans and insects and the high-water solubility of thiamethoxam can lead to the more severe toxicity of thiamethoxam to crustaceans. However, the effects of thiamethoxam on crustaceans are unclear. Therefore, a 96-h acute toxicity test was performed to explore the hepatotoxicity and neurotoxicity effects of thiamethoxam on Chinese mitten crab (Eriocheir sinensis) at concentrations 0 microg/L, 150 microg/L and 300 microg/L. The antioxidant and detoxification systems (including phases I and II) were significantly activated after exposure of juvenile crabs to thiamethoxam for 24sh in 300 microg/L group, whereas the toxic activation effect in 150 microg/L group was delayed. Moreover, a similar pattern was observed for the transcription levels of immune-related genes. Further analysis of inflammatory signaling pathway-related genes showed that thiamethoxam exposure with 300 microg/L for 24sh may induce a pro-inflammatory response through the NF-kappaB pathway. In contrast, the gene expression levels in 150 microg/L group were significantly upregulated compared with 0 microg/L group after 96sh. In addition, although the acute exposure of 150 microg/L thiamethoxam did not seem to induce significant neurotoxicity, the acetylcholinesterase activity was significantly decreased in 300 microg/L group after thiamethoxam exposure for 96sh. Correspondingly, thiamethoxam exposure with 300 microg/L for 24sh resulted in significantly downregulated transcriptional levels of synaptic transmission-related genes (e.g. dopamine-, gamma-aminobutyric acid- and serotonin-related receptors). Therefore, thiamethoxam may be harmful and cause potential toxic threats such as neurotoxicity and metabolic damage to crustaceans.
ESTHER : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedSearch : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedID: 36508784

Title : Narciclasine inhibits phospholipase A2 and regulates phospholipid metabolism to ameliorate psoriasis-like dermatitis - Kong_2022_Front.Immunol_13_1094375
Author(s) : Kong Y , Jiang J , Huang Y , Liu X , Jin Z , Li L , Wei F , Yin J , Zhang Y , Tong Q , Chen H
Ref : Front Immunol , 13 :1094375 , 2022
Abstract : INTRODUCTION: Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels. METHODS: The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action. RESULTS: Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions. DISCUSSION: Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug.
ESTHER : Kong_2022_Front.Immunol_13_1094375
PubMedSearch : Kong_2022_Front.Immunol_13_1094375
PubMedID: 36700214

Title : Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property - Liu_2022_Bioorg.Chem_126_105875
Author(s) : Liu W , Wu L , Li D , Huang Y , Liu M , Tian C , Liu X , Jiang X , Hu X , Gao X , Xu Z , Lu H , Zhao Q
Ref : Bioorg Chem , 126 :105875 , 2022
Abstract : Tacrine was the first approved drug by the FDA for the treatment of Alzheimer's disease (AD) but was withdrawn from the market due to its dose-dependent hepatotoxicity. Herein, we describe our efforts toward the discovery of a novel series of tacrine derivatives for cancer therapeutics. Intensive structural modifications of tacrine led to the identification of N-(4-{9-[(3S)-3-aminopyrrolidin-1-yl]-5,6,7,8-tetrahydroacridin-2-yl}pyridin-2-yl)cyclopropanecarboxamide hydrochloride ((S)-45, ZLWT-37) as a potent antiproliferative agent (GI(50) = 0.029 microM for HCT116). In addition, ZLWT-37 exhibited lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) compared to tacrine. The in vitro studies demonstrated that ZLWT-37 could significantly induce apoptosis and arrest the cell cycle in the G2/M phase in HCT116 cells. The in vivo studies revealed that compound ZLWT-37 showed excellent antitumor efficacy in HCT116 xenograft tumor model and favorable pharmacokinetics profiles (F% = 28.70%) as well as low toxicity in the acute toxicity test with a median lethal dose (LD(50)) of 380.3 mg/kg. Encouragingly, ZLWT-37 had no obvious hepatotoxicity, nephrotoxicity, and hematologic toxicity. Kinase assay suggested that ZLWT-37 possessed potent cyclin-dependent kinase 9 (CDK9) inhibitory activity (IC(50) = 0.002 microM) and good selectivity over CDK2 (IC(50) = 0.054 microM). Collectively, these findings indicate that compound ZLWT-37 is a promising anti-cancer agent that deserves further preclinical evaluation.
ESTHER : Liu_2022_Bioorg.Chem_126_105875
PubMedSearch : Liu_2022_Bioorg.Chem_126_105875
PubMedID: 35623141

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

Title : Development and structure-activity relationship of tacrine derivatives as highly potent CDK2\/9 inhibitors for the treatment of cancer - Wu_2022_Eur.J.Med.Chem_242_114701
Author(s) : Wu L , Liu W , Huang Y , Zhu C , Ma Q , Wu Q , Tian L , Feng X , Liu M , Wang N , Xu X , Liu X , Xu C , Qiu J , Xu Z , Zhao Q
Ref : Eur Journal of Medicinal Chemistry , 242 :114701 , 2022
Abstract : CDK2/9 are members of the CDKs family, which play key roles in the occurrence and development of many cancers by regulating cell cycle and transcriptional prolongation, respectively. To further optimize and discuss the structure-activity relationships (SARs), a series of tacrine-based compounds were designed and synthesized from the compound ZLWT-37, which was studied by our group previously but no detailed SARs study was conducted on CDK2/9. Among this series, compounds ZLMT-12 (35) exhibited the most potent antiproliferative activity (GI(50) = 0.006 microM for HCT116) and superior CDK2/9 inhibitory properties (CDK2: IC(50) = 0.011 microM, CDK9: IC(50) = 0.002 microM). Meanwhile, ZLMT-12 showed a weak inhibitory effect on acetylcholinesterase (AChE, IC(50) = 19.023 microM) and butyrylcholinesterase (BuChE, IC(50) = 2.768 microM). In addition, ZLMT-12 can suppress colony formation and migration in HCT116 cells, as well as induce the apoptosis and arrest the cell cycle in the S phase and G2/M phase. In vivo investigations revealed that ZLMT-12 inhibits tumor growth in the HCT116 xenograft tumor model at a low dose of 10 mg/kg without causing hepatotoxicity. The acute toxicity test showed low toxicity with a median lethal dosage (LD(50)) of 104.417 mg/kg. These findings showed that ZLMT-12 might be used as a drug candidate by targeting CDK2/9.
ESTHER : Wu_2022_Eur.J.Med.Chem_242_114701
PubMedSearch : Wu_2022_Eur.J.Med.Chem_242_114701
PubMedID: 36054949

Title : Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial - Zhu_2021_Trials_22_688
Author(s) : Zhu H , Cong L , Chen Y , Chen S , Chen L , Huang Z , Zhou J , Xiao J , Huang Y , Su D
Ref : Trials , 22 :688 , 2021
Abstract : BACKGROUND: Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer's disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery. METHODS: A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation. DISCUSSION: This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs. TRIAL REGISTRATION: NCT04423276 . Registered on 14 June 2020.
ESTHER : Zhu_2021_Trials_22_688
PubMedSearch : Zhu_2021_Trials_22_688
PubMedID: 34627332

Title : Insights into the microbial degradation and catalytic mechanisms of chlorpyrifos - Huang_2021_Environ.Res_194_110660
Author(s) : Huang Y , Zhang W , Pang S , Chen J , Bhatt P , Mishra S , Chen S
Ref : Environ Research , 194 :110660 , 2021
Abstract : Chlorpyrifos is extensively used worldwide as an insecticide to control various insect pests. Long-term and irregular applications of chlorpyrifos have resulted in large-scale soil, groundwater, sediment, and air pollution. Numerous studies have shown that chlorpyrifos and its major intermediate metabolite 3,5,6-trichloropyridinol (TCP) accumulate in non-target organisms through biomagnification and have a strong toxic effect on non-target organisms, including human beings. Bioremediation based on microbial metabolism is considered an eco-friendly and efficient strategy to remove chlorpyrifos residues. To date, a variety of bacterial and fungal species have been isolated and characterized for the biodegradation of chlorpyrifos and TCP. The metabolites and degradation pathways of chlorpyrifos have been investigated. In addition, the chlorpyrifos-degrading enzymes and functional genes in microbes have been reported. Hydrolases can catalyze the first step in ester-bond hydrolysis, and this initial regulatory metabolic reaction plays a key role in the degradation of chlorpyrifos. Previous studies have shown that the active site of hydrolase contains serine residues, which can initiate a catalytic reaction by nucleophilic attack on the P-atom of chlorpyrifos. However, few reviews have focused on the microbial degradation and catalytic mechanisms of chlorpyrifos. Therefore, this review discusses the deep understanding of chlorpyrifos degradation mechanisms with microbial strains, metabolic pathways, catalytic mechanisms, and their genetic basis in bioremediation.
ESTHER : Huang_2021_Environ.Res_194_110660
PubMedSearch : Huang_2021_Environ.Res_194_110660
PubMedID: 33387540

Title : Evaluation of Lipoprotein-Associated Phospholipase A2 as a Prognostic Biomarker in Chronic Kidney Disease - Qu_2021_Clin.Lab_67_
Author(s) : Qu H , Zhang G , Pan J , Huang Y , Lv W
Ref : Clin Lab , 67 : , 2021
Abstract : BACKGROUND: The leading cause of death in patients with chronic kidney disease (CKD) is atherosclerosis (AS). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a biomarker of atherosclerotic plaque stability. The aim of our study was to analyze the association of Lp-PLA2 with CKD complicated with carotid atherosclerotic stenosis (CAS). METHODS: Serum specimens were collected from 77 CKD patients and 39 healthy controls. Laboratory examination results including glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Lp-PLA2 were measured. Receiver operating characteristic (ROC) was drawn and the area under the curve (AUC) was calculated. RESULTS: Multivariate logistic regression analysis showed that age, gender, glucose, and Lp-PLA2 were considered as risks for CKD-CAS with odds ratios (OR) of 1.111 (95% CI: 1.055, 1.170), 5.123 (95% CI: 1.482, 17.714), 1.679 (95% CI: 1.123, 2.512), and 1.023 (95% CI: 1.008, 1.037), respectively. The AUC for Lp-PLA2 and glucose was 0.618 (p = 0.014) and 0.592 (p = 0.057), respectively. The best diagnostic value was archived by Lp-PLA2 with the cutoff value of 201.06 ng/mL. CONCLUSIONS: Lp-PLA2 is a potential prognostic and diagnostic biomarker for CKD-CAS.
ESTHER : Qu_2021_Clin.Lab_67_
PubMedSearch : Qu_2021_Clin.Lab_67_
PubMedID: 34383418

Title : Long non-coding RNA ABHD11-AS1 promotes colorectal cancer progression and invasion through targeting the integrin subunit alpha 5\/focal adhesion kinase\/phosphoinositide 3 kinase\/Akt signaling pathway - Luo_2021_Aging.(Albany.NY)_13_20179
Author(s) : Luo J , Jiang Y , Wu L , Zhuo D , Zhang S , Jiang X , Sun Y , Huang Y
Ref : Aging (Albany NY) , 13 :20179 , 2021
Abstract : Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.
ESTHER : Luo_2021_Aging.(Albany.NY)_13_20179
PubMedSearch : Luo_2021_Aging.(Albany.NY)_13_20179
PubMedID: 34375304
Gene_locus related to this paper: human-ABHD11

Title : Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity - Huang_2021_J.Inflamm.Res_14_6735
Author(s) : Huang Y , Liu C , Song X , An M , Liu M , Yao L , Famurewa AC , Olatunji OJ
Ref : J Inflamm Res , 14 :6735 , 2021
Abstract : BACKGROUND: Cisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats. MATERIALS AND METHODS: CDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration. RESULTS: CCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-alpha, IL-6 and IL-1beta and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology. CONCLUSION: The findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.
ESTHER : Huang_2021_J.Inflamm.Res_14_6735
PubMedSearch : Huang_2021_J.Inflamm.Res_14_6735
PubMedID: 34916822

Title : The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression - Li_2021_Eur.J.Med.Chem_229_114045
Author(s) : Li X , Li J , Huang Y , Gong Q , Fu Y , Xu Y , Huang J , You H , Zhang D , Mao F , Zhu J , Wang H , Zhang H
Ref : Eur Journal of Medicinal Chemistry , 229 :114045 , 2021
Abstract : Depression is one of the most frequent comorbid psychiatric symptoms of Alzheimer's disease (AD), and no efficacious drugs have been approved specifically for this purpose thus far. Herein, we proposed a novel therapeutic strategy that merged the key pharmacophores of the antidepressant vilazodone (5-HT(1A) receptor partial agonist and serotonin transporter inhibitor) and the anti-AD drug donepezil (acetylcholinesterase inhibitor) together to develop a series of multi-target-directed ligands for potential therapy of the comorbidity of AD and depression. Accordingly, 55 vilazodone-donepezil chimeric derivatives were designed and synthesized, and their triple-target activities against acetylcholinesterase, 5-HT(1A) receptor, and serotonin transporter were systematically evaluated. Among them, compound 5 displayed strong triple-target bioactivities in vitro, low hERG potassium channel inhibition and acceptable brain distribution. Importantly, oral intake of 5 mg/kg of the compound 5 dihydrochloride significantly alleviated the depressive symptoms and ameliorated cognitive dysfunction in mouse models. In brief, these results highlight vilazodone-donepezil chimeras as a prospective therapeutic approach for the treatment of the comorbidity of AD and depression.
ESTHER : Li_2021_Eur.J.Med.Chem_229_114045
PubMedSearch : Li_2021_Eur.J.Med.Chem_229_114045
PubMedID: 34922191

Title : Isolation and Insecticidal Activity of Essential Oil from Artemisia lavandulaefolia DC. against Plutella xylostella - Huang_2021_Toxins.(Basel)_13_
Author(s) : Huang X , Huang Y , Yang C , Liu T , Liu X , Yuan H
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Many plants show significant biological activity against pests due to their unique chemical constituents. It is important to identify effective constituents for their development and utilization as botanical pesticides. Our previous study showed that Artemisia lavandulaefolia essential oil had biological activity against Plutella xylostella. Here, we isolated and identified the constituents of essential oil from A. lavandulaefolia by silica gel column chromatography. The main constituents identified were eucalyptol and caryophyllene oxide, and they were confirmed by gas chromatography-mass spectrometry (GC-MS). Eucalyptol and caryophyllene oxide showed strong contact toxicity against P. xylostella larvae after 24 h of application (Median lethal dose, LD(50) = 76.97 microL/mL and 20.71 mg/mL. Furthermore, the two active constituents against P. xylostella adults showed significant fumigant activity (Mmedian lethal concentration, LC(50) = 3.25 microL/L and 1.06 mg/L, respectively. Finally, we measured the detoxification enzymes and acetylcholinesterase of the larvae treated with active constituents. The eucalyptol-treated larvae displayed enhanced carboxylesterase (CarE) and glutathione-S-transferase (GST) activities in an in vivo experiment, but it was lower for acetylcholinesterase (AchE) activity. The activities of the CarE and GST significantly decreased when exposed to caryophyllene oxide. In general, the two active constituents, eucalyptol and caryophyllene oxide, showed high insecticidal activity, which demonstrates their potential to be used as natural insecticides.
ESTHER : Huang_2021_Toxins.(Basel)_13_
PubMedSearch : Huang_2021_Toxins.(Basel)_13_
PubMedID: 34941680

Title : Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 Axis via a Positive NRF2-HO-1 Feedback Loop - Li_2021_Front.Oncol_11_679816
Author(s) : Li R , Zeng X , Yang M , Xu X , Feng J , Bao L , Xue B , Wang X , Huang Y
Ref : Front Oncol , 11 :679816 , 2021
Abstract : Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1.
ESTHER : Li_2021_Front.Oncol_11_679816
PubMedSearch : Li_2021_Front.Oncol_11_679816
PubMedID: 34123848

Title : Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6\/STAT3 pathway - Yang_2021_J.Obstet.Gynaecol.Res__
Author(s) : Yang X , Zhu Y , Shi Q , Zhao X , Huang Y , Yao F , Zhang Y , Wang Z
Ref : J Obstet Gynaecol Res , : , 2021
Abstract : AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling.
ESTHER : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedSearch : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedID: 33969570

Title : Discovery of novel beta-carboline derivatives as selective AChE inhibitors with GSK-3beta inhibitory property for the treatment of Alzheimer's disease - Liu_2021_Eur.J.Med.Chem_229_114095
Author(s) : Liu W , Liu X , Gao Y , Wu L , Huang Y , Chen H , Li D , Zhou L , Wang N , Xu Z , Jiang X , Zhao Q
Ref : Eur Journal of Medicinal Chemistry , 229 :114095 , 2021
Abstract : The natural product harmine, a representative beta-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC(50) = 0.27 microM) and selective BChE inhibition (IC(50) = 20.82 microM), as well as acceptable glycogen synthase kinase-3 (GSK-3beta) inhibition (IC(50) = 6.78 microM). Molecular docking studies and molecular dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3beta. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3beta over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies.
ESTHER : Liu_2021_Eur.J.Med.Chem_229_114095
PubMedSearch : Liu_2021_Eur.J.Med.Chem_229_114095
PubMedID: 34995924

Title : Near-infrared fluorescent probe for evaluating the acetylcholinesterase effect in the aging process and dietary restriction via fluorescence imaging - He_2021_J.Mater.Chem.B__
Author(s) : He N , Yu L , Xu M , Huang Y , Wang X , Chen L , Yue S
Ref : J Mater Chem B , : , 2021
Abstract : Dietary restriction (DR), as a natural intervention, not only benefits the neuroendocrine system, but also has an antiaging action. Acetylcholinesterase (AChE) is one of the most important bioactive substances and plays a major part in choline changes in the aging process. Thus, we aim to evaluate the effect of DR on AChE in the brains of aging animals. In this study, we synthesize a NIR fluorescent probe BD-AChE for the real-time and in situ monitoring of AChE level changes in living cells and living mice, notably in brains. In situ visualization with BD-AChE verified a decrease in the AchE level in the brains of mice aging models. Evidently, the prepared probe has the excellent capability of measuring AChE variation in the brains of aging mice with DR via NIR fluorescence bioimaging, indicating that long-term DR can effectively affect AChE levels in the brain. The attenuation of AChE level in the brain of aging mice after DR could be helpful in infering the advantageous impact of DR on age-related neurodegenerative disease, as a better treatment alternative in the future.
ESTHER : He_2021_J.Mater.Chem.B__
PubMedSearch : He_2021_J.Mater.Chem.B__
PubMedID: 33666613

Title : Atomically dispersed Fe\/Bi dual active sites single-atom nanozymes for cascade catalysis and peroxymonosulfate activation to degrade dyes - Chen_2021_J.Hazard.Mater_422_126929
Author(s) : Chen Q , Liu Y , Lu Y , Hou Y , Zhang X , Shi W , Huang Y
Ref : J Hazard Mater , 422 :126929 , 2021
Abstract : Constructing single-atom nanozymes (SAzymes) with densely exposed and dispersed double metal-N(x) catalytic sites for pollution remediation remains rare and challenging. Herein, we report a novel Fe-Bi bimetallic MOF-derived carbon supported Fe-N(4) and Bi-N(4) dual-site FeBi-NC SAzyme for cascade catalysis and peroxymonosulfate activation to degrade dye pollutants, which is synthesized from the Fe-doped Bi-MOF as a precursor. The formation of both Fe-N(4) and Bi-N(4) sites is demonstrated by XANES and EXAFS. The FeBi-NC SAzyme has high single atoms loadings of Fe (2.61 wt%) and Bi (8.01 wt%), and displays 5.9- and 9.8-fold oxidase mimicking activity enhancement relative to the Fe-NC and Bi-NC SAzymes, respectively. When integrated acetylcholinesterase (AChE) and FeBi-NC SAzyme, a cascade enzyme-nanozyme system is developed for selective and sensitive screening of AChE activity with a low detection limit of 1 x 10(-4) mU mL(-1). Both Fe-N(4) and Bi-N(4) in FeBi-NC display a strong binding energy and electron donating capability to promote peroxymonosulfate activation to generate highly active intermediates for rhodamine B degradation. 100% rhodamine B removal occurs within 5 min via FeBi-NC mediated activation of peroxymonosulfate. The DFT calculations reveal that high activity of FeBi-NC is due to the isolated Fe-N(4) and Bi-N(4) sites and their synergy.
ESTHER : Chen_2021_J.Hazard.Mater_422_126929
PubMedSearch : Chen_2021_J.Hazard.Mater_422_126929
PubMedID: 34523499

Title : Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia - Yang_2021_Bioorg.Med.Chem_37_116109
Author(s) : Yang GX , Sun JM , Zheng LL , Zhang L , Li J , Gan HX , Huang Y , Huang J , Diao XX , Tang Y , Wang R , Ma L
Ref : Bioorganic & Medicinal Chemistry , 37 :116109 , 2021
Abstract : A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
ESTHER : Yang_2021_Bioorg.Med.Chem_37_116109
PubMedSearch : Yang_2021_Bioorg.Med.Chem_37_116109
PubMedID: 33780813

Title : Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem\/progenitor cell compartment - Shi_2021_Animal.Model.Exp.Med_4_418
Author(s) : Shi G , Li X , Li K , Huang Y , Lei X , Bai L , Qin C
Ref : Animal Model Exp Med , 4 :418 , 2021
Abstract : BACKGROUND: Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis through self-renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low-density lipoprotein, chylomicrons, and triglyceride-rich lipoproteins. METHODS: The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence-activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL(+/-) HSC microenvironment were detected by transplantation assays using red fluorescent protein (RFP) transgenic mice. RESULTS: To explore the function of LPL in HSC regulation, heterozygous LPL-knockout mice (LPL(+/-)) were established and analyzed by FACS. LPL(+/-) mice displayed decreased hematopoietic stem/progenitor cell compartments. In vitro single-cell clonogenic assays and cell-cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57(KIP2) and p21(WAF1/CIP1) in LPL(+/-) mice was upregulated. CONCLUSIONS: LPL(+/-) mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.
ESTHER : Shi_2021_Animal.Model.Exp.Med_4_418
PubMedSearch : Shi_2021_Animal.Model.Exp.Med_4_418
PubMedID: 34977493

Title : Fast analysis of alkaloids from different parts of Mahonia bealei (Fort.) Carr studied for their anti-Alzheimer's activity using supercritical fluid chromatography - Huang_2021_J.Sep.Sci__
Author(s) : Huang Y , Wang T , Jiang Z
Ref : J Sep Sci , : , 2021
Abstract : In this study, a rapid and highly efficient method was developed for the separation of eight isoquinoline alkaloids using supercritical fluid chromatography. The separation conditions were carefully optimized including stationary phases, additives, backpressure and temperature. Compared to HPLC, the use of supercritical fluid chromatography could provide a 13 times faster separation. Subsequently, the method was validated and applied for the determination of eight alkaloids from different parts of Mahonia bealei (Fort.) Carr. (stem, root, leaf and seed). The results indicated a good repeatability with relative standard deviations for overall precisions lower than 3.2%. The limit of detection were between 0.4 microg/mL and 2.3 microg/mL while limit of quantitation ranged from 1.5 microg/mL to 7.5 microg/mL. Recovery ranged from 95.7 % to 102.5% indicating a validity of recovery. The content of total eight alkaloids was the highest in stem (66.0 microg/g) and root (65.1 microg/g) compared to leaf or seed. Moreover, anti-acetylcholinesterase activity for those extracts was evaluated by Ellman's colorimetric assay. As a result, the acetylcholinesterase inhibitory activity of the extracted samples was in the following decreasing order: stem> root > leaf or seed. In conclusion, the results indicated that supercritical fluid chromatography could be a useful tool for quality control of Mahonia bealei (Fort.) Carr. containing alkaloids as active compounds. This article is protected by copyright. All rights reserved.
ESTHER : Huang_2021_J.Sep.Sci__
PubMedSearch : Huang_2021_J.Sep.Sci__
PubMedID: 33650266

Title : Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias - A narrative review - Huang_2020_Pharmacol.Res.Perspect_8_e00622
Author(s) : Huang Y , Alsabbagh MW
Ref : Pharmacol Res Perspect , 8 :e00622 , 2020
Abstract : Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds "known-risk" category, a list where medications have a documented risk for acquired long-QT syndrome (ALQTS) and torsades de pointes (TdP) - a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point-of-view, aside from some case-reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real-world practice; this may have important implications with regards to changes in AChEI prescribing patterns.
ESTHER : Huang_2020_Pharmacol.Res.Perspect_8_e00622
PubMedSearch : Huang_2020_Pharmacol.Res.Perspect_8_e00622
PubMedID: 32691984

Title : Toxicological effects of nano- and micro-polystyrene plastics on red tilapia: Are larger plastic particles more harmless? - Ding_2020_J.Hazard.Mater_396_122693
Author(s) : Ding J , Huang Y , Liu S , Zhang S , Zou H , Wang Z , Zhu W , Geng J
Ref : J Hazard Mater , 396 :122693 , 2020
Abstract : Nanoplastics (NPs) and microplastics (MPs) are a heterogeneous class of pollutants with diverse sizes in aquatic environments. To evaluate the hazardous effects of N/MPs with different sizes, the accumulation, oxidative stress, cytochrome P450 (CYP) enzymes, neurotoxicity, and metabolomics changes were investigated in the red tilapia exposed to three sizes of polystyrene (PS) N/MPs (0.3, 5, and 70-90mum). After 14-d exposures, the largest particles (70-90mum) showed the highest accumulation levels in most cases. Exposures to PS-MPs (5 and 70-90mum) caused a more severe oxidative stress in red tilapia than PS-NPs. The activity of CYP3A-related enzyme was obviously inhibited by PS-NPs, whereas the CYP enzymes in the liver may not be sensitive to MP exposures. In the brain, only 5mumPS-MPs significantly inhibited the acetylcholinesterase activity. After exposures, the treatments with 0.3, 5, and 70-90mum N/MPs resulted in 31, 40, and 23 significantly differentially expressed metabolites, respectively, in which the pathway of tyrosine metabolism was significantly affected by all the three PS-N/MP exposures. Overall, the PS particles within the mum size posed more severe stress to red tilapia. Our results suggest that the toxicity of N/MPs may not show a simply monotonic negative correlation with their sizes.
ESTHER : Ding_2020_J.Hazard.Mater_396_122693
PubMedSearch : Ding_2020_J.Hazard.Mater_396_122693
PubMedID: 32353735

Title : Carbofuran toxicity and its microbial degradation in contaminated environments - Mishra_2020_Chemosphere_259_127419
Author(s) : Mishra S , Zhang W , Lin Z , Pang S , Huang Y , Bhatt P , Chen S
Ref : Chemosphere , 259 :127419 , 2020
Abstract : Carbofuran is one of the most toxic broad-spectrum and systemic N-methyl carbamate pesticide, which is extensively applied as insecticide, nematicide and acaricide for agricultural, domestic and industrial purposes. It is extremely lethal to mammals, birds, fish and wildlife due to its anticholinesterase activity, which inhibits acetyl-cholinesterase and butyrylcholinesterse activity. In humans, carbofuran is associated with endocrine disrupting activity, reproductive disorders, cytotoxic and genotoxic abnormalities. Therefore, cleanup of carbofuran-contaminated environments is of utmost concern and urgently needs an adequate, advanced and effective remedial technology. Microbial technology (bacterial, fugal and algal species) is a very potent, pragmatic and ecofriendly approach for the removal of carbofuran. Microbial enzymes and their catabolic genes exhibit an exceptional potential for bioremediation strategies. To understand the specific mechanism of carbofuran degradation and involvement of carbofuran hydrolase enzymes and genes, highly efficient genomic approaches are required to provide reliable information and unfold metabolic pathways. This review briefly discusses the carbofuran toxicity and its toxicological impact into the environment, in-depth understanding of carbofuran degradation mechanism with microbial strains, metabolic pathways, molecular mechanisms and genetic basis involved in degradation.
ESTHER : Mishra_2020_Chemosphere_259_127419
PubMedSearch : Mishra_2020_Chemosphere_259_127419
PubMedID: 32593003

Title : Chemical composition and larvicidal activity against Aedes mosquitoes of essential oils from Arisaema fargesii - Huang_2020_Pest.Manag.Sci_76_534
Author(s) : Huang Y , Lin M , Jia M , Hu J , Zhu L
Ref : Pest Manag Sci , 76 :534 , 2020
Abstract : BACKGROUND: Dengue fever is caused by the spread of dengue virus by Aedes mosquito vectors. Currently, the most effective way to control dengue is by preventing mosquitoes from spreading the disease. Arisaema fargesii is a Chinese herbal medicine commonly used to repel mosquitoes. In our laboratory, anti-mosquito chemical components were extracted from A. fargesii, and the effects of these substances on mosquito larvae were examined. RESULTS: In total, 48 compounds corresponding to 98.79% of the total oil were identified and the major compounds identified were linalool (12.38%), carvacrol (8.27%), eugenol (5.21%), and beta-selinene (5.36%). Essential oil had larvicidal activity against Ae. aegypti and Ae. albopictus with LC50 values of 40.49 mg/L, 47.01 mg/L, respectively. The LC50 values of carvacrol, eugenol, linalool and beta-selinene were 32.78, 56.34, 70.56, 136.03 mg/L against Ae. aegypti larvae, and 39.08, 52.07, 82.34, 151.74 mg/L, respectively, against Ae. albopictus larvae. Biochemical assays of Aedes larvae showed that the activities of acetylcholinesterase (AChE), monooxygenases (MO), glutathione-S-transferase (GST), p-Nitrophenyl acetate (p-NPA) esterase, alpha-esterase and beta-esterase were significantly affected by carvacrol. Essential oil induced the detoxification mechanism for the action of GST and MO. CONCLUSION: The result indicates that essential oil of A. fargesii and its isolated constituent have good inhibitory effects on the defense enzymes of Aedes mosquito larvae. A. fargesii essential oil can be used to control Aedes mosquito larvae to prevent the spread of dengue fever. (c) 2019 Society of Chemical Industry.
ESTHER : Huang_2020_Pest.Manag.Sci_76_534
PubMedSearch : Huang_2020_Pest.Manag.Sci_76_534
PubMedID: 31270930

Title : DNA damage, immunotoxicity, and neurotoxicity induced by deltamethrin on the freshwater crayfish, Procambarus clarkii - Hong_2020_Environ.Toxicol__
Author(s) : Hong Y , Huang Y , Yan G , Yin H , Huang Z
Ref : Environ Toxicol , : , 2020
Abstract : Pyrethroid pesticides are applied to both agricultural and aquacultural industries for pest control. However, information of their impact on the commercial important freshwater crayfish, Procambarus clarkii is scarce. Therefore, the present study aimed to characterize to effects of a commonly used pyrethroid pesticide, deltamethrin on DNA damage, immune response, and neurotoxicity in P. clarkii. Animals were exposed to 7, 14, and 28 ng/L of deltamethrin, which correspond to 1/8, 1/4, and 1/2 of the LC(50) (96 hours) of this pyrethroid to P. clarkii. Significant increase of olive tail moment (OTM) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was found after deltamethrin exposure in a dose-dependent way. Total hemocyte counts (THC) and activities of immune-related enzymes including acid phosphatase (ACP), lysozyme (LZM), and phenoloxidase (PO) were all decreased and significantly lower than control at concentration of 28 ng/L after 96 hours exposure. Acetylcholinesterase (AChE) activity, an indicator of neurotoxic effect was investigated and it was decreased significantly in muscles at 14 and 28 ng/L after 24 hours exposure. The level of intracellular reactive oxygen species (ROS) in hemocytes was also measured and the significant increase of ROS was found at 14 and 28 ng/L concentrations. The results revealed that deltamethrin induced DNA damage, immunotoxicity, and neurotoxicity in P. clarkii by excessive generation of ROS. Because of the dose-dependent responses of all parameters under exposure of deltamethrin at environmentally realistic concentrations, these parameters could be used as sensitive biomarkers for risk assessment of deltamethrin in aquaculture area.
ESTHER : Hong_2020_Environ.Toxicol__
PubMedSearch : Hong_2020_Environ.Toxicol__
PubMedID: 32757256

Title : Characterization of an acidic pectin methylesterase from Paenibacillus xylanexedens and its application in fruit processing - Zhong_2020_Protein.Expr.Purif_179_105798
Author(s) : Zhong L , Wang X , Fan L , Ye X , Li Z , Cui Z , Huang Y
Ref : Protein Expr Purif , 179 :105798 , 2020
Abstract : A pectinase-producing bacterial isolate, identified as Paenibacillus xylanexedens SZ 29, was screened by using the soil dilution plate with citrus pectin and congo red. A pectin methylesterase gene (Pxpme) was cloned and expressed in Escherichia coli. The gene coded for a protein with 334 amino acids and a calculated molecular mass of 36.76 kDa. PxPME showed the highest identity of 32.4% with the characterized carbohydrate esterase family 8 pectin methylesterase from Daucus carota. The recombined PxPME showed a specific activity with 39.38 U/mg against citrus pectin with >65% methylesterification. The optimal pH and temperature for PxPME activity were 5.0 and 45 degreeC. Its K(m) and V(max) value were determined to be 1.43 mg/mL and 71.5 mol/mg.min, respectively. Moreover, PxPME could increase the firmness of pineapple cubes by 114% when combined with CaCl(2). The acidic and mesophilic properties make PxPME a potential candidate for application in the fruit processing.
ESTHER : Zhong_2020_Protein.Expr.Purif_179_105798
PubMedSearch : Zhong_2020_Protein.Expr.Purif_179_105798
PubMedID: 33232801

Title : Design, synthesis and evaluation of diosgenin carbamate derivatives as multitarget anti-Alzheimer's disease agents - Yang_2020_Eur.J.Med.Chem_187_111913
Author(s) : Yang GX , Huang Y , Zheng LL , Zhang L , Su L , Wu YH , Li J , Zhou LC , Huang J , Tang Y , Wang R , Ma L
Ref : Eur Journal of Medicinal Chemistry , 187 :111913 , 2020
Abstract : In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Abeta activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 +/- 2.2%,10 muM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 +/- 3.4%, 10 muM) or Abeta (astrocytes protection = 70.2 +/- 6.5%, 10 muM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Abeta42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1beta, IL-6 and TNF-alpha level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Abeta activities.
ESTHER : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedSearch : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedID: 31837501

Title : New insights into the microbial degradation and catalytic mechanism of synthetic pyrethroids - Zhan_2020_Environ.Res_182_109138
Author(s) : Zhan H , Huang Y , Lin Z , Bhatt P , Chen S
Ref : Environ Research , 182 :109138 , 2020
Abstract : The significant applications of pyrethroid insecticides in agro-ecosystem and household environments have raised serious environmental concerns. Environmental bioremediation has emerged as an effective and eco-friendly approach to remove or neutralize hazardous compounds. Bioaugmentation accelerates pyrethroid degradation in liquid cultures and soil. Pyrethroid-degrading microorganisms have been extensively studied to cope with pyrethroid residues. Microorganisms primarily hydrolyze the ester bonds of pyrethroids, and their degradation pathways have been elaborated. The functional genes and enzymes involved in microbial degradation have also been screened and studied. Carboxylesterase plays a key role in pyrethroid degradation by cleaving its carboxylester linkage. The catalytic mechanism is dependent on a specific catalytic triad, consisting of three amino acid residues (glutamine, histidine, and serine) within the active site of the carboxylesterase enzyme. Pyrethroid-degrading strains and enzymes have proven to be effective for the bioremediation of pyrethroid-contaminated environments. In this review, we have summarized newly isolated pyrethroid-degrading strains and proposed the degradation pathways along with key functional genes/enzymes. To develop an efficient bioremediation strategy, pyrethroid-degrading microorganisms should be comprehensively explored.
ESTHER : Zhan_2020_Environ.Res_182_109138
PubMedSearch : Zhan_2020_Environ.Res_182_109138
PubMedID: 32069744

Title : Evaluation of modes of action of pesticides to Daphnia magna based on QSAR, excess toxicity and critical body residues - Wang_2020_Ecotoxicol.Environ.Saf_203_111046
Author(s) : Wang J , Yang Y , Huang Y , Zhang X , Qin WC , Wen Y , Zhao YH
Ref : Ecotoxicology & Environmental Safety , 203 :111046 , 2020
Abstract : Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna.
ESTHER : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedSearch : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedID: 32888614

Title : Esterase is a powerful tool for the biodegradation of pyrethroid insecticides - Bhatt_2020_Chemosphere_244_125507
Author(s) : Bhatt P , Bhatt K , Huang Y , Lin Z , Chen S
Ref : Chemosphere , 244 :125507 , 2020
Abstract : Agricultural and household applications of pyrethroid insecticides have significantly increased residual concentrations in living cells and environments. The enhanced concentration is toxic for living beings. Pyrethroid hydrolase enzyme (pyrethroid catalyzing esterase) regulates pyrethroid degradation, and has been well reported in various organisms (bacteria, fungi, insects and animals). Hydrolysis mechanisms of these esterases are different from others and properly function at factors viz., optimum temperature, pH and physicochemical environment. Active site of the enzyme contains common amino acids that play important role in pyrethroid catalysis. Immobilization technology emphasizes the development of better reusable efficiency of pyrethroid hydrolases to carry out large-scale applications for complete degradation of pyrethroids from the environments. In this review we have attempted to provide insights of pyrethroid-degrading esterases in different living systems along with complete mechanisms.
ESTHER : Bhatt_2020_Chemosphere_244_125507
PubMedSearch : Bhatt_2020_Chemosphere_244_125507
PubMedID: 31835049

Title : Promoting Active Sites in MOF-Derived Homobimetallic Hollow Nanocages as a High-Performance Multifunctional Nanozyme Catalyst for Biosensing and Organic Pollutant Degradation - Li_2020_ACS.Appl.Mater.Interfaces_12_2581
Author(s) : Li S , Hou Y , Chen Q , Zhang X , Cao H , Huang Y
Ref : ACS Appl Mater Interfaces , 12 :2581 , 2020
Abstract : Nanozymes are one of the ideal alternatives to natural enzymes for various applications. The rational design of nanozymes with improved catalytic activity stimulates increasing attention to address the low activity of current nanozymes. Here, we reported a general strategy to fabricate the Co-based homobimetallic hollow nanocages (HNCs) (C-CoM-HNC, M = Ni, Mn, Cu, and Zn) by ion-assistant solvothermal reaction and subsequent low-temperature calcination from metal-organic frameworks. The C-CoM-HNCs are featured with HNCs composed of interlaced nanosheets with homogeneous bimetallic oxide dispersion. The hierarchical structure and secondary metallic doping endow the C-CoM-HNC highly active sites. In particular, the Cu-doped C-CoCu-HNCs nanostructures exhibit superior performances over the other C-CoM-HNC as both the oxidase mimicking and peroxymonosulfate (PMS) activator. A sensitive bioassay for acetylcholinesterase (AChE) was established based on the excellent oxidase-like activity of C-CoCu-HNC, offering a linear detection range from 0.0001 to 1 mU/mL with an ultralow detection limit of 0.1 mU/L. As the PMS activator, the C-CoCu-HNC was applied for targeted organic pollutant (rhodamine B, RhB) degradation. A highly efficient RhB degradation was realized, along with good adaptability in a wide pH range and good reusability during the eight-cycle run. The results suggest that C-CoCu-HNC holds a practical potential for clinical diagnostics and pollution removal. Further density functional theory calculation reveals that Cu doping leads to a tighter connection and more negative adsorption energy for O2/PMS, as well as an upshifted d-band center in the C-CoCu-HNCs nanostructures. These changes facilitated the adsorption of O2/PMS on the C-CoCu-HNC surface for dissociation. This work not only offers a promising multifunctional nanozyme catalyst for clinical diagnostics and pollution removal but also gives some clues for the further development of novel nanozymes with high catalytic activities.
ESTHER : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedSearch : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedID: 31854974

Title : Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial - Wang_2020_Curr.Med.Res.Opin_36_1107
Author(s) : Wang W , Yao J , Guo X , Guo Y , Yan C , Liu K , Zhang Y , Wang X , Li H , Wen Z , Li S , Xiao X , Liu W , Li Z , Zhang L , Shao S , Ye S , Qin G , Li Y , Li F , Zhang X , Li X , Peng Y , Deng H , Xu X , Zhou L , Huang Y , Cao M , Xia X , Shi M , Dou J , Yuan J
Ref : Curr Med Res Opin , 36 :1107 , 2020
Abstract : Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
ESTHER : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedSearch : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedID: 32338063

Title : Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein - Liu_2020_Cell.Death.Differ__
Author(s) : Liu R , Wang X , Curtiss C , Sheikh MS , Huang Y
Ref : Cell Death Differ , : , 2020
Abstract : We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. We found that MGL directly interacted with XIAP and enhanced E3-ligase activity and proteasomal degradation of XIAP. MGL overexpression induced cell death that was coupled with caspase activation and reduced XIAP levels. N-terminus of MGL was found to mediate interactions with XIAP and induce cell death. MGL-deficient cells exhibited elevated XIAP levels and exhibited resistance to anticancer drugs. XIAP expression was significantly elevated in tissues of MGL-deficient animals as well as human lung cancers exhibiting reduced MGL expression. Thus, MGL appears to mediate its tumor-suppressive actions by inhibiting XIAP to induce cell death.
ESTHER : Liu_2020_Cell.Death.Differ__
PubMedSearch : Liu_2020_Cell.Death.Differ__
PubMedID: 32376875
Gene_locus related to this paper: human-MGLL

Title : A tunable bifunctional hollow Co(3)O(4)\/MO(3) (M = Mo, W) mixed-metal oxide nanozyme for sensing H(2)O(2) and screening acetylcholinesterase activity and its inhibitor - Zhang_2020_J.Mater.Chem.B_8_6459
Author(s) : Zhang X , Lu Y , Chen Q , Huang Y
Ref : J Mater Chem B , 8 :6459 , 2020
Abstract : A self-templated strategy was adopted to design hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides via the Mo or W doping of ZIF-67, and subsequent pyrolysis under an atmosphere of air at a low temperature of 450 degreesC. The hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides displayed tunable oxidase-like and peroxidase-like activities able to efficiently catalyze the oxidation of TMB to generate a deep blue color in the absence or presence of H2O2. Relative to that of the un-doped Co3O4, the oxidase mimic activity of the Mo-doped Co3O4 increased to 1.3 to 2.1-fold, while its peroxidase mimic activity increased to 7.1 to 19.9-fold, depending on different Mo doping amounts. The oxidase mimic activity of the W-doped Co3O4 increased to 2.1 to 2.3-fold, while its peroxidase mimic activity increased to 4.8 to 5.9-fold, depending on the different W doping amounts. The Mo- and W-doped Co3O4 nanohybrid exhibited both higher O2 and H2O2 activating capability, and their H2O2 activating capacity was superior to the O2 activating capability. Furthermore, the Mo- and W-doped Co3O4 nanohybrids exhibited similar O2 activating abilities, while the Mo-doped one displayed a higher H2O2 activating capability than the W-doped one. The discrepant peroxidase-like nature of Mo- and W-doped Co3O4 nanohybrids is likely attributed to their different catalytic mechanisms. The peroxidase-like activity of Mo-doped Co3O4 is highly related to the OH free radical, while that of W-doped Co3O4 is likely ascribed to the electron transfer between TMB and H2O2. The Km values of Co3O4/MoO3 for TMB and H2O2 were 0.0352 mM and 0.134 mM, which were 3.2- and 1.9-fold lower than that of pure Co3O4, respectively. A Co3O4/MoO3-based colorimetric platform was developed for the determination of H2O2 in the 0.1-200 microM range, with a limit of detection of 0.08 microM (3sigma). Based on the thiocholine (TCh) inhibition of the excellent peroxidase-like activity of Co3O4/MoO3 and the TCh generation via acetylcholinesterase (AChE) catalyzed hydrolysis of acetylthiocholine chloride (ATCh), the colorimetric platform was extended to screen AChE activity and its inhibitor.
ESTHER : Zhang_2020_J.Mater.Chem.B_8_6459
PubMedSearch : Zhang_2020_J.Mater.Chem.B_8_6459
PubMedID: 32597916

Title : Effect of chlorination on anti-acetylcholinesterase activity of organophosphorus insecticide solutions and contributions of the parent insecticides and their oxons to the activity - Matsushita_2020_Chemosphere_261_127743
Author(s) : Matsushita T , Fujita Y , Omori K , Huang Y , Matsui Y , Shirasaki N
Ref : Chemosphere , 261 :127743 , 2020
Abstract : Organophosphorus insecticides are known to be partly transformed to their respective oxons during the chlorination step of drinking water treatment. For most organophosphorus insecticides, the toxicological endpoint for determining acceptable daily intake levels is inhibition of acetylcholinesterase (AChE). Like the parent insecticides, oxons also inhibit AChE, so the presence of oxons in drinking water is also evaluated. However, no attention is paid to the possible presence of transformation products (TPs) other than oxons. In the present study, we determined whether the anti-AChE activity observed for chlorinated solutions of the organophosphorus insecticides malathion and methidathion could be solely attributed to the parent compounds and their oxons. Upon chlorination, both malathion and methidathion were immediately transformed to their oxons; the maximum transformation ratios were 60% and 30%, respectively, indicating that at least 40% and 70% of these compounds were transformed into other TPs. Before chlorination, malathion- and methidathion-containing solutions exhibited little to no anti-AChE activity, but the solutions showed strong activity after chlorination. The contributions of the parent insecticides and their oxons to the activities of the chlorinated samples were calculated from the concentrations of the compounds in the samples and dose-response curves for chemical standards of the compounds. For both the malathion-containing solution and the methidathion-containing solution, the calculated anti-AChE activities were almost the same as the observed activities at every chlorination time. This suggests that the observed activities could be attributed solely to the parent insecticides and their oxons, indicating that other TPs need not be considered.
ESTHER : Matsushita_2020_Chemosphere_261_127743
PubMedSearch : Matsushita_2020_Chemosphere_261_127743
PubMedID: 32721694

Title : Bisphenol F-Induced Neurotoxicity toward Zebrafish Embryos - Yuan_2019_Environ.Sci.Technol_53_14638
Author(s) : Yuan L , Qian L , Qian Y , Liu J , Yang K , Huang Y , Wang C , Li Y , Mu X
Ref : Environ Sci Technol , 53 :14638 , 2019
Abstract : In this study, the influence of bisphenol F (BPF) toward central nervous system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity toward zebrafish embryos, including inhibited locomotion, reduced moving distance, and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. Peripheral motor neuron development was significantly inhibited by BPF at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-seq assay implied that the transcriptional changes were not mediated by ERalpha. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, and acetylcholine) or acetylcholinesterase (Ache) enzyme activity after BPF exposure, indicating that BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentration.
ESTHER : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedSearch : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedID: 31702913

Title : Structural Insights into the Dual-Substrate Recognition and Catalytic Mechanisms of a Bifunctional Acetyl Ester-Xyloside Hydrolase from Caldicellulosiruptor lactoaceticus - Cao_2019_ACS.Catal_9_1739
Author(s) : Cao H , Sun L , Huang Y , Liu X , Yang D , Liu T , Jia X , Wen B , Gu T , Wang F , Xin F
Ref : ACS Catal , 9 :1739 , 2019
Abstract : Enzymes are usually characterized by their evolutionarily conserved catalytic domains; however, this work presents the incidental gain-of-function of an enzyme in a loop region by natural evolution of its amino acids. A bifunctional acetyl ester-xyloside hydrolase (CLH10) was heterologously expressed, purified, and characterized. The primary sequence of CLH10 contains the fragments of the conserved sequence of esterase and glycosidase, which distribute in a mixed type. The crystal structure revealed that the primary sequence folded into two independent structural regions to undertake both acetyl esterase and beta-1,4-xylanase hydrolase functions. CLH10 is capable of cleaving both the beta-1,4-xylosidic bond-linked main chain and the ester bond-linked acetylated side chain of xylan, which renders it valuable because it can degrade acetylated xylan within one enzyme. Significantly, the beta-1,4-xylanase activity of CLH10 appears to have been fortuitously obtained because of the variable Asp10 and Glu139 located in its loop region, which suggested that the exposed loop region might act as a potential hot-spot for the design and generation of promising enzyme function in both directed evolution and rational protein design.
ESTHER : Cao_2019_ACS.Catal_9_1739
PubMedSearch : Cao_2019_ACS.Catal_9_1739
Gene_locus related to this paper: 9firm-g2pvg6

Title : Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus - Chen_2019_Fish.Shellfish.Immunol_97_283
Author(s) : Chen H , Li J , Yan L , Cao J , Li D , Huang GY , Shi WJ , Dong W , Zha J , Ying GG , Zhong H , Wang Z , Huang Y , Luo Y , Xie L
Ref : Fish Shellfish Immunol , 97 :283 , 2019
Abstract : Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.
ESTHER : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedSearch : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedID: 31863904

Title : Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts - Zhang_2019_Cancer.Lett_465_36
Author(s) : Zhang L , Zhou J , Yan Y , Zhou X , Zhou Q , Du R , Hu S , Ge W , Huang Y , Xu H , Kong Y , Zheng H , Ding Y , Shen Y , Wang W
Ref : Cancer Letters , 465 :36 , 2019
Abstract : Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients.
ESTHER : Zhang_2019_Cancer.Lett_465_36
PubMedSearch : Zhang_2019_Cancer.Lett_465_36
PubMedID: 31479691

Title : Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis - Hu_2019_Biomed.Res.Int_2019_8642784
Author(s) : Hu G , Liu D , Tong H , Huang W , Hu Y , Huang Y
Ref : Biomed Res Int , 2019 :8642784 , 2019
Abstract : BACKGROUND: The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. METHODS: Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. RESULTS: Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02-1.13) and 1.11 (95% CI 1.04-1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01-1.15) and 1.11 (95% CI 1.02-1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03-1.54) and 1.56 (95% CI 1.21-2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07-1.56) and 1.68 (95% CI 1.12-2.53), respectively. CONCLUSIONS: Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk.
ESTHER : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedSearch : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedID: 31236414
Gene_locus related to this paper: human-PLA2G7

Title : Insight Into Microbial Applications for the Biodegradation of Pyrethroid Insecticides - Bhatt_2019_Front.Microbiol_10_1778
Author(s) : Bhatt P , Huang Y , Zhan H , Chen S
Ref : Front Microbiol , 10 :1778 , 2019
Abstract : Pyrethroids are broad-spectrum insecticides and presence of chiral carbon differentiates among various forms of pyrethroids. Microbial approaches have emerged as a popular solution to counter pyrethroid toxicity to marine life and mammals. Bacterial and fungal strains can effectively degrade pyrethroids into non-toxic compounds. Different strains of bacteria and fungi such as Bacillus spp., Raoultella ornithinolytica, Psudomonas flourescens, Brevibacterium sp., Acinetobactor sp., Aspergillus sp., Candida sp., Trichoderma sp., and Candia spp., are used for the biodegradation of pyrethroids. Hydrolysis of ester bond by enzyme esterase/carboxyl esterase is the initial step in pyrethroid biodegradation. Esterase is found in bacteria, fungi, insect and mammalian liver microsome cells that indicates its hydrolysis ability in living cells. Biodegradation pattern and detected metabolites reveal microbial consumption of pyrethroids as carbon and nitrogen source. In this review, we aim to explore pyrethroid degrading strains, enzymes and metabolites produced by microbial strains. This review paper covers in-depth knowledge of pyrethroids and recommends possible solutions to minimize their environmental toxicity.
ESTHER : Bhatt_2019_Front.Microbiol_10_1778
PubMedSearch : Bhatt_2019_Front.Microbiol_10_1778
PubMedID: 31428072

Title : Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients - Xu_2018_Mediators.Inflamm_2018_5201652
Author(s) : Xu L , Zhu B , Huang Y , Yang Z , Sun J , Xu Y , Zheng J , Kinloch S , Yin MT , Weng H , Wu N
Ref : Mediators Inflamm , 2018 :5201652 , 2018
Abstract : Background: Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods: BChE levels (in U/L) were measured in 505 patients; <4500 was defined as "low" and >/=4500 as "normal." Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan-Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results: A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 +/- 4.5% for patients with low BChE and 87.6 +/- 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0-3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). Conclusion: BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients.
ESTHER : Xu_2018_Mediators.Inflamm_2018_5201652
PubMedSearch : Xu_2018_Mediators.Inflamm_2018_5201652
PubMedID: 29736152

Title : [Effect of enteral nutrition tolerance assessment standardized process management on ventilator associated pneumonia and prognosis in patients with tracheotomy and long-term mechanical ventilation in intensive care unit] - Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
Author(s) : Wang C , Wang J , Wang B , Jing X , Huang Y
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 30 :1173 , 2018
Abstract : OBJECTIVE: To investigate the effect of enteral nutrition (EN) tolerance assessment standardized process management on nosocomial infection and prognosis in patients with tracheotomy and long-term mechanical ventilation (MV) in intensive care unit (ICU). METHODS: A prospective cohort study was conducted. Forty-six patients who required long-term MV due to tracheotomy admitted to ICU of Changzhou First People's Hospital from January 2015 to December 2017 were enrolled. Taking the standardized process management of EN tolerance assessment from June 30th, 2016 as the time spot, patients admitted from January 1st, 2015 to June 30th, 2016 were taken as the control group (25 cases) and patients admitted from July 1st, 2016 to December 31st, 2017 as the observation group (21 cases). The two groups were all given conventional EN treatment and conventional symptomatic supportive treatment. Patients in the observation group was given the EN tolerance standardized process management, and received the nutritional risk screening score. While the control group was given a conventional EN management protocol (nurses routinely reported to the doctor and then gave further action). The nutritional support related indicators within 30 days of treatment (including serum albumin, serum pre-albumin, serum cholinesterase), the EN feeding tolerance index (the average amount of gastrointestinal motility drugs used within 30 days, the average EN interruption time per patient, and the incidence of gastrointestinal bleeding) and the prognosis-related indicators [including the incidence of ventilator-associated pneumonia (VAP), the monthly average hospitalization cost, the proportion of drugs, and the ratio of antibiotics to drugs] were compared. RESULTS: Compared with the control group, serum albumin, pre-albumin and cholinesterase were significantly increased in the observation group [albumin (g/L): 32.86+/-4.83 vs. 28.16+/-3.62, pre-albumin (mg/L): 186.42+/-62.84 vs. 163.26+/-73.49, cholinesterase (U/L): 3 482.34+/-369.92 vs. 2 986.86+/-491.49, all P < 0.05], the average use of gastrointestinal motility drugs was significantly reduced (mg: 11.20+/-3.86 vs. 15.23+/-5.68, P < 0.05), the average EN interruption time was significantly longer in each patient (hours: 6.38+/-3.59 vs. 4.96+/-2.28, P < 0.05), and the incidence of gastrointestinal bleeding was significantly decreased (19.04% vs. 24.00%, P < 0.05), the incidence of VAP was significantly decreased (18.64% vs. 21.36%, P < 0.05), and the antibiotics accounted for a significant decrease (62.43% vs. 76.59%, P < 0.05), but there was no significant difference in the proportion of drugs and monthly average hospitalization expenses [drug ratio: 36.88% vs. 38.42%, monthly average hospitalization cost (ten thousand yuan): 4.36+/-0.57 vs. 4.39+/-0.49, both P > 0.05]. CONCLUSIONS: For the patients with tracheotomy and long-term MV of ICU, the enteral nutrition tolerance assessment standardized process management can improve the nutritional status, reduce the incidence of nosocomial infections, and improve the prognosis of the patients.
ESTHER : Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
PubMedSearch : Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
PubMedID: 30592953

Title : Antioxidative status, immunological responses, and heat shock protein expression in hepatopancreas of Chinese mitten crab, Eriocheir sinensis under the exposure of glyphosate - Hong_2018_Fish.Shellfish.Immunol_86_840
Author(s) : Hong Y , Huang Y , Yan G , Pan C , Zhang J
Ref : Fish Shellfish Immunol , 86 :840 , 2018
Abstract : As a broad-spectrum herbicide, glyphosate was extensively utilised in China for several decades. The contradiction between glyphosate spraying and crab breeding in the rice-crab co-culture system has become more obvious. In this study, the antioxidative status and immunological responses of Chinese mitten crab, Eriocheir sinensis, under sublethal exposure of glyphosate were investigated by detecting the antioxidative and immune-related enzyme activity, acetylcholinesterase (AChE) activity and relative mRNA expression of heat shock proteins (HSPs) in hepatopancreas. The results showed that high concentrations of glyphosate (44 and 98mg/L) could induce significant alteration of superoxide dismutase (SOD), peroxidase (POD), acid phosphatase (ACP), alkaline phosphatase (AKP), and phenoloxidase (PO) activities by first rising then falling during the exposure. However, AChE activity in all treatments including 4.4mg/L was inhibited markedly after 6h of exposure. In addition, the relative mRNA expression of HSP 60, HSP 70, and HSP 90 was significantly upregulated at both 48h and 96h. These results revealed that glyphosate has a prominent toxic effect on E. sinensis based on antioxidative and immunological response inhibition and AChE activity reduction even at the lowest concentration of 4.4mg/L, and a protective response by upregulation of HSPs was carried out by the species to ease the environmental stress.
ESTHER : Hong_2018_Fish.Shellfish.Immunol_86_840
PubMedSearch : Hong_2018_Fish.Shellfish.Immunol_86_840
PubMedID: 30572127

Title : Enzymatic Synthesis of Polyglycerol Fatty Acid Esters and Their Application as Emulsion Stabilizers - Peng_2018_J.Agric.Food.Chem_66_8104
Author(s) : Peng B , Xiong CY , Huang Y , Hu JN , Zhu XM , Deng ZY
Ref : Journal of Agricultural and Food Chemistry , 66 :8104 , 2018
Abstract : Polyglycerol ester is considered an excellent kind of food emulsifier. The aim of the current study was to synthesize polyglycerol fatty acid esters (PGFEs) with different-sized long-chain fatty acids (i.e. long-carbon fatty acid polyglycerol esters, L-PGFEs; medium-carbon fatty acid polyglycerol esters, M-PGFEs; and short-carbon fatty acid polyglycerol esters, S-PGFEs), using Lipozyme 435 as a catalyst in a solvent-free system. Thereafter, the physicochemical properties of the newly synthesized PGFEs and their potential applications as food emulsifiers were investigated. The maximum esterification efficiencies of L-PGFEs, M-PGFEs, and S-PGFEs were 69.37, 67.34, and 71.68%, respectively, at the optimum conditions: a reaction temperature of 84.48 degreeC, a reaction time of 6 h, a molar ratio of polyglycerol to fatty acid of 1.35:1, and 1.41 wt % enzyme usage (based on the total substrate mass). A high-performance liquid chromatograph equipped with an evaporative light-scattering detector (HPLC-ELSD) and an electrospray-ionization mass spectrometer (ESI-MS) were employed to identify the synthesized products. The results demonstrated that the main components of these PGFEs were dimeric glycerides (68.3%), triglycerides (13.13%), and a small amount of tetraglycerides (3.18%). The properties of the PGFEs were characterized by physical and chemical methods. Compared with M-PGFEs and S-PGFEs, L-PGFEs had the best physicochemical properties without any obvious odor. Further, the emulsion capabilities of these different long-chain PGFEs were evaluated via examining the particle sizes and storage stabilities and comparing them with those of glycerin monostearate (GMS). The results showed that the emulsions prepared with L-PGFEs had the best stability and the smallest particle sizes (16.8 nm) compared with those of M-PGFEs, S-PGFEs, and GMS, and they were not prone to oil-droplet coalescence or the separation of oil and water. From the current study, the newly synthesized PGFEs with long-chain fatty acids showed the best advantages as a food emulsifier compared with M-PGFEs, S-PGFEs, and even glycerin monostearate.
ESTHER : Peng_2018_J.Agric.Food.Chem_66_8104
PubMedSearch : Peng_2018_J.Agric.Food.Chem_66_8104
PubMedID: 29989410

Title : Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1 - Tang_2018_Life.Sci_213_166
Author(s) : Tang S , Lu C , Mo L , Wang X , Liang Z , Qin F , Liu Y , Huang H , Huang Y , Cai H , Xiao D , Guo S , Ouyang Y , Sun B , Li X
Ref : Life Sciences , 213 :166 , 2018
Abstract : AIMS: Protein phosphatase methylesterase-1 (PME-1) is a serine hydrolase that catalyzes protein phosphatase 2A (PP2A) demethylation and negatively regulates its activity. PME-1 is compartmentalized within cells to precisely control the demethylation of PP2A. This study investigated the localization of PME-1 in human fibroblast cells (HDF) under oxidative stress. MAIN METHODS: Alkaline demethylation and peptide competition assays were applied to detect the methylation sensitivity of anti-PP2Ac. The localization of PME-1, leucine carboxyl methyltransferase 1 (LCMT1), demethylated-phosphorylated-PP2Ac (dem-p-PP2Ac) and total PP2Ac was determined by immunofluorescence analysis, and protein expression was measured by Western blot. A HEK293 cell line stably expressing constructed PME-1-EGFP was used to dynamically monitor the nuclear export of PME-1 under oxidative stress. KEY RESULTS: After hydrogen peroxide (H(2)O(2)) treatment, the protein expression of PME-1 remained unchanged, while PME-1 facilitated redistribution from the nucleus to the cytoplasm in HDF according to immunofluorescence analysis. In constructed HEK293 cells, the EGFP-tagged PME-1 was exported from the nucleus to the cytoplasm after H(2)O(2) treatment, and nuclear export was eliminated after leptomycin B additions. Our observation of dem-p-PP2Ac species relocation from the nucleus to the cytoplasm under oxidative stress is consistent with the redistribution patterns of PME-1. Antioxidant N-acetyl cysteine can reverse the nuclear to cytoplasmic ratio of PME-1 proteins and dem-p-PP2Ac after H(2)O(2) exposure. SIGNIFICANCE: We found that PME-1 is exported from the nucleus to the cytoplasm upon H(2)O(2) treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress.
ESTHER : Tang_2018_Life.Sci_213_166
PubMedSearch : Tang_2018_Life.Sci_213_166
PubMedID: 30340029
Gene_locus related to this paper: human-PPME1

Title : Functional Analysis of a Carboxylesterase Gene Associated With Isoprocarb and Cyhalothrin Resistance in Rhopalosiphum padi (L.) - Wang_2018_Front.Physiol_9_992
Author(s) : Wang K , Huang Y , Li X , Chen M
Ref : Front Physiol , 9 :992 , 2018
Abstract : Carboxylesterase (CarE) is an important class of detoxification enzymes involved in insecticide resistance. However, the molecular mechanism of CarE-mediated insecticide resistance in Rhopalosiphum padi, a problematic agricultural pest, remains largely unknown. In the present study, an isoprocarb-resistant (IS-R) strain and a cyhalothrin-resistant (CY-R) strain were successively selected from a susceptible (SS) strain of R. padi. The enzyme activity indicated that enhanced carboxylesterase activity contributes to isoprocarb and cyhalothrin resistance. The expression levels of putative CarE genes were examined and compared among IS-R, CY-R, and SS strains, and only the R. padi carboxylesterase gene (RpCarE) was significantly over expressed in both the IS-R and CY-R strains compared to the SS strain. The coding region of the RpCarE gene was cloned and expressed in Escherichia coli. The purified RpCarE protein was able to catalyze the model substrate, alpha-naphtyl acetate (Kcat = 5.50 s(-1); Km = 42.98 muM). HPLC assay showed that the recombinant protein had hydrolase activity against isoprocarb and cyhalothrin. The modeling and docking analyses consistently indicated these two insecticide molecules fit snugly into the catalytic pocket of RpCarE. Taken together, these findings suggest that RpCarE plays an important role in metabolic resistance to carbamates and pyrethroids in R. padi.
ESTHER : Wang_2018_Front.Physiol_9_992
PubMedSearch : Wang_2018_Front.Physiol_9_992
PubMedID: 30090072

Title : Assessment of the oxidative and genotoxic effects of the glyphosate-based herbicide roundup on the freshwater shrimp, Macrobrachium nipponensis - Hong_2018_Chemosphere_210_896
Author(s) : Hong Y , Yang X , Huang Y , Yan G , Cheng Y
Ref : Chemosphere , 210 :896 , 2018
Abstract : In the present study, an acute toxic test was performed to assess the oxidative stress and genotoxic effects of the herbicide on the freshwater shrimp Macrobrachium nipponensis. The results showed that the 48-h and 96-h LC50 values of Roundup to M. nipponensis were 57.684mg/L and 11.237mg/L, respectively. For further investigation, the shrimps were exposed to sublethal concentrations of 0.35, 0.70, 1.40, 2.80 and 5.60mg/L for 96h. A significant decrease in total haemocytes count (THC) was observed at concentration of 5.60mg/L throughout the experiment. The level of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in all the treatments decreased in a dose- and time-dependent manner except for the concentration group of 0.35mg/L. The malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum increased significantly at concentrations of 2.80mg/L and 5.60mg/L. A significant decrease in acetylcholinesterase (AChE) activity was observed at each concentration (P0.05). In addition, the micronucleus (MN) frequency of haemocytes significantly increased (P0.05) at concentrations of 1.40, 2.80 and 5.60mg/L, whereas the comet ratio and %DNA in the tails exhibited a clear time- and dose-dependent response during the exposure. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants, and this dose-dependent relation suggests the sensitivity and availability of all the biomarkers. These results revealed that Roundup had a prominent toxic effect on M. nipponensis based on the antioxidative response inhibition and genotoxicity.
ESTHER : Hong_2018_Chemosphere_210_896
PubMedSearch : Hong_2018_Chemosphere_210_896
PubMedID: 30208549

Title : Modification-free carbon dots as turn-on fluorescence probe for detection of organophosphorus pesticides - Lin_2018_Food.Chem_245_1176
Author(s) : Lin B , Yan Y , Guo M , Cao Y , Yu Y , Zhang T , Huang Y , Wu D
Ref : Food Chem , 245 :1176 , 2018
Abstract : It is important to detect pesticides residues due to the concern over food safety. In this work, the burning ash of waste paper was used as carbon source to synthesize carbon dots (C-dots). The fluorescence of obtained C-dots could been turn off by Fe(3+) which was from Fe(2+) oxidized by H2O2, organophosphorus pesticides could effectively inhibit the production of H2O2 by destroying the acetylcholinesterase activity, so the fluorescence of C-dots hold turning on in the presence of organophosphorus pesticides. Based on above principle that the fluorescence intensity of C-dots was proportional to the pesticides concentration, take chlorpyrifos for example, a universal method for pesticides detection was established. The linear range was 0.01-1.0mug/mL with detection limit of 3ng/mL. The method was reliable and sensitive to actual samples. The imaging of chlorpyrifos on cabbages leaves indicated this method could be used for visualization detection of organophosphorus pesticides in vegetables.
ESTHER : Lin_2018_Food.Chem_245_1176
PubMedSearch : Lin_2018_Food.Chem_245_1176
PubMedID: 29287338

Title : Characterization of a Novel Thermo-Stable Lipasefrom Endophyte Pseudomonas putida in Pistacia chinensis Bunge - Song_2017_Appl.Biochem.Microbiol_53_524
Author(s) : Song C , Liu Z , Xie Q , Wang H , Huang Y , Ruan Y , Chen D
Ref : Applied Biochemistry and Microbiology , 53 :524 , 2017
Abstract : A novel lipolytic enzyme-producing endophytic strain PC2 was successfully isolated from the seeds of an ideal bioenergy plant Pistacia chinensis Bunge. Based on the analysis of morphology and 16S rRNA sequence, bacterial strain PC2 was identified as a subspecies of Pseudomonas putida, therefore named as P. putida PC2. Whole-genome sequencing showed PC2 contained a 1224-nucleotide lipase gene (named lip-PC2) predicted to encode a 407-amino-acid protein. Purified lipases from both the original PC2 strain and heterologously expressed Escherichia coli were nearly 50 kD with specific activity of 9.48 U/mL. LIP-PC2 displayed the maximal activity at 50C or pH 8.0, and maintained above 80% relative activity in the range of from 40 to 60degC or pH in the range of from 6.0 to 8.0, indicating thermostable and alkaline properties. Enzyme activity was enhanced by Mg2+, Na+ and Mn2+, but strongly inhibited by Cu2+, Zn2+ Co2+, EDTA as well as organic solvents and surfactants. Additionally, the analysis of amino acid sequence and structure indicated that LIP-PC2 was a novel member belonging to family I.3 of bacterial lipolytic enzymes and its catalytic triad was consisted of Ser-200, Asp-342 and His-374
ESTHER : Song_2017_Appl.Biochem.Microbiol_53_524
PubMedSearch : Song_2017_Appl.Biochem.Microbiol_53_524
Gene_locus related to this paper: psepu-a0a160gpc6

Title : Discovery of the leinamycin family of natural products by mining actinobacterial genomes - Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
Author(s) : Pan G , Xu Z , Guo Z , Hindra , Ma M , Yang D , Zhou H , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Cheng J , Van Nieuwerburgh F , Suh JW , Duan Y , Shen B
Ref : Proc Natl Acad Sci U S A , 114 :E11131 , 2017
Abstract : Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
ESTHER : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedSearch : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedID: 29229819
Gene_locus related to this paper: 9actn-a0a2m9jcs9 , 9actn-a0a2m9ijf7 , 9actn-a0a2m9iy91 , 9actn-a0a2m9k146 , 9actn-a0a2m9m5n6 , 9actn-a0a2m9ifq0 , 9actn-a0a1c4rpf7

Title : Depletion of juvenile hormone esterase extends larval growth in Bombyx mori - Zhang_2017_Insect.Biochem.Mol.Biol_81_72
Author(s) : Zhang Z , Liu X , Shiotsuki T , Wang Z , Xu X , Huang Y , Li M , Li K , Tan A
Ref : Insect Biochemistry & Molecular Biology , 81 :72 , 2017
Abstract : Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production.
ESTHER : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedSearch : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedID: 28057597

Title : Aqueous extracts from asparagus stems prevent memory impairments in scopolamine-treated mice - Sui_2017_Food.Funct_8_1460
Author(s) : Sui Z , Qi C , Huang Y , Ma S , Wang X , Le G , Sun J
Ref : Food Funct , 8 :1460 , 2017
Abstract : Aqueous extracts from Asparagus officinalis L. stems (AEAS) are rich in polysaccharides, gamma-amino butyric acid (GABA), and steroidal saponin. This study was designed to investigate the effects of AEAS on learning, memory, and acetylcholinesterase-related activity in a scopolamine-induced model of amnesia. Sixty ICR mice were randomly divided into 6 groups (n = 10) including the control group (CT), scopolamine group (SC), donepezil group (DON), low, medium, and high dose groups of AEAS (LS, MS, HS; 1.6 mL kg-1, 8 mL kg-1, 16 mL kg-1). The results showed that 8 mL kg-1 of AEAS used in this study significantly reversed scopolamine-induced cognitive impairments in mice in the novel object recognition test (P < 0.05) and the Y-maze test (P < 0.05), and also improved the latency to escape in the Morris water maze test (P < 0.05). Moreover, it significantly increased acetylcholine and inhibited acetylcholinesterase activity in the hippocampus, which was directly related to the reduction in learning and memory impairments. It also reversed scopolamine-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) and the cAMP response element-binding protein (CREB) mRNA expression. AEAS protected against scopolamine-induced memory deficits. In conclusion, AEAS protected learning and memory function in mice by enhancing the activity of the cholinergic nervous system, and increasing BDNF and CREB expression. This suggests that AEAS has the potential to prevent cognitive impairments in age-related diseases, such as Alzheimer's disease.
ESTHER : Sui_2017_Food.Funct_8_1460
PubMedSearch : Sui_2017_Food.Funct_8_1460
PubMedID: 28275781

Title : Metabolism of KO143, an ABCG2 inhibitor - Liu_2017_Drug.Metab.Pharmacokinet_32_193
Author(s) : Liu K , Zhu J , Huang Y , Li C , Lu J , Sachar M , Li S , Ma X
Ref : Drug Metab Pharmacokinet , 32 :193 , 2017
Abstract : The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice. K1 is an analog of KO143 without the ester group. We found that the metabolic stability of K1 was significantly improved in HLM when compared to KO143. These data suggest that the ester group in KO143 is the major cause of the poor metabolic stability of KO143. The data from this study can be used to guide the development of KO143 analogs with better metabolic properties.
ESTHER : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedSearch : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedID: 28619281

Title : Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene aryl esters from the mycelium of Armillaria mellea - Li_2016_J.Ethnopharmacol_184_119
Author(s) : Li Z , Wang Y , Jiang B , Li W , Zheng L , Yang X , Bao Y , Sun L , Huang Y , Li Y
Ref : J Ethnopharmacol , 184 :119 , 2016
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. MATERIALS AND METHODS: A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. RESULTS: Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65microg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. CONCLUSIONS: Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95microg/mL) and lower activity for L02 cells (16.05microg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase.
ESTHER : Li_2016_J.Ethnopharmacol_184_119
PubMedSearch : Li_2016_J.Ethnopharmacol_184_119
PubMedID: 26952552
Gene_locus related to this paper: armos-armb

Title : Yu Ping Feng San reverses cisplatin-induced multi-drug resistance in lung cancer cells via regulating drug transporters and p62\/TRAF6 signalling - Lou_2016_Sci.Rep_6_31926
Author(s) : Lou JS , Yan L , Bi CWC , Chan GK , Wu KQY , Liu EYL , Huang Y , Yao P , Du CY , Dong TTX , Tsim KWK
Ref : Sci Rep , 6 :31926 , 2016
Abstract : Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP)-resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug-resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling.
ESTHER : Lou_2016_Sci.Rep_6_31926
PubMedSearch : Lou_2016_Sci.Rep_6_31926
PubMedID: 27558312

Title : Strain Prioritization and Genome Mining for Enediyne Natural Products - Yan_2016_MBio_7_e02104
Author(s) : Yan X , Ge H , Huang T , Hindra , Yang D , Teng Q , Crnovcic I , Li X , Rudolf JD , Lohman JR , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Van Nieuwerburgh F , Rader C , Duan Y , Shen B
Ref : MBio , 7 : , 2016
Abstract : The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE: Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.
ESTHER : Yan_2016_MBio_7_e02104
PubMedSearch : Yan_2016_MBio_7_e02104
PubMedID: 27999165
Gene_locus related to this paper: 9actn-a0a1q5ckn8 , 9actn-a0a1q5j3v0 , 9actn-a0a1q5kj90 , 9actn-a0a1q5jti2 , 9actn-a0a1q5luf4 , 9actn-a0a1q4w3c8 , 9actn-a0a1q4wvf2 , 9actn-a0a1q4yuw0 , 9actn-a0a1q5diu2 , 9actn-a0a1q5dxi1 , 9actn-a0a1q5ftj7 , 9actn-a0a1q5h9t1 , 9actn-a0a1q5k3r2 , 9actn-a0a1q5l4j4 , 9actn-a0a1q5l7v2 , 9actn-a0a1q5ltu8 , 9actn-a0a1q5m0p6 , 9actn-a0a1q5mza2 , 9pseu-a0a1q4yle9 , 9pseu-a0a1q4ylg6 , 9actn-a0a1q5hn40 , 9actn-a0a1q4zi93 , 9actn-a0a1q5d7w2 , 9actn-a0a1q5mn15 , 9pseu-a0a1q4xtq2 , 9actn-a0a1q5le62 , 9actn-a0a1q5fgx4 , strsp-TnmK1 , strsp-TnmK2 , strun-UcmK2 , 9actn-a0a1q4w6n9 , 9actn-a0a1q4yc91 , 9actn-a0a1q4yun2 , 9actn-a0a1q5g588 , 9actn-a0a1q5h571 , 9actn-a0a1q5kh06 , 9actn-a0a1q5lnf3 , 9actn-a0a1q5n7d1 , 9actn-a0a1q5n4g6

Title : Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase - Chupak_2016_Bioorg.Med.Chem_24_1455
Author(s) : Chupak LS , Zheng X , Hu S , Huang Y , Ding M , Lewis MA , Westphal RS , Blat Y , McClure A , Gentles RG
Ref : Bioorganic & Medicinal Chemistry , 24 :1455 , 2016
Abstract : N-Benzylic-substituted glycine sulfonamides that reversibly inhibit diacylglycerol (DAG) lipases are reported. Detailed herein are the structure activity relationships, profiling characteristics and physico-chemical properties for the first reported series of DAG lipase (DAGL) inhibitors that function without covalent attachment to the enzyme. Highly potent examples are presented that represent valuable tool compounds for studying DAGL inhibition and constitute important leads for future medicinal chemistry efforts.
ESTHER : Chupak_2016_Bioorg.Med.Chem_24_1455
PubMedSearch : Chupak_2016_Bioorg.Med.Chem_24_1455
PubMedID: 26917221

Title : Functional characterization of an alpha-esterase gene involving malathion detoxification in Bactrocera dorsalis (Hendel) - Wang_2016_Pestic.Biochem.Physiol_130_44
Author(s) : Wang LL , Lu XP , Meng LW , Huang Y , Wei D , Jiang HB , Smagghe G , Wang JJ
Ref : Pestic Biochem Physiol , 130 :44 , 2016
Abstract : Extensive use of insecticides in many orchards has prompted resistance development in the oriental fruit fly, Bactrocera dorsalis (Hendel). In this study, a laboratory selected strain of B. dorsalis (MR) with a 21-fold higher resistance to malathion was used to examine the resistance mechanisms to this organophosphate insecticide. Carboxylesterase (CarE) was found to be involved in malathion resistance in B. dorsalis from the synergism bioassay by CarE-specific inhibitor triphenylphosphate (TPP). Molecular studies further identified a previously uncharacterized alpha-esterase gene, BdCarE2, that may function in the development of malathion resistance in B. dorsalis via gene upregulation. This gene is predominantly expressed in the Malpighian tubules, a key insect tissue for detoxification. The transcript levels of BdCarE2 were also compared between the MR and a malathion-susceptible (MS) strain of B. dorsalis, and it was significantly more abundant in the MR strain. No sequence mutation or gene copy changes were detected between the two strains. Functional studies using RNA interference (RNAi)-mediated knockdown of BdCarE2 significantly increased the malathion susceptibility in the adult files. Furthermore, heterologous expression of BdCarE2 combined with cytotoxicity assay in Sf9 cells demonstrated that BdCarE2 could probably detoxify malathion. Taken together, the current study bring new molecular evidence supporting the involvement of CarE-mediated metabolism in resistance development against malathion in B. dorsalis and also provide bases on functional analysis of insect alpha-esterase associated with insecticide resistance.
ESTHER : Wang_2016_Pestic.Biochem.Physiol_130_44
PubMedSearch : Wang_2016_Pestic.Biochem.Physiol_130_44
PubMedID: 27155483
Gene_locus related to this paper: bacdo-a0a034w7m1

Title : Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis - He_2015_Clin.Sci.(Lond)_129_49
Author(s) : He T , Hu J , Yan G , Li L , Zhang D , Zhang Q , Chen B , Huang Y
Ref : Clinical Science (Lond) , 129 :49 , 2015
Abstract : The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis.
ESTHER : He_2015_Clin.Sci.(Lond)_129_49
PubMedSearch : He_2015_Clin.Sci.(Lond)_129_49
PubMedID: 25700221

Title : Overexpression of two alpha-esterase genes mediates metabolic resistance to malathion in the oriental fruit fly, Bactrocera dorsalis (Hendel) - Wang_2015_Insect.Mol.Biol_24_467
Author(s) : Wang LL , Huang Y , Lu XP , Jiang XZ , Smagghe G , Feng ZJ , Yuan GR , Wei D , Wang JJ
Ref : Insect Molecular Biology , 24 :467 , 2015
Abstract : Esterase has been reported to be involved in malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel). However, the underlying molecular mechanism of the esterase-mediated resistance remains largely unknown in this species. Here, with the use of a strain selected for malathion resistance in the laboratory (MR), we found that two overexpressed alpha-esterase genes, namely BdCarE4 and BdCarE6, predominant in the adult midgut and fat body, function in conferring malathion resistance in B. dorsalis. Notably, these two genes were found to be mostly close to the esterase E3, which are usually implicated in detoxifying organophosphate insecticides. The transcript levels of BdCarE4 and BdCarE6 were investigated and compared between the MR and a susceptible (MS) strain of B. dorsalis. Both genes were significantly up-regulated in the MR strain, which was consistent with the enhanced esterase activity in the MR strain. However, no changes in either the coding sequence or gene copy number were observed between the two strains. Subsequently, heterologous expression combined with cytotoxicity assay in Sf9 cells demonstrated that BdCarE4 and BdCarE6 can probably detoxify malathion. Furthermore, RNA interference-mediated knockdown of each of these two genes significantly increased malathion susceptibility in the MR strain adults. In conclusion, these results expand our molecular understanding of the important role of alpha-esterases during the development of resistance to organophosphorous insecticides in B. dorsalis.
ESTHER : Wang_2015_Insect.Mol.Biol_24_467
PubMedSearch : Wang_2015_Insect.Mol.Biol_24_467
PubMedID: 25940547

Title : Resurfaced fluorescent protein as a sensing platform for label-free detection of copper(II) ion and acetylcholinesterase activity - Lei_2015_Anal.Chem_87_1974
Author(s) : Lei C , Wang Z , Nie Z , Deng H , Hu H , Huang Y , Yao S
Ref : Analytical Chemistry , 87 :1974 , 2015
Abstract : Protein engineering by resurfacing is an efficient approach to provide new molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new variant of green fluorescent protein (GFP) containing 39 histidine residues in the primary sequence that was developed by protein resurfacing. Herein, taking H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+) sensing was developed based on the unique multivalent metal ion-binding property of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further applied for the turn-on fluorescence detection of acetylcholinesterase (AChE) activity. The assay was based on the reaction between Cu(2+) and thiocholine, the hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening inhibitors of AChE. Furthermore, the practicability of this method was demonstrated by the detection of pesticide residue (carbaryl) in real food samples. Hence, the successful applications of H39GFP in the detection of metal ion and enzyme activity present the prospect of resurfaced proteins as versatile biosensing platforms.
ESTHER : Lei_2015_Anal.Chem_87_1974
PubMedSearch : Lei_2015_Anal.Chem_87_1974
PubMedID: 25560517

Title : A Promising PET Tracer for Imaging of alpha(7) Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand - Teodoro_2015_Molecules_20_18387
Author(s) : Teodoro R , Scheunemann M , Deuther-Conrad W , Wenzel B , Fasoli FM , Gotti C , Kranz M , Donat CK , Patt M , Hillmer A , Zheng MQ , Peters D , Steinbach J , Sabri O , Huang Y , Brust P
Ref : Molecules , 20 :18387 , 2015
Abstract : Changes in the expression of alpha(7) nicotinic acetylcholine receptors (alpha(7) nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET). We report on a series of new ligands for alpha(7) nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR) of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT(3) receptor, we selected the compound 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-fluorodibenzo-[b,d]thiophene 5,5-dioxide (10a) for radiolabeling and further evaluation in vivo. Radiosynthesis of [18F]10a was optimized and transferred to an automated module. Dynamic PET imaging studies with [18F]10a in piglets and a monkey demonstrated high uptake of radioactivity in the brain, followed by washout and target-region specific accumulation under baseline conditions. Kinetic analysis of [18F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [18F]10a ([18F]DBT-10) has high potential to provide clinically relevant information about the expression and availability of alpha(7) nAChR in the brain.
ESTHER : Teodoro_2015_Molecules_20_18387
PubMedSearch : Teodoro_2015_Molecules_20_18387
PubMedID: 26473809

Title : Evaluation of the sensitivity of the novel alpha4beta2* nicotinic acetylcholine receptor PET radioligand (18) F-(-)-NCFHEB to increases in synaptic acetylcholine levels in rhesus monkeys - Gallezot_2014_Synapse_68_556
Author(s) : Gallezot JD , Esterlis I , Bois F , Zheng MQ , Lin SF , Kloczynski T , Krystal JH , Huang Y , Sabri O , Carson RE , Cosgrove KP
Ref : Synapse , 68 :556 , 2014
Abstract : OBJECTIVE: (18) F-(-)-NCFHEB (also known as (18) F-(-)-Flubatine) is a new radioligand to image alpha4beta2* nicotinic acetylcholine receptors in vivo with positron emission tomography (PET), with faster kinetics than previous radioligands such as (18) F-2-F-A85380. The goal of this study was to assess the sensitivity of (18) F-(-)-NCFHEB-PET to increases in synaptic acetylcholine concentration induced by acetylcholinesterase inhibitors.
METHODS: Two rhesus monkeys were scanned four times each on a Focus 220 scanner: first at baseline, then during two bolus plus infusions of physostigmine (0.06-0.28 mg/kg), and finally following a bolus injection of donepezil (0.25 mg/kg). The arterial input function and the plasma free fraction fP were measured. (18) F-(-)-NCFHEB volume of distribution VT was estimated using the multilinear analysis MA1 and then normalized by plasma free fraction fP .
RESULTS: (18) F-(-)-NCFHEB fP was 0.89 +/- 0.04. At baseline, (18) F-(-)-NCFHEB VT /fP ranged from 7.9 +/- 1.3 mL plasma/cm(3) tissue in the cerebellum to 34.3 +/- 8.4 mL plasma/cm(3) tissue in the thalamus. Physostigmine induced a dose-dependent reduction of (18) F-(-)-NCFHEB VT /fP of 34 +/- 9% in the putamen, 32 +/- 8% in the thalamus, 25 +/- 8% in the cortex, and 23 +/- 10% in the hippocampus. With donepezil, (18) F-(-)-NCFHEB VT /fP was reduced by 24 +/- 2%, 14 + 3% and 14 +/- 5%, 10 +/- 6% in the same regions. CONCLUSION: (18) F-(-)-NCFHEB can be used to detect changes in synaptic acetylcholine concentration and is a promising tracer to study acetylcholine dynamics with shorter scan durations than previous radioligands. Synapse 68:556-564, 2014. (c) 2014 Wiley Periodicals, Inc.
ESTHER : Gallezot_2014_Synapse_68_556
PubMedSearch : Gallezot_2014_Synapse_68_556
PubMedID: 25043426

Title : Characterization of two putative prolinases (PepR1 and PepR2) from Lactobacillus plantarum WCFS1: Occurrence of two isozymes with structural similarity and different catalytic properties - Huang_2014_Biochim.Biophys.Acta_1854_91
Author(s) : Huang Y , Tanaka T
Ref : Biochimica & Biophysica Acta , 1854 :91 , 2014
Abstract : Two putative prolinases (PepR1 and PepR2) of Lactobacillus plantarum WCSF1 share 48.5% amino acid sequence identity (55.5% at the DNA level); however, PepR1 exhibits over 80% identity at the protein level with other lactobacilli prolinases while PepR2 exhibits only 51% or less identity. In this study, the putative genes were overexpressed in Escherichia coli, purified to gel electrophoretic homogeneity, and then characterized. Purified PepR1 and PepR2 hydrolyzed Pro-Xaa dipeptide substrates at similar rates, proving their nature as prolinases. Structural analyses using circular dichroism, dynamic light scattering, gel filtration, and molecular modelling revealed that the two prolinases have similar structural characteristics: high beta-sheet content, homotetrameric structure, and similar folding to the PepI/PepL/PepR peptidase family. However, kinetic and thermodynamic analyses of PepR1 and PepR2 indicated differences in many aspects: optimum temperatures (25 and 30 degrees C, respectively), optimum pH (pH7.5 and 8.0, respectively), substrate specificities (high stringency of PepR2), kinetic parameters, and thermal stability (29 and 48 degrees C, respectively). Also, these prolinases behaved differently towards inhibitor treatments, suggesting structural and/or functional differences in their active sites. Differences in the two prolinases would contribute to a diversity of catalytic activities, so that they work together cooperatively and complementarily to hydrolyze proline-containing peptides with broader specificity, working pH, working temperature, and higher efficiency, thus allowing adaptation to a wider range of environments.
ESTHER : Huang_2014_Biochim.Biophys.Acta_1854_91
PubMedSearch : Huang_2014_Biochim.Biophys.Acta_1854_91
PubMedID: 25463046

Title : Endothelial Lipase-384A\/C Polymorphism Is Associated with Acute Coronary Syndrome and Lipid Status in Elderly Uygur Patients in Xinjiang - Huang_2014_Genet.Test.Mol.Biomarkers_18_781
Author(s) : Huang D , Xie X , Ma YT , Huang Y , Ma X
Ref : Genet Test Mol Biomarkers , 18 :781 , 2014
Abstract : OBJECTIVE: To explore the relationship between the endothelial lipase (EL) gene promoter -384A/C polymorphism and acute coronary syndrome (ACS) and lipid status in elderly Uygur patients in Xinjiang.
METHODS: The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the EL gene promoter -384A/C genotype in 341 cases of elderly patients with ACS and 380 healthy subjects.
RESULTS: In an elderly Chinese Han population, the EL-384A/C genotype and allele frequency distribution were significantly different between the ACS group and the control group (p<0.05); the frequency of the CC genotype in the ACS group was significantly higher than that in the control group (p<0.05). After adjusting for gender, age, diabetes, hypertension, smoking, hyperlipidemia, and other cardiovascular risk factors, the difference remains statistically significant (p<0.05). In the ACS group, C allele carriers had significantly higher serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol concentrations compared to AA genotypes (all p<0.05). CONCLUSION: EL-384A/C polymorphism was significantly associated with the ACS and lipids profile in an elderly Uygur population in Xinjiang.
ESTHER : Huang_2014_Genet.Test.Mol.Biomarkers_18_781
PubMedSearch : Huang_2014_Genet.Test.Mol.Biomarkers_18_781
PubMedID: 25291260

Title : Purification of an amide hydrolase DamH from Delftia sp. T3-6 and its gene cloning, expression, and biochemical characterization - Wang_2014_Appl.Microbiol.Biotechnol_98_7491
Author(s) : Wang F , Hou Y , Zhou J , Li Z , Huang Y , Cui Z
Ref : Applied Microbiology & Biotechnology , 98 :7491 , 2014
Abstract : A highly active amide hydrolase (DamH) was purified from Delftia sp. T3-6 using ammonium sulfate precipitation, diethylaminoethyl anion exchange, hydrophobic interaction chromatography, and Sephadex G-200 gel filtration. The molecular mass of the purified enzyme was estimated to be 32 kDa by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The sequence of the N-terminal 15 amino acid residues was determined to be Gly-Thr-Ser-Pro-Gln-Ser-Asp-Phe-Leu-Arg-Ala-Leu-Phe-Gln-Ser. Based on the N-terminal sequence and results of peptide mass fingerprints, the gene (damH) was cloned by PCR amplification and expressed in Escherichia coli BL21(DE3). DamH was a bifunctional hydrolase showing activity to amide and ester bonds. The specific activities of recombinant DamH were 5,036 U/mg for 2'-methyl-6'-ethyl-2- chloroacetanilide (CMEPA) (amide hydrolase function) and 612 U/mg for 4-nitrophenyl acetate (esterase function). The optimum substrate of DamH was CMEPA, with K m and k cat values of 0.197 mM and 2,804.32 s(-1), respectively. DamH could also hydrolyze esters such as 4-nitrophenyl acetate, glycerol tributyrate, and caprolactone. The optimal pH and temperature for recombinant DamH were 6.5 and 35 degrees C, respectively; the enzyme was activated by Mn(2+) and inhibited by Cu(2+), Zn(2+), Ni(2+), and Fe(2+). DamH was inhibited strongly by phenylmethylsulfonyl and SDS and weakly by ethylenediaminetetraacetic acid and dimethyl sulfoxide.
ESTHER : Wang_2014_Appl.Microbiol.Biotechnol_98_7491
PubMedSearch : Wang_2014_Appl.Microbiol.Biotechnol_98_7491
PubMedID: 24723294

Title : Complete Genome Sequence of the p-Nitrophenol-Degrading Bacterium Pseudomonas putida DLL-E4 - Hu_2014_Genome.Announc_2_e00596
Author(s) : Hu X , Wang J , Wang F , Chen Q , Huang Y , Cui Z
Ref : Genome Announc , 2 : , 2014
Abstract : The first complete genome sequence of a p-nitrophenol (PNP)-degrading bacterium is reported here. Pseudomonas putida DLL-E4, a Gram-negative bacterium isolated from methyl-parathion-polluted soil, can utilize PNP as the sole carbon and nitrogen source. P. putida DLL-E4 has a 6,484,062 bp circular chromosome that contains 5,894 genes, with a G+C content of 62.46%.
ESTHER : Hu_2014_Genome.Announc_2_e00596
PubMedSearch : Hu_2014_Genome.Announc_2_e00596
PubMedID: 24948765
Gene_locus related to this paper: psepu-q9wwz4 , psepu-a0a059uyg1

Title : Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES - Weltzin_2014_Eur.J.Pharmacol_732_159
Author(s) : Weltzin MM , Huang Y , Schulte MK
Ref : European Journal of Pharmacology , 732 :159 , 2014
Abstract : A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors.
ESTHER : Weltzin_2014_Eur.J.Pharmacol_732_159
PubMedSearch : Weltzin_2014_Eur.J.Pharmacol_732_159
PubMedID: 22732654

Title : Identification of differentially expressed proteins and phosphorylated proteins in rice seedlings in response to strigolactone treatment - Chen_2014_PLoS.One_9_e93947
Author(s) : Chen F , Jiang L , Zheng J , Huang R , Wang H , Hong Z , Huang Y
Ref : PLoS ONE , 9 :e93947 , 2014
Abstract : Strigolactones (SLs) are recently identified plant hormones that inhibit shoot branching and control various aspects of plant growth, development and interaction with parasites. Previous studies have shown that plant D10 protein is a carotenoid cleavage dioxygenase that functions in SL biosynthesis. In this work, we used an allelic SL-deficient d10 mutant XJC of rice (Oryza sativa L. spp. indica) to investigate proteins that were responsive to SL treatment. When grown in darkness, d10 mutant seedlings exhibited elongated mesocotyl that could be rescued by exogenous application of SLs. Soluble protein extracts were prepared from d10 mutant seedlings grown in darkness in the presence of GR24, a synthetic SL analog. Soluble proteins were separated on two-dimensional gels and subjected to proteomic analysis. Proteins that were expressed differentially and phosphoproteins whose phosphorylation status changed in response to GR24 treatment were identified. Eight proteins were found to be induced or down-regulated by GR24, and a different set of 8 phosphoproteins were shown to change their phosphorylation intensities in the dark-grown d10 seedlings in response to GR24 treatment. Analysis of these proteins revealed that they are important enzymes of the carbohydrate and amino acid metabolic pathways and key components of the cellular energy generation machinery. These proteins may represent potential targets of the SL signaling pathway. This study provides new insight into the complex and negative regulatory mechanism by which SLs control shoot branching and plant development.
ESTHER : Chen_2014_PLoS.One_9_e93947
PubMedSearch : Chen_2014_PLoS.One_9_e93947
PubMedID: 24699514

Title : Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex - Huang_2013_J.Clin.Invest_123_3815
Author(s) : Huang Y , Wu Z , Riwanto M , Gao S , Levison BS , Gu X , Fu X , Wagner MA , Besler C , Gerstenecker G , Zhang R , Li XM , Didonato AJ , Gogonea V , Tang WH , Smith JD , Plow EF , Fox PL , Shih DM , Lusis AJ , Fisher EA , Didonato JA , Landmesser U , Hazen SL
Ref : J Clinical Investigation , 123 :3815 , 2013
Abstract : Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
ESTHER : Huang_2013_J.Clin.Invest_123_3815
PubMedSearch : Huang_2013_J.Clin.Invest_123_3815
PubMedID: 23908111

Title : Isolation and characterization of carbendazim-degrading Rhodococcus erythropolis djl-11 - Zhang_2013_PLoS.One_8_e74810
Author(s) : Zhang X , Huang Y , Harvey PR , Li H , Ren Y , Li J , Wang J , Yang H
Ref : PLoS ONE , 8 :e74810 , 2013
Abstract : Carbendazim (methyl 1H-benzimidazol-2-yl carbamate) is one of the most widely used fungicides in agriculture worldwide, but has been reported to have adverse effects on animal health and ecosystem function. A highly efficient carbendazim-degrading bacterium (strain dj1-11) was isolated from carbendazim-contaminated soil samples via enrichment culture. Strain dj1-11 was identified as Rhodococcus erythropolis based on morphological, physiological and biochemical characters, including sequence analysis of the 16S rRNA gene. In vitro degradation of carbendazim (1000 mg.L(-1)) by dj1-11 in minimal salts medium (MSM) was highly efficient, and with an average degradation rate of 333.33 mg.L(-1).d(-1) at 28 degreesC. The optimal temperature range for carbendazim degradation by dj1-11 in MSM was 25-30 degreesC. Whilst strain dj1-11 was capable of metabolizing cabendazim as the sole source of carbon and nitrogen, degradation was significantly (P<0.05) increased by addition of 12.5 mM NH4NO3. Changes in MSM pH (4-9), substitution of NH4NO3 with organic substrates as N and C sources or replacing Mg(2+) with Mn(2+), Zn(2+) or Fe(2+) did not significantly affect carbendazim degradation by dj1-11. During the degradation process, liquid chromatography-mass spectrometry (LC-MS) detected the metabolites 2-aminobenzimidazole and 2-hydroxybenzimidazole. A putative carbendazim-hydrolyzing esterase gene was cloned from chromosomal DNA of djl-11 and showed 99% sequence homology to the mheI carbendazim-hydrolyzing esterase gene from Nocardioides sp. SG-4G.
ESTHER : Zhang_2013_PLoS.One_8_e74810
PubMedSearch : Zhang_2013_PLoS.One_8_e74810
PubMedID: 24098350
Gene_locus related to this paper: 9acto-c8cp46

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

Title : Comparative genomic hybridization and transcriptome analysis with a pan-genome microarray reveal distinctions between JP2 and non-JP2 genotypes of Aggregatibacter actinomycetemcomitans - Huang_2013_Mol.Oral.Microbiol_28_1
Author(s) : Huang Y , Kittichotirat W , Mayer MP , Hall R , Bumgarner R , Chen C
Ref : Mol Oral Microbiol , 28 :1 , 2013
Abstract : It was postulated that the highly virulent JP2 genotype of Aggregatibacter actinomycetemcomitans may possess a constellation of distinct virulence determinants not found in non-JP2 genotypes. This study compared the genome content and the transcriptome of the serotype b JP2 genotype and the closely related serotype b non-JP2 genotype of A. actinomycetemcomitans. A custom-designed pan-genomic microarray of A. actinomycetemcomitans was constructed and validated against a panel of 11 sequenced reference strains. The microarray was subsequently used for comparative genomic hybridization of serotype b strains of JP2 (six strains) and non-JP2 (six strains) genotypes, and for transcriptome analysis of strains of JP2 (three strains) and non-JP2 (two strains). Two JP2-specific and two non-JP2-specific genomic islands were identified. In one instance, distinct genomic islands were found to be inserted into the same locus among strains of different genotypes. Transcriptome analysis identified five operons, including the leukotoxin operon, to have at least two genes with an expression ratio of 2 or greater between genotypes. Two of the differentially expressed operons were members of the membrane-bound nitrate reductase system (nap operon) and the Tol-Pal system of gram-negative bacterial species. This study is the first to demonstrate the differences in the full genome content and gene expression between A. actinomycetemcomitans strains of JP2 and non-JP2 genotypes. The information is essential for designing hypothesis-driven experiments to examine the pathogenic mechanisms of A. actinomycetemcomitans.
ESTHER : Huang_2013_Mol.Oral.Microbiol_28_1
PubMedSearch : Huang_2013_Mol.Oral.Microbiol_28_1
PubMedID: 23194436
Gene_locus related to this paper: aggac-i1xqw9 , aggad-c9r4e8

Title : A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides - Yi_2013_Anal.Chem_85_11464
Author(s) : Yi Y , Zhu G , Liu C , Huang Y , Zhang Y , Li H , Zhao J , Yao S
Ref : Analytical Chemistry , 85 :11464 , 2013
Abstract : Sensitive, rapid, and simple detection methods for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents are in urgent demand. A novel label-free silicon quantum dots (SiQDs)-based sensor was designed for ultrasensitive detection of pesticides. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce betaine and H2O2 which can quench the photoluminescence (PL) of SiQDs. Upon the addition of pesticides, the activity of AChE is inhibited, leading to the decrease of the generated H2O2, and hence the PL of SiQDs increases. By measuring the increase in SiQDs PL, the inhibition efficiency of pesticide to AChE activity was evaluated. It was found that the inhibition efficiency was linearly dependent on the logarithm of the pesticides concentration. Consequently, pesticides, such as carbaryl, parathion, diazinon, and phorate, were determined with the SiQDs PL sensing method. The lowest detectable concentrations for carbaryl, parathion, diazinon, and phorate reached 7.25 x 10(-9), 3.25 x 10(-8), 6.76 x 10(-8), and 1.9 x 10(-7) g/L, respectively, which were much lower than those previously reported. The detecting results of pesticide residues in food samples via this method agree well with those from high-performance liquid chromatography. The simple strategy reported here should be suitable for on-site pesticides detection, especially in combination with other portable platforms.
ESTHER : Yi_2013_Anal.Chem_85_11464
PubMedSearch : Yi_2013_Anal.Chem_85_11464
PubMedID: 24160846

Title : Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer - Sun_2013_Oncogene_32_234
Author(s) : Sun H , Jiang L , Luo X , Jin W , He Q , An J , Lui K , Shi J , Rong R , Su W , Lucchesi C , Liu Y , Sheikh MS , Huang Y
Ref : Oncogene , 32 :234 , 2013
Abstract : Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth.
ESTHER : Sun_2013_Oncogene_32_234
PubMedSearch : Sun_2013_Oncogene_32_234
PubMedID: 22349814

Title : The duck genome and transcriptome provide insight into an avian influenza virus reservoir species - Huang_2013_Nat.Genet_45_776
Author(s) : Huang Y , Li Y , Burt DW , Chen H , Zhang Y , Qian W , Kim H , Gan S , Zhao Y , Li J , Yi K , Feng H , Zhu P , Li B , Liu Q , Fairley S , Magor KE , Du Z , Hu X , Goodman L , Tafer H , Vignal A , Lee T , Kim KW , Sheng Z , An Y , Searle S , Herrero J , Groenen MA , Crooijmans RP , Faraut T , Cai Q , Webster RG , Aldridge JR , Warren WC , Bartschat S , Kehr S , Marz M , Stadler PF , Smith J , Kraus RH , Ren L , Fei J , Morisson M , Kaiser P , Griffin DK , Rao M , Pitel F , Wang J , Li N
Ref : Nat Genet , 45 :776 , 2013
Abstract : The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its beta-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
ESTHER : Huang_2013_Nat.Genet_45_776
PubMedSearch : Huang_2013_Nat.Genet_45_776
PubMedID: 23749191
Gene_locus related to this paper: anapl-BCHE , anapl-r0lw36 , anapl-r0m5n4 , anapl-thioe , anapl-u3iqr9 , anapl-r0l4n7 , anapl-u3j4v8 , anapl-u3icy5 , anapl-u3ivv9 , anapl-u3j4g1 , anapl-u3j4i2 , anapl-u3j4v5 , anapl-r0kv25 , anapl-u3ild2 , anapl-u3imh5 , anapl-b6dzk9 , anapl-u3imp7 , anapl-u3i5h5 , anapl-u3id17 , anapl-r0m1y3 , anapl-r0lhc4 , anapl-r0ktn0 , anapl-r0l8l1 , anapl-r0lin6 , anapl-r0jhf3

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J , Liu G , Liu J , Zhou H , Zhou W , Yu Q , An N , Chen Y , Cai Q , Wang B , Liu B , Min J , Huang Y , Wu H , Li Z , Zhang Y , Yin Y , Song W , Jiang J , Jackson SA , Wing RA , Chen M
Ref : Nat Commun , 4 :1595 , 2013
Abstract : The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.
ESTHER : Chen_2013_Nat.Commun_4_1595
PubMedSearch : Chen_2013_Nat.Commun_4_1595
PubMedID: 23481403
Gene_locus related to this paper: orysa-Q6ZDG3 , orysa-q6h415 , orysj-q6yse8 , orysa-q33aq0 , orybr-j3l7k2 , orybr-j3m138 , orybr-j3l6m8 , orybr-j3m3b3 , orybr-j3l8d1 , orybr-j3kza5 , orybr-j3mnb5 , orybr-j3n4p4 , orybr-j3lg73 , orybr-j3l342 , orybr-j3msi2 , orybr-j3nb83 , orybr-j3mpc5

Title : Functional alpha7beta2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid beta peptides - Liu_2012_BMC.Neurosci_13_155
Author(s) : Liu Q , Huang Y , Shen J , Steffensen S , Wu J
Ref : BMC Neurosci , 13 :155 , 2012
Abstract : BACKGROUND: beta-amyloid (Abeta) accumulation is described as a hallmark of Alzheimer's disease (AD). Abeta perturbs a number of synaptic components including nicotinic acetylcholine receptors containing alpha7 subunits (alpha7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric alpha7beta2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Abeta exposure. To extend our previous work, we evaluated the expression and pharmacology of alpha7beta2-nAChRs in hippocampal interneurons and their sensitivity to Abeta.
RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional alpha7beta2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-beta-erythroidine (DHbetaE), a nAChR beta2* subunit selective blocker, and alpha7 and beta2 subunit interaction using immunoprecipitation assay. In addition, alpha7beta2-nAChRs were sensitive to 1 nM oligomeric Abeta. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Abeta modulation of cholinergic signaling in hippocampal GABAergic interneurons via alpha7beta2-nAChRs could be an early and critical event in Abeta-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.
ESTHER : Liu_2012_BMC.Neurosci_13_155
PubMedSearch : Liu_2012_BMC.Neurosci_13_155
PubMedID: 23272676

Title : Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer's disease - Chao_2012_Bioorg.Med.Chem.Lett_22_6498
Author(s) : Chao X , He X , Yang Y , Zhou X , Jin M , Liu S , Cheng Z , Liu P , Wang Y , Yu J , Tan Y , Huang Y , Qin J , Rapposelli S , Pi R
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :6498 , 2012
Abstract : A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 5e showed the highest selectivity in inhibiting acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced beta-amyloid(1-40) aggregation, as well as had potent neuroprotective effects against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22 cells.
ESTHER : Chao_2012_Bioorg.Med.Chem.Lett_22_6498
PubMedSearch : Chao_2012_Bioorg.Med.Chem.Lett_22_6498
PubMedID: 22981331

Title : Genome sequence of the facultative anaerobic arsenite-oxidizing and nitrate-reducing bacterium Acidovorax sp. strain NO1 - Huang_2012_J.Bacteriol_194_1635
Author(s) : Huang Y , Li H , Rensing C , Zhao K , Johnstone L , Wang G
Ref : Journal of Bacteriology , 194 :1635 , 2012
Abstract : Acidovorax sp. strain NO1, isolated from gold mine soil, was shown to be a facultative anaerobic arsenite-oxidizing and nitrate-reducing bacterium. The reported draft genome predicts the presence of genes involved in arsenic metabolism, nitrate reduction, phosphate transport, and multiple metal resistances and indicates putative horizontal gene transfer events.
ESTHER : Huang_2012_J.Bacteriol_194_1635
PubMedSearch : Huang_2012_J.Bacteriol_194_1635
PubMedID: 22374962
Gene_locus related to this paper: 9burk-h0bst5 , 9burk-h0btc1 , 9burk-h0bvx7 , 9burk-h0c063 , 9burk-h0bxd3 , 9burk-h0c434 , 9burk-h0bzn8

Title : Intranasal administration of TAT-haFGF(14-154) attenuates disease progression in a mouse model of Alzheimer's disease - Lou_2012_Neurosci_223_225
Author(s) : Lou G , Zhang Q , Xiao F , Xiang Q , Su Z , Zhang L , Yang P , Yang Y , Zheng Q , Huang Y
Ref : Neuroscience , 223 :225 , 2012
Abstract : Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 ug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress.
ESTHER : Lou_2012_Neurosci_223_225
PubMedSearch : Lou_2012_Neurosci_223_225
PubMedID: 22885230

Title : First genome sequence of a Burkholderia pseudomallei Isolate in China, strain BPC006, obtained from a melioidosis patient in Hainan - Fang_2012_J.Bacteriol_194_6604
Author(s) : Fang Y , Huang Y , Li Q , Chen H , Yao Z , Pan J , Gu J , Tang B , Wang HG , Yu B , Tong YG , Zou QM , Mao XH
Ref : Journal of Bacteriology , 194 :6604 , 2012
Abstract : Melioidosis, caused by Burkholderia pseudomallei, is considered to be endemic to Northern Australia and Southeast Asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. Here we report the first genome sequence of Burkholderia pseudomallei strain BPC006, obtained from a melioidosis patient in Hainan, China. The genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp.
ESTHER : Fang_2012_J.Bacteriol_194_6604
PubMedSearch : Fang_2012_J.Bacteriol_194_6604
PubMedID: 23144371
Gene_locus related to this paper: burma-a5tq93 , burma-q62mq7

Title : Fo Shou San, an ancient Chinese herbal decoction, protects endothelial function through increasing endothelial nitric oxide synthase activity - Bi_2012_PLoS.One_7_e51670
Author(s) : Bi CWC , Xu L , Tian XY , Liu J , Zheng KY , Lau CW , Lau DT , Choi RC , Dong TTX , Huang Y , Tsim KWK
Ref : PLoS ONE , 7 :e51670 , 2012
Abstract : Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.
ESTHER : Bi_2012_PLoS.One_7_e51670
PubMedSearch : Bi_2012_PLoS.One_7_e51670
PubMedID: 23284736

Title : Fibroblast activation protein-alpha promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions - Huang_2011_Clin.Exp.Metastasis_28_567
Author(s) : Huang Y , Simms AE , Mazur A , Wang S , Leon NR , Jones B , Aziz N , Kelly T
Ref : Clinical & Experimental Metastasisis , 28 :567 , 2011
Abstract : Fibroblast activation protein-alpha (FAP) is a cell surface, serine protease of the post-prolyl peptidase family that is expressed in human breast cancer but not in normal tissues. Previously, we showed that FAP expression increased tumor growth rates in a mouse model of human breast cancer. Here the role of the proteolytic activities of FAP in promoting tumor growth, matrix degradation and invasion was investigated. Mammary fat pads of female SCID mice were inoculated with breast cancer cells that express FAP and the mice treated with normal saline or Val-boroPro (talabostat); Glu-boroPro (PT-630); or 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine (LAF-237) that inhibit prolyl peptidases. Other mice were injected with breast cancer cells expressing a catalytically inactive mutant of FAP and did not receive inhibitor treatment. PT-630 and LAF-237 did not slow growth of tumors produced by any of the three cell lines expressing FAP. Talabostat slightly decreased the growth rates of the FAP-expressing tumors but because PT-630 and LAF-237 did not, the growth retardation was likely not related to the inhibition of FAP or the related post-prolyl peptidase dipeptidyl peptidase IV. Breast cancer cells expressing a catalytically inactive mutant of FAP (FAP(S624A)) also produced tumors that grew rapidly. In vitro studies revealed that cells expressing wild type FAP or FAP(S624A) degrade extracellular matrix (ECM) more extensively, accumulate higher levels of matrix metalloproteinase-9 (MMP-9) in conditioned medium, are more invasive in type I collagen gels, and have altered signaling compared to control transfectants that do not express FAP and form slow growing tumors. We conclude that the proteolytic activity of FAP participates in matrix degradation, but other functions of the protein stimulate increased tumor growth.
ESTHER : Huang_2011_Clin.Exp.Metastasis_28_567
PubMedSearch : Huang_2011_Clin.Exp.Metastasis_28_567
PubMedID: 21604185

Title : Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases - Hu_2011_J.Chromatogr.A_1218_6646
Author(s) : Hu Z , Sun Y , Du F , Niu W , Xu F , Huang Y , Li C
Ref : Journal of Chromatography A , 1218 :6646 , 2011
Abstract : Simmitecan (L-P) is an anticancer ester prodrug, which involves activation to chimmitecan (L-2-Z). In the current study, a liquid chromatography/tandem mass spectrometry-based method was developed for simultaneous determination of L-P and L-2-Z in various plasma samples. Because L-P is rapidly converted to L-2-Z by blood carboxylesterase during and after sampling, which hampers accurate determination of L-P and L-2-Z in the biological samples, different carboxylesterase inhibitors were tested. As a result, bis(4-nitrophenyl)phosphate gave the best results with respect to inhibitory capability, hemolysis, and matrix effects and was used to deactivate blood carboxylesterases when sampling. The plasma samples were precipitated with acetonitrile and the resulting supernatants were separated using a pulse gradient method on a C18 column. Irinotecan and camptothecin were used as internal standards for quantification of L-P and L-2-Z, respectively. Protonated L-P, L-2-Z and their internal standards were generated by electrospray ionization and their precursor-product ion pairs (m/z 599-->124, 405-->361, 587-->195, and 349-->305, respectively) were used for measurement. The newly developed bioanalytical assay processed favorable accuracy and precision with lower limits of quantification of 2.1 nM for L-P and 3.4 nM for L-2-Z, and was successfully applied to pharmacokinetic studies in tumor-bearing nude mice, rats, and dogs. There are substantial species differences in the ester activity. The experimental strategies illustrated in our report may be adopted for measurement of other prodrugs (including irinotecan) or drugs subject to ester hydrolysis, as well as their metabolites, in biological matrices.
ESTHER : Hu_2011_J.Chromatogr.A_1218_6646
PubMedSearch : Hu_2011_J.Chromatogr.A_1218_6646
PubMedID: 21839460

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

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

Title : Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques - Yan_2011_Nat.Biotechnol_29_1019
Author(s) : Yan G , Zhang G , Fang X , Zhang Y , Li C , Ling F , Cooper DN , Li Q , Li Y , van Gool AJ , Du H , Chen J , Chen R , Zhang P , Huang Z , Thompson JR , Meng Y , Bai Y , Wang J , Zhuo M , Wang T , Huang Y , Wei L , Li J , Wang Z , Hu H , Yang P , Le L , Stenson PD , Li B , Liu X , Ball EV , An N , Huang Q , Fan W , Zhang X , Wang W , Katze MG , Su B , Nielsen R , Yang H , Wang X
Ref : Nat Biotechnol , 29 :1019 , 2011
Abstract : The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.
ESTHER : Yan_2011_Nat.Biotechnol_29_1019
PubMedSearch : Yan_2011_Nat.Biotechnol_29_1019
PubMedID: 22002653
Gene_locus related to this paper: macfa-BCHE , macfa-g7nzc0 , macfa-g7nze2 , macfa-g7p4b9 , macfa-g7pa87 , macfa-g7pd01 , macfa-g7q259 , macfa-3neur , macfa-g8f585 , macfa-KANSL3 , macfa-q4r8p0 , macfa-SPG21 , macfa-TEX30 , macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6sz31 , macmu-f6the6 , macmu-f6zkq5 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-g7npb8 , macmu-g7nq39 , macmu-KANSL3 , macmu-TEX30 , macfa-g7pgg6 , macmu-g7n4x3 , macfa-g7nzx2 , macfa-g8f4f7 , macmu-f7ba84 , macfa-g7psx7 , macmu-h9er02 , macfa-g8f3k0 , macfa-a0a2k5w1n7 , macmu-g7mxj6 , macfa-g7pbk1 , macfa-a0a2k5urk5 , macfa-a0a2k5wye4 , macfa-g7pe14 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macfa-g7nxn9 , macmu-a0a1d5rh04 , macmu-h9fud6 , macfa-g8f3e1 , macfa-i7gcw6 , macmu-f6qwx1 , macmu-f7h4t2 , macfa-a0a2k5wkd0 , macfa-a0a2k5v7v4 , macfa-g7p7y3 , macfa-a0a2k5uqq3 , macmu-i2cu80 , macfa-g8f5i1 , macmu-f7h550 , macmu-f7gkb9 , macfa-a0a2k5tui1

Title : Novel lipolytic genes from the microbial metagenomic library of the South China Sea marine sediment - Hu_2010_FEMS.Microbiol.Ecol_72_228
Author(s) : Hu Y , Fu C , Huang Y , Yin Y , Cheng G , Lei F , Lu N , Li J , Ashforth EJ , Zhang L , Zhu B
Ref : FEMS Microbiol Ecol , 72 :228 , 2010
Abstract : Metagenomic cloning is a powerful tool for the discovery of novel genes and biocatalysts from environmental microorganisms. Based on activity screening of a marine sediment microbial metagenomic library, a total of 19 fosmid clones showing lipolytic activity were identified. After subcloning, 15 different lipolytic genes were obtained; their encoded proteins showed 32-68% amino acid identity with proteins in the database. Multiple sequence alignment and phylogenetic tree analysis demonstrated that most of these predicted proteins are new members of known families of bacterial lipolytic enzymes. However, two proteins, FLS18C and FLS18D, could not be assigned to any known family, thus probably representing a novel family of the bacterial lipolytic enzyme. The activity assay results indicated that most of these lipolytic enzymes showed optimum temperature for hydrolysis at 40-50 degrees C with p-nitrophenol butyrate as a substrate. The lipolytic gene fls18D was overexpressed, and the resulting protein FLS18D was characterized as an alkaline esterase. Furthermore, the whole sequence of fosmid pFL18 containing FLS18C and FLS18D was shotgun sequenced, and a total of 26 ORFs on it were analyzed and annotated.
ESTHER : Hu_2010_FEMS.Microbiol.Ecol_72_228
PubMedSearch : Hu_2010_FEMS.Microbiol.Ecol_72_228
PubMedID: 20337707
Gene_locus related to this paper: 9bact-b8y567 , 9bact-b8y568 , 9bact-b8y561 , 9bact-b8y562 , 9bact-b8y566 , 9bact-b8y553 , 9bact-b8y558 , 9bact-b8y563

Title : Deregulation of sphingolipid metabolism in Alzheimer's disease - He_2010_Neurobiol.Aging_31_398
Author(s) : He X , Huang Y , Li B , Gong CX , Schuchman EH
Ref : Neurobiology of Aging , 31 :398 , 2010
Abstract : Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta (Abeta) peptide and hyperphosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Abeta oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pre-treatment of the neurons with purified, recombinant AC prevented the cells from undergoing Abeta-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Abeta deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis.
ESTHER : He_2010_Neurobiol.Aging_31_398
PubMedSearch : He_2010_Neurobiol.Aging_31_398
PubMedID: 18547682

Title : [Molecular characterization and evolutional analysis of liportein lipase and hepatic lipase gene in Chinese Sturgeon and other six freshwater fishes] - Huang_2010_Dongwuxue.Yanjiu_31_239
Author(s) : Huang Y , Liang XF , Wang L , Li GZ , Liu XX , Yao Y
Ref : Dongwuxue Yanjiu , 31 :239 , 2010
Abstract : In order to study the structural, functional and molecular evolutional relationship of fish liportein lipase (LPL) and hepatic lipase (HL) genes, seven liver LPL and HL cDNA partial sequences were isolated from Acipenser sinensis, Hypophthalmichthys molitrix, Aristichthys nobilis, Ctenopharyngodon idellus, Cirrhinus molitorella, Oreochromis niloticus, Channa maculate by RT-PCR. Three full-length cDNA sequences of LPL, HL of Acipenser sinensis and LPL of Hypophthalmichthys molitrix were obtained by RACEs. From the sequence analysis and homologous results, the amino acid sequences of LPL and HL are relatively conserved in mammals, birds and fishes. Taken together with these obtained amino acid sequences and sequences of all known LPL, HL, EL and PL from other vertebrates, a phylogenetic tree was constructed by neighbor-joining method. The result supports that all of them belong to lipase family.
ESTHER : Huang_2010_Dongwuxue.Yanjiu_31_239
PubMedSearch : Huang_2010_Dongwuxue.Yanjiu_31_239
PubMedID: 20672411
Gene_locus related to this paper: acibe-a0a075ekg6 , oreni-i3j210 , hypmo-g7z072

Title : Optimization of lipase-catalyzed transesterification of lard for biodiesel production using response surface methodology - Huang_2010_Appl.Biochem.Biotechnol_160_504
Author(s) : Huang Y , Zheng H , Yan Y
Ref : Appl Biochem Biotechnol , 160 :504 , 2010
Abstract : Biodiesel, an alternative diesel fuel made from renewable biological resources, has become more and more attractive recently. Combined use of two immobilized lipases with complementary position specificity instead of one lipase is a potential way to significantly reduce cost of lipase-catalyzed biodiesel production. In this study, the process of biodiesel production from lard catalyzed by the combined use of Novozym435 (non-specific) and Lipozyme TLIM (1,3-specific) was optimized by response surface methodology. The optimal reaction conditions were 0.04 of amount of lipase/oil (w/w), 0.49 of proportion of Novozym435/total lipases (w/w), 0.55 of quantity of tert-butanol/oil (v/v), 5.12 of quantity of methanol/oil (mol/mol), and 20 h of reaction time, by which 97.2% of methyl ester (ME) yield was attained, very close to the predicted value (97.6%). This optimal reaction condition could be true of other similar reactions with plant and animal oil resources; their ME yield could be higher than 95%. The lipases regenerated by washing with organic solvent after each reaction cycle could be continuously reused for 20 cycles without any loss of activity, exhibiting very high manipulation stability.
ESTHER : Huang_2010_Appl.Biochem.Biotechnol_160_504
PubMedSearch : Huang_2010_Appl.Biochem.Biotechnol_160_504
PubMedID: 18931953

Title : DPP-4 (CD26) inhibitor alogliptin inhibits TLR4-mediated ERK activation and ERK-dependent MMP-1 expression by U937 histiocytes - Ta_2010_Atherosclerosis_213_429
Author(s) : Ta NN , Li Y , Schuyler CA , Lopes-Virella MF , Huang Y
Ref : Atherosclerosis , 213 :429 , 2010
Abstract : Dipeptidyl peptidase-4 (DPP-4)/CD26, a cell surface glycoprotein, is expressed by a variety of cells including T cells, B cells, NK cells, and macrophages. Although it has been shown that DPP-4/CD26 is involved in T cell activation, its role in biological functions in macrophages has not been well investigated. In this study, we used alogliptin, a specific inhibitor of DPP 4/CD26, to study the effect of DPP-4/CD26 on the activation of the extracellular signal-regulated kinase (ERK) that plays a critical role in the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) in U937 histiocytes. Results showed that 1nM of alogliptin inhibited ERK phosphorylation induced by lipopolysaccharide (LPS), a ligand for toll-like receptor (TLR)4, by 91%. Furthermore, results showed that alogliptin inhibited LPS-stimulated MMP-1 expression in a concentration-dependent manner and 1nM of alogliptin inhibited MMP-1 expression by 60%. To confirm the involvement of the ERK pathway in MMP-1 expression by U937 cells, we showed that PD98059, a specific inhibitor for the ERK pathway, blocked LPS-stimulated MMP-1 expression. In addition to MMP-1, our study showed that alogliptin also inhibited MMP-9, -12 and -15, but had no effect on TIMP-1 and -2 expression. Taken together, this study showed for the first time that the inhibition of DPP-4/CD26 by alogliptin suppressed TLR4-mediated ERK activation and ERK-dependent MMP expression by U937 cells, suggesting that DPP-4/CD26 may play an important role in macrophage-mediated inflammation response and tissue remodeling.
ESTHER : Ta_2010_Atherosclerosis_213_429
PubMedSearch : Ta_2010_Atherosclerosis_213_429
PubMedID: 20843518

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

Title : A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors - Hu_2009_Biotechnol.Lett_31_979
Author(s) : Hu CX , Huang H , Zhang L , Huang Y , Shen ZF , Cheng KD , Du GH , Zhu P
Ref : Biotechnol Lett , 31 :979 , 2009
Abstract : Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC(50) of 6.5 microM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z' value of 0.73 and S/N ratio of 6.89.
ESTHER : Hu_2009_Biotechnol.Lett_31_979
PubMedSearch : Hu_2009_Biotechnol.Lett_31_979
PubMedID: 19267232

Title : A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides - Liu_2009_J.Neurosci_29_918
Author(s) : Liu Q , Huang Y , Xue F , Simard AR , DeChon J , Li G , Zhang J , Lucero L , Wang M , Sierks M , Hu G , Chang Y , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 29 :918 , 2009
Abstract : Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies.
ESTHER : Liu_2009_J.Neurosci_29_918
PubMedSearch : Liu_2009_J.Neurosci_29_918
PubMedID: 19176801

Title : Morphing activity between structurally similar enzymes: from heme-free bromoperoxidase to lipase - Chen_2009_Biochemistry_48_11496
Author(s) : Chen B , Cai Z , Wu W , Huang Y , Pleiss J , Lin Z
Ref : Biochemistry , 48 :11496 , 2009
Abstract : In this study, to explore the plasticity of the alpha/beta-hydrolase fold family, we converted bromoperoxidase A2 (BPO-A2) from Streptomyces aureofaciens to a lipase by structure comparison with lipase A (LipA) from Bacillus subtilis. These two enzymes have similar structures (2.1 A rmsd) and a very low level of sequence identity ( approximately 18%). A variant BL1 was constructed by deleting the caplike domain of BPO-A2 and further fine-tuning the newly formed substrate binding site. The lipase activity was successfully transplanted on BL1, while the halogenation activity was totally lost. BL1 also showed higher hydrolytic activities toward long chain p-nitrophenyl esters, such as p-nitrophenyl caprylate (3.7-fold) and p-nitrophenyl palmitate (7.0-fold), while its activity toward a short chain ester (p-nitrophenyl acetate) decreased dramatically, to only 1.2% of that of BPO-A2. After two rounds of directed evolution and site-directed mutagenesis on selected residues, several mutants with both improved hydrolytic activities and substrate preferences toward long chain substrates were obtained. The highest hydrolytic activity toward p-nitrophenyl palmitate of the best mutant BL1-2-E8-plusI was improved by 40-fold compared with that of BL1. These results demonstrate the possibility of manipulating the caplike domain of alpha/beta-hydrolase fold enzymes and provide further understanding of the structure-function relationship of the alpha/beta-hydrolase fold enzymes. The design strategy used in this study could serve as a useful approach for constructing variants with targeted catalytic properties using the alpha/beta-hydrolase fold.
ESTHER : Chen_2009_Biochemistry_48_11496
PubMedSearch : Chen_2009_Biochemistry_48_11496
PubMedID: 19883129

Title : The complete genome and proteome of Laribacter hongkongensis reveal potential mechanisms for adaptations to different temperatures and habitats - Woo_2009_PLoS.Genet_5_e1000416
Author(s) : Woo PC , Lau SK , Tse H , Teng JL , Curreem SO , Tsang AK , Fan RY , Wong GK , Huang Y , Loman NJ , Snyder LA , Cai JJ , Huang JD , Mak W , Pallen MJ , Lok S , Yuen KY
Ref : PLoS Genet , 5 :e1000416 , 2009
Abstract : Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish-borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors-such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases-are present. Proteomes of L. hongkongensis HLHK9 cultured at 37 degrees C (human body temperature) and 20 degrees C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)-NAGK-20 and NAGK-37-in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20 degrees C, whereas NAGK-37 showed higher expression at 37 degrees C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria. Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.
ESTHER : Woo_2009_PLoS.Genet_5_e1000416
PubMedSearch : Woo_2009_PLoS.Genet_5_e1000416
PubMedID: 19283063
Gene_locus related to this paper: larhh-c1d5s6 , larhh-c1d7j8 , larhh-c1d8b4 , larhh-c1d8q3 , larhh-c1db23 , larhh-metx , larhh-c1d9y5

Title : Human recombinant butyrylcholinesterase purified from the milk of transgenic goats interacts with beta-amyloid fibrils and suppresses their formation in vitro - Podoly_2008_Neurodegener.Dis_5_232
Author(s) : Podoly E , Bruck T , Diamant S , Melamed-Book N , Weiss A , Huang Y , Livnah O , Langermann S , Wilgus H , Soreq H
Ref : Neurodegener Dis , 5 :232 , 2008
Abstract : BACKGROUND In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with beta-amyloid (Abeta) fibrils.
AIMS: In vitro testing of the significance of this phenomenon to AD progress.
METHODS: A thioflavine T (ThT) fluorogenic assay, photo-induced cross-linking and quantifiable electron microscopy served to compare the effect on Abeta fibril formation induced by highly purified recombinant human BChE (rBChE) produced in the milk of transgenic goats with that of serum-derived human BChE.
RESULTS: Both proteins at 1:50 and 1:25 ratios to Abeta dose-dependently prolonged the ThT lag time and reduced the apparent rate of Abeta fibril formation compared to Abeta alone. Photo-induced cross-linking tests showed that rBChE prolonged the persistence of amyloid dimers, trimers and tetramers in solution, whereas Abeta alone facilitated precipitation of such multimers from solution. Transmission electron microscopy showed that rBChE at 1:100 to Abeta prevented the formation of larger, over 150-nm-long, Abeta fibrils and reduced fibril branching compared to Abeta alone as quantified by macro programming of Image Pro Plus software.
CONCLUSION: Our findings demonstrate that rBChE interacts with Abeta fibrils and can attenuate their formation, extension and branching, suggesting further tests of rBChE, with unlimited supply and no associated health risks, as a therapeutic agent for delaying the formation of amyloid toxic oligomers in AD patients.
ESTHER : Podoly_2008_Neurodegener.Dis_5_232
PubMedSearch : Podoly_2008_Neurodegener.Dis_5_232
PubMedID: 18322399

Title : Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin - Huang_2008_BMC.Biotechnol_8_50
Author(s) : Huang YJ , Lundy PM , Lazaris A , Huang Y , Baldassarre H , Wang B , Turcotte C , Cote M , Bellemare A , Bilodeau AS , Brouillard S , Touati M , Herskovits P , Begin I , Neveu N , Brochu E , Pierson J , Hockley DK , Cerasoli DM , Lenz DE , Wilgus H , Karatzas CN , Langermann S
Ref : BMC Biotechnol , 8 :50 , 2008
Abstract : BACKGROUND: Human butyrylcholinesterase (huBChE) has been shown to be an effective antidote against multiple LD50 of organophosphorus compounds. A prerequisite for such use of huBChE is a prolonged circulatory half-life. This study was undertaken to produce recombinant huBChE fused to human serum albumin (hSA) and characterize the fusion protein.
RESULTS: Secretion level of the fusion protein produced in vitro in BHK cells was approximately 30 mg/liter. Transgenic mice and goats generated with the fusion constructs expressed in their milk a bioactive protein at concentrations of 0.04-1.1 g/liter. BChE activity gel staining and a size exclusion chromatography (SEC)-HPLC revealed that the fusion protein consisted of predominant dimers and some monomers. The protein was confirmed to have expected molecular mass of approximately 150 kDa by Western blot. The purified fusion protein produced in vitro was injected intravenously into juvenile pigs for pharmacokinetic study. Analysis of a series of blood samples using the Ellman assay revealed a substantial enhancement of the plasma half-life of the fusion protein (approximately 32 h) when compared with a transgenically produced huBChE preparation containing >70% tetramer (approximately 3 h). In vitro nerve agent binding and inhibition experiments indicated that the fusion protein in the milk of transgenic mice had similar inhibition characteristics compared to human plasma BChE against the nerve agents tested. CONCLUSION: Both the pharmacokinetic study and the in vitro nerve agent binding and inhibition assay suggested that a fusion protein retaining both properties of huBChE and hSA is produced in vitro and in vivo. The production of the fusion protein in the milk of transgenic goats provided further evidence that sufficient quantities of BChE/hSA can be produced to serve as a cost-effective and reliable source of BChE for prophylaxis and post-exposure treatment.
ESTHER : Huang_2008_BMC.Biotechnol_8_50
PubMedSearch : Huang_2008_BMC.Biotechnol_8_50
PubMedID: 18485214

Title : [The -384A >C polymorphism of endothelial lipase gene promoter region in Chinese healthy normolipidemic and endogenous hypertriglyceridemic subjects] - Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
Author(s) : Huang Y , Bai H , Fan P , Liu R , Liu Y , Liu BW
Ref : Zhonghua Yi Xue Yi Chuan Xue Za Zhi , 25 :443 , 2008
Abstract : OBJECTIVE: To investigate the effects of the -384A>C polymorphism in the promoter region of endothelial lipase (EL) gene on serum lipid and apolipoprotein levels in healthy normolipidemic (HTG) and endogenous hypertriglyceridemic (HTG) subjects.
METHODS: Two hundred and fourteen healthy normolipidemic and 103 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the radial immunadiffussion kits.
RESULTS: The frequency of the C allele at the -384A>C site in EL gene in the population (0.178) was higher than that of Japanese population (0.119) and Japanese Americans (0.115) (P < 0.01 and P < 0.01), respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers (A/C and C/C genotype carriers) had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA (5.23 +/- 0.74 mmol/L vs 4.93 +/- 0.74 mmol/L, P=0.025; 3.27 +/- 0.74 mmol/L vs 2.98 +/- 0.80 mmol/L, P=0.038; 3.81 +/- 0.73 mmol/L vs 3.49 +/- 0.85 mmol/L, P=0.031, respectively). Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group. CONCLUSION: These results suggest that the -384A>C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.
ESTHER : Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
PubMedSearch : Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
PubMedID: 18683147

Title : [Directed evolution of lipase of Bacillus pumilus YZ02 by error-prone PCR] - Huang_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_445
Author(s) : Huang Y , Cai Y , Yang J , Yan Y
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :445 , 2008
Abstract : Random mutagenesis on Bacillus pumilus lipase YZ02 gene was conducted by using error-prone PCR strategy. Through two cycles of directed evolution, two optimum mutants BpL1-7 and BpL2-1369 with lipase activity improved 2 folds and 6 folds respectively were screened. The sequence of BpL2-1369 lipase gene showed that four nucleotides substitution, T61C, C147T, A334G and T371A have occurred, and three of them caused amino acid changes. Thus, amine acid Ser21 was changed into Pro21, Arg112 to Gly112, and Leu124 to His124. According to the 3D structure of Bacillus pumilus lipase mimicked by SWISS-MODEL Repository, three mutated amino acids were located at the third amino acid of the first alpha-helix, the turn between the fourth and fifth beta fold, and the first amino acid of the fifth beta fold, respectively. The BpL and BpL2-1369 genes were ligated into pET28a vector, and transferred into E. coli BL21 (DE3). After induced by IPTG the lipases were purified and characterized. The results showed that the specific activity of the evolved lipase was 1.31-fold than that of the wild lipase, and the Km decreased from 8.24 mmol/L to 7.17 mmol/L. The pH stability of the evolved lipase was better than wild lipase when pH>8.0.
ESTHER : Huang_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_445
PubMedSearch : Huang_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_445
PubMedID: 18589821

Title : Lipase-catalyzed biodiesel production with methyl acetate as acyl acceptor - Huang_2008_Z.Naturforsch.C_63_297
Author(s) : Huang Y , Yan Y
Ref : Z Naturforsch C , 63 :297 , 2008
Abstract : Biodiesel is an alternative diesel fuel made from renewable biological resources. During the process of biodiesel production, lipase-catalyzed transesterification is a crucial step. However, current techniques using methanol as acyl acceptor have lower enzymatic activity; this limits the application of such techniques in large-scale biodiesel production. Furthermore, the lipid feedstock of currently available techniques is limited. In this paper, the technique of lipase-catalyzed transesterification of five different oils for biodiesel production with methyl acetate as acyl acceptor was investigated, and the transesterification reaction conditions were optimized. The operation stability of lipase under the obtained optimal conditions was further examined. The results showed that under optimal transesterification conditions, both plant oils and animal fats led to high yields of methyl ester: cotton-seed oil, 98%; rapeseed oil, 95%; soybean oil, 91%; tea-seed oil, 92%; and lard, 95%. Crude and refined cottonseed oil or lard made no significant difference in yields of methyl ester. No loss of enzymatic activity was detected for lipase after being repeatedly used for 40 cycles (ca. 800 h), which indicates that the operational stability of lipase was fairly good under these conditions. Our results suggest that cotton-seed oil, rape-seed oil and lard might substitute soybean oil as suitable lipid feedstock for biodiesel production. Our results also show that our technique is fit for various lipid feedstocks both from plants and animals, and presents a very promising way for the large-scale biodiesel production.
ESTHER : Huang_2008_Z.Naturforsch.C_63_297
PubMedSearch : Huang_2008_Z.Naturforsch.C_63_297
PubMedID: 18533477

Title : Type 2 diabetes mellitus and endothelial lipase - Shiu_2008_Atherosclerosis_198_441
Author(s) : Shiu SW , Tan KC , Huang Y , Wong Y
Ref : Atherosclerosis , 198 :441 , 2008
Abstract : OBJECTIVE: Endothelial lipase (EL), a new member of the triacylglycerol lipase family, modulates the metabolism of high-density lipoproteins and is upregulated by inflammatory cytokines. Since type 2 diabetes is associated with chronic subclinical inflammation, we have determined whether serum EL concentration is increased in type 2 diabetes and investigated the effect of insulin on EL. METHODS: 237 type 2 diabetic patients on oral anti-diabetic agents, 111 type 2 diabetic patients on insulin therapy and 226 non-diabetic controls were recruited. Serum EL was measured by ELISA. To investigate the effect of insulin on EL production by endothelial cells, human aortic endothelial cells were incubated with insulin and EL mRNA and protein in cell medium was measured. Serum EL was also measured in 16 diabetic subjects before and after starting insulin therapy. RESULTS: Serum EL level was highest in patients on oral anti-diabetic agents whereas those on insulin had similar EL level as controls (oral: 26.7+/-16.1ng/ml; insulin: 23.3+/-11.6, controls: 23.9+/-12.0; ANOVA p=0.04). In both controls and patients on oral anti-diabetic agents, EL correlated with log(CRP) (r=0.20, p=0.003; r=0.23, p<0.001, respectively) but no correlation was seen in patients on insulin. In vitro experiments showed that insulin significantly reduced EL mRNA and protein in human aortic endothelial cells in a dose-dependent manner. Serum EL concentration also significantly decreased in diabetic patients after starting insulin therapy (p<0.03). CONCLUSION: Serum EL concentration was increased in type 2 diabetic patients and was associated with the degree of subclinical inflammation and exogenous insulin therapy lowered serum EL concentration.
ESTHER : Shiu_2008_Atherosclerosis_198_441
PubMedSearch : Shiu_2008_Atherosclerosis_198_441
PubMedID: 18433755

Title : Genome characteristics of facultatively symbiotic Frankia sp. strains reflect host range and host plant biogeography - Normand_2007_Genome.Res_17_7
Author(s) : Normand P , Lapierre P , Tisa LS , Gogarten JP , Alloisio N , Bagnarol E , Bassi CA , Berry AM , Bickhart DM , Choisne N , Couloux A , Cournoyer B , Cruveiller S , Daubin V , Demange N , Francino MP , Goltsman E , Huang Y , Kopp OR , Labarre L , Lapidus A , Lavire C , Marechal J , Martinez M , Mastronunzio JE , Mullin BC , Niemann J , Pujic P , Rawnsley T , Rouy Z , Schenowitz C , Sellstedt A , Tavares F , Tomkins JP , Vallenet D , Valverde C , Wall LG , Wang Y , Medigue C , Benson DR
Ref : Genome Res , 17 :7 , 2007
Abstract : Soil bacteria that also form mutualistic symbioses in plants encounter two major levels of selection. One occurs during adaptation to and survival in soil, and the other occurs in concert with host plant speciation and adaptation. Actinobacteria from the genus Frankia are facultative symbionts that form N(2)-fixing root nodules on diverse and globally distributed angiosperms in the "actinorhizal" symbioses. Three closely related clades of Frankia sp. strains are recognized; members of each clade infect a subset of plants from among eight angiosperm families. We sequenced the genomes from three strains; their sizes varied from 5.43 Mbp for a narrow host range strain (Frankia sp. strain HFPCcI3) to 7.50 Mbp for a medium host range strain (Frankia alni strain ACN14a) to 9.04 Mbp for a broad host range strain (Frankia sp. strain EAN1pec.) This size divergence is the largest yet reported for such closely related soil bacteria (97.8%-98.9% identity of 16S rRNA genes). The extent of gene deletion, duplication, and acquisition is in concert with the biogeographic history of the symbioses and host plant speciation. Host plant isolation favored genome contraction, whereas host plant diversification favored genome expansion. The results support the idea that major genome expansions as well as reductions can occur in facultative symbiotic soil bacteria as they respond to new environments in the context of their symbioses.
ESTHER : Normand_2007_Genome.Res_17_7
PubMedSearch : Normand_2007_Genome.Res_17_7
PubMedID: 17151343
Gene_locus related to this paper: frasn-a8leg3 , fraaa-q0rau9 , fraaa-q0rbj9 , fraaa-q0rc03 , fraaa-q0rc89 , fraaa-q0rci1 , fraaa-q0rdx4 , fraaa-q0ref4 , fraaa-q0rel4 , fraaa-q0req5 , fraaa-q0rev2 , fraaa-q0rfl4 , fraaa-q0rfz5 , fraaa-q0rhz6 , fraaa-q0rjm3 , fraaa-q0rjt2 , fraaa-q0rkm8 , fraaa-q0rkv5 , fraaa-q0rl43 , fraaa-q0rlp9 , fraaa-q0rm04 , fraaa-q0rmn2 , fraaa-q0rmz5 , fraaa-q0rqg7 , fraaa-q0rr69 , fraaa-q0rrm7 , fraaa-q0rs07 , fraaa-q0rt07 , fraaa-q0rt55 , fraaa-q0rt70 , fraaa-q0rt91 , fraaa-q0rtc4 , fraaa-q0rte4 , fraaa-q0rtv2 , fraaa-q0rum6 , frasc-q2j5v5 , frasc-q2j8e6 , frasc-q2jct6 , frasn-a8kx42 , frasn-a8kyp2 , frasn-A8L0F8 , frasn-a8l0g7 , frasn-a8l1j7 , frasn-a8l1t9 , frasn-a8l4h8 , frasn-a8l7f8 , frasn-a8l8i4 , frasn-a8l8k8 , frasn-a8l9e9 , frasn-a8l051 , frasn-a8l115 , frasn-a8l161 , frasn-a8l265 , frasn-a8l268 , frasn-a8l720 , frasn-a8l745 , frasn-a8l755 , frasn-a8l875 , frasn-a8lab3 , frasn-a8lag3 , frasn-a8lb99 , frasn-a8lbd8 , frasn-a8lbj7 , frasn-a8lbj8 , frasn-a8lby7 , frasn-a8ldb7 , frasn-a8ldd0 , frasn-a8le91 , frasn-a8leg6 , frasn-a8leq6 , frasn-a8let0 , frasn-a8lf43 , frasn-a8lfg3 , frasn-a8lfl1 , frasn-a8lgw1 , frasn-a8lgy1 , frasc-q2j553 , frasn-a8l2m3 , fraaa-q0rd38 , frasc-q2j6h2 , frasn-a8lfl3 , frasn-a8leg7 , frasn-a8l5b8 , fraaa-q0rgz4 , fraaa-q0rtv3 , frasn-a8le98 , frasn-a8leb4

Title : Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning - Huang_2007_Proc.Natl.Acad.Sci.U.S.A_104_13603
Author(s) : Huang YJ , Huang Y , Baldassarre H , Wang B , Lazaris A , Leduc M , Bilodeau AS , Bellemare A , Cote M , Herskovits P , Touati M , Turcotte C , Valeanu L , Lemee N , Wilgus H , Begin I , Bhatia B , Rao K , Neveu N , Brochu E , Pierson J , Hockley DK , Cerasoli DM , Lenz DE , Karatzas CN , Langermann S
Ref : Proc Natl Acad Sci U S A , 104 :13603 , 2007
Abstract : Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat beta-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.
ESTHER : Huang_2007_Proc.Natl.Acad.Sci.U.S.A_104_13603
PubMedSearch : Huang_2007_Proc.Natl.Acad.Sci.U.S.A_104_13603
PubMedID: 17660298

Title : The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease - El-Sayed_2005_Science_309_409
Author(s) : El-Sayed NM , Myler PJ , Bartholomeu DC , Nilsson D , Aggarwal G , Tran AN , Ghedin E , Worthey EA , Delcher AL , Blandin G , Westenberger SJ , Caler E , Cerqueira GC , Branche C , Haas B , Anupama A , Arner E , Aslund L , Attipoe P , Bontempi E , Bringaud F , Burton P , Cadag E , Campbell DA , Carrington M , Crabtree J , Darban H , da Silveira JF , de Jong P , Edwards K , Englund PT , Fazelina G , Feldblyum T , Ferella M , Frasch AC , Gull K , Horn D , Hou L , Huang Y , Kindlund E , Klingbeil M , Kluge S , Koo H , Lacerda D , Levin MJ , Lorenzi H , Louie T , Machado CR , McCulloch R , McKenna A , Mizuno Y , Mottram JC , Nelson S , Ochaya S , Osoegawa K , Pai G , Parsons M , Pentony M , Pettersson U , Pop M , Ramirez JL , Rinta J , Robertson L , Salzberg SL , Sanchez DO , Seyler A , Sharma R , Shetty J , Simpson AJ , Sisk E , Tammi MT , Tarleton R , Teixeira S , Van Aken S , Vogt C , Ward PN , Wickstead B , Wortman J , White O , Fraser CM , Stuart KD , Andersson B
Ref : Science , 309 :409 , 2005
Abstract : Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
ESTHER : El-Sayed_2005_Science_309_409
PubMedSearch : El-Sayed_2005_Science_309_409
PubMedID: 16020725
Gene_locus related to this paper: tryb2-q6h9e3 , tryb2-q6ha27 , tryb2-q38cd5 , tryb2-q38cd6 , tryb2-q38cd7 , tryb2-q38dc1 , tryb2-q38de4 , tryb2-q38ds6 , tryb2-q38dx1 , tryb2-q380z6 , tryb2-q382l4 , tryb2-q383a9 , tryb2-q386e3 , tryb2-q387r7 , tryb2-q388n1 , tryb2-q389w3 , trybr-PEPTB , trycr-q4cq28 , trycr-q4cq94 , trycr-q4cq95 , trycr-q4cq96 , trycr-q4cqq5 , trycr-q4csm0 , trycr-q4cwv3 , trycr-q4cx66 , trycr-q4cxr6 , trycr-q4cyc3 , trycr-q4cyc5 , trycr-q4cyf6 , trycr-q4czy3 , trycr-q4d1s2 , trycr-q4d2n1 , trycr-q4d3a2 , trycr-q4d3x3 , trycr-q4d3y4 , trycr-q4d6h1 , trycr-q4d8h8 , trycr-q4d8h9 , trycr-q4d8i0 , trycr-q4d786 , trycr-q4d975 , trycr-q4da08 , trycr-q4dab1 , trycr-q4dap6 , trycr-q4dap7 , trycr-q4dbm2 , trycr-q4dbn1 , trycr-q4ddw7 , trycr-q4de42 , trycr-q4dhn8 , trycr-q4dkk8 , trycr-q4dkk9 , trycr-q4dm56 , trycr-q4dp03 , trycr-q4dqa6 , trycr-q4dry8 , trycr-q4dt91 , trycr-q4dvl8 , trycr-q4dvp1 , trycr-q4dvp2 , trycr-q4dw34 , trycr-q4dwm3 , trycr-q4dy49 , trycr-q4dy82 , trycr-q4dzp6 , trycr-q4e3m8 , trycr-q4e4t5 , trycr-q4e5d1 , trycr-q4e5z2 , trycr-q6y3z8 , trycr-Q94795 , trycr-TCPO

Title : In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia) as a potential nerve agent bioscavenger - Cerasoli_2005_Chem.Biol.Interact_157-158_363
Author(s) : Cerasoli DM , Griffiths EM , Doctor BP , Saxena A , Fedorko JM , Greig NH , Yu QS , Huang Y , Wilgus H , Karatzas CN , Koplovitz I , Lenz DE
Ref : Chemico-Biological Interactions , 157-158 :363 , 2005
Abstract : Previous studies in rodents and nonhuman primates have demonstrated that pretreatment with cholinesterases can provide significant protection against behavioral and lethal effects of nerve agent intoxication. Human butyrylcholinesterase (HuBuChE) purified from plasma has been shown to protect against up to 5 x LD50s of nerve agents in guinea pigs and non-human primates, and is currently being explored as a bioscavenger pretreatment for human use. A recombinant form of HuBuChE has been expressed in the milk of transgenic goats as a product called Protexia. Protexia was supplied by Nexia Biotechnologies (Que., Canada) as a purified solution with a specific activity of 600 U/mg. Initial in vitro studies using radiolabeled 3H-soman or 3H-DFP (diisopropyl fluorophosphate) demonstrated that these inhibitors specifically bind to Protexia. When Protexia was mixed with soman, sarin, tabun or VX using varying molar ratios of enzyme to nerve agent (8:1, 4:1, 1:1 and 1:4, respectively), the data indicated that 50% inhibition of enzyme activity occurs around the 1:1 molar ratio for each of the nerve agents. Protexia was further characterized for its interaction with pyridostigmine bromide and six unique carbamate inhibitors of cholinesterase. IC50 and Ki values for Protexia were determined to be very similar to those of HuBuChE purified from human plasma. These data suggest that Protexia has biochemical properties very similar to those HuBuChE when compared in vitro. Together these data the continued development of the goat milk-derived recombinant HuBuChE Protexia as a potential bioscavenger of organophosphorus nerve agents.
ESTHER : Cerasoli_2005_Chem.Biol.Interact_157-158_363
PubMedSearch : Cerasoli_2005_Chem.Biol.Interact_157-158_363
PubMedID: 16429486

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : The genome of the kinetoplastid parasite, Leishmania major - Ivens_2005_Science_309_436
Author(s) : Ivens AC , Peacock CS , Worthey EA , Murphy L , Aggarwal G , Berriman M , Sisk E , Rajandream MA , Adlem E , Aert R , Anupama A , Apostolou Z , Attipoe P , Bason N , Bauser C , Beck A , Beverley SM , Bianchettin G , Borzym K , Bothe G , Bruschi CV , Collins M , Cadag E , Ciarloni L , Clayton C , Coulson RM , Cronin A , Cruz AK , Davies RM , De Gaudenzi J , Dobson DE , Duesterhoeft A , Fazelina G , Fosker N , Frasch AC , Fraser A , Fuchs M , Gabel C , Goble A , Goffeau A , Harris D , Hertz-Fowler C , Hilbert H , Horn D , Huang Y , Klages S , Knights A , Kube M , Larke N , Litvin L , Lord A , Louie T , Marra M , Masuy D , Matthews K , Michaeli S , Mottram JC , Muller-Auer S , Munden H , Nelson S , Norbertczak H , Oliver K , O'Neil S , Pentony M , Pohl TM , Price C , Purnelle B , Quail MA , Rabbinowitsch E , Reinhardt R , Rieger M , Rinta J , Robben J , Robertson L , Ruiz JC , Rutter S , Saunders D , Schafer M , Schein J , Schwartz DC , Seeger K , Seyler A , Sharp S , Shin H , Sivam D , Squares R , Squares S , Tosato V , Vogt C , Volckaert G , Wambutt R , Warren T , Wedler H , Woodward J , Zhou S , Zimmermann W , Smith DF , Blackwell JM , Stuart KD , Barrell B , Myler PJ
Ref : Science , 309 :436 , 2005
Abstract : Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
ESTHER : Ivens_2005_Science_309_436
PubMedSearch : Ivens_2005_Science_309_436
PubMedID: 16020728
Gene_locus related to this paper: leima-e9ady6 , leima-L2464.12 , leima-L2802.02 , leima-OPB , leima-q4fw33 , leima-q4fwg8 , leima-q4fwj0 , leima-q4fya7 , leima-q4q0a1 , leima-q4q0t5 , leima-q4q0v0 , leima-q4q1h9 , leima-q4q2c9 , leima-q4q4j7 , leima-q4q4t6 , leima-q4q5j1 , leima-q4q6e9 , leima-q4q7v8 , leima-q4q8a8 , leima-q4q9g9 , leima-q4q080 , leima-q4q398 , leima-q4q615 , leima-q4q819 , leima-q4q871 , leima-q4q942 , leima-q4qae7 , leima-q4qb85 , leima-q4qdz7 , leima-q4qe26 , leima-q4qe31 , leima-q4qe85 , leima-q4qe86 , leima-q4qe87 , leima-q4qe90 , leima-q4qec8 , leima-q4qgz4 , leima-q4qgz5 , leima-q4qhs0 , leima-q4qj45

Title : Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution - Richards_2005_Genome.Res_15_1
Author(s) : Richards S , Liu Y , Bettencourt BR , Hradecky P , Letovsky S , Nielsen R , Thornton K , Hubisz MJ , Chen R , Meisel RP , Couronne O , Hua S , Smith MA , Zhang P , Liu J , Bussemaker HJ , van Batenburg MF , Howells SL , Scherer SE , Sodergren E , Matthews BB , Crosby MA , Schroeder AJ , Ortiz-Barrientos D , Rives CM , Metzker ML , Muzny DM , Scott G , Steffen D , Wheeler DA , Worley KC , Havlak P , Durbin KJ , Egan A , Gill R , Hume J , Morgan MB , Miner G , Hamilton C , Huang Y , Waldron L , Verduzco D , Clerc-Blankenburg KP , Dubchak I , Noor MA , Anderson W , White KP , Clark AG , Schaeffer SW , Gelbart W , Weinstock GM , Gibbs RA
Ref : Genome Res , 15 :1 , 2005
Abstract : We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25-55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species--but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.
ESTHER : Richards_2005_Genome.Res_15_1
PubMedSearch : Richards_2005_Genome.Res_15_1
PubMedID: 15632085
Gene_locus related to this paper: drome-BEM46 , drome-GH02439 , drops-ACHE , drops-b5dhd2 , drops-b5di70 , drops-b5djn7 , drops-b5dk96 , drops-b5dm12 , drops-b5dpe3 , drops-b5drp9 , drops-b5du62 , drops-b5dud8 , drops-b5dwa7 , drops-b5dwa8 , drops-b5dy09 , drops-b5dz85 , drops-b5dz86 , drops-b5e1k7 , drops-CG4390 , drops-est5a , drops-est5b , drops-est5c , drops-nrtac , drops-q2lyp3 , drops-q2lyp4 , drops-q2lyu3 , drops-q2lz68 , drops-q2m0u9 , drops-q2m169 , drops-q28wj5 , drops-q28wt2 , drops-q28wt8 , drops-q28zi3 , drops-q28zz1 , drops-q29a22 , drops-q29ad8 , drops-q29ad9 , drops-q29ae0 , drops-q29ae1 , drops-q29ay7 , drops-q29ay8 , drops-q29ay9 , drops-q29bq2 , drops-q29br3 , drops-q29d59 , drops-q29dc9 , drops-q29dd7 , drops-q29dp4 , drops-q29dw3 , drops-q29dw4 , drops-q29e16 , drops-q29ew0 , drops-q29f35 , drops-q29f66 , drops-q29fi0 , drops-q29fw0 , drops-q29fw9 , drops-q29g93 , drops-q29gb0 , drops-q29gs6 , drops-q29h54 , drops-b5dmp7 , drops-q29hd2 , drops-q29hu2 , drops-q29hu3 , drops-q29hv0 , drops-q29i09 , drops-q29js9 , drops-q29jt5 , drops-q29jt6 , drops-q29jy5 , drops-q29k25 , drops-q29kd5 , drops-q29kd6 , drops-q29ke5 , drops-q29kq9 , drops-q29kr1 , drops-q29kr3 , drops-q29kr5 , drops-q29kr8 , drops-q29kr9 , drops-q29ks6 , drops-q29kz0 , drops-q29kz1 , drops-q29l31 , drops-q29lf8 , drops-q29lv0 , drops-q29m07 , drops-q29m08 , drops-q29m27 , drops-q29m66 , drops-q29m81 , drops-q29mj7 , drops-q29mv2 , drops-q29mx0 , drops-q29n87 , drops-q29na5 , drops-q29na6 , drops-q29pe4 , drops-q29pk4 , drops-q290i1 , drops-q290k3 , drops-q290v8 , drops-q290v9 , drops-q290w0 , drops-q290z8 , drops-q291d5 , drops-q291e8 , drops-q291y3 , drops-q292f5 , drops-q292g6 , drops-q293n1 , drops-q293n4 , drops-q293n5 , drops-q293n6 , drops-q293y7 , drops-q294n3 , drops-q294n6 , drops-q294n7 , drops-q294n9 , drops-q294p0 , drops-q294p1 , drops-q294p3 , drops-q294p4 , drops-q294u9 , drops-q295h3 , drops-q296h2 , drops-q296x1 , drops-q296x2 , drops-q297h5 , drops-q298u8 , drope-b4gkk1

Title : Purification and characterization of an extracellular lipase from Geotrichum marinum - Huang_2004_Lipids_39_251
Author(s) : Huang Y , Locy R , Weete JD
Ref : Lipids , 39 :251 , 2004
Abstract : An extracellular lipase (EC from Geotrichum marinum was purified 76-fold with 46% recovery using Octyl Sepharose 4 Fast Flow and Bio-Gel A 1.5 m chromatography. The purified enzyme showed a prominent band on SDS-PAGE and a single band on native PAGE based on the activity staining. The molecular mass of the lipase was estimated to be 62 kDa using SDS-PAGE and Bio-Gel A chromatography, indicating that the lipase likely functions as a monomer. The pl of the lipase was determined to be 4.54. The apparent V(max) and Km were 1000 micromol/min/mg protein and 11.5 mM, respectively, using olive oil emulsified with taurocholic acid as substrate. The lipase demonstrated a pH optimum at pH 8.0 and a temperature optimum at 40 degrees C. At 6 mM, Na+, K+, Ca2+, and Mg2+ stimulated activity, but Na+ and K+ at 500 mM and Fe2+ and Mn2+ at 6 mM reduced lipase activity. The anionic surfactant, taurocholic acid, and the zwitterionic surfactant, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, enhanced the activity at 0.1 mM. Other anionic surfactants such as SDS and sodium dioctyl sulfosuccinate, the cationic surfactants methylbenzethonium bromide and cetyltriethylammonium bromide, and the nonionic surfactants Tween-20 and Triton X-100 inhibited the lipase activity to different extents. The lipase was found to have a preference for TG containing cis double bonds in their FA side chains, and the reaction rate increased with an increasing number of double bonds in the side chain. The lipase had a preference for ester bonds at the sn-1 and sn-3 positions over the ester bond at the sn-2 position.
ESTHER : Huang_2004_Lipids_39_251
PubMedSearch : Huang_2004_Lipids_39_251
PubMedID: 15233404

Title : Synthesis of novel potent dipeptidyl peptidase IV inhibitors with enhanced chemical stability: interplay between the N-terminal amino acid alkyl side chain and the cyclopropyl group of alpha-aminoacyl-l-cis-4,5-methanoprolinenitrile-based inhibitors - Magnin_2004_J.Med.Chem_47_2587
Author(s) : Magnin DR , Robl JA , Sulsky RB , Augeri DJ , Huang Y , Simpkins LM , Taunk PC , Betebenner DA , Robertson JG , Abboa-Offei BE , Wang A , Cap M , Xin L , Tao L , Sitkoff DF , Malley MF , Gougoutas JZ , Khanna A , Huang Q , Han SP , Parker RA , Hamann LG
Ref : Journal of Medicinal Chemistry , 47 :2587 , 2004
Abstract : A series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-stimulated insulin secretion, and DPP-IV inhibition shows clinical benefit as a novel mechanism for treatment of type 2 diabetes. However, many of the reversible inhibitors to date suffer from chemical instability stemming from an amine to nitrile intramolecular cyclization. Installation of a cyclopropyl moiety at either the 3,4- or 4,5-position of traditional 2-cyanopyrrolidide proline mimetics led to compounds with potent inhibitory activity against the enzyme. Additionally, cis-4,5-methanoprolinenitriles with beta-branching in the N-terminal amino acid provided enhanced chemical stability and high inhibitory potency. This class of inhibitors also exhibited the ability to suppress prandial glucose elevations after an oral glucose challenge in male Zucker rats.
ESTHER : Magnin_2004_J.Med.Chem_47_2587
PubMedSearch : Magnin_2004_J.Med.Chem_47_2587
PubMedID: 15115400

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : Annotation of the Drosophila melanogaster euchromatic genome: a systematic review - Misra_2002_Genome.Biol_3_RESEARCH0083
Author(s) : Misra S , Crosby MA , Mungall CJ , Matthews BB , Campbell KS , Hradecky P , Huang Y , Kaminker JS , Millburn GH , Prochnik SE , Smith CD , Tupy JL , Whitfied EJ , Bayraktaroglu L , Berman BP , Bettencourt BR , Celniker SE , de Grey AD , Drysdale RA , Harris NL , Richter J , Russo S , Schroeder AJ , Shu SQ , Stapleton M , Yamada C , Ashburner M , Gelbart WM , Rubin GM , Lewis SE
Ref : Genome Biol , 3 :RESEARCH0083 , 2002
Abstract : BACKGROUND: The recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences.
RESULTS: Although the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins. We annotated transposable elements and non-protein-coding RNAs as new features, and extended the annotation of untranslated (UTR) sequences and alternative transcripts to include more than 70% and 20% of genes, respectively. Finally, cDNA sequence provided evidence for dicistronic transcripts, neighboring genes with overlapping UTRs on the same DNA sequence strand, alternatively spliced genes that encode distinct, non-overlapping peptides, and numerous nested genes.
CONCLUSIONS: Identification of so many unusual gene models not only suggests that some mechanisms for gene regulation are more prevalent than previously believed, but also underscores the complex challenges of eukaryotic gene prediction. At present, experimental data and human curation remain essential to generate high-quality genome annotations.
ESTHER : Misra_2002_Genome.Biol_3_RESEARCH0083
PubMedSearch : Misra_2002_Genome.Biol_3_RESEARCH0083
PubMedID: 12537572
Gene_locus related to this paper: drome-a1z6g9 , drome-abhd2 , drome-ACHE , drome-CG8058 , drome-CG8093 , drome-CG8233 , drome-CG8425 , drome-CG9059 , drome-CG9186 , drome-CG9542 , drome-CG10982 , drome-CG11309 , drome-CG11406 , drome-CG11598 , drome-CG17097 , drome-glita , drome-KRAKEN , drome-nrtac , drome-OME , drome-q7k274 , drome-q9vux3

Title : Cloning and expression pattern of the human NDRG3 gene - Zhao_2001_Biochim.Biophys.Acta_1519_134
Author(s) : Zhao W , Tang R , Huang Y , Wang W , Zhou Z , Gu S , Dai J , Ying K , Xie Y , Mao Y
Ref : Biochimica & Biophysica Acta , 1519 :134 , 2001
Abstract : We report the cloning and expression pattern of a novel N-myc downstream-regulated gene 3 (NDRG3), located on human chromosome 20q11.21-11.23. The NDRG3 cDNA is 2588 base pair in length, encoding a 363 amino acid polypeptide highly related to mouse Ndr3 protein. Northern blot reveals that NDRG3 is highly expressed in testis, prostate and ovary. By in situ hybridization, the NDRG3 mRNA was localized to the outer layers of seminiferous epithelium, indicating that it may play a role in spermatogenesis.
ESTHER : Zhao_2001_Biochim.Biophys.Acta_1519_134
PubMedSearch : Zhao_2001_Biochim.Biophys.Acta_1519_134
PubMedID: 11406283

Title : Cloning, heterologous expression and co-assembly of Mpbeta1, a nicotinic acetylcholine receptor subunit from the aphid Myzus persicae - Huang_2000_Neurosci.Lett_284_116
Author(s) : Huang Y , Williamson MS , Devonshire AL , Windass JD , Lansdell SJ , Millar NS
Ref : Neuroscience Letters , 284 :116 , 2000
Abstract : Nicotinic acetylcholine receptors (nAChRs) play a major role in excitatory synaptic transmission in insects and are also the target site for chloronicotinyl insecticides such as imidacloprid. Here we report the cloning and characterization of a novel nAChR beta subunit, Mpbeta1, from the aphid Myzus persicae, an economically important pest species. Sequence analysis has identified an open reading frame of 509 amino acids with features typical of nAChR subunits. The Mpbeta1 gene is expressed as a single major transcript of 4.6 kb, considerably larger than the predicted length of the Mpbeta1 open reading frame (1527 bp). By heterologous expression in Drosophila S2 cells, the Mpbeta1 subunit has been shown to co-assemble with the previously cloned nAChR subunits Mpalpha1 and Mpalpha2. In contrast, no co-assembly of Mpbeta1 could be detected with either Mpalpha3 or Mpalpha4. With the aim of gaining a clearer insight into the influence of subunit composition upon assembly, the ability of M. persicae nAChR subunits to co-assemble with vertebrate nAChR subunits has also been examined.
ESTHER : Huang_2000_Neurosci.Lett_284_116
PubMedSearch : Huang_2000_Neurosci.Lett_284_116
PubMedID: 10771176

Title : Molecular characterization and imidacloprid selectivity of nicotinic acetylcholine receptor subunits from the peach-potato aphid Myzus persicae - Huang_1999_J.Neurochem_73_380
Author(s) : Huang Y , Williamson MS , Devonshire AL , Windass JD , Lansdell SJ , Millar NS
Ref : Journal of Neurochemistry , 73 :380 , 1999
Abstract : The recent introduction of the chloronicotinyl insecticide imidacloprid, targeting insect nicotinic acetylcholine receptors (nAChRs), emphasises the importance of a detailed molecular characterisation of these receptors. We are investigating the molecular diversity of insect nAChR subunit genes in an important agricultural pest, the peach-potato aphid Myzus persicae. Two M. persicae alpha-subunit cDNAs, Mp alpha1 and Mp alpha2, have been cloned previously. Here we report the isolation of three novel alpha-subunit genes (Mp alpha3-5) with overall amino acid sequence identities between 43 and 76% to characterised insect nAChR subunits. Alignment of their amino acid sequences with other invertebrate and vertebrate nAChR subunits suggests that the insect alpha subunits evolved in parallel to the vertebrate neuronal nAChRs and that the insect non-alpha subunits are clearly different from vertebrate neuronal beta and muscle non-alpha subunits. The discovery of novel subtypes in M. persicae is a further indicator of the complexity of the insect nAChR gene family. Heterologous co-expression of M. persicae nAChR alpha-subunit cDNAs with the rat beta2 in Drosophila S2 cells resulted in high-affinity binding of nicotinic radioligands. The affinity of recombinant nAChRs for [3H]imidacloprid was influenced strongly by the alpha subtype. This is the first demonstration that imidacloprid selectively acts on Mp alpha2 and Mp alpha3 subunits, but not Mp alpha1, in M. persicae.
ESTHER : Huang_1999_J.Neurochem_73_380
PubMedSearch : Huang_1999_J.Neurochem_73_380
PubMedID: 10386991

Title : Characterization of the acetylcholinesterase gene from insecticide-resistant houseflies (Musca domestica) - Huang_1997_Chin.J.Biotechnol_13_177
Author(s) : Huang Y , Qiao C , Williamson MS , Devonshire AL
Ref : Chin J Biotechnol , 13 :177 , 1997
Abstract : Acetylcholinesterase (AChE) is the target site for the organophosphates and carbamates in insects. Widespread use of these two classes of insecticides has led to the selection of resistance. Target modification was regarded as a molecular mechanism in some resistance species. The altered AChEs with reduced sensitivity to inhibition are related to this resistance. AChE genes from two insecticide-resistant housefly (Musca domestica) strains D3 and Kash were isolated and sequenced using RT-PCR and streptavidin-linked magnetic bead techniques. The cDNAs have a 2082-bp open reading frame from which the complete amino acid sequence of AChE has been deduced. Some differences in nucleotide sequence and four-point mutations of amino acid were found compared to a susceptible strain, i.e., the Cooper strain. Three substitutions are likely to confer insecticide insensitivity, which seems that D3 and Kash belong to CH2 pattern of resistance.
ESTHER : Huang_1997_Chin.J.Biotechnol_13_177
PubMedSearch : Huang_1997_Chin.J.Biotechnol_13_177
PubMedID: 9429779
Gene_locus related to this paper: musdo-ACHE

Title : Bile salt stimulated cholesterol esterase increases uptake of high density lipoprotein-associated cholesteryl esters by HepG2 cells - Li_1996_Biochemistry_35_6657
Author(s) : Li F , Huang Y , Hui DY
Ref : Biochemistry , 35 :6657 , 1996
Abstract : Bile salt stimulated cholesterol esterase is predominantly synthesized in the pancreas. However, this enzyme is also synthesized by the liver and was found to be present in plasma. The physiologic role of the systemic cholesterol esterase has not been clearly defined. In the current study, the human hepatoma cell line HepG2 was used as a model to determine the role of cholesterol esterase on hepatic uptake of high density lipoprotein (HDL)-associated cholesteryl esters. The results showed that hepatic uptake of the cholesteryl esters analog [3H]cholesteryl ether on reconstituted HDL was inhibited by anti-cholesterol esterase antibodies. The HDL-associated cholesteryl ester transported to HepG2 cells was also increased 2-fold in the presence of taurocholate, an activator of the cholesterol esterase. These results suggest that liver-derived cholesterol esterase may play an important role in cellular uptake of cholesteryl esters from HDL. This hypothesis was supported by demonstrating the ability of exogenously added cholesterol esterase to further enhance hepatic uptake of HDL-associated cholesteryl esters. The results of the current study also showed that cholesterol esterase increased free-to-esterified cholesterol ratio in the lipoprotein. Thus, alteration of HDL structure and composition contributes to the cholesterol esterase-induced cellular uptake of HDL-associated cholesteryl esters. On the basis of these observations, we propose that liver-derived cholesterol esterase may play an important role in lipoprotein metabolism.
ESTHER : Li_1996_Biochemistry_35_6657
PubMedSearch : Li_1996_Biochemistry_35_6657
PubMedID: 8639615
Gene_locus related to this paper: human-CES1

Title : Granulocyte-macrophage colony-stimulating factor\/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells - Bhalla_1992_Blood_80_2883
Author(s) : Bhalla K , Tang C , Ibrado AM , Grant S , Tourkina E , Holladay C , Hughes M , Mahoney ME , Huang Y
Ref : Blood , 80 :2883 , 1992
Abstract : High dose Ara-C (HIDAC) induces programmed cell death (PCD) or apoptosis in vitro in human myeloid leukemia cells, which correlates with the inhibition of their clonogenic survival. Hematopoietic growth factors (HGFs) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells. We examined the effect of pIXY 321 (a GM-CSF/IL-3 fusion protein) on HIDAC-induced PCD and related gene expressions as well as HIDAC-mediated colony growth inhibition of human myeloid leukemia cells. Unlike the previously described effects of HGFs on normal bone marrow progenitor cells, exposure to pIXY 321 alone for up to 24 hours did not suppress PCD in HL-60 or KG-1 cells. However, exposure to pIXY 321 for 20 hours followed by a combined treatment with Ara-C plus pIXY 321 for 4 or 24 hours versus treatment with Ara-C alone significantly enhanced the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of c-jun expression and a significant decrease in BCL-2. In addition, the treatment with pIXY 321 plus HIDAC versus HIDAC alone produced a significantly greater inhibition of HL-60 colony growth. These findings highlight an additional mechanism of HIDAC-induced leukemic cell death that is augmented by cotreatment with pIXY 321 and may contribute toward an improved antileukemic activity of HIDAC.
ESTHER : Bhalla_1992_Blood_80_2883
PubMedSearch : Bhalla_1992_Blood_80_2883
PubMedID: 1450413

Title : Metabolic fate of pancreas-derived cholesterol esterase in intestine: an in vitro study using Caco-2 cells - Huang_1990_J.Lipid.Res_31_2029
Author(s) : Huang Y , Hui DY
Ref : J Lipid Res , 31 :2029 , 1990
Abstract : Bile salt-stimulated cholesterol esterase is synthesized in the pancreatic acinar cells and is released into the intestinal lumen where it catalyzes cholesterol absorption. In the current study, Caco-2 cells were used as an in vitro model to study the interaction between the pancreatic cholesterol esterase with intestinal cells. Results showed that addition of increasing concentrations of cholesterol esterase in the incubation medium increased the uptake of micellar cholesteryl oleate by Caco-2 cells. The cholesterol esterase also increased the cellular uptake of the nonhydrolyzable cholesteryl linoleoyl ether. However, maximum uptake of the cholesteryl ether analog was 50% of that for cholesteryl oleate. The initial interaction of cholesterol esterase with Caco-2 cells was mediated by binding of the protein to a low affinity and high capacity binding site on the cell surface. Cholesterol esterase bound to the cell surface could be internalized via a monensin-sensitive mechanism. The cholesterol esterase taken up by the cells had a short residence time and was either degraded or was rapidly re-secreted from the cells. Chloroquine had no effect on the degradation or re-secretion of cholesterol esterase by Caco-2 cells, indicating that lysosomes were not involved with these processes. The cholesterol esterase taken up by the cells was not available to mediate further cholesterol uptake. These results indicated that the bile salt-stimulated cholesterol esterase secreted from pancreas could facilitate intestinal lipid absorption only transiently. The data suggest that the regulation of cholesterol esterase synthesis and secretion by the pancreas may be important for regulation of cholesterol absorption.
ESTHER : Huang_1990_J.Lipid.Res_31_2029
PubMedSearch : Huang_1990_J.Lipid.Res_31_2029
PubMedID: 2086702