Huang F

References (28)

Title : Mechanisms of biochar assisted di-2-ethylhexyl phthalate (DEHP) biodegradation in tomato rhizosphere by metabolic and metagenomic analysis - Lin_2024_Chemosphere__141520
Author(s) : Lin Z , Wu W , Yang C , Yang G , Wei T , Huang F , Li H , Ren L , Liang Y , Zhang D , Li Z , Zhen Z
Ref : Chemosphere , :141520 , 2024
Abstract : The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.
ESTHER : Lin_2024_Chemosphere__141520
PubMedSearch : Lin_2024_Chemosphere__141520
PubMedID: 38395368

Title : Peptidomimetics based on ammonium decasubstituted pillar[5]arenes: Influence of the alpha-amino acid residue nature on cholinesterase inhibition - Nazarova_2023_Bioorg.Chem_141_106927
Author(s) : Nazarova A , Padnya P , Kharlamova A , Petrov K , Yusupov G , Zelenikhin P , Bukharov M , Hua B , Huang F , Stoikov I
Ref : Bioorg Chem , 141 :106927 , 2023
Abstract : Cholinesterase inhibitors are a group of medicines that are widely used for the treatment of cognitive impairments accompanying Alzheimer's disease as well as for the treatment of pathological muscle weaknesses syndromes such as myasthenia gravis. The search for novel non-toxic and effective cholinesterase inhibitors for creating neuroprotective and neurotransmitter agents is an urgent interdisciplinary problem. For the first time, the application of water-soluble pillar[5]arenes containing amino acid residues as effective cholinesterase inhibitors was shown. The influence of the nature of aliphatic and aromatic alpha-amino acid residues (glycine, l-alanine, l-phenylalanine and l-tryptophan) on self-assembly, aggregate's stability, cytotoxicity on A549 and LEK cells and cholinesterase inhibition was studied. It was found that the studied compounds with aliphatic amino acid residues showed a low inhibitory ability against cholinesterases. It was established that the pillar[5]arene containing fragments of l-phenylalanine is the most promising inhibitor of butyrylcholinesterase (IC(50) = 0.32 +/- 0.01 microM), the pillar[5]arene with l-tryptophan residues is the most promising inhibitor of acetylcholinesterase (IC(50) = 0.32 +/- 0.01 microM). This study has shown a possible application of peptidomimetics based on pillar[5]arenes to inhibit cholinesterase, as well as control the binding affinity to a particular enzyme in a structure-dependent manner.
ESTHER : Nazarova_2023_Bioorg.Chem_141_106927
PubMedSearch : Nazarova_2023_Bioorg.Chem_141_106927
PubMedID: 37866207

Title : Exploring the inhibitory potential of KPHs-AL-derived GLLF peptide on pancreatic lipase and cholesterol esterase activities - Huang_2023_Food.Chem_439_138108
Author(s) : Huang F , Dai Q , Zheng K , Ma Q , Liu Y , Jiang S , Jiang W , Yan X
Ref : Food Chem , 439 :138108 , 2023
Abstract : The effective modulation of pancreatic lipase and cholesterol esterase activities proves critical in maintaining circulatory triglycerides and cholesterol levels within physiological boundaries. In this study, peptides derived from KPHs-AL, produced through the enzymatic hydrolysis of skipjack tuna dark muscle using alkaline protease, have a specific inhibitory effect on pancreatic lipase and cholesterol esterase. It is hypothesized that these peptides target and modulate the activities of enzymes by inducing conformational changes within their binding pockets, potentially impacting the catalytic functions of both pancreatic lipase and cholesterol esterase. Results revealed these peptides including AINDPFIDL, FLGM, GLLF and WGPL, were found to nestle into the binding site groove of pancreatic lipase and cholesterol esterase. Among these, GLLF stood out, demonstrating potent inhibition with IC(50) values of 0.1891 mg/mL and 0.2534 mg/mL for pancreatic lipase and cholesterol esterase, respectively. The kinetics studies suggested that GLLF competed effectively with substrates for the enzyme active sites. Spectroscopic analyses, including ultraviolet-visible, fluorescence quenching, and circular dichroism, indicated that GLLF binding induced conformational changes within the enzymes, likely through hydrogen bond formation and hydrophobic interactions, thereby increasing structural flexibility. Molecular docking and molecular dynamics simulations supported these findings, showing GLLF's stable interaction with vital active site residues. These findings position GLLF as a potent inhibitor of key digestive enzymes, offering insights into its role in regulating lipid metabolism and highlighting its potential as functional ingredient.
ESTHER : Huang_2023_Food.Chem_439_138108
PubMedSearch : Huang_2023_Food.Chem_439_138108
PubMedID: 38061297

Title : The Therapeutic Effects of Seven Lycophyte Compounds on Cell Models of Alzheimer's Disease - Guo_2022_J.Alzheimers.Dis__
Author(s) : Guo Q , Cai Q , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : J Alzheimers Dis , : , 2022
Abstract : BACKGROUND: As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. To search for new analogs or derivatives of Hup-A, we produced five Lycophyte alkaloids and two analogues by chemical synthesis: Lyconadins A-E, H-R-NOB, and 2JY-OBZ4. OBJECTIVE: To systematically evaluated the therapeutic effects of the seven compounds on AD cell models. METHODS: We assessed the effects of the seven compounds on cell viability via CCK-8 kit and used HEK293-hTau cells and N2a-hAPP cells as AD cell models to evaluate their potential therapeutic effects. We examined their effects on cholinesterase activity by employing the mice primary neuron. RESULTS: All compounds did not affect cell viability; in addition, Lyconadin A and 2JY-OBZ4 particularly increased cell viability. Lyconadin D and Lyconadin E restored tau phosphorylation at Thr231, and H-R-NOB and 2JY-OBZ4 restored tau phosphorylation at Thr231 and Ser396 in GSK-3beta-transfected HEK293-hTau cells. 2JY-OBZ4 decreased the level of PP2Ac-pY307 and increased the level of PP2Ac-mL309, supporting that 2JY-OBZ4 may activate PP2A. Lyconadin B, Lyconadin D, Lyconadin E, H-R-NOB, and 2JY-OBZ4 increased sAbetaPPalpha level in N2a-hAPP cells. 2JY-OBZ4 decreased the levels of BACE1 and sAbetaPPbeta, thereby reduced Abeta production. Seven compounds exhibited weaker AChE activity inhibition efficiency than Hup-A. Among them, 2JY-OBZ4 showed the strongest AChE inhibition activity with an inhibition rate of 17% at 10microM. CONCLUSION: Among the seven lycophyte compounds, 2JY-OBZ4 showed the most expected effects on promoting cell viability, downregulating tau hyperphosphorylation, and Abeta production and inhibiting AChE in AD.
ESTHER : Guo_2022_J.Alzheimers.Dis__
PubMedSearch : Guo_2022_J.Alzheimers.Dis__
PubMedID: 36189599

Title : Novel small molecular compound 2JY-OBZ4 alleviates AD pathology in cell models via regulating multiple targets - Guo_2022_Aging.(Albany.NY)_14_
Author(s) : Guo Q , Wu G , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : Aging (Albany NY) , 14 : , 2022
Abstract : Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, characterized by cognitive deficits and memory dysfunction, which is clinically incurable so far. Novel small molecular compound 2JY-OBZ4 is one of structural analogue of Huperzine A (Hup-A), an anti-AD drug in China. In our previous work, 2JY-OBZ4 exhibited potent effects on tau hyperphosphorylation, Abeta production and acetylcholinesterase (AChE) activity. However, 2JY-OBZ4's anti-AD effects and the underlying molecular mechanisms remain unclear. We here reported that 2JY-OBZ4 resisted tau hyperphosphorylation at Thr181 and Ser396 sites in HEK293-hTau cells transfected with GSK-3beta, decreased tau phosphorylation via upregulating the activity of PP2A in HEK293-hTau cells and reduced Abeta production through regulating protein levels of APP cleavage enzymes in N2a-hAPP cells. Meanwhile, we found that 2JY-OBZ4 had no adverse effects on cell viability of mice primary neuron even at high concentration, and ameliorated synaptic loss induced by human oligomeric Abeta42. 2JY-OBZ4 had moderate AChE inhibitory activity with the half maximal inhibitory concentration (IC50) to be 39.48 microg/ml in vitro, which is more than two times higher than Hup-A. Together, 2JY-OBZ4 showed promising therapeutic effects in AD cell models through regulating multiple targets. The research provides a new candidate for the therapeutic development of AD.
ESTHER : Guo_2022_Aging.(Albany.NY)_14_
PubMedSearch : Guo_2022_Aging.(Albany.NY)_14_
PubMedID: 36227154

Title : The Patatin-Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1\/NF-B and p38 MAPK Pathways - Zhao_2022_Int.J.Mol.Sci_23_
Author(s) : Zhao Z , Heier C , Pang H , Wang Y , Huang F , Chang P
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Lysophosphatidylcholine (LPC) is a bioactive lipid that modulates macrophage polarization during immune responses, inflammation, and tissue remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) is a lysophospholipase with a preference for LPC. However, the role of PNPLA7 in macrophage polarization as an LPC hydrolase has not been explored. In the current study, we found that PNPLA7 is highly expressed in naive macrophages and downregulated upon lipopolysaccharide (LPS)-induced polarization towards the classically activated (M1) phenotype. Consistently, overexpression of PNPLA7 suppressed the expression of proinflammatory M1 marker genes, including interleukin 1beta (IL-1beta), IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-alpha), whereas knockdown of PNPLA7 augmented the inflammatory gene expression in LPS-challenged macrophages. PNPLA7 overexpression and knockdown increased and decreased Sirtuin1 (SIRT1) mRNA and protein levels, respectively, and affected the acetylation of the nuclear factor-kappa B (NF-kappaB) p65 subunit, a key transcription factor in M1 polarization. In addition, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK) were suppressed and enhanced by PNPLA7 overexpression and knockdown, respectively. Taken together, these findings suggest that PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-kappaB- and p38 MAPK-dependent pathways.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_
PubMedID: 36499308

Title : The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells - He_2022_Metabolites_12_
Author(s) : He L , Huang F , Wang Y , Wu Y , Xu L , Chang P
Ref : Metabolites , 12 : , 2022
Abstract : As an endoplasmic reticulum (ER)-anchored phospholipase, neuropathy target esterase (NTE) catalyzes the deacylation of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). The catalytic domain of NTE (NEST) exhibits comparable activity to NTE and binds to lipid droplets (LD). In the current study, the nucleotide monophosphate (cNMP)-binding domains (CBDs) were firstly demonstrated not to be essential for the ER-targeting of NTE, but to be involved in the normal ER distribution and localization to LD. NEST was associated with LD surface and influenced LD formation in human neuroblastoma cells. Overexpression of NEST enhances triacylglycerol (TG) accumulation upon oleic acid loading. Quantitative targeted lipidomic analysis shows that overexpression of NEST does not alter diacylglycerol levels but reduces free fatty acids content. NEST not only lowered levels of LPC and acyl-LPC, but not PC or alkyl-PC, but also widely altered levels of other lipid metabolites. Qualitative PCR indicates that the increase in levels of TG is due to the expression of diacylglycerol acyltransferase 1 gene by NEST overexpression. Thus, NTE may broadly regulate lipid metabolism to play roles in LD biogenesis in cells.
ESTHER : He_2022_Metabolites_12_
PubMedSearch : He_2022_Metabolites_12_
PubMedID: 35888761

Title : Moringa Oleifera Alleviates Abeta Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP\/PS1 Mice - Mahaman_2022_Nutrients_14_
Author(s) : Mahaman YAR , Feng J , Huang F , Salissou MTM , Wang J , Liu R , Zhang B , Li H , Zhu F , Wang X
Ref : Nutrients , 14 : , 2022
Abstract : Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Abeta and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Abeta burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.
ESTHER : Mahaman_2022_Nutrients_14_
PubMedSearch : Mahaman_2022_Nutrients_14_
PubMedID: 36296969

Title : Active site architecture of an acetyl xylan esterase indicates a novel cold adaptation strategy - Zhang_2021_J.Biol.Chem__100841
Author(s) : Zhang Y , Ding HT , Jiang WX , Zhang X , Cao HY , Wang JP , Li CY , Huang F , Zhang XY , Chen XL , Zhang YZ , Li PY
Ref : Journal of Biological Chemistry , :100841 , 2021
Abstract : SGNH-type acetyl xylan esterases (AcXEs) play important roles in marine and terrestrial xylan degradation, which are necessary for removing acetyl side groups from xylan. However, only a few cold-adapted AcXEs have been reported, and the underlying mechanisms for their cold adaptation are still unknown due to the lack of structural information. Here, a cold-adapted AcXE, AlAXEase, from the Arctic marine bacterium Arcticibacterium luteifluviistationis SM1504(T) was characterized. AlAXEase could deacetylate xylooligosaccharides and xylan, which, together with its homologs, indicates a novel SGNH-type carbohydrate esterase family. AlAXEase showed the highest activity at 30 degreesC and retained over 70% activity at 0 degreesC, but had unusual thermostability with a T(m) value of 56 degreesC. To explain the cold adaption mechanism of AlAXEase, we next solved its crystal structure. AlAXEase has similar noncovalent stabilizing interactions to its mesophilic counterpart at the monomer level and forms stable tetramers in solution, which may explain its high thermostability. However, a long loop containing the catalytic residues Asp200 and His203 in AlAXEase was found to be flexible due to the reduced stabilizing hydrophobic interactions and increased destabilizing asparagine and lysine residues, leading to a highly flexible active site. Structural and enzyme kinetic analyses combined with molecular dynamics simulations at different temperatures revealed that the flexible catalytic loop contributes to the cold adaptation of AlAXEase by modulating the distance between the catalytic His203 in this loop and the nucleophilic Ser32. This study reveals a new cold adaption strategy adopted by the thermostable AlAXEase, shedding light on the cold adaption mechanisms of AcXEs.
ESTHER : Zhang_2021_J.Biol.Chem__100841
PubMedSearch : Zhang_2021_J.Biol.Chem__100841
PubMedID: 34058201

Title : An efficient and robust continuous-flow bioreactor for the enzymatic preparation of phytosterol esters based on hollow lipase microarray - Xu_2021_Food.Chem_372_131256
Author(s) : Xu L , Wang J , Huang F , Zheng M
Ref : Food Chem , 372 :131256 , 2021
Abstract : In this study, a continuous-flow bioreactor packed with well-organized lipase microarrays was developed for the sustainable synthesis of functional lipid-phytosterol esters (PEs). Hollow mesoporous silicon spheres with a suitable pore size were prepared for lipase immobilization, and the hydrophobic modification endowed the lipase with excellent catalytic activity and stability. The results showed that the condensely packed lipase microarrays offered large specific surface areas and guaranteed the thorough interaction between the lipase and substrates in the continuous-flow bioreactor. Meanwhile, the substrate could pass through the reactor at 1 mL/min with a high conversion of 93.6% due to the hollow structure of the packing spheres. Moreover, the reactors were able to produce 1564 g PEs/g catalyst in a continuous 30-day processing period, which set the highest records for PEs synthesis. This sustainable and highly-converting flow system provided a feasible path for scale-up production of PEs in the food processing area.
ESTHER : Xu_2021_Food.Chem_372_131256
PubMedSearch : Xu_2021_Food.Chem_372_131256
PubMedID: 34627092

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

Title : Lipoprotein-associated phospholipase A2: The story continues - Huang_2020_Med.Res.Rev_40_79
Author(s) : Huang F , Wang K , Shen J
Ref : Med Res Rev , 40 :79 , 2020
Abstract : Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein-associated phospholipase A2 (Lp-PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation-related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp-PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp-PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp-PLA2 have been reported recently, while novel inhibitors were identified through a fragment-based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp-PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp-PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp-PLA2, identify more potent and selective Lp-PLA2 inhibitors, and discover the potential indications of Lp-PLA2 inhibitors.
ESTHER : Huang_2020_Med.Res.Rev_40_79
PubMedSearch : Huang_2020_Med.Res.Rev_40_79
PubMedID: 31140638
Gene_locus related to this paper: human-PLA2G7

Title : Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis - Cai_2020_Plant.Biotechnol.J_18_814
Author(s) : Cai Y , Cai X , Wang Q , Wang P , Zhang Y , Cai C , Xu Y , Wang K , Zhou Z , Wang C , Geng S , Li B , Dong Q , Hou Y , Wang H , Ai P , Liu Z , Yi F , Sun M , An G , Cheng J , Shi Q , Xie Y , Shi X , Chang Y , Huang F , Chen Y , Hong S , Mi L , Sun Q , Zhang L , Zhou B , Peng R , Zhang X , Liu F
Ref : Plant Biotechnol J , 18 :814 , 2020
Abstract : The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes.
ESTHER : Cai_2020_Plant.Biotechnol.J_18_814
PubMedSearch : Cai_2020_Plant.Biotechnol.J_18_814
PubMedID: 31479566
Gene_locus related to this paper: gosra-a0a0d2pzd7

Title : Complex role of titanium dioxide nanoparticles in the trophic transfer of arsenic from Nannochloropsis maritima to Artemia salina nauplii - Yang_2018_Aquat.Toxicol_198_231
Author(s) : Yang F , Zeng L , Luo Z , Wang Z , Huang F , Wang Q , Drobne D , Yan C
Ref : Aquat Toxicol , 198 :231 , 2018
Abstract : Increasing concern has been focused on the potential risks associated with the trophic transfer to aquatic organisms of ambient contaminants in the presence of titanium dioxide nanoparticles (nano-TiO2). This study investigated the influence of nano-TiO2 on the trophic transfer of arsenic (As) from the microalgae Nannochloropsis maritima to the brine shrimp Artemia salina nauplii. We found that nano-TiO2 could significantly facilitate As sorption on N. maritima within an exposure period of 24h, and this sorption subsequently led to higher As trophic transfer from the algae to A. salina according to trophic transfer factors (TTFAs+nano-TiO2>TTFAs). However, after 48h of depuration, the retention of As in A. salina fed As-nano-TiO2-contaminated algae was even lower than that in A. salina fed As-contaminated algae at the same exposure concentrations. This result indicates that the increased food chain transfer of As in the presence of nano-TiO2 can be explained by adsorption of As onto nano-TiO2 in contaminated food (algae), but the bioavailability of As in A. salina is reduced after the introduction of nanoparticles. Although the stress enzyme activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in A. salina at a lower As concentration treatment in the presence of nano-TiO2 were not significantly changed, they increased with higher exposure concentrations of As with or without nano-TiO2. Our study highlighted the complex role of nanomaterials in the transfer of ambient contaminants via trophic chains and the potential of nano-TiO2 to reduce the bioavailability of As via trophic transfer to saltwater zooplankton.
ESTHER : Yang_2018_Aquat.Toxicol_198_231
PubMedSearch : Yang_2018_Aquat.Toxicol_198_231
PubMedID: 29558708

Title : Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2 - Liu_2017_J.Med.Chem_60_10231
Author(s) : Liu Q , Huang F , Yuan X , Wang K , Zou Y , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 60 :10231 , 2017
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer's disease, and diabetic macular edema. Here we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor with a 300-fold potency improvement. Subsequently, by the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency were obtained. After preliminary evaluation of the properties of drug-likeness in vitro and in vivo, compound 37 stands out from this congeneric series of inhibitors for good inhibitory activity and favorable oral bioavailability in male Sprague-Dawley rats, providing a quality candidate for further development. The present study thus clearly demonstrates the power and advantage of integrally employing fragment screening, crystal structures determination, virtual screening, and medicinal chemistry in an efficient lead discovery project, providing a good example for structure-based drug design.
ESTHER : Liu_2017_J.Med.Chem_60_10231
PubMedSearch : Liu_2017_J.Med.Chem_60_10231
PubMedID: 29193967
Gene_locus related to this paper: human-PLA2G7

Title : Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro - Bai_2016_Int.J.Biol.Macromol_96_214
Author(s) : Bai Y , Liu L , Zhang R , Huang F , Deng Y , Zhang M
Ref : Int J Biol Macromol , 96 :214 , 2016
Abstract : An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by beta-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function.
ESTHER : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedSearch : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedID: 27908719

Title : Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans - Wang_2016_Mol.Biol.Evol_33_3144
Author(s) : Wang Z , Xu S , Du K , Huang F , Chen Z , Zhou K , Ren W , Yang G
Ref : Molecular Biology Evolution , 33 :3144 , 2016
Abstract : Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans.
ESTHER : Wang_2016_Mol.Biol.Evol_33_3144
PubMedSearch : Wang_2016_Mol.Biol.Evol_33_3144
PubMedID: 27651393
Gene_locus related to this paper: souch-a0a1d8i1n4

Title : Revised Genome Sequence of the Purple Photosynthetic Bacterium Blastochloris viridis - Liu_2016_Genome.Announc_4_e01520
Author(s) : Liu LN , Faulkner M , Liu X , Huang F , Darby AC , Hall N
Ref : Genome Announc , 4 : , 2016
Abstract : Blastochloris viridis is a unique anaerobic, phototrophic purple bacterium that produces bacteriochlorophyll b. Here we report an improved genome sequence of Blastochloris viridis DSM133, which is instrumental to the studies of photosynthesis, metabolic versatility, and genetic engineering of this microorganism.
ESTHER : Liu_2016_Genome.Announc_4_e01520
PubMedSearch : Liu_2016_Genome.Announc_4_e01520
PubMedID: 26798090
Gene_locus related to this paper: blavi-a0a0h5b6a9

Title : Rannasangpei Is a Therapeutic Agent in the Treatment of Vascular Dementia - Wu_2016_Evid.Based.Complement.Alternat.Med_2016_2530105
Author(s) : Wu P , Luo Y , Zhen L , Hu X , Shang Y , Liao Y , Xue H , Huang F , Xiao W
Ref : Evid Based Complement Alternat Med , 2016 :2530105 , 2016
Abstract : Rannasangpei (RSNP) is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD) was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO). Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM) test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT) and reducing the acetylcholinesterase (AChE); the treatment of RSNP could also reboot the level of superoxide dismutase (SOD) and decrease malondialdehyde (MDA). Moreover, Western blot and quantitative PCR (Q-PCR) results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.
ESTHER : Wu_2016_Evid.Based.Complement.Alternat.Med_2016_2530105
PubMedSearch : Wu_2016_Evid.Based.Complement.Alternat.Med_2016_2530105
PubMedID: 27293454

Title : Vagus Nerve Attenuates Hepatocyte Apoptosis upon Ischemia-Reperfusion via alpha7 Nicotinic Acetylcholine Receptor on Kupffer Cells in Mice - Ni_2016_Anesthesiology_125_1005
Author(s) : Ni M , Fu H , Huang F , Zhao T , Chen JK , Li DJ , Shen FM
Ref : Anesthesiology , 125 :1005 , 2016
Abstract : BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a complication of liver surgery. As much as 50% of hepatocytes undergo apoptosis within the first 24 h of reperfusion. The neurotransmitters of the vagus nerve can activate alpha7 nicotinic acetylcholine receptor (alpha7nAChR) on macrophages. The function of Kupffer cells (KCs) determines HIR injury. We hypothesize that the vagus nerve could attenuate HIR-induced hepatocyte apoptosis by activating alpha7nAChR on KCs.
METHODS: Hepatic vagotomized C57BL/6J mice, KC-eliminated C57BL/6J mice, and alpha7nAChR mice were used for HIR. Primary KCs and hepatocytes were subjected to hypoxia/reoxygenation (HR). Liver injury, hepatocyte apoptosis, reactive oxygen species (ROS) production, and soluble CD163 were measured.
RESULTS: Hepatic vagotomy and alpha7nAChR caused higher levels of alanine transaminase and liver caspase-3 and -8 activity by HIR. Activating alpha7nAChR attenuated these changes in wild-type but not in the alpha7nAChR mice. Furthermore, activating alpha7nAChR diminished hepatic injury and reduced liver apoptosis by HIR in vagotomized mice. In vitro, activating alpha7nAChR reduced apoptosis of hepatocytes cocultured with KCs that suffered HR. Similar to the effects by catalase, activating alpha7nAChR on KCs reduced ROS and H2O2 by HR. The supernatant from KCs, with alpha7nAChR activated or catalase treated, prevented hepatocyte apoptosis by HR. Finally, KC elimination reduced HIR-induced H2O2 production in mice. Activating alpha7nAChR significantly attenuated soluble CD163 both in mice by HIR (serum: 240 +/- 34 vs. 446 +/- 72; mean +/- SD; n = 8; P < 0.01) and in KCs by HR (supernatant: 4.23 +/- 0.06 vs. 5.60 +/- 0.18; n = 3; P < 0.01).
CONCLUSIONS: The vagus nerve could minimize HIR-induced liver apoptosis through activating alpha7nAChR on KCs possibly by preventing their excessive ROS production.
ESTHER : Ni_2016_Anesthesiology_125_1005
PubMedSearch : Ni_2016_Anesthesiology_125_1005
PubMedID: 27560466

Title : Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP\/PS1 transgenic mice and scopolamine-induced memory impairment mice - He_2015_Eur.J.Pharmacol_768_96
Author(s) : He D , Wu H , Wei Y , Liu W , Huang F , Shi H , Zhang B , Wu X , Wang C
Ref : European Journal of Pharmacology , 768 :96 , 2015
Abstract : Harmine, a beta-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.
ESTHER : He_2015_Eur.J.Pharmacol_768_96
PubMedSearch : He_2015_Eur.J.Pharmacol_768_96
PubMedID: 26526348

Title : Evidence of multiple\/cross resistance to Bt and organophosphate insecticides in Puerto Rico population of the fall armyworm, Spodoptera frugiperda - Zhu_2015_Pestic.Biochem.Physiol_122_15
Author(s) : Zhu YC , Blanco CA , Portilla M , Adamczyk J , Luttrell R , Huang F
Ref : Pestic Biochem Physiol , 122 :15 , 2015
Abstract : Fall armyworm (FAW) is a damaging pest of many economic crops. Long-term use of chemical control prompted resistance development to many insecticide classes. Many populations were found to be significantly less susceptible to major Bt toxins expressed in transgenic crops. In this study, a FAW strain collected from Puerto Rico (PR) with 7717-fold Cry1F-resistance was examined to determine if it had also developed multiple/cross resistance to non-Bt insecticides. Dose response assays showed that the PR strain developed 19-fold resistance to acephate. Besides having a slightly smaller larval body weight and length, PR also evolved a deep (2.8%) molecular divergence in mitochondrial oxidase subunit II. Further examination of enzyme activities in the midgut of PR larvae exhibited substantial decreases of alkaline phosphatase (ALP), aminopeptidase (APN), 1-NA- and 2-NA-specific esterase, trypsin, and chymotrypsin activities, and significant increases of PNPA-specific esterase and glutathione S-transferase (GST) activities. When enzyme preparations from the whole larval body were examined, all three esterase, GST, trypsin, and chymotrypsin activities were significantly elevated in the PR strain, while ALP and APN activities were not significantly different from those of susceptible strain. Data indicated that multiple/cross resistances may have developed in the PR strain to both Bt toxins and conventional insecticides. Consistently reduced ALP provided evidence to support an ALP-mediated Bt resistance mechanism. Esterases and GSTs may be associated with acephate resistance through elevated metabolic detoxification. Further studies are needed to clarify whether and how esterases, GSTs, and other enzymes (such as P450s) are involved in cross resistance development to Bt and other insecticide classes.
ESTHER : Zhu_2015_Pestic.Biochem.Physiol_122_15
PubMedSearch : Zhu_2015_Pestic.Biochem.Physiol_122_15
PubMedID: 26071802

Title : Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics - Zhang_2014_Nat.Commun_5_3849
Author(s) : Zhang Y , Zhang K , Fang A , Han Y , Yang J , Xue M , Bao J , Hu D , Zhou B , Sun X , Li S , Wen M , Yao N , Ma LJ , Liu Y , Zhang M , Huang F , Luo C , Zhou L , Li J , Chen Z , Miao J , Wang S , Lai J , Xu JR , Hsiang T , Peng YL , Sun W
Ref : Nat Commun , 5 :3849 , 2014
Abstract : Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U. virens that encodes 8,426 predicted genes. The genome has ~25% repetitive sequences that have been affected by repeat-induced point mutations. Evolutionarily, U. virens is close to the entomopathogenic Metarhizium spp., suggesting potential host jumping across kingdoms. U. virens possesses reduced gene inventories for polysaccharide degradation, nutrient uptake and secondary metabolism, which may result from adaptations to the specific floret infection and biotrophic lifestyles. Consistent with their potential roles in pathogenicity, genes for secreted proteins and secondary metabolism and the pathogen-host interaction database genes are highly enriched in the transcriptome during early infection. We further show that 18 candidate effectors can suppress plant hypersensitive responses. Together, our analyses offer new insights into molecular mechanisms of evolution, biotrophy and pathogenesis of U. virens.
ESTHER : Zhang_2014_Nat.Commun_5_3849
PubMedSearch : Zhang_2014_Nat.Commun_5_3849
PubMedID: 24846013
Gene_locus related to this paper: ustvr-a0a063bxn3

Title : Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 - Zhang_2014_Crit.Care.Med_42_e345
Author(s) : Zhang H , Wang T , Zhang K , Liu Y , Huang F , Zhu X , Wang MH , Tang W , Wang J , Huang H
Ref : Critical Care Medicine , 42 :e345 , 2014
Abstract : OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN
RESULTS: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2.
CONCLUSIONS: Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.
ESTHER : Zhang_2014_Crit.Care.Med_42_e345
PubMedSearch : Zhang_2014_Crit.Care.Med_42_e345
PubMedID: 24448199

Title : Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage - He_2014_Neural.Regen.Res_9_1985
Author(s) : He Y , Zhu J , Huang F , Qin L , Fan W , He H
Ref : Neural Regen Res , 9 :1985 , 2014
Abstract : The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.
ESTHER : He_2014_Neural.Regen.Res_9_1985
PubMedSearch : He_2014_Neural.Regen.Res_9_1985
PubMedID: 25598781

Title : A review of clinical pharmacokinetics and pharmacodynamics of galantamine, a reversible acetylcholinesterase inhibitor for the treatment of Alzheimer's disease, in healthy subjects and patients - Huang_2010_Curr.Clin.Pharmacol_5_115
Author(s) : Huang F , Fu Y
Ref : Curr Clin Pharmacol , 5 :115 , 2010
Abstract : Galantamine is a reversible acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. Following oral administration, galantamine is rapidly absorbed and reaches C(max) in approximately one hour for immediate release (IR) tablets and four hours for extended-release (ER) capsules. Food has no clinically important effects on the absorption of galantamine. Galantamine displays dose-proportional pharmacokinetics over a dose range of 8-32 mg and 8-24 mg for IR and ER formulations, respectively. The elimination half-life of galantamine is about 7-8 hours. Galantamine has low protein binding (28.3-33.8%) and has an apparent steady-state volume of distribution (V(ss)) of 193 L. Approximately 20-25% of the galantamine dose administered is excreted unchanged in urine. No clinically significant effects of age, gender, and race have been observed on galantamine pharmacokinetics. The exposures to galantamine in patients with moderate and severe renal impairment are 37% and 67% higher, respectively than in healthy subjects, whereas the exposure to galantamine is approximately 30% higher in patients with moderate hepatic impairment. Co-administration of galantamine with ketoconazole (CYP 3A4 strong inhibitor) or paroxetine (CYP 2D6 strong inhibitor) leads to a 30% and 40% increase, respectively, in galantamine exposure compared to galantamine given alone.
ESTHER : Huang_2010_Curr.Clin.Pharmacol_5_115
PubMedSearch : Huang_2010_Curr.Clin.Pharmacol_5_115
PubMedID: 20156150

Title : Immobilization of acetylcholinesterase in lipid membranes deposited on self-assembled monolayers - Milkani_2010_Langmuir_26_18884
Author(s) : Milkani E , Khaing AM , Huang F , Gibson DG , Gridley S , Garceau N , Lambert CR , McGimpsey WG
Ref : Langmuir , 26 :18884 , 2010
Abstract : Human red blood cell acetylcholinesterase was incorporated into planar lipid membranes deposited on alkanethiol self-assembled monolayers (SAMs) on gold substrates. Activity of the protein in the membrane was detected with a standard photometric assay and was determined to be similar to the protein in detergent solution or incorporated in lipid vesicles. Monolayer and bilayer lipid membranes were generated by fusing liposomes to hydrophobic and hydrophilic SAMs, respectively. Liposomes were formed by the injection method using the lipid dimyristoylphosphatidylcholine (DMPC). The formation of alkanethiol SAMs and lipid monolayers on SAMs was confirmed by sessile drop goniometry, ellipsometry, and electrochemical impedance spectroscopy. In this work, we report acetylcholinesterase immobilization in lipid membranes deposited on SAMs formed on the gold surface and compare its activity to enzyme in solution.
ESTHER : Milkani_2010_Langmuir_26_18884
PubMedSearch : Milkani_2010_Langmuir_26_18884
PubMedID: 21087026

Title : Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase - Li_2004_Chem.Biol_11_107
Author(s) : Li TL , Huang F , Haydock SF , Mironenko T , Leadlay PF , Spencer JB
Ref : Chemical Biology , 11 :107 , 2004
Abstract : The gene cluster encoding biosynthesis of the clinically important glycopeptide antibiotic teicoplanin has been cloned from Actinoplanes teichomyceticus. Forty-nine putative open reading frames (ORFs) were identified within an 89 kbp genetic locus and assigned roles in teicoplanin biosynthesis, export, resistance, and regulation. Two ORFs, designated orfs 1 and 10*, showed significant homology to known glycosyltransferases. When heterologously expressed in Escherichia coli, these glycosyltransferases were shown to catalyze the transfer of UDP-(N-acetyl)-glucosamine onto, respectively, 3-chloro-beta-hydroxytyrosine-6 (3-Cl-6betaHty) and 4-hydroxyphenylglycine-4 (4Hpg) of the teicoplanin heptapeptide aglycone. The product of another ORF, orf11*, was demonstrated in vitro to transfer n-acetyl-, n-butyryl-, and n-octanoyl-groups from acyl-CoA donors either to a free UDP-aminosugar or to an aminosugar moiety in the teicoplanin pseudoaglycone, thus identifying Orf11* as the key acyltransferase in teicoplanin maturation. These findings should accelerate the combinatorial engineering of new and improved glycopeptide drugs.
ESTHER : Li_2004_Chem.Biol_11_107
PubMedSearch : Li_2004_Chem.Biol_11_107
PubMedID: 15113000
Gene_locus related to this paper: actti-q6zzg3 , actti-q6zzj3 , actti-q6zzg0