Wang F

References (159)

Title : The Overexpression of Zea mays Strigolactone Receptor Gene D14 Enhances Drought Resistance in Arabidopsis thaliana L - Zhang_2024_Int.J.Mol.Sci_25_
Author(s) : Zhang C , Wang F , Jiao P , Liu J , Zhang H , Liu S , Guan S , Ma Y
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Strigolactones (SLs) represent a recently identified class of plant hormones that are crucial for plant tillering and mycorrhizal symbiosis. The D14 gene, an essential receptor within the SLs signaling pathway, has been well-examined in crops, like rice (Oryza sativa L.) and Arabidopsis (Arabidopsis thaliana L.), yet the research on its influence in maize (Zea mays L.) remains scarce. This study successfully clones and establishes Arabidopsis D14 gene overexpression lines (OE lines). When compared with the wild type (WT), the OE lines exhibited significantly longer primary roots during germination. By seven weeks of age, these lines showed reductions in plant height and tillering, alongside slight decreases in rosette and leaf sizes, coupled with early aging symptoms. Fluorescence-based quantitative assays indicated notable hormonal fluctuations in OE lines versus the WT, implying that D14 overexpression disrupts plant hormonal homeostasis. The OE lines, exposed to cold, drought, and sodium chloride stressors during germination, displayed an especially pronounced resistance to drought. The drought resistance of OE lines, as evident from dehydration-rehydration assays, outmatched that of the WT lines. Additionally, under drought conditions, the OE lines accumulated less reactive oxygen species (ROS) as revealed by the assessment of the related physiological and biochemical parameters. Upon confronting the pathogens Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), post-infection, fluorescence quantitative investigations showed a significant boost in the salicylic acid (SA)-related gene expression in OE lines compared to their WT counterparts. Overall, our findings designate the SL receptor D14 as a key upregulator of drought tolerance and a regulator in the biotic stress response, thereby advancing our understanding of the maize SL signaling pathway by elucidating the function of the pivotal D14 gene.
ESTHER : Zhang_2024_Int.J.Mol.Sci_25_
PubMedSearch : Zhang_2024_Int.J.Mol.Sci_25_
PubMedID: 38279328

Title : Inhibition of soluble epoxide hydrolase enhances the dentin-pulp complex regeneration mediated by crosstalk between vascular endothelial cells and dental pulp stem cells - Kong_2024_J.Transl.Med_22_61
Author(s) : Kong L , Li J , Bai Y , Xu S , Zhang L , Chen W , Gao L , Wang F
Ref : J Transl Med , 22 :61 , 2024
Abstract : BACKGROUND: Revascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like endothelial cells subtype (POTCs) specialized to dentinogenesis was identified. We have confirmed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor targeting epoxyeicosatrienoic acids (EETs) metabolism, promotes bone growth and regeneration by angiogenesis and osteogenesis coupling. We hypothesized that TPPU could also promote revascularization and induce POTCs to contribute to pulp-dentin complex regeneration. Here, we in vitro and in vivo characterized the potential effect of TPPU on the coupling of angiogenesis and odontogenesis and investigated the relevant mechanism, providing new ideas for pulp-dentin regeneration by targeting sEH. METHODS: In vitro effects of TPPU on the proliferation, migration, and angiogenesis of dental pulp stem cells (DPSCs), human umbilical vein endothelial cells (HUVECs) and cocultured DPSCs and HUVECs were detected using cell counting kit 8 (CCK8) assay, wound healing, transwell, tube formation and RT-qPCR. In vivo, Matrigel plug assay was performed to outline the roles of TPPU in revascularization and survival of grafts. Then we characterized the VEGFR2 + POTCs around odontoblast layer in the molar of pups from C57BL/6 female mice gavaged with TPPU. Finally, the root segments with DPSCs mixed with Matrigel were implanted subcutaneously in BALB/c nude mice treated with TPPU and the root grafts were isolated for histological staining. RESULTS: In vitro, TPPU significantly promoted the migration and tube formation capability of cocultured DPSCs and HUVECs. ALP and ARS staining and RT-qPCR showed that TPPU promoted the osteogenic and odontogenic differentiation of cultured cells, treatment with an anti-TGF-beta blocking antibody abrogated this effect. Knockdown of HIF-1alpha in HUVECs significantly reversed the effect of TPPU on the expression of angiogenesis, osteogenesis and odontogenesis-related genes in cocultured cells. Matrigel plug assay showed that TPPU increased VEGF/VEGFR2-expressed cells in transplanted grafts. TPPU contributed to angiogenic-odontogenic coupling featured by increased VEGFR2 + POTCs and odontoblast maturation during early dentinogenesis in molar of newborn pups from C57BL/6 female mice gavaged with TPPU. TPPU induced more dental pulp-like tissue with more vessels and collagen fibers in transplanted root segment. CONCLUSIONS: TPPU promotes revascularization of dental pulp regeneration by enhancing migration and angiogenesis of HUVECs, and improves odontogenic differentiation of DPSCs by TGF-beta. TPPU boosts the angiogenic-odontogenic coupling by enhancing VEGFR2 + POTCs meditated odontoblast maturation partly via upregulating HIF-1alpha, which contributes to increasing pulp-dentin complex for tissue-engineered pulp regeneration.
ESTHER : Kong_2024_J.Transl.Med_22_61
PubMedSearch : Kong_2024_J.Transl.Med_22_61
PubMedID: 38229161

Title : Uncovering hidden dangers: The combined toxicity of abamectin and lambda-cyhalothrin on honey bees - Chen_2024_Sci.Total.Environ__173126
Author(s) : Chen X , Wang F , Guo H , Liu X , Wu S , Lv L , Tang T
Ref : Sci Total Environ , :173126 , 2024
Abstract : Studying the toxic effects of pesticides on bees has consistently been a prominent area of interest for researchers. Nonetheless, existing research has predominantly concentrated on individual toxicity assessments, leaving a gap in our understanding of mixed toxicity. This study delves into the individual and combined toxic effects of abamectin (ABA) and lambda-cyhalothrin (LCY) on honey bees (Apis mellifera) in laboratory settings. We discovered that ABA (96 h-LC(50) value of 0.079 mg/L) exhibited greater acute toxicity to honey bees compared to LCY (96 h-LC(50) value of 9.177 mg/L). Moreover, the mixture of ABA and LCY presented an acute antagonistic effect on honey bees. Additionally, our results indicated that exposure to LCY, at medium concentration, led to a reduction in the abundance of gut core bacterium Snodgrassella. However, an increase in the abundance of Bifidobacterium was noted when exposed to a medium concentration of LCY and its mixture with ABA. Transcriptomic analysis revealed significant regulation of certain genes in the medium concentration of all three treatments compared to the control group, primarily enriching in metabolism and immune-related pathways. Following chronic exposure to field-relevant concentrations of ABA, LCY, and their mixture, there were significant alterations in the activities of immunity-related enzyme polyphenol oxidase (PPO) and detoxification enzymes glutathione S-transferase (GST) and carboxylesterase (CarE). Additionally, the expression of four genes (abaecin, cyp9e2, cyp302a1, and GstD1) associated with immune and detoxification metabolism was significantly altered. These findings suggest a potential health risk posed by the insecticides ABA and LCY to honey bees. Despite exhibiting antagonistic effects, mixed exposure still induced damage to bees at all levels. This study advances our knowledge of the potential adverse effects of individual or combined exposure to these two pesticides on non-target pollinators and offers crucial guidance for the use of insecticides in agricultural production.
ESTHER : Chen_2024_Sci.Total.Environ__173126
PubMedSearch : Chen_2024_Sci.Total.Environ__173126
PubMedID: 38734105

Title : A Versatile Thioesterase Involved in Dimerizationduring Cinnamoyl Lipid Biosynthesis - Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
Author(s) : Deng Z , Liu C , Wang F , Song N , Liu J , Li H , Liu S , Li T , Liu Z , Xiao F , Li W
Ref : Angew Chem Int Ed Engl , :e202402010 , 2024
Abstract : The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatic dimerization remains unknown. In this work, an unusual"gene-within-gene"thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with alpha/beta-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6Pi-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatic dimerization process, possibly via an unprecedent Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6Pi-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.
ESTHER : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedSearch : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedID: 38462490
Gene_locus related to this paper: 9actn-YsfF

Title : Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry - Lai_2024_Chem.Sci_15_2545
Author(s) : Lai C , Tang Z , Liu Z , Luo P , Zhang W , Zhang T , Dong Z , Liu X , Yang X , Wang F
Ref : Chem Sci , 15 :2545 , 2024
Abstract : Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.
ESTHER : Lai_2024_Chem.Sci_15_2545
PubMedSearch : Lai_2024_Chem.Sci_15_2545
PubMedID: 38362424

Title : Vitamin B6 ameliorates acute pancreatitis by suppressing the caspase3 signaling pathway - Xu_2024_BMC.Gastroenterol_24_151
Author(s) : Xu H , Yue H , Ge H , Wang F
Ref : BMC Gastroenterol , 24 :151 , 2024
Abstract : BACKGROUND: Acute pancreatitis (AP) is a prevalent exocrine inflammatory disorder of the pancreas characterized by pancreatic inflammation and injury to acinar cells. Vitamin B6 (VB6) is a vital nutrient that plays a significant role in preserving human health and has anti-inflammatory and anti-apoptotic effects. METHODS: This study aimed to explore the potential pancreatic protective effects of VB6 in mitigating pancreatic inflammation and apoptosis induced by taurocholate sodium (TLCS) in an AP model and to assess the underlying mechanism of action. AP was induced in SpragueDawley (SD) rats through TLCS administration and lipopolysaccharide (LPS)-treated AR42J cells, followed by treatment with VB6. RESULTS: Various parameters associated with AP were assessed in both plasma and pancreatic tissues. VB6 has been shown to ameliorate the severity of AP through various mechanisms. It effectively reduces the levels of serum amylase, lipase, and inflammatory factors, thereby mitigating histological injury to the pancreas. Moreover, VB6 inhibited pancreatic apoptosis by downregulating bax expression and up-regulating Bcl2 expression in TLCS-treated rats. Additionally, VB6 suppressed the expression of caspase3. The anti-inflammatory and anti-apoptotic effects of VB6 observed in LPS-treated AR42J cells are consistent with those observed in a rat model of AP. CONCLUSIONS: These results suggest that VB6 exerts anti-inflammatory and anti-apoptotic effects through inhibition of the caspase3 signaling pathway and has a protective effect against AP.
ESTHER : Xu_2024_BMC.Gastroenterol_24_151
PubMedSearch : Xu_2024_BMC.Gastroenterol_24_151
PubMedID: 38698325

Title : Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice - Zhang_2023_J.Ethnopharmacol__117416
Author(s) : Zhang Q , Li Y , Fan B , Wang F , Li Z , Carlos Pires Dias A , Liu X , Wang Q
Ref : J Ethnopharmacol , :117416 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.
ESTHER : Zhang_2023_J.Ethnopharmacol__117416
PubMedSearch : Zhang_2023_J.Ethnopharmacol__117416
PubMedID: 37981114

Title : New advances in clinical application of neostigmine: no longer focusing solely on increasing skeletal muscle strength - Si_2023_Front.Pharmacol_14_1227496
Author(s) : Si S , Zhao X , Su F , Lu H , Zhang D , Sun L , Wang F , Xu L
Ref : Front Pharmacol , 14 :1227496 , 2023
Abstract : Neostigmine is a clinical cholinesterase inhibitor, that is, commonly used to enhance the function of the cholinergic neuromuscular junction. Recent studies have shown that neostigmine regulates the immune-inflammatory response through the cholinergic anti-inflammatory pathway, affecting perioperative neurocognitive function. This article reviews the relevant research evidence over the past 20 years, intending to provide new perspectives and strategies for the clinical application of neostigmine.
ESTHER : Si_2023_Front.Pharmacol_14_1227496
PubMedSearch : Si_2023_Front.Pharmacol_14_1227496
PubMedID: 37601044

Title : Identification, evolution, and expression of GDSL-type Esterase\/Lipase (GELP) gene family in three cotton species: a bioinformatic analysis - Duan_2023_BMC.Genomics_24_795
Author(s) : Duan L , Wang F , Shen H , Xie S , Chen X , Xie Q , Li R , Cao A , Li H
Ref : BMC Genomics , 24 :795 , 2023
Abstract : BACKGROUND: GDSL esterase/lipases (GELPs) play important roles in plant growth, development, and response to biotic and abiotic stresses. Presently, an extensive and in-depth analysis of GELP family genes in cotton is still not clear enough, which greatly limits the further understanding of cotton GELP function and regulatory mechanism. RESULTS: A total of 389 GELP family genes were identified in three cotton species of Gossypium hirsutum (193), G. arboreum (97), and G. raimondii (99). These GELPs could be classified into three groups and eight subgroups, with the GELPs in same group to have similar gene structures and conserved motifs. Evolutionary event analysis showed that the GELP family genes tend to be diversified at the spatial dimension and certain conservative at the time dimension, with a trend of potential continuous expansion in the future. The orthologous or paralogous GELPs among different genomes/subgenomes indicated the inheritance from genome-wide duplication during polyploidization, and the paralogous GELPs were derived from chromosomal segment duplication or tandem replication. GELP genes in the A/D subgenome underwent at least three large-scale replication events in the evolutionary process during the period of 0.6-3.2 MYA, with two large-scale evolutionary events between 0.6-1.8 MYA that were associated with tetraploidization, and the large-scale duplication between 2.6-9.1 MYA that occurred during diploidization. The cotton GELPs indicated diverse expression patterns in tissue development, ovule and fiber growth, and in response to biotic and abiotic stresses, combining the existing cis-elements in the promoter regions, suggesting the GELPs involvements of functions to be diversification and of the mechanisms to be a hormone-mediated manner. CONCLUSIONS: Our results provide a systematic and comprehensive understanding the function and regulatory mechanism of cotton GELP family, and offer an effective reference for in-depth genetic improvement utilization of cotton GELPs.
ESTHER : Duan_2023_BMC.Genomics_24_795
PubMedSearch : Duan_2023_BMC.Genomics_24_795
PubMedID: 38129780

Title : Dextran-assisted ultrasonic exfoliation of two-dimensional metal-organic frameworks to evaluate acetylcholinesterase activity and inhibitor screening - Wang_2023_Anal.Chim.Acta_1243_340815
Author(s) : Wang F , Liu M , Niu X , Xia L , Qu F
Ref : Anal Chim Acta , 1243 :340815 , 2023
Abstract : Acetylcholinesterase (AChE) is regarded as a biomarker of Alzheimer's disease (AD), and its inhibitors show great potential in AD therapy as AChE can increase the neurotoxicity of the amyloid component that induces AD. Because of this, it is crucial and significant to develop a simple and highly sensitive strategy to monitor AChE levels and screen highly efficient AChE inhibitors. Herein, we synthesize an ultrathin two-dimensional (2D) metal-organic framework (MOF) based on copper-catecholate (Cu-CAT) via dextran assisted ultrasound exfoliation, followed by construction of a sensitive sensor for the monitoring AChE and screening of its inhibitors. By adding AChE, the acetylthiocholine (ATCh) substrate is hydrolyzed to be thiocholine (TCh), which decreases the peroxidase-like activity of Cu-CAT nanosheets (Cu-CAT NSs), impairing the signal reaction of 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized-TMB (ox-TMB). In the presence of an AChE inhibitor, the signal can be gradually restored. The newly developed sensor shows high sensitivity and selectivity for AChE and huperzine A (HA, an effective drug for AD, an acetylcholine receptor antagonist), as well as for AD drug discovery from traditional Chinese herbs. The limit of detection of the sensor for AChE is 0.01 mU mL(-1) and the average IC(50) value of HA is 30.81 nM under the optimal of catalysis conditions. Compared with the 3D bulk Cu-CAT, the current 2D Cu-CAT NSs exhibit higher peroxidase activity due to more catalytic active site exposure. This study provides a strategy to prepare an ultrathin 2D MOF with high catalytic activity and new insights for the construction of a biosensor to monitor AChE and new AD drugs.
ESTHER : Wang_2023_Anal.Chim.Acta_1243_340815
PubMedSearch : Wang_2023_Anal.Chim.Acta_1243_340815
PubMedID: 36697184

Title : Design, synthesis, and biological evaluation of novel tryptanthrin derivatives as selective acetylcholinesterase inhibitors for the treatment of Alzheimer's disease - Xia_2023_Bioorg.Chem_143_106980
Author(s) : Xia J , Dong S , Yang L , Wang F , Xing S , Du J , Li Z
Ref : Bioorg Chem , 143 :106980 , 2023
Abstract : Two novel series of tryptanthrin (TRYP) derivatives were designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Inhibition assay against cholinesterase (ChE) indicated that these derivatives can act as acetylcholinesterase (AChE) inhibitors with selectivity over butyrylcholinesterase (BuChE). Among them, n1 exhibited the most excellent ChE inhibitory potency (AChE, IC(50) = 12.17 +/- 1.50 nM; BuChE, IC(50) = 6.29 +/- 0.48 micro; selectivity index = 517). Molecular docking studies indicated that compound n1 can interact with amino acid residues in the catalytic active site and peripheral anionic site of AChE and the molecular dynamics (MD) simulation studies demonstrated that the AChE-n1 complex had good stability. N1 also exhibited anti-amyloid-beta (Abeta) aggregation (63.48 % +/- 1.02 %, 100 micro) and anti-neuroinflammation activity (NO, IL-1beta, TNF-alpha; IC(50) = 2.13 +/- 0.54 micro, 2.21 +/- 0.37 micro, 2.47 +/- 0.07 micro, respectively), and n1 had neuroprotective and metal-chelating properties. Further studies indicated n1 had proper blood-brain barrier permeability in the Parallel artificial membrane permeation assay. In vivo studies found that n1 effectively improved learning and memory impairment in scopolamine-induced AD mouse models. Nissl staining ofmice hippocampaltissue sections revealed that n1 restored neuronal cells in the hippocampus CA3 and CA1 regions. These findings suggested that n1 can be a promising compound for further development of multifunctional agents for AD treatment.
ESTHER : Xia_2023_Bioorg.Chem_143_106980
PubMedSearch : Xia_2023_Bioorg.Chem_143_106980
PubMedID: 38006789

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

Title : Discovery of a new highly pathogenic toxin involved in insect sepsis - Zhang_2023_Microbiol.Spectr__e0142223
Author(s) : Zhang Y , Li H , Wang F , Liu C , Reddy GVP , Li Z , Sun Y , Zhao Z
Ref : Microbiol Spectr , :e0142223 , 2023
Abstract : Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25 degreesC while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
ESTHER : Zhang_2023_Microbiol.Spectr__e0142223
PubMedSearch : Zhang_2023_Microbiol.Spectr__e0142223
PubMedID: 37787562

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 : 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 : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : CES1-Triggered Liver-Specific Cargo Release of CRISPR\/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration - Zhao_2023_Adv.Sci.(Weinh)__e2300502
Author(s) : Zhao Y , Li Y , Wang F , Gan X , Zheng T , Chen M , Wei L , Chen J , Yu C
Ref : Adv Sci (Weinh) , :e2300502 , 2023
Abstract : The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA). The copolymer can self-assemble with Cas9-mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG-b-P(Met/n-PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low-density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed-point release, which expand the application of CRISPR delivery systems.
ESTHER : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedSearch : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedID: 37083231

Title : Rational Design of Esterase-Insensitive Fluorogenic Probes for In Vivo Imaging - Guo_2023_ACS.Sens__
Author(s) : Guo WY , Fu YX , Mei LC , Chen Z , Zhang ZY , Wang F , Yang WC , Liu G , Yang GF
Ref : ACS Sens , : , 2023
Abstract : Small-molecule fluorogenic probes are indispensable tools for performing research in biomedical fields and chemical biology. Although numerous cleavable fluorogenic probes have been developed to investigate various bioanalytes, few of them meet the baseline requirements for in vivo biosensing for disease diagnosis due to their insufficient specificity resulted from the remarkable esterase interferences. To address this critical issue, we developed a general approach called fragment-based fluorogenic probe discovery (FBFPD) to design esterase-insensitive probes for in vitro and in vivo applications. With the designed esterase-insensitive fluorogenic probe, we successfully achieved light-up in vivo imaging and quantitative analysis of cysteine. This strategy was further extended to design highly specific fluorogenic probes for other representative targets, sulfites, and chymotrypsin. The present study expands the bioanalytical toolboxes available and offers a promising platform to develop esterase-insensitive cleavable fluorogenic probes for in vivo biosensing and bioimaging for the early diagnosis of diseases.
ESTHER : Guo_2023_ACS.Sens__
PubMedSearch : Guo_2023_ACS.Sens__
PubMedID: 37146071

Title : Biochemical characterization of an alkaline and detergent-stable Lipase from Fusarium annulatum Bugnicourt strain CBS associated with olive tree dieback - Dab_2023_PLoS.One_18_e0286091
Author(s) : Dab A , Hasnaoui I , Mechri S , Allala F , Bouacem K , Noiriel A , Bouanane-Darenfed A , Saalaoui E , Asehraou A , Wang F , Abousalham A , Jaouadi B
Ref : PLoS ONE , 18 :e0286091 , 2023
Abstract : This work describes a novel extracellular lipolytic carboxylester hydrolase named FAL, with lipase and phospholipase A1 (PLA1) activity, from a newly isolated filamentous fungus Ascomycota CBS strain, identified as Fusarium annulatum Bunigcourt. FAL was purified to about 62-fold using ammonium sulphate precipitation, Superdex(a) 200 Increase gel filtration and Q-Sepharose Fast Flow columns, with a total yield of 21%. The specific activity of FAL was found to be 3500 U/mg at pH 9 and 40 degreesC and 5000 U/mg at pH 11 and 45 degreesC, on emulsions of triocanoin and egg yolk phosphatidylcholine, respectively. SDS-PAGE and zymography analysis estimated the molecular weight of FAL to be 33 kDa. FAL was shown to be a PLA1 with a regioselectivity to the sn-1 position of surface-coated phospholipids esterified with alpha-eleostearic acid. FAL is a serine enzyme since its activity on triglycerides and phospholipids was completely inhibited by the lipase inhibitor Orlistat (40 microM). Interestingly, compared to Fusarium graminearum lipase (GZEL) and the Thermomyces lanuginosus lipase (Lipolase(a)), this novel fungal (phospho)lipase showed extreme tolerance to the presence of non-polar organic solvents, non-ionic and anionic surfactants, and oxidants, in addition to significant compatibility and stability with some available laundry detergents. The analysis of washing performance showed that it has the capability to efficiently eliminate oil-stains. Overall, FAL could be an ideal choice for application in detergents.
ESTHER : Dab_2023_PLoS.One_18_e0286091
PubMedSearch : Dab_2023_PLoS.One_18_e0286091
PubMedID: 37205651

Title : Exploration of the SIRT1-mediated BDNF-TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis - Wang_2023_Front.Public.Health_11_1247294
Author(s) : Wang F , Li Y , Tang D , Yang B , Tian T , Tian M , Meng N , Xie W , Zhang C , He Z , Zhu X , Ming D , Liu Y
Ref : Front Public Health , 11 :1247294 , 2023
Abstract : INTRODUCTION: Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments. METHODS: This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting. RESULTS: All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities. DISCUSSION: Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.
ESTHER : Wang_2023_Front.Public.Health_11_1247294
PubMedSearch : Wang_2023_Front.Public.Health_11_1247294
PubMedID: 37711250

Title : Efficient Expression of Candida antarctica Lipase B in Pichia pastoris and Its Application in Biodiesel Production - Xiao_2023_Appl.Biochem.Biotechnol__
Author(s) : Xiao D , Li X , Zhang Y , Wang F
Ref : Appl Biochem Biotechnol , : , 2023
Abstract : Lipase B from Candida antarctica (CALB) is an important biocatalyst with many potential applications. However, original CALB is usually with lower enzyme activity and also costly to produce from Candida antarctica; hence, it is often necessary to prepare recombinant CALB through gene heterologous expression. In this research, seven promoters and five signal peptides were compared respectively for expressing codon-optimized CALB in Pichia pastoris, and then recombinant P. pastoris containing 3 copies of calb gene were obtained by screening with high concentrations of antibiotics under the condition of the optimal combination. In a 1.3-L bioreactor, the maximum CALB activity and total protein content reached 444.46 +/- 18.81 U/mL and 5.41 +/- 0.1 g/L, respectively, after about 9 days of incubation in FM22 medium, which were 34 times and 20 times higher than the initial strains, respectively. In addition, the obtained CALB was used to catalyze the transesterification of acidified gutter oil with methanol, suggesting a promising pathway to convert waste or low quality of bio-oil feedstocks with high amount of free fatty acids into biodiesel by using recombinant CALB as catalyst. The results can provide with a good reference for efficient expression of CALB and enhancing lipase production in P. pastoris. It is supposed to bring with new possibility for the bio-production of other valuable proteins.
ESTHER : Xiao_2023_Appl.Biochem.Biotechnol__
PubMedSearch : Xiao_2023_Appl.Biochem.Biotechnol__
PubMedID: 36723721

Title : Targeting soluble epoxide hydrolase promotes osteogenic-angiogenic coupling via activating SLIT3\/HIF-1alpha signalling pathway - Gao_2023_Cell.Prolif__e13403
Author(s) : Gao L , Chen W , Li L , Li J , Kongling W , Zhang Y , Yang X , Zhao Y , Bai J , Wang F
Ref : Cell Prolif , :e13403 , 2023
Abstract : Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross-talk between co-cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co-cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31(hi) EMCN(hi) endothelial cells (ECs) and SLIT3 and HIF-1alpha expression levels in co-cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif-1alpha in HUVECs impaired the formation of CD31(hi) EMCN(hi) ECs and reversed TPPU-induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs-derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF-1alpha signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair.
ESTHER : Gao_2023_Cell.Prolif__e13403
PubMedSearch : Gao_2023_Cell.Prolif__e13403
PubMedID: 36636821

Title : Research Mechanism and Progress of the Natural Compound Curcumin in Treating Alzheimers Disease - Li_2023_Mini.Rev.Med.Chem__
Author(s) : Li L , Wang F , Jia X , Yao L , Liu Y
Ref : Mini Rev Med Chem , : , 2023
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. AD patients usually present symptoms, such as cognitive dysfunction, progressive memory loss, and other manifestations. With the increasing number of AD cases worldwide, there is an urgent need to develop effective drug treatments. Currently, drugs targeting AD symptoms may not change or prevent the progression of the disease. Curcumin, a polyphenol extracted from the turmeric herb, has been used for the treatment of AD. In this review, we summarized both cellular and animal studies and described the mechanism of action of curcumin in altering the pathological features of AD. Curcumin attenuates the formation of amyloid-beta plaques and promotes its decomposition, reduces the phosphorylation of tau, improves its clearance rate, and binds with copper to reduce cholesterol. It changes the activity of microglia, suppresses acetylcholinesterase, regulates insulin signal transduction, and exhibits antioxidant properties. Studies have found that curcumin can promote nerve repair and has a significant effect on AD. However, the low bioavailability of curcumin may hinder its use as a therapeutic agent. If this limitation can be overcome, curcumin may emerge as a promising drug for the treatment of AD.
ESTHER : Li_2023_Mini.Rev.Med.Chem__
PubMedSearch : Li_2023_Mini.Rev.Med.Chem__
PubMedID: 37929738

Title : Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers - Li_2023_Clinics.(Sao.Paulo)_78_100208
Author(s) : Li J , Wen Z , Lou Y , Chen J , Gao L , Li X , Wang F
Ref : Clinics (Sao Paulo) , 78 :100208 , 2023
Abstract : OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.
ESTHER : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedSearch : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedID: 37148830

Title : Improving the activity and thermostability of PETase from Ideonella sakaiensis through modulating its post-translational glycan modification - Deng_2023_Commun.Biol_6_39
Author(s) : Deng B , Yue Y , Yang J , Yang M , Xing Q , Peng H , Wang F , Li M , Ma L , Zhai C
Ref : Commun Biol , 6 :39 , 2023
Abstract : The large-scale preparation of Polyehylene terephthalate (PET) hydrolysing enzymes in low-cost is critical for the biodegradation of PET in industry. In the present study, we demonstrate that the post-translational glycosylation of Pichia pastoris makes it a remarkable host for the heterologous expression of PETase from Ideonella sakaiensis 201-F6 (IsPETase). Taking advantage of the abundant N- and O-linked glycosylation sites in IsPETase and the efficient post-translational modification in endoplasmic reticulum, IsPETase is heavily glycosylated during secretory expression with P. pastoris, which improves the specific activity and thermostability of the enzyme dramatically. Moreover, the specific activity of IsPETase increased further after the bulky N-linked polysaccharide chains were eliminated by Endo-beta-N-acetylglucosaminidase H (Endo H). Importantly, the partially deglycosylated IsPETase still maintained high thermostability because of the remaining mono- and oligo-saccharide residues on the protein molecules. Consequently, the partially deglycosylated IsPETase was able to be applied at 50 degreesC and depolymerized raw, untreated PET flakes completely in 2 to 3 days. This platform was also applied for the preparation of a famous variant of IsPETase, Fast-PETase, and the same result was achieved. Partially deglycosylated Fast-PETase demonstrates elevated efficiency in degrading postconsumer-PET trays under 55 degreesC than 50 degreesC, the reported optimal temperature of Fast-PETase. The present study provides a strategy to modulate thermostable IsPETase through glycosylation engineering and paves the way for promoting PET biodegradation from laboratories to factories.
ESTHER : Deng_2023_Commun.Biol_6_39
PubMedSearch : Deng_2023_Commun.Biol_6_39
PubMedID: 36639437
Gene_locus related to this paper: idesa-peth

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

Title : First display of Haloalkane Dehalogenase LinB on the Surface of Bacillus subtilis Spore - Wang_2023_Protein.Pept.Lett__
Author(s) : Wang F , Liu X , Song T , Pei C , Huang Q , Jiang H , Xi H
Ref : Protein Pept Lett , : , 2023
Abstract : BACKGROUND: LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode. OBJECTIVE: In order to display Haloalkane dehalogenase LinB on the surface of Bacillus subtilis spore. METHOD: We have constituted the B. subtilis spore surface display system of halogenated alkanes dehalogenase LinB by gene recombination. RESULTS: Data revealed that LinB can display on spore surface successfully. The hydrolyzing HD analogue 2-chloroethyl ethylsulfide (2-CEES) activity of displayed LinB spores was 4.30+/-0.09 U/mL, and its specific activity was 0.78+/-0.03U/mg. Meanwhile, LinB spores showed a stronger stress resistance activity on 2-CEES than free LinB. This study obtained B. subtilis spores of LinB (phingobium japonicum UT26) with enzyme activity that was not reported before. CONCLUSION: Spore surface display technology uses resistance spore as the carrier to guarantee LinB activity, enhances its stability, and reduces the production cost, thus expanding the range of its application.
ESTHER : Wang_2023_Protein.Pept.Lett__
PubMedSearch : Wang_2023_Protein.Pept.Lett__
PubMedID: 37946356

Title : TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation - Dang_2023_Sci.Rep_13_1574
Author(s) : Dang H , Chen W , Chen L , Huo X , Wang F
Ref : Sci Rep , 13 :1574 , 2023
Abstract : Inflammation-induced autophagy is a double-edged sword. Dysfunction of autophagy impairs the differentiation capacity of mesenchymal stem cells and enhances inflammation-induced bone loss. Tooth extraction with periodontal and/or endodontic lesions exacerbates horizontal and vertical resorption of alveolar bone during the healing period. Alveolar socket preservation (ASP) procedure following tooth extraction has important clinical implications for future prosthodontic treatments. Studies have shown that epoxyeicosatrienoic acids (EETs) have significant anti-inflammatory effects and participate in autophagy. However, whether EETs can minimize alveolar bone resorption and contribute to ASP by regulating autophagy levels under inflammatory conditions remain elusive. Here, we figured out that LPS-induced inflammatory conditions increased the inflammatory cytokine and inhibited osteogenic differentiation of human dental pulp stem cells (hDPSCs), and led to excessive autophagy of hDPSCs. Moreover, we identified that increased EETs levels using TPPU, a soluble epoxide hydrolase inhibitor, reversed these negative outcomes. We further demonstrated the potential of TPPU to promote early healing of extraction sockets and ASP, and speculated that it was related to autophagy. Taken together, these results suggest that targeting inhibition of soluble epoxide hydrolase using TPPU plays a protective role in the differentiation and autophagy of mesenchymal stem cells and provides potential feasibility for applying TPPU for ASP, especially under inflammatory conditions.
ESTHER : Dang_2023_Sci.Rep_13_1574
PubMedSearch : Dang_2023_Sci.Rep_13_1574
PubMedID: 36709403

Title : Discovery of novel deoxyvasicinone derivatives with benzenesulfonamide substituents as multifunctional agents against Alzheimer's disease - Dong_2023_Eur.J.Med.Chem_264_116013
Author(s) : Dong S , Xia J , Wang F , Yang L , Xing S , Du J , Zhang T , Li Z
Ref : Eur Journal of Medicinal Chemistry , 264 :116013 , 2023
Abstract : A series of deoxyvasicinone derivatives with benzenesulfonamide substituents were designed and synthesized to find a multifunctional anti-Alzheimer's disease (AD) drug. The results of the biological activity evaluation indicated that most compounds demonstrated selective inhibition of acetylcholinesterase (AChE). Among them, g17 exhibited the most potent inhibitory effect on AChE (IC(50) = 0.24 +/- 0.04 microM). Additionally, g17 exhibited promising properties as a metal chelator and inhibitor of amyloid beta peptides self-aggregation (68.34 % +/- 1.16 %). Research on oxidative stress has shown that g17 displays neuroprotective effects and effectively suppresses the intracellular accumulation of reactive oxygen species. Besides, g17 demonstrated remarkable anti-neuroinflammatory effects by significantly reducing the production of pro-inflammatory cytokines (such as NO, IL-1beta, and TNF-alpha) and inhibiting the expression of inflammatory mediators iNOS and COX-2. In vivo studies showed that g17 significantly improved AD model mice's cognitive and memory abilities. Histological examination of mouse hippocampal tissue sections using hematoxylin and eosin staining revealed that g17 effectively mitigates neuronal damage. Considering the multifunctional properties of g17, it is regarded as a promising lead compound for treating AD.
ESTHER : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedSearch : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedID: 38052155

Title : Major biotransformation of phthalic acid esters in Eisenia fetida: Mechanistic insights and association with catalytic enzymes and intestinal symbionts - Fan_2022_Environ.Int_171_107712
Author(s) : Fan X , Gu C , Jin Z , Cai J , Bian Y , Wang F , Chen H , Jiang X
Ref : Environ Int , 171 :107712 , 2022
Abstract : Phthalic acid esters (PAEs) are an important group of organic pollutants that are widely used as plasticizers in the environment. The PAEs in soil organisms are likely to be biotransformed into a variety of metabolites, and the combined toxicity of PAEs and their metabolites might be more serious than PAEs alone. However, there are only a few studies on PAE biotransformation by terrestrial animals, e.g. earthworms. Herein, the key biotransformation pathways of PAEs and their association with catalytic enzymes and intestinal symbionts in earthworms were studied using in vivo and in vitro incubation approaches. The widely distributed PAE in soil, dibutyl phthalate (DBP), was proven to be biotransformed rapidly together with apparent bioaccumulation in earthworms. The biotransformation of PAE congeners with medium or long side chains appeared to be faster compared with those with short side chains. DBP was biotransformed into butyl methyl phthalate (BMP), monobutyl phthalate (MBP), and phthalic acid (PA) through esterolysis and transesterification. Besides, the generation of small quantities of low-molecular weight metabolites via beta-oxidation, decarboxylation or ring-cleavage, was also observed, especially when the appropriate proportion of NADPH coenzyme was applied to transfer electrons for oxidases. Interestingly, the esterolysis of PAEs was mainly regulated by the cytoplasmic carboxylesterase (CarE) in earthworms, with a Michaelis constant (K(m)) of 0.416smM in the catalysis of DBP. The stronger esterolysis in non-intestinal tissues indicated that the CarE was primarily secreted by non-intestinal tissues of earthworms. Additionally, the intestinal symbiotic bacteria of earthworms could respond to PAE stress, leading to the changes in their diversity and composition. The enrichment of some genera e.g. Bacillus and Paracoccus, and the enhancement of metabolism function, e.g. amino acids, energy, lipids biosynthesis and oxidase secretion, indicated their important role in the degradation of PAEs.
ESTHER : Fan_2022_Environ.Int_171_107712
PubMedSearch : Fan_2022_Environ.Int_171_107712
PubMedID: 36577298

Title : A turn-on fluorescent probe based on ESIPT and AIEE mechanisms for the detection of butyrylcholinesterase activity in living cells and in non-alcoholic fatty liver of zebrafish - Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
Author(s) : Pei X , Fang Y , Gu H , Zheng S , Bin X , Wang F , He M , Lu S , Chen X
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 287 :122044 , 2022
Abstract : Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are two important cholinesterase enzymes in human metabolism which are closely related to various diseases of the liver. BChE and AChE are difficult to be distinguished due to their similarity in biochemical properties. Therefore, developing BChE-specific probes with high sensitivity and low background reading is desirable for the relevant biological applications. Herein, we reported the design and synthesis of a fluorescent probe HBT-BChE for biological detection and imaging of BChE. The probe is triggered by BChE-mediated hydrolysis, releasing a fluorophore that holds AIEE and ESIPT properties with large Stokes shift (>100 nm), rendering the probe features of low background interference and high sensitivity. The probe can also distinguish BChE from AChE with a low detection limit of 7.540 x 10(-4) U/mL. Further in vitro studies have shown the ability of HBT-BChE to detect intracellular BChE activity, as well as to evaluate the efficiency of the BChE inhibitor. More importantly, the in vivo studies of imaging the BChE activity level in liver tissues using zebrafish as the model animal demonstrated the potential of HBT-BChE as a powerful tool for non-alcoholic fatty liver disease.
ESTHER : Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
PubMedSearch : Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
PubMedID: 36327810

Title : Engineering the Thermostability of the Mono- and Diacylglycerol Lipase SMG1 for the Synthesis of Diacylglycerols - Li_2022_Foods_11_4069
Author(s) : Li L , Wang Y , Cui R , Wang F , Lan D
Ref : Foods , 11 :4069 , 2022
Abstract : Diacylglycerols (DAGs) display huge application prospectives in food industries. Therefore, new strategies to produce diacylglycerides are needed. Malassezia globose lipase (SMG1) could be used to synthesize DAGs. However, the poor thermostability of SMG1 seriously hampers its application. Herein, a rational design was used to generate a more thermostable SMG1. Compared with the wild type (WT), the M5D mutant (Q34P/A37P/M176V/G177A/M294R/ G28C-P206C), which contains five single-point mutations and one additional disulfide bond, displayed a 14.0 degreesC increase in the melting temperature (T(m)), 5 degreesC in the optimal temperature, and 1154.3-fold in the half-life (t(1/2)) at 55 degreesC. Meanwhile, the specific activity towards DAGs of the M5D variant was improved by 3.0-fold compared to the WT. Molecular dynamics (MD) simulations revealed that the M5D mutant showed an improved rigid structure. Additionally, the WT and the M5D variants were immobilized and used for the production of DAGs. Compared with the WT, the immobilized M5D-catalyzed esterification showed a 9.1% higher DAG content and a 22.9% increase in residual activity after nine consecutive cycles. This study will pave the way for the industrial application of SMG1.
ESTHER : Li_2022_Foods_11_4069
PubMedSearch : Li_2022_Foods_11_4069
PubMedID: 36553811
Gene_locus related to this paper: malgo-a8puy1

Title : Peroxidase-like activity of Ru-N-C nanozymes in colorimetric assay of acetylcholinesterase activity - Yan_2022_Anal.Chim.Acta_1191_339362
Author(s) : Yan B , Wang F , He S , Liu W , Zhang C , Chen C , Lu Y
Ref : Anal Chim Acta , 1191 :339362 , 2022
Abstract : Herein, the Ru-N-C nanozymes with abundant active Ru-N(x) sites have been successfully prepared by pyrolyzing Ru(acac)(3) trapped zeolitic-imidazolate-frameworks (Ru(acac)(3)@ZIF-8). Taking advantages of the remarkable peroxidase-mimicking activity, outstanding stability and reusability of Ru-N-C nanozymes, a novel biosensing system with explicit mechanism is strategically fabricated for sensitively determining acetylcholinesterase (AChE) and tacrine. The limit of detection for AChE activity can achieve as low as 0.0433 mU mL(-1), and the IC(50) value of tacrine for AChE is about 0.190 micromol L(-1). The robust analytical performance in serums test verifies the great application potential of this assay in real matrix. Furthermore, "INH" and "IMPLICATION-AND" logic gates are rationally constructed based on the proposed colorimetric sensor. This work not only provides one sustainable and effective avenue to fabricate Ru-N-C-based peroxidase mimic with high catalytic performance, and also gives new impetuses for developing novel biosensors by applying Ru-N-C-based enzyme mimics as substitutes for the natural enzyme.
ESTHER : Yan_2022_Anal.Chim.Acta_1191_339362
PubMedSearch : Yan_2022_Anal.Chim.Acta_1191_339362
PubMedID: 35033267

Title : Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain - Yan_2022_Environ.Sci.Ecotechnol_12_100198
Author(s) : Yan Z , Feng C , Jin X , Wang F , Liu C , Li N , Qiao Y , Bai Y , Wu F , Giesy JP
Ref : Environ Sci Ecotechnol , 12 :100198 , 2022
Abstract : Organophosphate esters (OPEs) are widespread in various environmental media, and can disrupt thyroid endocrine signaling pathways. Mechanisms by which OPEs disrupt thyroid hormone (TH) signal transduction are not fully understood. Here, we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways. OPEs can bind to transthyretin (TTR) and thyroxine-binding globulin, thereby affecting the transport of TH in the blood, and to the brain by TTR through the blood-brain barrier. When GH3 cells were exposed to OPEs, cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH. Cresyl diphenyl phosphate was shown to be an effective antagonist of TH. Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis. Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, signaling pathways related to thyroid endocrine functions, such as receptor-ligand binding and regulation of hormone levels, were identified as being affected by exposure to OPEs. Effects were also associated with the biosynthesis and metabolism of lipids, and neuroactive ligand-receptor interactions. These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.
ESTHER : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedSearch : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedID: 36157343

Title : The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study - Wu_2022_Food.Res.Int_158_111497
Author(s) : Wu M , Liu M , Wang F , Cai J , Luo Q , Li S , Zhu J , Tang Z , Fang Z , Wang C , Chen H
Ref : Food Res Int , 158 :111497 , 2022
Abstract : The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC(50) values of 0.1974 +/- 0.0047, 0.2589 +/- 0.0131, 1.0905 +/- 0.0598 and 1.503 +/- 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of alpha-helix and reducing beta-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.
ESTHER : Wu_2022_Food.Res.Int_158_111497
PubMedSearch : Wu_2022_Food.Res.Int_158_111497
PubMedID: 35840206

Title : A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis - Yin_2022_Front.Nutr_9_1018733
Author(s) : Yin K , Yang J , Wang F , Wang Z , Xiang P , Xie X , Sun J , He X , Zhang X
Ref : Front Nutr , 9 :1018733 , 2022
Abstract : This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 microg RE/mg E) and total phenolics content (TPC) (47.97 microg GAE/mg E), EtOAc showed the strongest DPPH scavenging ability (IC(50) value = 29.56 microg/mL), ABTS (+) scavenging ability (IC(50) value = 84.60 microg/mL), and ferric reducing antioxidant power (FRAP) (889.62 microg FeSO(4)/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best alpha-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC(50) values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC(50) values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds' abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug.
ESTHER : Yin_2022_Front.Nutr_9_1018733
PubMedSearch : Yin_2022_Front.Nutr_9_1018733
PubMedID: 36313078

Title : Late onset of neutral lipid storage disease due to a rare PNPLA2 mutation in a patient with myopathy and cardiomyopathy -
Author(s) : Tian Y , Wang S , Wang F , Yi L , Dong M , Huang X
Ref : Chinese Medical Journal (Engl) , 135 :2389 , 2022
PubMedID: 36535014

Title : Dual-Modal Nanoscavenger for Detoxification of Organophosphorus Compounds - Zou_2022_ACS.Appl.Mater.Interfaces__
Author(s) : Zou S , Wang B , Wang Q , Liu G , Song J , Zhang F , Li J , Wang F , He Q , Zhu Y , Zhang L
Ref : ACS Appl Mater Interfaces , : , 2022
Abstract : Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.
ESTHER : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedID: 36089739

Title : 3D origami paper-based ratiometric fluorescent microfluidic device for visual point-of-care detection of alkaline phosphatase and butyrylcholinesterase - Zhu_2021_Biosens.Bioelectron_196_113691
Author(s) : Zhu Y , Tong X , Wei Q , Cai G , Cao Y , Tong C , Shi S , Wang F
Ref : Biosensors & Bioelectronics , 196 :113691 , 2021
Abstract : On-site multiplex enzyme detection is crucial for diagnosis, therapeutics and prognostic. To date, it is still a daunting challenge to develop portable, low-cost, and efficient multi-enzyme detection methods. Herein, a novel sample-in-result-out platform integrating ratiometric fluorescent assays with 3D origami microfluidic paper-based device (microPAD) was developed for simultaneous visual point-of-care testing (POCT) of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Cascade catalytic reaction with the same two fluorescent signal indicators was rationally designed to ratiometric fluorescent detection of ALP and BChE: substrate of ALP (pyrophosphate) and product of BChE (thiocholine) can strongly complex with Cu(2+), Cu(2+) oxidizes o-phenylenediamine to fluorescent 2,3-diaminophenazine (oxOPD) (emission, 565 nm), oxOPD quenches the fluorescence of carbon dots (CDs, emission at 445 nm) via inner filter effect, thus oxOPD/CDs values are relevant to ALP and BChE activities. Then 3D origami microPAD composing of four layers and two parallel channels was fabricated and simply prepared by one-step plotting with black oil-based marker and specific metal molds. After simple folding and unfolding neighboring layers to sequentially initiate reactions of pre-loaded reagents, fluorescent images on the detection zone can be captured by smartphone and analyzed by red-green-blue software for quantitative analysis. Under optimal conditions, the proposed platform was successfully performed to detect ALP and BChE with activity difference at 3 orders of magnitude in human serum samples without any pretreatment procedures. Excellent selectivity, good precision, favorable linear range, and high accuracy were exhibited. Importantly, the platform opens a promising horizon for high-throughput POCT of multiplex biomarkers.
ESTHER : Zhu_2021_Biosens.Bioelectron_196_113691
PubMedSearch : Zhu_2021_Biosens.Bioelectron_196_113691
PubMedID: 34637993

Title : Directed evolution of feruloyl esterase from Lactobacillus acidophilus and its application for ferulic acid production - Liu_2021_Bioresour.Technol_332_124967
Author(s) : Liu S , Soomro L , Wei X , Yuan X , Gu T , Li Z , Wang Y , Bao Y , Wang F , Wen B , Xin F
Ref : Bioresour Technol , 332 :124967 , 2021
Abstract : Producing ferulic acid (FA) from the natural substrate with feruloyl esterase is promising in industries, screening and engineering new enzymes with high efficiency to increase the FA yield is of great concern. Here, the feruloyl esterase of Lactobacillus acidophilus (FAELac) was heterologous expressed and the FAELac with different oligomerization states was separated. Interestingly, the activity of dimer was 37-fold higher than high-polymer. To further enhance the efficiency of FAELac, eight mutants were generated based on the simulated structure, of which Q198A, Q134T enhanced the catalytic efficiency by 5.4- and 4.3-fold in comparison with the wild type. Moreover, higher yields of FA (2.21, 6.60, and 1.67 mg/g substrate, respectively) were released by the mutants from de-starched wheat bran, insoluble wheat arabinoxylan, and steam-exploded corn stover. These results indicated that improving the purification process, engineering new FAELac and substrates bias studies hold great potential for increasing FA production yield.
ESTHER : Liu_2021_Bioresour.Technol_332_124967
PubMedSearch : Liu_2021_Bioresour.Technol_332_124967
PubMedID: 33845316
Gene_locus related to this paper: lacac-q5fi30

Title : A reverse catalytic triad Asp containing loop shaping a wide substrate binding pocket of a feruloyl esterase from Lactobacillus plantarum - Zhang_2021_Int.J.Biol.Macromol_184_92
Author(s) : Zhang H , Wen B , Liu Y , Du G , Wei X , Khandaker S , Zhou H , Fan S , Wang F , Wang Y , Xin F
Ref : Int J Biol Macromol , 184 :92 , 2021
Abstract : Feruloyl esterase is an indispensable biocatalyst in food processing, pesticide and pharmaceutical industries, catalyzing the cleavage of the ester bond cross-linked between the polysaccharide side chain of hemicellulose and ferulic acid in plant cell walls. LP_0796 from Lactobacillus plantarum was identified as a feruloyl esterase that may have potential applications in the food industry, but the lack of the substrate recognition and catalytic mechanisms limits its application. Here, LP_0796 showed the highest activity towards methyl caffeate at pH 6.6 and 40 degreesC. The crystal structure of LP_0796 was determined at 2.5 A resolution and featured a catalytic triad Asp195-containing loop facing the opposite direction, thus forming a wider substrate binding pocket. Molecular docking simulation and site-directed mutagenesis studies further demonstrated that in addition to the catalytic triad (Ser94, Asp195, His225), Arg125 and Val128 played essential roles in the function of the active site. Our data also showed that Asp mutation of Ala23 and Ile198 increased the catalytic efficiency to 4- and 5-fold, respectively. Collectively, this work provided a better understanding of the substrate recognition and catalytic mechanisms of LP_0796 and may facilitate the future protein design of this important feruloyl esterase.
ESTHER : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedSearch : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedID: 34116094
Gene_locus related to this paper: lacpl-LP.0796

Title : Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb - Wang_2021_Fitoterapia_156_105069
Author(s) : Wang X , Wang F , Wu J , Chen SQ , Jiang CS , Yang SP , Wang C , Cai YS
Ref : Fitoterapia , 156 :105069 , 2021
Abstract : Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and alpha-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and alpha-glucosidase.
ESTHER : Wang_2021_Fitoterapia_156_105069
PubMedSearch : Wang_2021_Fitoterapia_156_105069
PubMedID: 34743932

Title : One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase - Liu_2021_J.Org.Chem__
Author(s) : Liu C , Wang Y , Liu J , Chen A , Xu J , Zhang R , Wang F , Nie K , Deng L
Ref : J Org Chem , : , 2021
Abstract : 4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.
ESTHER : Liu_2021_J.Org.Chem__
PubMedSearch : Liu_2021_J.Org.Chem__
PubMedID: 34085515

Title : Neuroprotective effects of protocatechuic acid on sodium arsenate induced toxicity in mice: Role of oxidative stress, inflammation, and apoptosis - Li_2021_Chem.Biol.Interact__109392
Author(s) : Li Z , Liu Y , Wang F , Gao Z , Elhefny MA , Habotta OA , Abdel Moneim AE , Kassab RB
Ref : Chemico-Biological Interactions , :109392 , 2021
Abstract : Arsenic is a toxic metalloid abundantly found in nature and used in many industries. Consumption of contaminated water mainly results in human exposure to arsenic. Toxicity (arsenicosis) resulting from arsenic exposure causes cerebral neurodegeneration. Protocatechuic acid (PCA), a phenol derived from edible plants, has antioxidant properties. The present study investigated the neuroprotective potential of PCA against arsenic-induced neurotoxicity in mice. Male Swiss albino mice were divided into four groups: (i) orally administered physiological saline, (ii) orally administered 100 mg/kg PCA, (iii) orally administered 5 mg/kg NaAsO(2), and (iv) orally administered 100 mg/kg PCA 120 min prior to oral administration of 5 mg/kg NaAsO(2). Each group received its respective treatment for 1 week, after which cortical tissues from each group were analyzed for various parameters of oxidative stress, proinflammatory cytokines, apoptosis-related proteins, and changes in histopathology. NaAsO(2)-treatment resulted in a significant increase in lipid peroxidation (LPO), inducible nitric oxide synthetase (iNOs), and NO levels, with a decrease in the levels of both enzymatic (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and non-enzymatic (glutathione) antioxidant markers. Arsenic increased proinflammatory cytokine (tumor necrosis factor-alpha and interleukin-1beta) levels, enhanced caspase-3 and Bax expression, and reduced Bcl-2 expression. Furthermore, arsenic-exposure in mice decreased significantly acetylcholinesterase activity and brain-derived neurotrophic factor level in the cerebral cortex. Histopathological examination revealed changes in nerve cell cyto-architecture and distribution in arsenic-exposed brain tissue sections. PCA treatment before arsenic administration resulted in a positive shift in the oxidative stress and cytokine levels with decreased levels of LPO, iNOS, and NO. PCA pre-treatment considerably attenuated arsenic-associated histopathological changes in murine brain tissue. This study suggested that the presence of PCA may be responsible for the prevention of arsenic-induced neurotoxicity.
ESTHER : Li_2021_Chem.Biol.Interact__109392
PubMedSearch : Li_2021_Chem.Biol.Interact__109392
PubMedID: 33497687

Title : The Impact of ABCB1 and CES1 Polymorphisms on Dabigatran Pharmacokinetics in Healthy Chinese Subjects - Liu_2021_Pharmgenomics.Pers.Med_14_477
Author(s) : Liu Y , Yang C , Qi W , Pei Z , Xue W , Zhu H , Dong M , Guo Y , Cong D , Wang F
Ref : Pharmgenomics Pers Med , 14 :477 , 2021
Abstract : Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatran-related genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on C(max) and AUC(0-).
ESTHER : Liu_2021_Pharmgenomics.Pers.Med_14_477
PubMedSearch : Liu_2021_Pharmgenomics.Pers.Med_14_477
PubMedID: 33935512

Title : The alpha-Helical Cap Domain of a Novel Esterase from Gut Alistipes shahii Shaping the Substrate-Binding Pocket - Wei_2021_J.Agric.Food.Chem__
Author(s) : Wei X , Wang YL , Wen BT , Liu SJ , Wang L , Sun L , Gu TY , Li Z , Bao Y , Fan SL , Zhou H , Wang F , Xin F
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : The human gut microbiota regulates nutritional metabolism, especially by encoding specific ferulic acid esterases (FAEs) to release functional ferulic acid (FA) from dietary fiber. In our previous study, we observed seven upregulated FAE genes during in vitro fecal slurry fermentation using wheat bran. Here, a 29 kDa FAE (AsFAE) from Alistipes shahii of Bacteroides was characterized and identified as the type-A FAE. The X-ray structure of AsFAE has been determined, revealing a unique alpha-helical domain comprising five alpha-helices, which was first characterized in FAEs from the gut microbiota. Further molecular docking analysis and biochemical studies revealed that Tyr100, Thr122, Tyr219, and Ile220 are essential for substrate binding and catalytic efficiency. Additionally, Glu129 and Lys130 in the cap domain shaped the substrate-binding pocket and affected the substrate preference. This is the first report on A. shahii FAE, providing a theoretical basis for the dietary metabolism in the human gut.
ESTHER : Wei_2021_J.Agric.Food.Chem__
PubMedSearch : Wei_2021_J.Agric.Food.Chem__
PubMedID: 33979121
Gene_locus related to this paper: 9bact-d4inh0

Title : Resistance of Bemisia tabaci Mediterranean (Q-biotype) to pymetrozine: resistance risk assessment, cross-resistance to six other insecticides and detoxification enzyme assay - Wang_2021_Pest.Manag.Sci_77_2114
Author(s) : Wang F , Liu J , Shuai S , Miao C , Chi B , Chen P , Wang K , Li H , Liu Y
Ref : Pest Manag Sci , 77 :2114 , 2021
Abstract : BACKGROUND: The whitefly Bemisia tabaci (Gennadius) is a severe pest that affects many field and glasshouse crops worldwide and has developed resistance to insecticides in most chemical classes. Pymetrozine, a neuroactive pyridine azomethine, is selective towards piercing-sucking pests in Hemiptera. The aim of this study was to assess the resistance of B. tabaci Mediterranean (MED) to pymetrozine in the laboratory. RESULTS: After successive selection of 18 generations of MED in the presence of using pymetrozine, there was an 11.28-fold increase in the median lethal concentration (LC(50) ). When the realized heritability (h(2) ) of B. tabaci to pymetrozine in the field was assumed to be the value estimated in the laboratory (h(2) = 0.1360) and the mortality was 70-90%, only 7.2-15.9 generations were estimated to be needed to obtain a ten-fold increase in resistance to pymetrozine. Compared with the susceptible populations (G(0) ), the Pyme-SEL strain (G(18) ) showed a low level of cross-resistance to neonicotinoids (nitenpyram, imidacloprid, acetamiprid, and thiamethoxam) and no cross-resistance to chlorpyrifos or abamectin. With the G(0) and the Pyme-SEL strains (G(11) and G(18) ) as test strains, the activity of multifunctional oxidase exhibited the greatest increase during selection, while the activities of carboxylesterase and glutathione-S-transferase did not change significantly. CONCLUSION: This study show that a potential risk of development of resistance to pymetrozine exists in B. tabaci after continuous application. During the application of pymetrozine to control B. tabaci in the field, the frequency of its use in combination with neonicotinoids should be used with caution. 2020 Society of Chemical Industry.
ESTHER : Wang_2021_Pest.Manag.Sci_77_2114
PubMedSearch : Wang_2021_Pest.Manag.Sci_77_2114
PubMedID: 33332688

Title : Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development - Li_2021_Plant.J__
Author(s) : Li S , Li Y , Chen L , Zhang C , Wang F , Li H , Wang M , Wang Y , Nan F , Xie D , Yan J
Ref : Plant J , : , 2021
Abstract : Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.
ESTHER : Li_2021_Plant.J__
PubMedSearch : Li_2021_Plant.J__
PubMedID: 33860570

Title : Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder - Zou_2021_Open.Biol_11_200306
Author(s) : Zou M , Liu Y , Xie S , Wang L , Li D , Li L , Wang F , Zhang Y , Xia W , Sun C , Wu L
Ref : Open Biol , 11 :200306 , 2021
Abstract : Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg(-1), which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.
ESTHER : Zou_2021_Open.Biol_11_200306
PubMedSearch : Zou_2021_Open.Biol_11_200306
PubMedID: 33529552

Title : Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open BloodBrain Barrier for Treatment of Alzheimer's Disease - Wang_2021_Front.Pharmacol_12_615104
Author(s) : Wang F , Wei XX , Chang LS , Dong L , Wang YL , Li NN
Ref : Front Pharmacol , 12 :615104 , 2021
Abstract : Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer's disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood-brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood-brain barrier in an AD rat model. Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood-brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery. Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups. Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats.
ESTHER : Wang_2021_Front.Pharmacol_12_615104
PubMedSearch : Wang_2021_Front.Pharmacol_12_615104
PubMedID: 33746754

Title : DECR1 directly activates HSL to promote lipolysis in cervical cancer cells - Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
Author(s) : Zhou H , Zhang J , Yan Z , Qu M , Zhang G , Han J , Wang F , Sun K , Wang L , Yang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159090 , 2021
Abstract : Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth.
ESTHER : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedSearch : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedID: 34896618

Title : The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage - Gunn_2020_Proc.Natl.Acad.Sci.U.S.A_117_10254
Author(s) : Gunn KH , Roberts BS , Wang F , Strauss JD , Borgnia MJ , Egelman EH , Neher SB
Ref : Proc Natl Acad Sci U S A , 117 :10254 , 2020
Abstract : Lipases are enzymes necessary for the proper distribution and utilization of lipids in the human body. Lipoprotein lipase (LPL) is active in capillaries, where it plays a crucial role in preventing dyslipidemia by hydrolyzing triglycerides from packaged lipoproteins. Thirty years ago, the existence of a condensed and inactive LPL oligomer was proposed. Although recent work has shed light on the structure of the LPL monomer, the inactive oligomer remained opaque. Here we present a cryo-EM reconstruction of a helical LPL oligomer at 3.8-A resolution. Helix formation is concentration-dependent, and helices are composed of inactive dihedral LPL dimers. Heparin binding stabilizes LPL helices, and the presence of substrate triggers helix disassembly. Superresolution fluorescent microscopy of endogenous LPL revealed that LPL adopts a filament-like distribution in vesicles. Mutation of one of the helical LPL interaction interfaces causes loss of the filament-like distribution. Taken together, this suggests that LPL is condensed into its inactive helical form for storage in intracellular vesicles.
ESTHER : Gunn_2020_Proc.Natl.Acad.Sci.U.S.A_117_10254
PubMedSearch : Gunn_2020_Proc.Natl.Acad.Sci.U.S.A_117_10254
PubMedID: 32332168
Gene_locus related to this paper: bovin-lipli , human-LPL

Title : Secondary metabolites of Galactomyces geotrichum from Laminaria japonica ameliorate cognitive deficits and brain oxidative stress in D-galactose induced Alzheimer's disease mouse model - Wang_2020_Nat.Prod.Res__1
Author(s) : Wang F , Chen T
Ref : Nat Prod Res , :1 , 2020
Abstract : Accumulating evidences have shown the beneficial effects of natural products for Alzheimer's disease (AD) treatment. The present study was designed to investigate the neuroprotective effects of secondary metabolites of Galactomyces geotrichum (SMGG) on D-galactose induced AD mice. SMGG was extracted and its toxicological evaluation was conducted. To explore the neuroprotective mechanism responsible for anti-AD activity of SMGG, spatial learning and memory behavioral, oxidative stress levels, acetylcholinesterase and choline acetyltransferase activity assays were employed. The AD mice received SMGG treatment exhibited significant improvement in cognitive performance, enhanced antioxidant capacity, decreased acetylcholinesterase activity and increased choline acetyltransferase activity. Meanwhile, SMGG had no toxicity and seven compounds were separated from it: 7,8-dimethyl-iso-alloxazine, 1-methyl-3-benzyl-6-(4-hydroxybenzyl)-2,5-piperzainedione, cyclo-(Phe-Pro), cyclo-(Leu-Pro), cyclo-(Pro-Gly), cyclo-(Gly-Leu) and uracil, respectively. Overall, these data suggested that SMGG protects the brain against D-galactose induced cognitive impairment, oxidative damages and acetylcholine content decrease in AD mice.
ESTHER : Wang_2020_Nat.Prod.Res__1
PubMedSearch : Wang_2020_Nat.Prod.Res__1
PubMedID: 32292060

Title : Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007 - Han_2020_Bioorg.Chem_96_103646
Author(s) : Han W , Cai J , Zhong W , Xu G , Wang F , Tian X , Zhou X , Liu Q , Liu Y , Wang J
Ref : Bioorg Chem , 96 :103646 , 2020
Abstract : Three new compounds, including two new 3,4,6-trisubstituted alpha-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), alpha-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 mug/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.
ESTHER : Han_2020_Bioorg.Chem_96_103646
PubMedSearch : Han_2020_Bioorg.Chem_96_103646
PubMedID: 32036160

Title : Characterization of a novel halotolerant esterase from Chromohalobacter canadensis isolated from salt well mine - Wang_2020_3.Biotech_10_430
Author(s) : Wang M , Ai L , Zhang M , Wang F , Wang C
Ref : 3 Biotech , 10 :430 , 2020
Abstract : A esterase gene was characterized from a halophilic bacterium Chromohalobacter canadensis which was originally isolated from a salt well mine. Sequence analysis showed that the esterase, named as EstSHJ2, contained active site serine encompassed by a conserved pentapeptide motif (GSSMG). The EstSHJ2 was classified into a new lipase/esterase family by phylogenetic association analysis. Molecular weight of EstSHJ2 was 26 kDa and the preferred substrate was p-NP butyrate. The EstSHJ2 exhibited a maximum activity at 2.5 M NaCl concentration. Intriguingly, the optimum temperature, pH and stability of EstSHJ2 were related to NaCl concentration. At 2.5 M NaCl concentration, the optimum temperature and pH of EstSHJ2 were 65 C and pH 9.0, and enzyme remained 81% active after 80 C treatment for 2 h. Additionally, the EstSHJ2 showed strong tolerance to metal ions and organic solvents. Among these, 10 mM K(+), Ca(2+) , Mg(2+) and 30% hexane, benzene, toluene has significantly improved activity of EstSHJ2. The EstSHJ2 was the first reported esterase from Chromohalobacter canadensis, and may carry considerable potential for industrial applications under extreme conditions.
ESTHER : Wang_2020_3.Biotech_10_430
PubMedSearch : Wang_2020_3.Biotech_10_430
PubMedID: 32983823
Gene_locus related to this paper: 9gamm-EstSHJ2

Title : Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer's Disease - Xu_2020_Int.J.Mol.Sci_21_
Author(s) : Xu J , Wang F , Guo J , Xu C , Cao Y , Fang Z , Wang Q
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer's disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein-protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.
ESTHER : Xu_2020_Int.J.Mol.Sci_21_
PubMedSearch : Xu_2020_Int.J.Mol.Sci_21_
PubMedID: 32197305

Title : Optimization of chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone to sigma-caprolactone using response surface methodology - Zhang_2020_Biotechnol.Prog_36_e2901
Author(s) : Zhang Y , Jiang W , Lv K , Sun Y , Gao X , Zhao Q , Ren W , Wang F , Liu J
Ref : Biotechnol Prog , 36 :e2901 , 2020
Abstract : sigma-Caprolactone (sigma-CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of sigma-CL synthesis through chemoenzymatic Baeyer-Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of sigma-CL was 98.06% with about 1.2 M sigma-CL concentration that has a substantial increase mainly due to both better stability of the cross-linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5 degreesC. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R(2) value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of sigma-CL (p < .0006).
ESTHER : Zhang_2020_Biotechnol.Prog_36_e2901
PubMedSearch : Zhang_2020_Biotechnol.Prog_36_e2901
PubMedID: 31465150

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

Title : Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions - Wei_2020_J.Am.Chem.Soc__
Author(s) : Wei T , Lu S , Sun J , Xu Z , Yang X , Wang F , Ma Y , Shi Y , Chen X
Ref : Journal of the American Chemical Society , : , 2020
Abstract : Photolabile groups offer promising tools to study biological processes with highly spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-D-aspartate receptors (NMDARs) and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.
ESTHER : Wei_2020_J.Am.Chem.Soc__
PubMedSearch : Wei_2020_J.Am.Chem.Soc__
PubMedID: 32023409

Title : Insight into the Functional Diversification of Lipases in the Endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae) by Genome-scale Annotation and Expression Analysis - Wang_2020_Insects_11_
Author(s) : Wang J , Song J , Fang Q , Yao H , Wang F , Song Q , Ye G
Ref : Insects , 11 : , 2020
Abstract : Lipases play essential roles in digestion, transport, and processing of dietary lipids in insects. For parasitoid wasps with a unique life cycle, lipase functions could be multitudinous in particular. Pteromalus puparum is a pupal endoparasitoid of butterflies. The female adult deposits eggs into its host, along with multifunctional venom, and the developing larvae consume host as its main nutrition source. Parasitoid lipases are known to participate in the food digestion process, but the mechanism remains unclear. P. puparum genome and transcriptome data were interrogated. Multiple alignments and phylogenetic trees were constructed. We annotated a total of 64 predicted lipase genes belonging to five lipase families and suggested that eight venom and four salivary lipases could determine host nutrition environment post-parasitization. Many putative venom lipases were found with incomplete catalytic triads, relatively long beta9 loops, and short lids. Data analysis reveals the loss of catalytic activities and weak triacylglycerol (TAG) hydrolytic activities of lipases in venom. Phylogenetic trees indicate various predicted functions of lipases in P. puparum. Our information enriches the database of parasitoid lipases and the knowledge of their functional diversification, providing novel insight into how parasitoid wasps manipulate host lipid storage by using venom lipases.
ESTHER : Wang_2020_Insects_11_
PubMedSearch : Wang_2020_Insects_11_
PubMedID: 32260574

Title : Bemisia tabaci (Hemiptera: Aleyrodidae) Insecticide Resistance in Shandong Province, China - Wang_2020_J.Econ.Entomol_113_911
Author(s) : Wang F , Liu J , Chen P , Li HY , Ma JJ , Liu YJ , Wang K
Ref : J Econ Entomol , 113 :911 , 2020
Abstract : The Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex comprises important pests and virus vectors in agricultural crops worldwide. In China, B. tabaci has spread to more than 20 provinces and caused severe losses of vegetables, fruits, and ornamental plants. However, B. tabaci has developed resistance to many insecticidal classes in Shandong Province, eastern China. In this study, we investigated the cryptic species, insecticide resistance and detoxifying enzymes of B. tabaci from six representative locations exhibiting severe damage in Shandong. At four of the six locations, B. tabaci Mediterranean (MED) comprised 100% of the samples collected. In a further two locations, species composition was predominantly (>94%) MED with B. tabaci Middle East-Asia Minor 1 (MEAM1), comprising a low proportion (<6%) of the samples collected. For all field populations, avermectin was the most effective insecticide against adult B. tabaci, pyriproxyfen had a significant effect on B. tabaci eggs and field populations were susceptible to pymetrozine. Six field populations of B. tabaci have developed low-to-moderate resistance to neonicotinoids. The detoxifying enzyme activity of carboxylesterase, glutathione S-transferase, and multifunctional oxidase were quantified. Multifunctional oxidase and glutathione S-transferase activity were positively correlated with insecticide resistance in several B. tabaci populations.
ESTHER : Wang_2020_J.Econ.Entomol_113_911
PubMedSearch : Wang_2020_J.Econ.Entomol_113_911
PubMedID: 31800055

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

Title : Oncogenic role of ABHD5 in endometrial cancer - Zhou_2019_Cancer.Manag.Res_11_2139
Author(s) : Zhou Q , Wang F , Zhou K , Huang K , Zhu Q , Luo X , Yu J , Shi Z
Ref : Cancer Manag Res , 11 :2139 , 2019
Abstract : Background: Abhydrolase domain containing 5 (ABHD5) functions as a tumor suppressor in colorectal and prostate cancers. The aim of this study was to investigate the roles of ABHD5 in endometrial cancer. Materials and methods: ABHD5 expression was detected in clinical samples by immunohistochemical staining. Cell proliferation and invasion were evaluated with the Cell Counting Kit-8 and Transwell assay, respectively. Western blotting was performed to analyze protein expression. Glucose uptake was assessed by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose. Lactate production was detected by a lactate assay kit. Results: In the present study, ABHD5 was overexpressed in endometrial cancer tissues, and its expression was closely correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. In addition, we observed that the knockdown of ABHD5 inhibited cell proliferation, invasion, glucose uptake and lactate production in HEC-1A cells, which expressed high levels of ABHD5. Conversely, the opposite effects were observed when ABHD5 was ectopically expressed in Ishikawa cells, which had low levels of ABHD5. Furthermore, the changes in glycolysis regulators (enolase 1 [ENO1], glucose transporter 1 [GLUT1] and lactate dehydrogenase A [LDHA]) and epithelial-to-mesenchymal transition-related proteins (E-cadherin and Snail) in HEC-1A cells with ABHD5 knockdown were consistent with the effects of ABHD5 on glycolysis and cell invasion. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was increased, while the phosphorylated AKT (p-AKT) was decreased when ABHD5 was downregulated. Notably, treatment with the allosteric AKT inhibitor MK-2206 completely abolished the effects caused by ABHD5 overexpression in Ishikawa cells. Finally, ABHD5 knockdown potently suppressed tumor growth in vivo. Conclusion: Overall, these results suggest that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway.
ESTHER : Zhou_2019_Cancer.Manag.Res_11_2139
PubMedSearch : Zhou_2019_Cancer.Manag.Res_11_2139
PubMedID: 30936746
Gene_locus related to this paper: human-ABHD5

Title : Exploring the influence of phospholipid monolayer conformation and environmental conditions on the interfacial binding of Gibberella Zeae lipase - Wang_2019_Int.J.Biol.Macromol_132_1051
Author(s) : Wang F , Chen W , Abousalham A , Yang B , Wang Y
Ref : Int J Biol Macromol , 132 :1051 , 2019
Abstract : The involvement of different parameters on Gibberella zeae lipase (GZEL) membrane binding were characterized by using monomolecular film technology and circular dichroism spectroscopy. Among four kinds of phospholipid monolayers, 1,2dimyristoylsnglycero3phosphoethanolamine have the highest maximum insertion pressure (MIP) value. Comparing the GZEL adsorption to phosphatidylcholine monolayers with different acyl chains in sn-1 and sn-2 positions, the higher MIP values were found for 1,2dilauroylsnglycero3phosphocholine. Significantly improvement between 1,2dioleoylsnglycero3phosphocholine and 1,2distearoylsnglycero3phosphocholine suggested that the presence of fatty acid unsaturation may affect protein adsorption by changing the chemical structure in each phospholipid. The MIP value was shown higher (48.6mNm(-1)) at pH5 and pH6 (47.5+/-1.9mNm(-1)) but decreased significantly (34.2mNm(-1)) at pH9. This may indicate that the proportion of helices in the protein decreases with the alteration of the catalytic center, thus affecting the binding of the protein to its substrate. The MIP values obviously decreased with increasing salt ion concentration, suggesting that excessive salt ion concentration may destabilize the secondary and tertiary structures of the protein, thereby affecting the characteristics of its adsorption at the interfaces. Present studies improve our understanding on the protein-membrane interaction of this enzyme.
ESTHER : Wang_2019_Int.J.Biol.Macromol_132_1051
PubMedSearch : Wang_2019_Int.J.Biol.Macromol_132_1051
PubMedID: 30922913
Gene_locus related to this paper: gibze-q6wer3

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
PubMedID:
Gene_locus related to this paper: 9firm-g2pvg6

Title : Kinetic model of the enzymatic Michael addition for synthesis of mitomycin analogs catalyzed by immobilized lipase from T. laibacchii - Zhang_2019_Mol.Catal_466_146
Author(s) : Zhang Y , Zhao Y , Gao X , Jiang W , Li Z , Yao Q , Yang F , Wang F , Liu J
Ref : Molecular Catalysis , 466 :146 , 2019
Abstract : The present study investigates the kinetic model of the enzymatic Michael addition of butylamine to 2-methyl-1,4-benzoquinone to form 2-methyl-3-n-butylaminoyl-1-hydro-4-quinone in citrate buffer solution (pH 7.0). The yield of the product of 98% was achieved, mainly due to the excellent regioselectivity of immobilized lipase from T. laibacchii. The immobilized preparation used here was obtained by a method of purification and in situ immobilization. Through the purification using a PEG 4000/ K2HPO4 aqueous two-phase system (ATPS), the T. laibacchii lipase was partitioned predominantly in the PEG-rich top phase where diatomite was added to achieve in situ immobilization via interfacial activation on the hydrophobic support. A proposed reaction mechanism of the Michael addition involves (1) the oxyanion hole polarizes the alpha,beta-unsaturated carbonyl of 2-methyl-1,4 -benzoquinone, increasing its electrophilic ability, (2) the catalytic histidine deprotonates the nucleophile n-butyl amine. A modified sequential mechanism including ordered and random sequential bi-bi was proposed for the first, and it is beneficial to add these modification mechanisms to the family of enzyme complex reaction mechanism because the mechanism is partly expanded. The kinetic parameters were directly obtained by combining the numerical integration toolbox ode45 to solve differential equations and the nonlinear optimization toolbox fmincon for error minimizing objective function. A very satisfactory agreement between experimental data and model results was obtained based on the modified random bi-bi mechanism, implying that the enzymatic Michael addition may follow the modified random bi-bi mechanism. The mass transfer limitations were investigated, and it is found that both internal and external mass transfer limitations could be ignored.
ESTHER : Zhang_2019_Mol.Catal_466_146
PubMedSearch : Zhang_2019_Mol.Catal_466_146
PubMedID:

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

Title : Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol - Sun_2019_Front.Bioeng.Biotechnol_7_486
Author(s) : Sun M , Nie K , Wang F , Deng L
Ref : Front Bioeng Biotechnol , 7 :486 , 2019
Abstract : Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-alpha. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by lipases was investigated in this research. The results indicated that the commercial immobilized lipase Novozym 435 has the best regio-selectivity on the amide group. Based on the experimental results and in silico simulation, it was found that the mechanism of specific N-acyl selectivity of lipase was not only from intramolecular migration and proton shuttle mechanism, but also from the special structure of active site of enzyme. The optimal reaction yield of aromatic amide compound in a solvent-free system with lipase loading of 15 wt% (to the weight of total substrate) reached 89.41 +/- 2.8% with very few of byproducts detected (0.21 +/- 0.1% ester and 0.64 +/- 0.2% diacetylated compound). Compare to other reported works, this work have the advantages such as low enzyme loading, solvent free, and high N-acylation selectivity. Meanwhile, this Novozym 435 lipase based synthesis method has an excellent regio-selectivity on most kinds of amino alcohol compounds. Compared to the chemical method, the enzymatic synthesis exhibited high regio-selectivity, and conversion rates. The method could be a promising alternative strategy for the synthesis of aromatic alkanolamides.
ESTHER : Sun_2019_Front.Bioeng.Biotechnol_7_486
PubMedSearch : Sun_2019_Front.Bioeng.Biotechnol_7_486
PubMedID: 32039186

Title : Efficient Preservation of Acetylcholinesterase at Room Temperature for Facile Detection of Organophosphorus Pesticide - Tang_2019_Anal.Sci_35_401
Author(s) : Tang W , Yang J , Wang F , Li Z
Ref : Anal Sci , 35 :401 , 2019
Abstract : A simple and inexpensive strategy is reported to facilitate the detection of an organophosphorus pesticide by acetylcholinesterase (AChE). Pullulan is able to preserve AChE at room temperature, but the activity of conserved AChE varies significantly depending on the time, stir and volume of solution to dissolve it. The reason is that AChE entrapped in pullulan tablet remains in an inactive state to avoid denaturalization and deactivation. There is a reactivation process to gradually recover the enzyme activity during dissolution of the tablet. Stirring would interrupt this procedure and lead to a loss of enzyme activity. Dissolution of the tablet for 5 min with a volume of 15 muL could facilitate full recovery of AChE activity. The feasibility of activated AChE for organophosphorus pesticide detection was evaluated using malaoxon. These results contribute to the understanding of preservation mechanism by pullulan and the development of easy-to-use enzyme assays.
ESTHER : Tang_2019_Anal.Sci_35_401
PubMedSearch : Tang_2019_Anal.Sci_35_401
PubMedID: 30555106

Title : Candidate detoxification-related genes in brown planthopper, Nilaparvata lugens, in response to beta-asarone based on transcriptomic analysis - Xu_2019_Ecotoxicol.Environ.Saf_185_109735
Author(s) : Xu X , Li X , Wang F , Han K , Liu Z , Fan L , Hua H , Cai W , Yao Y
Ref : Ecotoxicology & Environmental Safety , 185 :109735 , 2019
Abstract : Nilaparvata lugens(Stal) is a serious pest of rice and has evolved different levels of resistance against most chemical pesticides. beta-asarone is the main bioactive insecticidal compound of Acorus calamus L. that shows strong insecticidal activity against pests. In this study, we conducted a bioassay experiment to determine the contact toxicity of beta-asarone to N. lugens nymphs. The LD30 sublethal dose was 0.106mug per nymph, with 95% confidence limits of 0.070-0.140mug. We applied the LD30 concentration of beta-asarone to nymphs for 24h or 72h and then performed a transcriptome sequence analysis by referencing the N. lugens genome to characterize the variation. The transcriptomic analysis showed that several GO terms and KEGG pathways presented significant changes. Individually, 126 differentially expressed genes (DEGs), including 72 upregulated and 54 downregulated genes, were identified at 24h, and 1771 DEGs, including 882 upregulated and 889 downregulated genes, were identified at 72h. From the DEGs, we identified a total of 40 detoxification-related genes, including eighteen Cytochrome P450 monooxygenase genes (P450s), three Glutathione S-transferase genes, one Carboxylesterase gene, twelve UDP-glucosyltransferases and six ATP-binding cassette genes. We selected the eighteen P450s for subsequent verification by quantitative PCR. These findings indicated that beta-asarone presented strong contact toxicity to N. lugens nymphs and induced obvious variation of detoxification-related genes that may be involved in the response to beta-asarone.
ESTHER : Xu_2019_Ecotoxicol.Environ.Saf_185_109735
PubMedSearch : Xu_2019_Ecotoxicol.Environ.Saf_185_109735
PubMedID: 31586846

Title : Single-particle enumeration-based ultrasensitive enzyme activity quantification with fluorescent polymer nanoparticles - Han_2019_Nanoscale_11_14793
Author(s) : Han Y , Ye Z , Wang F , Chen T , Wei L , Chen L , Xiao L
Ref : Nanoscale , 11 :14793 , 2019
Abstract : Acetylcholinesterase (AChE) plays a vital role in nerve conduction through rapidly hydrolyzing the neurotransmitter acetylcholine (ACh) and is correlated with Alzheimer's disease. In this work, a label-free single-particle enumeration (SPE) method for the quantitative detection of acetylcholinesterase (AChE) activity is developed. The design is based on the fluorescence resonance energy transfer (FRET) between fluorescent conjugated polymer nanoparticles (FCPNPs) and MnO2 nanosheets. The fluorescence of FCPNPs can be effectively quenched by MnO2 nanosheets via hydrogen bonding interaction. In the presence of acetylcholinesterase (AChE), acetylthiocholine (ATCh) could be hydrolyzed to thiocholine (TCh), which can reduce MnO2 to Mn2+ and trigger the decomposition of MnO2 nanosheets. As a result, the fluorescence of FCPNPs is restored. Taking advantage of the superior brightness and stable fluorescence emission from individual FCPNPs, the accurate quantification of AChE is achieved by statistically counting the fluorescent particles on the glass slide surface. A linear range from 5 to 1600 muU mL-1 is obtained for AChE assay and the limit-of-detection (LOD) is 1.02 muU mL-1, which is far below the spectroscopic measurements in bulk solution. In the human serum sample, satisfactory recovery efficiencies are determined in a range of 91.0%-103.0%. Furthermore, pesticide carbaryl as an inhibitor of AChE activity was detected. The LOD is 1.12 pg mL-1 with linear responses ranging from 5 to 300 pg mL-1, which demonstrates the feasibility of this approach for AChE inhibitor screening. As a consequence, the label-free SPE-based method affords a promising platform for the sensitive detection of target molecules in the future.
ESTHER : Han_2019_Nanoscale_11_14793
PubMedSearch : Han_2019_Nanoscale_11_14793
PubMedID: 31353389

Title : Bacillus subtilis Spore Surface Display of Haloalkane Dehalogenase DhaA - Wang_2019_Curr.Microbiol_76_1161
Author(s) : Wang F , Song T , Jiang H , Pei C , Huang Q , Xi H
Ref : Curr Microbiol , 76 :1161 , 2019
Abstract : The haloalkane dehalogenase DhaA can degrade sulfur mustard (2,2'-dichlorethyl sulfide; also known by its military designation HD) in a rapid and environmentally safe manner. However, DhaA is sensitive to temperature and pH, which limits its applications in natural or harsh environments. Spore surface display technology using resistant spores as a carrier to ensure enzymatic activity can reduce production costs and extend the range of applications of DhaA. To this end, we cloned recombinant Bacillus subtilis spores pHY300PLK-cotg-dhaa-6his/DB104(FH01) for the delivery of DhaA from Rhodococcus rhodochrous NCIMB 13064. A dot blotting showed that the fusion protein CotG-linker-DhaA accounted for 0.41% +/- 0.03% (P < 0.01) of total spore coat proteins. Immunofluorescence analyses confirmed that DhaA was displayed on the spore surface. The hydrolyzing activity of DhaA displayed on spores towards the HD analog 2-chloroethyl ethylsulfide was 1.74 +/- 0.06 U/mL (P < 0.01), with a specific activity was 0.34 +/- 0.04 U/mg (P < 0.01). This is the first demonstration that DhaA displayed on the surface of B. subtilis spores retains enzymatic activity, which suggests that it can be used effectively in real-world applications including bioremediation of contaminated environments.
ESTHER : Wang_2019_Curr.Microbiol_76_1161
PubMedSearch : Wang_2019_Curr.Microbiol_76_1161
PubMedID: 31278426
Gene_locus related to this paper: xanau-halo1

Title : High-level expression of Humicola insolens cutinase in Pichia pastoris without carbon starvation and its use in cotton fabric bioscouring - Hong_2019_J.Biotechnol_304_10
Author(s) : Hong R , Sun Y , Su L , Gu L , Wang F , Wu J
Ref : J Biotechnol , 304 :10 , 2019
Abstract : Huimcola insolens cutinase (HiC) was heterologously expressed in Pichia pastoris. To avoid a carbon starvation step, fermentation was conducted using combinations of sorbitol with glycerol and methanol in the cell growth and induction phases, respectively. The cutinase productivity (27.71 U mL(-1) h(-1)) was 9.93 U mL(-1) h(-1) greater than that achieved using traditional two-phase methods, and a cutinase activity of 2660 U mL(-1), using p-nitrophenyl butyrate as substrate, was achieved after only 96 h in a 3-L bioreactor. Subsequently, the combination of HiC with Thermobifida fusca cutinase (TfC) in cotton fabric bioscouring was evaluated by monitoring the wettability and dyeability of the fabric. Treatment with 20 U mL(-1) of HiC at 80 degrees C for 5 min followed by 30 U mL(-1) of TfC at 50 degrees C for 1 h gave the best results. The total treatment time was shorter and performance was better than those seen with the alkali method.
ESTHER : Hong_2019_J.Biotechnol_304_10
PubMedSearch : Hong_2019_J.Biotechnol_304_10
PubMedID: 31400343

Title : Thiocholine-triggered reaction in personal glucose meters for portable quantitative detection of organophosphorus pesticide - Tang_2019_Anal.Chim.Acta_1060_97
Author(s) : Tang W , Yang J , Wang F , Wang J , Li Z
Ref : Anal Chim Acta , 1060 :97 , 2019
Abstract : A portable and user-friendly method using personal glucose meters for on-site quantitative detection of organophosphorus pesticide (OP) was developed. The inhibition of organophosphorus compounds on acetylcholinesterase (AChE) leads to reduced yields of thiocholine formed by the enzymatic hydrolysis of acetylthiocholine chloride. Ferricyanide ([Fe(CN)6](3-)), the mediator used in glucose test strips for electron transfer to the electrode, can be rapidly reduced to ferrocyanide ([Fe(CN)6](4-)) by thiocholine. This reaction enables direct measurement of thiocholine by personal glucose meters in the same way as measuring the glucose in blood, offering an interesting choice to quantify OP. After incubation of AChE for 30min and enzymatic reaction of 10min, the yield of thiocholine was measured by a personal glucose meter, achieving detection limit of 5mugL(-1) for paraoxon. The proposed method was successfully applied to the detection in apples and cucumbers, presenting promising potential for on-site OP detection in food samples.
ESTHER : Tang_2019_Anal.Chim.Acta_1060_97
PubMedSearch : Tang_2019_Anal.Chim.Acta_1060_97
PubMedID: 30902336

Title : Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation - Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
Author(s) : Gan L , Guo M , Si J , Zhang J , Liu Z , Zhao J , Wang F , Yan J , Li H , Zhang H
Ref : Artif Cells Nanomed Biotechnol , 47 :4202 , 2019
Abstract : Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 muM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.
ESTHER : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedSearch : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedID: 31713449

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

Title : Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice - Lu_2018_Phytother.Res_32_1056
Author(s) : Lu C , Lv J , Dong L , Jiang N , Wang Y , Wang Q , Li Y , Chen S , Fan B , Wang F , Liu X
Ref : Phytother Res , 32 :1056 , 2018
Abstract : 20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 mumol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
ESTHER : Lu_2018_Phytother.Res_32_1056
PubMedSearch : Lu_2018_Phytother.Res_32_1056
PubMedID: 29468740

Title : Molecular Characterization and Bioactivity of Coumarin Derivatives from the Fruits of Cucumis bisexualis - Ma_2018_J.Agric.Food.Chem_66_5540
Author(s) : Ma QG , Wei RR , Yang M , Huang XY , Wang F , Sang ZP , Liu WM , Yu Q
Ref : Journal of Agricultural and Food Chemistry , 66 :5540 , 2018
Abstract : Cucumis bisexualis (Cucurbitaceae) is known as "mapao egg" or "muskmelon egg", which has been widely used as a wild melon in Chinese folk. Nine new coumarin derivatives (1-9), named 7-hydroxy-3-(4',6'-dihydroxy-5'-isopropyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chro-men-2-one (1), 7-hydroxy-3-(5'-prenyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (2), 3-(6'-hydroxy-5'-prenyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (3), 3-(5'-ethyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (4), 3-(4',6'-dihydroxy-5'-dimeth-ylallyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (5), 3-[4',6'-dihydroxy-5'-(2-pro-penyl)-3'',3''-dimethyl-2 H-chromen]-14,15-dimethyl-pyrano-chromen-2-one (6), 3-(6'-dihydroxy-5'-isopropanol-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (7), 3-(5'-iso-pentenol-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (8), 3-(4',6'-dihydr-oxy-5'-prenyl-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (9), together with 12 known compounds (10-21), were isolated and identified by spectroscopic analysis and references from the active site (EtOAc soluble fraction) of the fruits of C. bisexualis for the first time. Compounds (1-21) were evaluated for antiacetylcholinesterase (AChE) and hepatoprotective activities for the first time. Compounds 1, 3, 5, 6, 7, and 9 showed anti-AChE activities with IC50 values ranging from 11.23 to 89.69 muM, and compounds 2, 4, 12, 15, 17, 18, and 19 (10 muM) exhibited moderate hepatoprotective activities. These findings shed much light on a better understanding of the anti-AChE and hepatoprotective effects of these coumarin derivatives and provided new insights into developing better anti-AChE and hepatoprotective drugs in the future.
ESTHER : Ma_2018_J.Agric.Food.Chem_66_5540
PubMedSearch : Ma_2018_J.Agric.Food.Chem_66_5540
PubMedID: 29775541

Title : Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes - Gabrusiewicz_2018_Oncoimmunology_7_e1412909
Author(s) : Gabrusiewicz K , Li X , Wei J , Hashimoto Y , Marisetty AL , Ott M , Wang F , Hawke D , Yu J , Healy LM , Hossain A , Akers JC , Maiti SN , Yamashita S , Shimizu Y , Dunner K , Zal MA , Burks JK , Gumin J , Nwajei F , Rezavanian A , Zhou S , Rao G , Sawaya R , Fuller GN , Huse JT , Antel JP , Li S , Cooper L , Sulman EP , Chen C , Geula C , Kalluri R , Zal T , Heimberger AB
Ref : Oncoimmunology , 7 :e1412909 , 2018
Abstract : Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14(+) cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.
ESTHER : Gabrusiewicz_2018_Oncoimmunology_7_e1412909
PubMedSearch : Gabrusiewicz_2018_Oncoimmunology_7_e1412909
PubMedID: 29632728

Title : Characterization of two novel thermostable esterases from Thermoanaerobacterium thermosaccharolyticum - Li_2018_Protein.Expr.Purif_152_64
Author(s) : Li W , Shi H , Ding H , Wang L , Zhang Y , Li X , Wang F
Ref : Protein Expr Purif , 152 :64 , 2018
Abstract : This paper first describes characterization of two thermostable esterases (ThLip1 and ThLip2) from the thermophilic bacterium Thermoanaerobacterium thermosaccharolyticum DSM 571. The recombinant esterase ThLip1 was active at 80 degrees C, pH 6.5 and maintained approx. 85% of original activity after 2h incubation at 75 degrees C. Kinetic parameters, Km, Vmax and kcat/Km for 4-Nitrophenyl caprylate (pNPC) were 3.52+/-0.47mM, 191.18+/-1.82mumolmin(-1) mg(-1) and 20.80+/-0.07mM(-1)s(-1), respectively. The purified recombinant esterase ThLip2 was optimally active at pH 6.5 and 75 degrees C and it was stable against a pH range of 6.0-8.0 possessing 2h half-life at 80 degrees C. Kinetic experiments at 75 degrees C with pNPC as a substrate gave a Km of 3.37mM, Vmax of 578.14mumolmin(-1) mg(-1)and kcat of 231.2 s(-1). The hydrolysis of linalyl acetate were carried out using ThLip1 and ThLip2 as catalyst, affording linalool yields over 140mg/l in 10h.
ESTHER : Li_2018_Protein.Expr.Purif_152_64
PubMedSearch : Li_2018_Protein.Expr.Purif_152_64
PubMedID: 29684442

Title : Lipase-mediated direct in situ ring-opening polymerization of E-caprolactone formed by a chemo-enzymatic method - Zhang_2018_J.Biotechnol_281_74
Author(s) : Zhang Y , Lu P , Sun Q , Li T , Zhao L , Gao X , Wang F , Liu J
Ref : J Biotechnol , 281 :74 , 2018
Abstract : A novel method to synthesize poly(sigma-caprolactone) (PCL) through a three-step, lipase-mediated chemo-enzymatic reaction from cyclohexanone using an immobilized lipase from Trichosporon laibacchii (T. laibacchii) CBS5791 was developed. The immobilized preparation with 1280 U. g(-1) used here was obtained by a method of purification and in situ immobilization where the crude intracellular lipase (cell homogenate) was subjected to partial purification by an aqueous two-phase system (ATPS) consisting of 12% (w/w) polyethylene glycol (PEG) 4000 and 13% (w/w) potassium phosphate (K(2)HPO(4)) and then in situ immobilization directly on diatomite from the top PEG-rich phase of ATPS. In this multi-step process, the sigma-caprolactone (sigma-CL) produced by lipase-mediated one-pot two-step chemo-enzymatic oxidation of cyclohexanone was directly subjected to in situ ring-opening polymerization (ROP) started by adding highly hydrophobic solvents. It is necessary to note that sigma-CL synthesis and its subsequent ROP were catalyzed by the same lipase. The impact of various reaction parameters, e.g., solvent, cyclohexanone: hydrogen peroxide molar ratio, hydrogen peroxide forms and reaction temperature were investigated. Toluene was selected as a preferred solvent due to supporting the highest molecular weight (M(n) = 2168) and moderate sigma-CL conversion (65.42%). Through the optimization of reaction conditions, PCL was produced with a M(n) of 2283 at 50 degreesC for 24 h. These results reveal that this lipase-mediated direct ring-opening polymerization of in situ formed sigma-CL is an alternative route to the conventional synthesis of PCL.
ESTHER : Zhang_2018_J.Biotechnol_281_74
PubMedSearch : Zhang_2018_J.Biotechnol_281_74
PubMedID: 29908204

Title : Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy - Gong_2018_Exp.Ther.Med_15_620
Author(s) : Gong L , Jiang C , Liu L , Wan S , Tan W , Ma S , Jia X , Wang M , Hu A , Shi Y , Zhang Y , Shen Y , Wang F , Chen Y
Ref : Exp Ther Med , 15 :620 , 2018
Abstract : Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy.
ESTHER : Gong_2018_Exp.Ther.Med_15_620
PubMedSearch : Gong_2018_Exp.Ther.Med_15_620
PubMedID: 29403547

Title : Function of C-terminal peptides on enzymatic and interfacial adsorption properties of lipase from Gibberella zeae - Wang_2018_Biochim.Biophys.Acta.Gen.Subj_1862_2623
Author(s) : Wang F , Zhang H , Czarna A , Chen W , Yang B , Wang Y
Ref : Biochimica & Biophysica Acta Gen Subj , 1862 :2623 , 2018
Abstract : BACKGROUND: The crystal structure of lipase from Gibberella zeae (GZEL) indicates that its C-terminal extension is composed of a loop and a alpha-helix. This structure is unique, possibly providing novel evidence on lipase mechanisms. METHODS: Two C-terminally truncated mutants (GZEL-Delta(alpha-helix) and GZEL-Delta(alpha-helix+loop)) were constructed. The role of these secondary structure segments on enzymatic activities and interfacial binding properties of GZEL was investigated by using conventional pH-stat method and monomolecular film techniques. In addition, inactive variants (Ser144Ala) of wild-type GZEL and two truncated mutants were constructed and produced specifically for interfacial binding experiments. RESULTS: Compared to the wild-type GZEL, lipase and phospholipase activities were significantly decreased in the two mutants. Deletion of the alpha-helix had great influence on the lipase activity of GZEL, resulting in residual 7.3% activity; the additional deletion of the loop led to 8.1% lipase activity. As for the phospholipase function, residual activities of 63.0% and 35.4% were maintained for GZEL-Delta(alpha-helix) and GZEL-Delta(alpha-helix+loop), respectively. Findings obtained with monomolecular film experiments further indicated that the reduction in phospholipase activity occurred with the anionic phospholipid as substrate, but was not seen with zwitterionic phospholipid. Results of the maximum insertion pressure, synergy factor and binding kinetic parameters documented that the alpha-helix structure of GZEL strongly influence the binding and insertion of enzyme to the phospholipid monolayer. Moreover, the interfacial binding function of alpha-helix was partly conformed by connecting to the C-terminal of Aspergillus oryzae lipase. GENERAL SIGNIFICANCE: Our results provide important information on the understanding of the structure-function relationship of GZEL.
ESTHER : Wang_2018_Biochim.Biophys.Acta.Gen.Subj_1862_2623
PubMedSearch : Wang_2018_Biochim.Biophys.Acta.Gen.Subj_1862_2623
PubMedID: 30025859

Title : COX-2\/sEH Dual Inhibitor PTUPB Potentiates the Antitumor Efficacy of Cisplatin - Wang_2018_Mol.Cancer.Ther_17_474
Author(s) : Wang F , Zhang H , Ma AH , Yu W , Zimmermann M , Yang J , Hwang SH , Zhu D , Lin TY , Malfatti M , Turteltaub KW , Henderson PT , Airhart S , Hammock BD , Yuan J , de Vere White RW , Pan CX
Ref : Mol Cancer Ther , 17 :474 , 2018
Abstract : Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in antitumor activity and has organ-protective effects. The goal of this study was to determine the antitumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC, or combinations thereof. Mouse experiments were performed with two different PDX models. PTUPB potentiated cisplatin and GC therapy, resulting in significantly reduced tumor growth and prolonged survival. PTUPB plus cisplatin was no more toxic than cisplatin single-agent treatment as assessed by body weight, histochemical staining of major organs, blood counts, and chemistry. The combination of PTUPB and cisplatin increased apoptosis and decreased phosphorylation in the MAPK/ERK and PI3K/AKT/mTOR pathways compared with controls. PTUPB treatment did not alter platinum-DNA adduct levels, which is the most critical step in platinum-induced cell death. The in vitro study using the combination index method showed modest synergy between PTUPB and platinum agents only in 5637 cell line among several cell lines examined. However, PTUPB is very active in vivo by inhibiting angiogenesis. In conclusion, PTUPB potentiated the antitumor activity of cisplatin-based treatment without increasing toxicity in vivo and has potential for further development as a combination chemotherapy partner. Mol Cancer Ther; 17(2); 474-83. (c)2017 AACR.
ESTHER : Wang_2018_Mol.Cancer.Ther_17_474
PubMedSearch : Wang_2018_Mol.Cancer.Ther_17_474
PubMedID: 29284644

Title : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity - Turcot_2018_Nat.Genet_50_26
Author(s) : Turcot V , Lu Y , Highland HM , Schurmann C , Justice AE , Fine RS , Bradfield JP , Esko T , Giri A , Graff M , Guo X , Hendricks AE , Karaderi T , Lempradl A , Locke AE , Mahajan A , Marouli E , Sivapalaratnam S , Young KL , Alfred T , Feitosa MF , Masca NGD , Manning AK , Medina-Gomez C , Mudgal P , Ng MCY , Reiner AP , Vedantam S , Willems SM , Winkler TW , Abecasis G , Aben KK , Alam DS , Alharthi SE , Allison M , Amouyel P , Asselbergs FW , Auer PL , Balkau B , Bang LE , Barroso I , Bastarache L , Benn M , Bergmann S , Bielak LF , Bluher M , Boehnke M , Boeing H , Boerwinkle E , Boger CA , Bork-Jensen J , Bots ML , Bottinger EP , Bowden DW , Brandslund I , Breen G , Brilliant MH , Broer L , Brumat M , Burt AA , Butterworth AS , Campbell PT , Cappellani S , Carey DJ , Catamo E , Caulfield MJ , Chambers JC , Chasman DI , Chen YI , Chowdhury R , Christensen C , Chu AY , Cocca M , Collins FS , Cook JP , Corley J , Corominas Galbany J , Cox AJ , Crosslin DS , Cuellar-Partida G , D'Eustacchio A , Danesh J , Davies G , Bakker PIW , Groot MCH , Mutsert R , Deary IJ , Dedoussis G , Demerath EW , Heijer M , Hollander AI , Ruijter HM , Dennis JG , Denny JC , Angelantonio E , Drenos F , Du M , Dube MP , Dunning AM , Easton DF , Edwards TL , Ellinghaus D , Ellinor PT , Elliott P , Evangelou E , Farmaki AE , Farooqi IS , Faul JD , Fauser S , Feng S , Ferrannini E , Ferrieres J , Florez JC , Ford I , Fornage M , Franco OH , Franke A , Franks PW , Friedrich N , Frikke-Schmidt R , Galesloot TE , Gan W , Gandin I , Gasparini P , Gibson J , Giedraitis V , Gjesing AP , Gordon-Larsen P , Gorski M , Grabe HJ , Grant SFA , Grarup N , Griffiths HL , Grove ML , Gudnason V , Gustafsson S , Haessler J , Hakonarson H , Hammerschlag AR , Hansen T , Harris KM , Harris TB , Hattersley AT , Have CT , Hayward C , He L , Heard-Costa NL , Heath AC , Heid IM , Helgeland O , Hernesniemi J , Hewitt AW , Holmen OL , Hovingh GK , Howson JMM , Hu Y , Huang PL , Huffman JE , Ikram MA , Ingelsson E , Jackson AU , Jansson JH , Jarvik GP , Jensen GB , Jia Y , Johansson S , Jorgensen ME , Jorgensen T , Jukema JW , Kahali B , Kahn RS , Kahonen M , Kamstrup PR , Kanoni S , Kaprio J , Karaleftheri M , Kardia SLR , Karpe F , Kathiresan S , Kee F , Kiemeney LA , Kim E , Kitajima H , Komulainen P , Kooner JS , Kooperberg C , Korhonen T , Kovacs P , Kuivaniemi H , Kutalik Z , Kuulasmaa K , Kuusisto J , Laakso M , Lakka TA , Lamparter D , Lange EM , Lange LA , Langenberg C , Larson EB , Lee NR , Lehtimaki T , Lewis CE , Li H , Li J , Li-Gao R , Lin H , Lin KH , Lin LA , Lin X , Lind L , Lindstrom J , Linneberg A , Liu CT , Liu DJ , Liu Y , Lo KS , Lophatananon A , Lotery AJ , Loukola A , Luan J , Lubitz SA , Lyytikainen LP , Mannisto S , Marenne G , Mazul AL , McCarthy MI , McKean-Cowdin R , Medland SE , Meidtner K , Milani L , Mistry V , Mitchell P , Mohlke KL , Moilanen L , Moitry M , Montgomery GW , Mook-Kanamori DO , Moore C , Mori TA , Morris AD , Morris AP , Muller-Nurasyid M , Munroe PB , Nalls MA , Narisu N , Nelson CP , Neville M , Nielsen SF , Nikus K , Njolstad PR , Nordestgaard BG , Nyholt DR , O'Connel JR , O'Donoghue ML , Olde Loohuis LM , Ophoff RA , Owen KR , Packard CJ , Padmanabhan S , Palmer CNA , Palmer ND , Pasterkamp G , Patel AP , Pattie A , Pedersen O , Peissig PL , Peloso GM , Pennell CE , Perola M , Perry JA , Perry JRB , Pers TH , Person TN , Peters A , Petersen ERB , Peyser PA , Pirie A , Polasek O , Polderman TJ , Puolijoki H , Raitakari OT , Rasheed A , Rauramaa R , Reilly DF , Renstrom F , Rheinberger M , Ridker PM , Rioux JD , Rivas MA , Roberts DJ , Robertson NR , Robino A , Rolandsson O , Rudan I , Ruth KS , Saleheen D , Salomaa V , Samani NJ , Sapkota Y , Sattar N , Schoen RE , Schreiner PJ , Schulze MB , Scott RA , Segura-Lepe MP , Shah SH , Sheu WH , Sim X , Slater AJ , Small KS , Smith AV , Southam L , Spector TD , Speliotes EK , Starr JM , Stefansson K , Steinthorsdottir V , Stirrups KE , Strauch K , Stringham HM , Stumvoll M , Sun L , Surendran P , Swift AJ , Tada H , Tansey KE , Tardif JC , Taylor KD , Teumer A , Thompson DJ , Thorleifsson G , Thorsteinsdottir U , Thuesen BH , Tonjes A , Tromp G , Trompet S , Tsafantakis E , Tuomilehto J , Tybjaerg-Hansen A , Tyrer JP , Uher R , Uitterlinden AG , Uusitupa M , Laan SW , Duijn CM , Leeuwen N , van Setten J , Vanhala M , Varbo A , Varga TV , Varma R , Velez Edwards DR , Vermeulen SH , Veronesi G , Vestergaard H , Vitart V , Vogt TF , Volker U , Vuckovic D , Wagenknecht LE , Walker M , Wallentin L , Wang F , Wang CA , Wang S , Wang Y , Ware EB , Wareham NJ , Warren HR , Waterworth DM , Wessel J , White HD , Willer CJ , Wilson JG , Witte DR , Wood AR , Wu Y , Yaghootkar H , Yao J , Yao P , Yerges-Armstrong LM , Young R , Zeggini E , Zhan X , Zhang W , Zhao JH , Zhao W , Zhou W , Zondervan KT , Rotter JI , Pospisilik JA , Rivadeneira F , Borecki IB , Deloukas P , Frayling TM , Lettre G , North KE , Lindgren CM , Hirschhorn JN , Loos RJF
Ref : Nat Genet , 50 :26 , 2018
Abstract : Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
ESTHER : Turcot_2018_Nat.Genet_50_26
PubMedSearch : Turcot_2018_Nat.Genet_50_26
PubMedID: 29273807

Title : Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity - Chiu_2018_Am.J.Physiol.Heart.Circ.Physiol_314_H82
Author(s) : Chiu AP , Bierende D , Lal N , Wang F , Wan A , Vlodavsky I , Hussein B , Rodrigues B
Ref : American Journal of Physiology Heart Circ Physiol , 314 :H82 , 2018
Abstract : In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable beta-endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC. EC glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) captures this released enzyme at its basolateral side and shuttles it across to its luminal side. We tested whether the diabetes-induced increase of transforming growth factor-beta (TGF-beta) can influence the myocyte and EC to help transfer LPL to the vascular lumen to generate triglyceride-FA. In response to high glucose and EC heparanase secretion, this endoglycosidase is taken up by the cardiomyocyte (Wang Y, Chiu AP, Neumaier K, Wang F, Zhang D, Hussein B, Lal N, Wan A, Liu G, Vlodavsky I, Rodrigues B. Diabetes 63: 2643-2655, 2014) to stimulate matrix metalloproteinase-9 expression and the conversion of latent to active TGF-beta. In the cardiomyocyte, TGF-beta activation of RhoA enhances actin cytoskeleton rearrangement to promote LPL trafficking and secretion onto cell surface HSPG. In the EC, TGF-beta signaling promotes mesodermal homeobox 2 translocation to the nucleus, which increases the expression of GPIHBP1, which facilitates movement of LPL to the vascular lumen. Collectively, our data suggest that in the diabetic heart, TGF-beta actions on the cardiomyocyte promotes movement of LPL, whereas its action on the EC facilitates LPL shuttling. NEW & NOTEWORTHY Endothelial cells, as first responders to hyperglycemia, release heparanase, whose subsequent uptake by cardiomyocytes amplifies matrix metalloproteinase-9 expression and activation of transforming growth factor-beta. Transforming growth factor-beta increases lipoprotein lipase secretion from cardiomyocytes and promotes mesodermal homeobox 2 to enhance glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1-dependent transfer of lipoprotein lipase across endothelial cells, mechanisms that accelerate fatty acid utilization by the diabetic heart.
ESTHER : Chiu_2018_Am.J.Physiol.Heart.Circ.Physiol_314_H82
PubMedSearch : Chiu_2018_Am.J.Physiol.Heart.Circ.Physiol_314_H82
PubMedID: 28986359

Title : ShHTL7 is a non-canonical receptor for strigolactones in root parasitic weeds -
Author(s) : Yao R , Wang F , Ming Z , Du X , Chen L , Wang Y , Zhang W , Deng H , Xie D
Ref : Cell Res , 27 :838 , 2017
PubMedID: 28059066
Gene_locus related to this paper: strhe-ShHTL7

Title : 20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice - Lu_2017_Chem.Biol.Interact_279_64
Author(s) : Lu C , Dong L , Lv J , Wang Y , Fan B , Wang F , Liu X
Ref : Chemico-Biological Interactions , 279 :64 , 2017
Abstract : 20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 mumol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD).
ESTHER : Lu_2017_Chem.Biol.Interact_279_64
PubMedSearch : Lu_2017_Chem.Biol.Interact_279_64
PubMedID: 29133030

Title : Recombinant Lipase from Gibberella zeae Exhibits Broad Substrate Specificity: A Comparative Study on Emulsified and Monomolecular Substrate - Wang_2017_Int.J.Mol.Sci_18_
Author(s) : Wang F , Zhang H , Zhao Z , Wei R , Yang B , Wang Y
Ref : Int J Mol Sci , 18 : , 2017
Abstract : Using the classical emulsified system and the monomolecular film technique, the substrate specificity of recombinant Gibberella zeae lipase (rGZEL) that originates from Gibberella zeae was characterized in detail. Under the emulsified reaction system, both phospholipase and glycolipid hydrolytic activities were observed, except for the predominant lipase activity. The optimum conditions for different activity exhibition were also determined. Compared with its lipase activity, a little higher ratio of glycolipid hydrolytic activity (0.06) than phospholipase activity (0.02) was found. rGZEL preferred medium chain-length triglycerides, while lower activity was found for the longer-chain triglyceride. Using the monomolecular film technique, we found that the preference order of rGZEL to different phospholipids was 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS) > 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (PG) > 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) > l-alpha-phosphatidylinositol (PI) > cardiolipin (CL) > 3-sn-phosphatidic acid sodium salt (PA) > l-alpha-phosphatidylethanolamine (PE), while no hydrolytic activity was detected for sphingomyelin (SM). Moreover, rGZEL showed higher galactolipase activity on 1,2-distearoyimonoglactosylglyceride (MGDG). A kinetic study on the stereo- and regioselectivity of rGZEL was also performed by using three pairs of pseudodiglyceride enantiomers (DDGs). rGZEL presented higher preference for distal DDG enantiomers than adjacent ester groups, however, no hydrolytic activity to the sn-2 position of diglyceride analogs was found. Furthermore, rGZEL preferred the R configuration of DDG enantiomers. Molecular docking results were in concordance with in vitro tests.
ESTHER : Wang_2017_Int.J.Mol.Sci_18_
PubMedSearch : Wang_2017_Int.J.Mol.Sci_18_
PubMedID: 28718792
Gene_locus related to this paper: gibze-q6wer3

Title : Hypericum perforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in Aluminum chloride-induced Alzheimer's disease rats - Cao_2017_Biomed.Pharmacother_91_931
Author(s) : Cao Z , Wang F , Xiu C , Zhang J , Li Y
Ref : Biomed Pharmacother , 91 :931 , 2017
Abstract : Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative diseases. Aluminum, a neurotoxic metal, is considered as the pathological hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a neuroprotective agent that can prevent neurodegenerative pathologies through antioxidants, anti-inflammatory and regulating neurotransmitter release in animal model of neuropathy. The present study aimed to identify the potential neuroprotective of HPE on AlCl3-induced AD rats. Rats were treated with AlCl3 for 90days to induce behavioral, biochemical, and neurochemical similar to AD. From 31thday, the rats were treated with HPE for 60days. Our results showed HPE improved cognitive function in AlCl3-induced AD rats, and attenuated AlCl3-induced increase in acetylcholinesterase activity and glutamic acid level as well as decreased in noradrenaline and dopamine level. In addition, HPE reversed AlCl3-induced hippocampal pathology including amyloid-beta (Abeta) accumulation (elevated Abeta42 level and amyloid plaques), oxidative stress (increased reactive oxygen species level and thiobarbituric acid reactive substances level, decreased glutathione level and superoxide dismutase activity) and neuroinflammatory (increased mRNA expressions of Interleukin-1beta, Interleukin-6, Tumor necrosis factor-alpha and major histocompatibility complex class II) in hippocampus of rats. Thus, HPE is conferred neuroprotection against AlCl3-induced AD like pathology.
ESTHER : Cao_2017_Biomed.Pharmacother_91_931
PubMedSearch : Cao_2017_Biomed.Pharmacother_91_931
PubMedID: 28514831

Title : O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3 - Wu_2017_J.Biol.Chem_292_10014
Author(s) : Wu D , Zhao L , Feng Z , Yu C , Ding J , Wang L , Wang F , Liu D , Zhu H , Xing F , Conaway JW , Conaway RC , Cai Y , Jin J
Ref : Journal of Biological Chemistry , 292 :10014 , 2017
Abstract : The human males absent on the first (MOF)-containing histone acetyltransferase nonspecific lethal (NSL) complex comprises nine subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase, isoform 1 (OGT1). However, whether the O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remain unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3. Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8. Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex. Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3. In addition, wheat germ agglutinin affinity purification verified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O-GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3. This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1(C964A), that lacks O-GlcNAc transferase activity. Furthermore, stabilization of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4 Lys-5, Lys-8, and Lys-16 in cells. These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3.
ESTHER : Wu_2017_J.Biol.Chem_292_10014
PubMedSearch : Wu_2017_J.Biol.Chem_292_10014
PubMedID: 28450392
Gene_locus related to this paper: human-KANSL3

Title : Hormone-sensitive lipase deficiency alters gene expression and cholesterol content of mouse testis - Wang_2017_Reproduction_153_175
Author(s) : Wang F , Chen Z , Ren X , Tian Y , Liu C , Jin P , Li Z , Zhang F , Zhu B
Ref : Reproduction , 153 :175 , 2017
Abstract : Hormone-sensitive lipase-knockout (HSL-/-) mice exhibit azoospermia for unclear reasons. To explore the basis of sterility, we performed the following three experiments. First, HSL protein distribution in the testis was determined. Next, transcriptome analyses were performed on the testes of three experimental groups. Finally, the fatty acid and cholesterol levels in the testes with three different genotypes studied were determined. We found that the HSL protein was present from spermatocyte cells to mature sperm acrosomes in wild-type (HSL+/+) testes. Spermiogenesis ceased at the elongation phase of HSL-/- testes. Transcriptome analysis indicated that genes involved in lipid metabolism, cell membrane, reproduction and inflammation-related processes were disordered in HSL-/- testes. The cholesterol content was significantly higher in HSL-/- than that in HSL+/+ testis. Therefore, gene expression and cholesterol ester content differed in HSL-/- testes compared to other testes, which may explain the sterility of male HSL-/- mice.
ESTHER : Wang_2017_Reproduction_153_175
PubMedSearch : Wang_2017_Reproduction_153_175
PubMedID: 27920259

Title : Enhancement of methanol resistance of Yarrowia lipolytica lipase 2 using beta-cyclodextrin as an additive: Insights from experiments and molecular dynamics simulation - Cao_2017_Enzyme.Microb.Technol_96_157
Author(s) : Cao H , Jiang Y , Zhang H , Nie K , Lei M , Deng L , Wang F , Tan T
Ref : Enzyme Microb Technol , 96 :157 , 2017
Abstract : The methanol resistance of lipase is a critical parameter in enzymatic biodiesel production. In the present work, the methanol resistance of Yarrowia lipolytica Lipase 2 (YLLIP2) was significantly improved using beta-cyclodextrin (beta-CD) as an additive. According to the results, YLLIP2 with beta-CD exhibited approximately 7000U/mg specific activity in 30wt% methanol for 60min compared with no activity without beta-CD under the same conditions. Molecular dynamics (MD) simulation results indicated that the beta-CD molecules weakened the conformational change of YLLIP2 and maintained a semi-open state of the lid by overcoming the interference caused by methanol molecules. Furthermore, the beta-CD molecule could directly stabilize "pathway" regions (e.g., Asp61-Asp67) and indirectly stabilize "pathway" regions (e.g., Gly44-Phe50) by forming hydrogen bonds with "pathway" regions and nearby "pathway" regions, respectively. The regions stabilized by the beta-CD molecule then prevented the closure of active pockets, thus retaining the enzymatic activity of YLLIP2 with beta-CD in methanol solvent.
ESTHER : Cao_2017_Enzyme.Microb.Technol_96_157
PubMedSearch : Cao_2017_Enzyme.Microb.Technol_96_157
PubMedID: 27871377

Title : Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats - Wang_2017_Mol.Med.Rep_16_3233
Author(s) : Wang F , Wu Z , Zha X , Cai Y , Wu B , Jia X , Zhu D
Ref : Mol Med Rep , 16 :3233 , 2017
Abstract : The aim of the present study was to observe the effects of the concurrent administration of thyroxine (T4) and an acetylcholinesterase (AChE) inhibitor, donepezil (DON), on the hypothyroidisminduced ultrastructural changes of the prefrontal cortex (PFC) in adult rats. The acetylcholine (ACh) content and AChE activity was assessed, as well as the expressions of synaptotagmin1 (syt1) and SNAP25 were analyzed in the rats. Adding 0.05% propylthiouracil to rats' drinking water induced a hypothyroid rat model. The animals were treated with T4 and DON administered separately or in combination from the fifth week. Transmission electron microscope analysis revealed that hypothyroidism induced marked ultrastructural changes, including the neurons, the synapses and the myelin sheath in the PFC. T4 or DON treatment improved the morphologic features of the PFC, and the performance of the T4 combined DON group was the closest to the control group. Moreover, hypothyroidism significantly decreased the content of ACh (29.8%) and activity of AChE (27.8%), which were restored to control values by T4 admi-nistration. In addition, DON treatment restored ACh content to normal. At the protein level, hypothyroidism increased the levels of syt1 and SNAP25 in the PFC, both of which were not restored to control values following T4 administration, while concurrent administration of T4 and DON was able to induce this effect. These results suggested that adultonset hypothyroidism induce morphological, biochemical and molecular alterations in the PFC, combined administration of T4 and DON induce plastic changes in the PFC, different from that of the standard T4 therapy, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2017_Mol.Med.Rep_16_3233
PubMedSearch : Wang_2017_Mol.Med.Rep_16_3233
PubMedID: 28713915

Title : A sensitive acetylcholinesterase biosensor based on gold nanorods modified electrode for detection of organophosphate pesticide - Lang_2016_Talanta_156-157_34
Author(s) : Lang Q , Han L , Hou C , Wang F , Liu A
Ref : Talanta , 156-157 :34 , 2016
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor, based on gold nanorods (AuNRs), was developed for the detection of organophosphate pesticide. Compared with Au@Ag heterogeneous NRs, AuNRs exhibited excellent electrocatalytic properties, which can electrocatalytically oxidize thiocholine, the hydrolysate of acetylthiocholine chloride (ATCl) by AChE at +0.55V (vs. SCE). The AChE/AuNRs/GCE biosensor was fabricated on basis of the inhibition of AChE activity by organophosphate pesticide. The biosensor could detect paraoxon in the linear range from 1nM to 5muM and dimethoate in the linear range from 5nM to 1muM, respectively. The detection limits of paraoxon and dimethoate were 0.7nM and 3.9nM, which were lower than the reported AChE biosensor. The proposed biosensor could restore to over 95% of its original current, which demonstrated the good reactivation. Moreover, the biosensor can be applicable to real water sample measurement. Thus, the biosensor exhibited low applied potential, high sensitivity and good stability, providing a promising tool for analysis of pesticides.
ESTHER : Lang_2016_Talanta_156-157_34
PubMedSearch : Lang_2016_Talanta_156-157_34
PubMedID: 27260432

Title : A Semiautomated Structure-Based Method To Predict Substrates of Enzymes via Molecular Docking: A Case Study with Candida antarctica Lipase B - Yao_2016_J.Chem.Inf.Model_56_1979
Author(s) : Yao Z , Zhang L , Gao B , Cui D , Wang F , He X , Zhang JZ , Wei D
Ref : J Chem Inf Model , 56 :1979 , 2016
Abstract : The discovery of unique substrates is important for developing potential applications of enzymes. However, the experimental procedures for substrate identification are laborious, time-consuming, and expensive. Although in silico structure-based approaches show great promise, recent extensive studies have shown that these approaches remain a formidable challenge for current biocomputational methodologies. Here we present an open-source, extensible, and flexible software platform for predicting enzyme substrates called THEMIS, which performs in silico virtual screening for potential catalytic targets of an enzyme on the basis of the enzyme's catalysis mechanism. On the basis of a generalized transition state theory of enzyme catalysis, we introduce a modified docking procedure called "mechanism-based restricted docking" (MBRD) for novel substrate recognition from molecular docking. Comprising a series of utilities written in C/Python, THEMIS automatically executes parallel-computing MBRD tasks and evaluates the results with various molecular mechanics (MM) criteria such as energy, distance, angle, and dihedral angle to help identify desired substrates. Exhaustive sampling and statistical measures were used to improve the robustness and reproducibility of the method. We used Candida antarctica lipase B (CALB) as a test system to demonstrate the effectiveness of our computational prediction of (non)substrates. A novel MM score function for CALB substrate identification derived from the near-attack conformation was used to evaluate the possibility of chemical transformation. A highly positive rate of 93.4% was achieved from a CALB substrate library with 61 known substrates and 35 nonsubstrates, and the screening rate has reached 103 compounds/day (96 CPU cores, 100 samples/compound). The performance shows that the present method is perhaps the first reported scheme to meet the requirement for practical applicability to enzyme studies. An additional study was performed to validate the universality of our method. In this verification we employed two distinct enzymes, nitrilase Nit6803 and SDR Gox2181, where the correct rates of both enzymes exceeded 90%. The source code used will be released under the GNU General Public License (GPLv3) and will be free to download. We believe that the present method will provide new insights into enzyme research and accelerate the development of novel enzyme applications.
ESTHER : Yao_2016_J.Chem.Inf.Model_56_1979
PubMedSearch : Yao_2016_J.Chem.Inf.Model_56_1979
PubMedID: 27529495

Title : Drug Therapy for Behavioral and Psychological Symptoms of Dementia - Wang_2016_Curr.Neuropharmacol_14_307
Author(s) : Wang F , Feng TY , Yang S , Preter M , Zhou JN , Wang XP
Ref : Curr Neuropharmacol , 14 :307 , 2016
Abstract : Dementia, which can be induced by diverse factors, is a clinical syndrome characterized by the decline of cognitive function. Behavioral and psychological symptoms of dementia (BPSD) include depression, agitation, and aggression. Dementia causes a heavy burden on patients and their caregivers. Patients with BPSD should be assessed comprehensively by practitioners and offered appropriate non-pharmacologic and pharmacologic therapy. Nonpharmacologic therapy has been recommended as the basal treatment for BPSD; however, pharmacologic therapy is required under many situations. Medications, including antipsychotic agents, antidepressants, sedative and hypnotic agents, mood stabilizers, cholinesterase inhibitors, and amantadine, are extensively used in clinical practice. We have reviewed the progression of pharmacologic therapy for BPSD.
ESTHER : Wang_2016_Curr.Neuropharmacol_14_307
PubMedSearch : Wang_2016_Curr.Neuropharmacol_14_307
PubMedID: 26644152

Title : Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification - Yang_2016_Nanoscale_8_9537
Author(s) : Yang J , Fan L , Wang F , Luo Y , Sui X , Li W , Zhang X , Wang Y
Ref : Nanoscale , 8 :9537 , 2016
Abstract : The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.
ESTHER : Yang_2016_Nanoscale_8_9537
PubMedSearch : Yang_2016_Nanoscale_8_9537
PubMedID: 26730700

Title : The Association Between Epoxide Hydrolase Genetic Variant and Effectiveness of Nicotine Replacement Therapy in a Han Chinese Population -
Author(s) : Wang F , Liu Y , Guo S , Chen D , Sun H
Ref : Neurosci Bull , 32 :545 , 2016
PubMedID: 27783326

Title : ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats - Liu_2016_CNS.Neurosci.Ther_22_220
Author(s) : Liu JM , Wu PF , Rao J , Zhou J , Shen ZC , Luo H , Huang JG , Liang X , Long LH , Xie QG , Jiang FC , Wang F , Chen JG
Ref : CNS Neurosci Ther , 22 :220 , 2016
Abstract : AIMS: Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro.
METHODS: We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO).
RESULTS: ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of (18) F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET).
CONCLUSIONS: ST09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton.
ESTHER : Liu_2016_CNS.Neurosci.Ther_22_220
PubMedSearch : Liu_2016_CNS.Neurosci.Ther_22_220
PubMedID: 26813743

Title : DWARF14 is a non-canonical hormone receptor for strigolactone - Yao_2016_Nature_536_469
Author(s) : Yao R , Ming Z , Yan L , Li S , Wang F , Ma S , Yu C , Yang M , Chen L , Li Y , Yan C , Miao D , Sun Z , Yan J , Sun Y , Wang L , Chu J , Fan S , He W , Deng H , Nan F , Li J , Rao Z , Lou Z , Xie D
Ref : Nature , 536 :469 , 2016
Abstract : Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
ESTHER : Yao_2016_Nature_536_469
PubMedSearch : Yao_2016_Nature_536_469
PubMedID: 27479325
Gene_locus related to this paper: arath-AtD14

Title : Cardiomyocyte VEGF Regulates Endothelial Cell GPIHBP1 to Relocate Lipoprotein Lipase to the Coronary Lumen During Diabetes Mellitus - Chiu_2016_Arterioscler.Thromb.Vasc.Biol_36_145
Author(s) : Chiu AP , Wan A , Lal N , Zhang D , Wang F , Vlodavsky I , Hussein B , Rodrigues B
Ref : Arterioscler Thromb Vasc Biol , 36 :145 , 2016
Abstract : OBJECTIVE: Lipoprotein lipase (LPL)-mediated triglyceride hydrolysis is the major source of fatty acid for cardiac energy. LPL, synthesized in cardiomyocytes, is translocated across endothelial cells (EC) by its transporter glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Previously, we have reported an augmentation in coronary LPL, which was linked to an increased expression of GPIHBP1 following moderate diabetes mellitus. We examined the potential mechanism by which hyperglycemia amplifies GPIHBP1. APPROACH AND
RESULTS: Exposure of rat aortic EC to high glucose induced GPIHBP1 expression and amplified LPL shuttling across these cells. This effect coincided with an elevated secretion of heparanase. Incubation of EC with high glucose or latent heparanase resulted in secretion of vascular endothelial growth factor (VEGF). Primary cardiomyocytes, being a rich source of VEGF, when cocultured with EC, restored EC GPIHBP1 that is lost because of cell passaging. Furthermore, recombinant VEGF induced EC GPIHBP1 mRNA and protein expression within 24 hours, an effect that could be prevented by a VEGF neutralizing antibody. This VEGF-induced increase in GPIHBP1 was through Notch signaling that encompassed Delta-like ligand 4 augmentation and nuclear translocation of the Notch intracellular domain. Finally, cardiomyocytes from severely diabetic animals exhibiting attenuation of VEGF were unable to increase EC GPIHBP1 expression and had lower LPL activity at the vascular lumen in perfused hearts. CONCLUSION: EC, as the first responders to hyperglycemia, can release heparanase to liberate myocyte VEGF. This growth factor, by activating EC Notch signaling, is responsible for facilitating GPIHBP1-mediated translocation of LPL across EC and regulating LPL-derived fatty acid delivery to the cardiomyocytes.
ESTHER : Chiu_2016_Arterioscler.Thromb.Vasc.Biol_36_145
PubMedSearch : Chiu_2016_Arterioscler.Thromb.Vasc.Biol_36_145
PubMedID: 26586663

Title : APA-style human milk fat analogue from silkworm pupae oil: Enzymatic production and improving storage stability using alkyl caffeates - Liu_2015_Sci.Rep_5_17909
Author(s) : Liu X , Wang X , Pang N , Zhu W , Zhao X , Wang F , Wu F , Wang J
Ref : Sci Rep , 5 :17909 , 2015
Abstract : Silkworm pupae oil derived from reeling waste is a rich source of alpha-linolenic acid (ALA), which has multipal applications. ALAs were added in sn-1, 3 positions in a triacylglycerol (TAG) to produce an APA-human milk fat analogues (APA-HMFAs, A: alpha-linolenic acid, P: palmitic acid). The optimum condition is that tripalmitin to free fatty acids of 1:12 (mole ratio) at 65 degreeC for 48 h using lipase Lipozyme RM IM. Results show that, the major TAG species that comprised APA-HMFAs were rich in ALA and palmitic acid, which contained 64.52% total unsaturated fatty acids (UFAs) and 97.05% PA at the sn-2 position. The melting point of APA was -27.5 degreeC which is much lower than tripalmitin (40.5 degreeC) indicating more plastic character. In addition, the practical application of alkyl caffeates as liposoluble antioxidants in APA was developed. Alkyl caffeate showed a superior IC50 (1.25-1.66 g/mL) compared to butyl hydroxy anisd (1.67 g/mL) and L-ascorbic acid-6-palmitate (L-AP) (1.87 g/mL) in DPPH analysis. The addition of ethyl caffeate to oil achieved a higher UFAs content (73.58%) at high temperatures. Overall, APA was obtained from silkworm pupae oil successfully, and the addition of caffeates extended storage ranges for APA-HMFAs.
ESTHER : Liu_2015_Sci.Rep_5_17909
PubMedSearch : Liu_2015_Sci.Rep_5_17909
PubMedID: 26643045

Title : Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect - Guo_2015_Neuromuscul.Disord_25_257
Author(s) : Guo Y , Menezes MJ , Menezes MP , Liang J , Li D , Riley LG , Clarke NF , Andrews PI , Tian L , Webster R , Wang F , Liu X , Shen Y , Thorburn DR , Keating BJ , Engel A , Hakonarson H , Christodoulou J , Xu X
Ref : Neuromuscular Disorders , 25 :257 , 2015
Abstract : Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes.
ESTHER : Guo_2015_Neuromuscul.Disord_25_257
PubMedSearch : Guo_2015_Neuromuscul.Disord_25_257
PubMedID: 25557462

Title : Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers - Pang_2015_ACS.Nano_9_6450
Author(s) : Pang Z , Hu CM , Fang RH , Luk BT , Gao W , Wang F , Chuluun E , Angsantikul P , Thamphiwatana S , Lu W , Jiang X , Zhang L
Ref : ACS Nano , 9 :6450 , 2015
Abstract : Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent. Through in vitro studies, we demonstrated that the biomimetic nanoparticles retain the enzymatic activity of membrane-bound AChE and are able to bind to a model organophosphate, dichlorvos, precluding its inhibitory effect on other enzymatic substrates. In a mouse model of organophosphate poisoning, the nanoparticles were shown to improve the AChE activity in the blood and markedly improved the survival of dichlorvos-challenged mice.
ESTHER : Pang_2015_ACS.Nano_9_6450
PubMedSearch : Pang_2015_ACS.Nano_9_6450
PubMedID: 26053868

Title : Strategy to Overcome Effect of Raw Materials on Enzymatic Process of Biodiesel from Non-edible Oils Using Candida sp. 99-125 Lipase - Nie_2015_Appl.Biochem.Biotechnol_177_1176
Author(s) : Nie K , Wang F , Tan T , Liu L
Ref : Appl Biochem Biotechnol , 177 :1176 , 2015
Abstract : Non-edible oils are preferred raw materials for biodiesel production. However, the properties of raw materials significantly affect the synthesis process, leading to difficulties to design one process suitable for any kind of raw material. In this study, the composition of five typical non-edible oils was analyzed. The major difference was the content of free fatty acids, reflected from their acid values. The influence of different oils was investigated by using lipase from Candida sp. 99-125. At low lipase dosage and low water content, the conversion was found proportional to the acid value. However, by increasing the water content or lipase dosage, we observed that the conversions for all kinds of oils used in this study could exceed 80 %. Time course analysis indicates that the lipase used in this study catalyzed hydrolysis followed by esterification, rather than direct transesterification. Accumulation of free fatty acids at the very beginning was necessary. A high water content facilitated the hydrolysis of oils with low acid value. This lipase showed capability to transform all the oils by controlling the water content.
ESTHER : Nie_2015_Appl.Biochem.Biotechnol_177_1176
PubMedSearch : Nie_2015_Appl.Biochem.Biotechnol_177_1176
PubMedID: 26280803

Title : Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo - Zhang_2015_Neurosci_305_169
Author(s) : Zhang Q , Li J , Liu C , Song C , Li P , Yin F , Xiao Y , Jiang W , Zong A , Zhang X , Wang F
Ref : Neuroscience , 305 :169 , 2015
Abstract : In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Abeta)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Abeta25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Abeta1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Abeta peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease.
ESTHER : Zhang_2015_Neurosci_305_169
PubMedSearch : Zhang_2015_Neurosci_305_169
PubMedID: 26254241

Title : Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats - Wang_2015_Mol.Med.Rep_11_775
Author(s) : Wang F , Zeng X , Zhu Y , Ning D , Liu J , Liu C , Jia X , Zhu D
Ref : Mol Med Rep , 11 :775 , 2015
Abstract : A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a signi fi cant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2015_Mol.Med.Rep_11_775
PubMedSearch : Wang_2015_Mol.Med.Rep_11_775
PubMedID: 25371181

Title : [Effect of PON1 overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning] - Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
Author(s) : Wu B , Wang F , Zhou J , Hou Y , Hong G , Zhao G , Ge Y , Liu Y , Qiu Q , Lu Z
Ref : Zhonghua Yi Xue Za Zhi , 95 :2955 , 2015
Abstract : OBJECTIVE: To investigate the effect of paraoxonase1 (PON1) overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning.
METHODS: Mouse diaphragmatic muscle cells were cultured routinely and infected with overexpression lentivirus. Cells were divided into normal control group, DDVP group, LV-GFP + DDVP group, LV-PON1 + DDVP group. Cell viability was determined by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. The mRNA and protein expression of PON1 and Nrf2 in mouse diaphragmatic muscle cells was measured by RT-PCR and Western blot. Enzyme-linked immunosorbent assay was used to determine levels of acetyl cholinesterase (AchE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) in mouse diaphragmatic muscle cells. The activity of superoxide dismutase (SOD) and catalase (CAT) as well as malondialdehyde (MDA) content in cells was measured by chemical colorimetry.
RESULTS: After induced by 0, 80, 160, 320, 640 micromol/L DDVP for 24 hours, the viability of mouse diaphragmatic muscle cells was (100 +/- 3.82)%, (82.13 +/- 2.60)%, (53.57 +/- 5.05)%, (30.77 +/- 3.30)%, (14.20 +/- 2.19)% respectively, changing in a concentration-dependent manner (P < 0.05). After induced by 160 micromol/L DDVP for 0, 6, 12, 24 hours, the viability of mouse diaphragmatic muscle cells was (100.17 +/- 2.74)%, (76.13 +/- 6.01)%, (66.53 +/- 3.55)%, (53.57 +/- 5.05)%, changing in a time-dependent manner (P < 0.05). The PON1 protein level in LV-PON1 group was higher than that of blank control group (0.370 +/- 0.015 vs 0.232 +/- 0.004, 0.197 +/- 0.015 vs 0.037 +/- 0.003, P < 0.05). The cell viability of LV-PON1 group is higher than that of DDVP group at different time point after induction of DDVP (P < 0.05). After induced by DDVP for 24 hours, the cell apoptosis rate and MDA content in LV-PON1 group were lower than those of DDVP group (P < 0.05). While levels of AchE, PON1 and Nrf2 protein expression, SOD and CAT, HO-1 and NQO-1 were higher than those of DDVP group (P < 0.05).
CONCLUSIONS: The overexpression of PON1 could effectively alleviate AchE inhibition by DDVP and induce Nrf2 expression to exert antioxidant effect, thus protected the mouse diaphragmatic muscle cells.
ESTHER : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedSearch : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedID: 26814074

Title : Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism - Wang_2014_Exp.Ther.Med_7_529
Author(s) : Wang N , Cai Y , Wang F , Zeng X , Jia X , Tao F , Zhu D
Ref : Exp Ther Med , 7 :529 , 2014
Abstract : Adult-onset hypothyroidism induces various impairments in hippocampus-dependent cognitive function, in which numerous synaptic proteins and neurotransmitters are involved. Donepezil (DON), an acetylcholinesterase inhibitor, has been shown to be efficient in improving cognitive function. The aim of the present study was to investigate the effects of adult-onset hypothyroidism on the expression levels of the synaptic proteins syntaxin-1 and munc-18, as well as the content of the neurotransmitter acetylcholine (ACh) in the hippocampus. In addition, the study explored the effects of thyroxin (T4) and DON treatment on the altered parameters. The study involved 55 Sprague-Dawley rats that were randomly divided into five groups: Control, hypothyroid (0.05% 6-n-propyl-2-thiouracil; added to the drinking water), hypothyroid treated with T4 (6 mug/100 g body weight once daily; intraperitoneal injection), hypothyroid treated with DON (0.005%; added to the drinking water) and hypothyroid treated with a combination of the two drugs (6 mug/100 g T4 and 0.005% DON). The concentration of ACh was determined in the homogenized hippocampus of each animal by alkaline hydroxylamine colorimetry. The protein levels of syntaxin-1 and munc-18 were determined by immunohistochemistry. The results showed that the content of ACh in the hippocampi of the hypothyroid rats was significantly decreased compared with that in the controls and that T4 monotherapy and DON administration restored the ACh content to normal values. In the hippocampi of the hypothyroid group, munc-18 was expressed at significantly lower levels, while the expression levels of syntaxin-1 were increased compared with the levels in the control group. Treatment with T4 alone restored the expression of syntaxin-1 but failed to normalize munc-18 expression levels. The co-administration of T4 and DON returned the munc-18 levels to normal values. These observations indicate that adult-onset hypothyroidism induces alterations in the levels of munc-18, syntaxin-1 and ACh in the hippocampus. Syntaxin-1 and ACh levels were restored by T4 monotherapy while munc-18 levels were not. In addition, the co-administration of T4 and DON resulted in more effective restoration than either alone. The thyroid hormone has a direct effect on metabolism of hippocampal ACh in adult rats and DON is helpful for treatment of synaptic protein impairment induced by hypothyroidism.
ESTHER : Wang_2014_Exp.Ther.Med_7_529
PubMedSearch : Wang_2014_Exp.Ther.Med_7_529
PubMedID: 24520241

Title : The role of temperature and solvent microenvironment on the activity of Yarrowia lipolytica Lipase 2: Insights from molecular dynamics simulation - Cao_2014_J.Mol.Catal.B.Enzym_97_270
Author(s) : Cao H , Deng L , Lei M , Wang F , Tan TW
Ref : J Mol Catal B Enzym , 109 :101 , 2014
Abstract : The influence of temperature and solvent on the activity of Yarrowia lipolytica Lipase 2 (YLLIP2) was investigated. This was done by interpreting experimental results with theoretical molecular modeling of the enzyme structure by using molecular dynamic (MD) simulation. The transient open conformation of YLLIP2 was obtained. It was employed for exploring the structural rearrangement of the lid and the catalytic triad (Ser162, Asp230, and His289) at different temperatures and in different solvents. The calculated results indicated that the opened extent of the lid was positively correlated with temperature and the structural rearrangement of the catalytic triad was the crucial factor for the decreased activity of YLLIP2 at higher temperature. The polar solvent molecule approaches the catalytic triad of YLLIP2 more easily and has a stronger interaction with His289 than the non-polar solvent molecule. The interaction between His289 and Asp230 was affected by the higher temperature (333 K) whereas the interaction between His289 and Ser162 was affected by the polar solvent molecule (acetone and ethanol).
ESTHER : Cao_2014_J.Mol.Catal.B.Enzym_97_270
PubMedSearch : Cao_2014_J.Mol.Catal.B.Enzym_97_270
PubMedID:

Title : An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome - Bian_2014_J.Proteomics_96_253
Author(s) : Bian Y , Song C , Cheng K , Dong M , Wang F , Huang J , Sun D , Wang L , Ye M , Zou H
Ref : J Proteomics , 96 :253 , 2014
Abstract : UNLABELLED: Protein phosphorylation is one of the most common post-translational modifications. It plays key roles in regulating diverse biological processes of liver tissues. To better understand the role of protein phosphorylation in liver functions, it is essential to perform in-depth phosphoproteome analysis of human liver. Here, an enzyme assisted reversed-phase-reversed-phase liquid chromatography (RP-RPLC) approach with both RPLC separations operated with optimized acidic mobile phase was developed. High orthogonal separation was achieved by trypsin digestion of the Glu-C generated peptides in the fractions collected from the first RPLC separation. The phosphoproteome coverage was further improved by using two types of instruments, i.e. TripleTOF 5600 and LTQ Orbitrap Velos. A total of 22,446 phosphorylation sites, corresponding to 6526 nonredundant phosphoproteins were finally identified from normal human liver tissues. Of these sites, 15,229 sites were confidently localized with Ascore>/=13. This dataset was the largest phosphoproteome dataset of human liver. It can be a public resource for the liver research community and holds promise for further biology studies. BIOLOGICAL SIGNIFICANCE: The enzyme assisted approach enabled the two RPLC separations operated both with optimized acidic mobile phases. The identifications from TripleTOF 5600 and Orbitrap Velos are highly complementary. The largest phosphoproteome dataset of human liver was generated.
ESTHER : Bian_2014_J.Proteomics_96_253
PubMedSearch : Bian_2014_J.Proteomics_96_253
PubMedID: 24275569
Gene_locus related to this paper: human-LIPC

Title : Intestinal Cgi-58 deficiency reduces postprandial lipid absorption - Xie_2014_PLoS.One_9_e91652
Author(s) : Xie P , Guo F , Ma Y , Zhu H , Wang F , Xue B , Shi H , Yang J , Yu L
Ref : PLoS ONE , 9 :e91652 , 2014
Abstract : Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.
ESTHER : Xie_2014_PLoS.One_9_e91652
PubMedSearch : Xie_2014_PLoS.One_9_e91652
PubMedID: 24618586

Title : Engineering of Yarrowia lipolytica lipase Lip8p by circular permutation to alter substrate and temperature characteristics - Sheng_2014_J.Ind.Microbiol.Biotechnol_41_757
Author(s) : Sheng J , Ji XF , Wang F , Sun M
Ref : J Ind Microbiol Biotechnol , 41 :757 , 2014
Abstract : Applications of lipases are mainly based on their catalytic efficiency and substrate specificity. In this study, circular permutation (CP), an unconventional protein engineering technique, was employed to acquire active mutants of Yarrowia lipolytica lipase Lip8p. A total of 21 mutant lipases exhibited significant shifts in substrate specificity. Cp128, the most active enzyme mutant, showed higher catalytic activity (14.5-fold) and higher affinity (4.6-fold) (decreased K m) to p-nitrophenyl-myristate (pNP-C14) than wild type (WT). Based on the three-dimensional (3D) structure model of the Lip8p, we found that most of the functional mutation occurred in the surface-exposed loop region in close proximity to the lid domain (S112-F122), which implies the steric effect of the lid on lipase activity and substrate specificity. The temperature properties of Cp128 were also investigated. In contrast to the optimal temperature of 45 degrees C for the WT enzyme, Cp128 exhibited the maximal activity at 37 degrees C. But it is noteworthy that there is no change in thermostability.
ESTHER : Sheng_2014_J.Ind.Microbiol.Biotechnol_41_757
PubMedSearch : Sheng_2014_J.Ind.Microbiol.Biotechnol_41_757
PubMedID: 24627048

Title : Gephyrin Clusters Are Absent from Small Diameter Primary Afferent Terminals Despite the Presence of GABAA Receptors - Lorenzo_2014_J.Neurosci_34_8300
Author(s) : Lorenzo LE , Godin AG , Wang F , St-Louis M , Carbonetto S , Wiseman PW , Ribeiro-da-Silva A , De Koninck Y
Ref : Journal of Neuroscience , 34 :8300 , 2014
Abstract : Whereas both GABAA receptors (GABAARs) and glycine receptors (GlyRs) play a role in control of dorsal horn neuron excitability, their relative contribution to inhibition of small diameter primary afferent terminals remains controversial. To address this, we designed an approach for quantitative analyses of the distribution of GABAAR-subunits, GlyR alpha1-subunit and their anchoring protein, gephyrin, on terminals of rat spinal sensory afferents identified by Calcitonin-Gene-Related-Peptide (CGRP) for peptidergic terminals, and by Isolectin-B4 (IB4) for nonpeptidergic terminals. The approach was designed for light microscopy, which is compatible with the mild fixation conditions necessary for immunodetection of several of these antigens. An algorithm was designed to recognize structures with dimensions similar to those of the microscope resolution. To avoid detecting false colocalization, the latter was considered significant only if the degree of pixel overlap exceeded that expected from randomly overlapping pixels given a hypergeometric distribution. We found that both CGRP(+) and IB4(+) terminals were devoid of GlyR alpha1-subunit and gephyrin. The alpha1 GABAAR was also absent from these terminals. In contrast, the GABAAR alpha2/alpha3/alpha5 and beta3 subunits were significantly expressed in both terminal types, as were other GABAAR-associated-proteins (alpha-Dystroglycan/Neuroligin-2/Collybistin-2). Ultrastructural immunocytochemistry confirmed the presence of GABAAR beta3 subunits in small afferent terminals. Real-time quantitative PCR (qRT-PCR) confirmed the results of light microscopy immunochemical analysis. These results indicate that dorsal horn inhibitory synapses follow different rules of organization at presynaptic versus postsynaptic sites (nociceptive afferent terminals vs inhibitory synapses on dorsal horn neurons). The absence of gephyrin clusters from primary afferent terminals suggests a more diffuse mode of GABAA-mediated transmission at presynaptic than at postsynaptic sites.
ESTHER : Lorenzo_2014_J.Neurosci_34_8300
PubMedSearch : Lorenzo_2014_J.Neurosci_34_8300
PubMedID: 24920633

Title : Potential mechanisms of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose VOCs - Wang_2014_Inhal.Toxicol_26_250
Author(s) : Wang F , Li C , Liu W , Jin Y
Ref : Inhal Toxicol , 26 :250 , 2014
Abstract : Abstract To investigate effects of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose volatile organic compounds (VOCs) and the possible mechanism for these effects, 60 male Kunming mice were exposed in 5 similar static chambers, 0 (control) and 4 different doses of VOCs mixture (G1-4) for consecutively 90 d at 2 h/d. The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.05 + 0.05 + 0.10 + 0.10 mg/m(3), 0.10 + 0.11 + 0.20 + 0.20 mg/m(3), 0.50 + 0.55 + 1.00 + 1.00 mg/m(3), 1.00 +1.10 + 2.00 + 2.00 mg/m(3), respectively, which corresponded to 1/2, 1, 5, and 10 times of indoor air quality standard in China. Morris water maze (MWM) and Grip strength (GS) test were performed in the last 7 weeks. One day following VOCs exposure, oxidative stress markers, neurotransmitters, and cholinergic system enzymes in brain were examined. In addition, the expressions of N-methyl-d-aspartate (NMDA) receptor in hippocampus were determined. VOCs exposure induced behavioral impairment of mice in MWM and GS test. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutamic acid (Glu) were significantly increased, while the acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and acetylcholine (ACh) levels, and the expression of NMDA receptor were significantly decreased in VOCs exposed groups. Results showed that sub-chronic exposure to low-dose VOCs induced damage on physique and motor function, as well as impairment on learning and memory capacity of mice. Oxidative damage, abnormal metabolism of neurotransmitters and cholinergic system enzymes, and the alternation of NMDA receptor expression may be the possible mechanism for VOCs-induced neurotoxicity.
ESTHER : Wang_2014_Inhal.Toxicol_26_250
PubMedSearch : Wang_2014_Inhal.Toxicol_26_250
PubMedID: 24568580

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 : Colorimetric and fluorometric assays for acetylcholinesterase and its inhibitors screening based on a fluorescein derivate - Wang_2014_Bioorg.Med.Chem.Lett_24_552
Author(s) : Wang B , Wang H , Wang F , Zhou G , Wang Y , Kambam S , Chen X
Ref : Bioorganic & Medicinal Chemistry Lett , 24 :552 , 2014
Abstract : A fluorescein-based sensor was developed for the AChE activity assay and the inhibitor screening. The sensor provided the dual assay methods for the screening of AChE activity in the presence or absence of inhibitor. The colorimetric and fluorometric assays were based on the following processes: (1) owing to the hydrolysis of acetylthiocholine in the presence of AChE, the fluorescein-based probe can rapidly induce 1,4-addition of the hydrolysis product thiocholine to alpha,beta-unsaturated ketone in the compound 1, resulting in strong fluorescence and absorption changes; (2) in the presence of the corresponding inhibitor, the fluorescence enhancement or the absorption change would be inhibited in that the formation of thiocholine was hindered.
ESTHER : Wang_2014_Bioorg.Med.Chem.Lett_24_552
PubMedSearch : Wang_2014_Bioorg.Med.Chem.Lett_24_552
PubMedID: 24360998

Title : PEG1\/MEST and IGF2 DNA methylation in CIN and in cervical cancer - Vidal_2014_Clin.Transl.Oncol_16_266
Author(s) : Vidal AC , Henry NM , Murphy SK , Oneko O , Nye M , Bartlett JA , Overcash F , Huang Z , Wang F , Mlay P , Obure J , Smith J , Vasquez B , Swai B , Hernandez B , Hoyo C
Ref : Clin Transl Oncol , 16 :266 , 2014
Abstract : INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND
METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios.
RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations.
CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.
ESTHER : Vidal_2014_Clin.Transl.Oncol_16_266
PubMedSearch : Vidal_2014_Clin.Transl.Oncol_16_266
PubMedID: 23775149

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 : Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers exposed to organophosphate pesticides - Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
Author(s) : Zhang X , Sui H , Li H , Zheng J , Wang F , Li B , Zhang Y
Ref : Exp Biol Med (Maywood) , 239 :232 , 2014
Abstract : Paraoxonase (PON1) is one of the major players in the detoxification of organophosphates (OPs). This study presents our investigation into the effect of OPs on serum PON1 activity and the distribution of common PON1 polymorphisms in Han Chinese workers with repeated high exposure to OP pesticides, and the factors modulating PON1 activity. In all, 400 participants, including 180 workers exposed to OP pesticides occupationally, and 220 controls were investigated. Serum PON1 and cholinesterase (ChE) activity were measured, and genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. The association between PON1 activity and PON1 polymorphisms, and the influencing factors of PON1 activity, were analyzed. The results revealed that repeated OP exposures significantly decreased serum PON1 and ChE activity (P < 0.05), although the exposed workers did not complain of health problems. Higher L and R allele frequencies for the L55M and Q192R polymorphisms of PON1 were observed. PON1 polymorphisms (especially the Q192R polymorphism) and pesticide exposures significantly affected serum PON1 activity in the study population. Therefore, the results of this investigation indicate PON1 polymorphisms and pesticide exposures may be important risk predictors for OP poisoning in the Han Chinese population, who display very high frequencies of the M allele and R allele for PON1 polymorphisms at the positions 55 and 192, respectively.
ESTHER : Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
PubMedSearch : Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
PubMedID: 24326413

Title : Fe(3)O(4) magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent - Liang_2013_Anal.Chem_85_308
Author(s) : Liang M , Fan K , Pan Y , Jiang H , Wang F , Yang D , Lu D , Feng J , Zhao J , Yang L , Yan X
Ref : Analytical Chemistry , 85 :308 , 2013
Abstract : Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 muM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.
ESTHER : Liang_2013_Anal.Chem_85_308
PubMedSearch : Liang_2013_Anal.Chem_85_308
PubMedID: 23153113

Title : Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye - Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
Author(s) : Liu D , Wang Z , Jin A , Huang X , Sun X , Wang F , Yan Q , Ge S , Xia N , Niu G , Liu G , Hight Walker AR , Chen X
Ref : Angew Chem Int Ed Engl , 52 :14065 , 2013
Abstract : Seeing is believing: A rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction has been developed. Owing to signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of the assay is based on solution color change, which can be easily observed by the naked eye alone.
ESTHER : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedSearch : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedID: 24155243

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers - Zhang_2013_J.Occup.Environ.Med_55_1001
Author(s) : Zhang M , Wang Y , Wang Q , Yang D , Zhang J , Wang F , Gu Q
Ref : J Occup Environ Med , 55 :1001 , 2013
Abstract : OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers.
METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined.
RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase.
CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.
ESTHER : Zhang_2013_J.Occup.Environ.Med_55_1001
PubMedSearch : Zhang_2013_J.Occup.Environ.Med_55_1001
PubMedID: 23969497

Title : Lipase-catalyzed synthesis and characterization of polymers by cyclodextrin as support architecture - Liu_2013_Carbohydr.Polym_92_633
Author(s) : Liu W , Wang F , Tan T , Chen B
Ref : Carbohydr Polym , 92 :633 , 2013
Abstract : Diesters and diols were successfully converted into aliphatic polyesters by enzymatic lipase Candida sp.99-125 catalysis, with beta-cyclodextrin acting as supporting architecture (in a similar way as chaperone proteins). No organic solvents were used. The polytransesterification was a much greener process, being solvent-free and without metal residues. Lipase Candida sp.99-125 showed a high catalytic activity for bulkpolymerization of diesters and diols with various numbers of methylene groups in their chains. beta-Cyclodextrin encircled the linear polymer chain and maintained the chain in a proper configuration to avoid its coagulation. Lipase initiated the polymerization and beta-cyclodextrin threaded onto the polymer chain to control the structure for producing high molecular weight polyesters. From a combination of diesters and diols, polyesters with a high molecular weight of 62,100Da were obtained at 70 degrees C. The corresponding polyesters showed an excellent thermal stability till 350 degrees C and had a strong ability to crystallize with up to 72% crystallinity, contributing to their high storage modulus.
ESTHER : Liu_2013_Carbohydr.Polym_92_633
PubMedSearch : Liu_2013_Carbohydr.Polym_92_633
PubMedID: 23218346

Title : Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca(2+) overload - Wang_2012_Bioorg.Med.Chem_20_6513
Author(s) : Wang Y , Wang F , Yu JP , Jiang FC , Guan XL , Wang CM , Li L , Cao H , Li MX , Chen JG
Ref : Bioorganic & Medicinal Chemistry , 20 :6513 , 2012
Abstract : In this study, a series of multipotent phenylthiazole-tacrine hybrids (7a-7e, 8, and 9a-9m) were synthesized and biologically evaluated. Screening results showed that phenylthiazole-tacrine hybrids were potent cholinesterase inhibitors with pIC(50) (-logIC(50)) value ranging from 5.78+/-0.05 to 7.14+/-0.01 for acetylcholinesterase (AChE), and from 5.75+/-0.03 to 10.35+/-0.15 for butyrylcholinesterase (BCHE). The second series of phenylthiazole-tacrine hybrids (9a-9m) could efficiently prevent Abeta(1-42) self-aggregation. The structure-activity relationship revealed that their inhibitory potency relied on the type of middle linker and substitutions at 4'-position of 4-phenyl-2-aminothiazole. In addition, 7a and 7c also displayed the Ca(2+) overload blockade effect in the primary cultured cortical neurons. Consequently, these compounds emerged as promising molecules for the therapy of Alzheimer's disease.
ESTHER : Wang_2012_Bioorg.Med.Chem_20_6513
PubMedSearch : Wang_2012_Bioorg.Med.Chem_20_6513
PubMedID: 23000296

Title : Multifunctional mercapto-tacrine derivatives for treatment of age-related neurodegenerative diseases - Wang_2012_J.Med.Chem_55_3588
Author(s) : Wang Y , Guan XL , Wu PF , Wang CM , Cao H , Li L , Guo XJ , Wang F , Xie N , Jiang FC , Chen JG
Ref : Journal of Medicinal Chemistry , 55 :3588 , 2012
Abstract : Cooperating mercapto groups with tacrine in a single molecular, novel multifunctional compounds have been designed and synthesized. These mercapto-tacrine derivatives displayed a synergistic pharmacological profile of long-term potentiation enhancement, cholinesterase inhibition, neuroprotection, and less hepatotoxicity, emerging as promising molecules for the therapy of age-related neurodegenerative diseases.
ESTHER : Wang_2012_J.Med.Chem_55_3588
PubMedSearch : Wang_2012_J.Med.Chem_55_3588
PubMedID: 22420827

Title : Lhx8 promote differentiation of hippocampal neural stem\/progenitor cells into cholinergic neurons in vitro - Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
Author(s) : Shi J , Li H , Jin G , Zhu P , Tian M , Qin J , Tan X , Zhao S , Wang F , Hua Y , Xiao Y
Ref : In Vitro Cell Developmental Biology Anim , 48 :603 , 2012
Abstract : Lhx8, also named L3, is a recently identified member of the LIM homeobox gene family. Previously, we found acetylcholinesterase (AChE)-positive cells in fimbria-fornix (FF) transected rat hippocampal subgranular zone (SGZ). In the present study, we detected choline acetyltransferase (ChAT)-positive cholinergic cells in hippocampal SGZ after FF transaction, and these ChAT-positive cells were double labeled by Lhx8. Then we overexpressed Lhx8 during neural differentiation of hippocampal neural stem/progenitor cells on adherent conditions using lentivirus Lenti6.3-Lhx8. The result indicated that overexpression of Lhx8 did not affect the proportion of MAP2-positive neurons, but increased the proportion of ChAT-positive cells in vitro. These results suggested that FF-transected hippocampal niche promoted the ChAT/Lhx8-positive cholinergic neurons generation in rodent hippocampus, and Lhx8 was not associated with the MAP2-positive neurons differentiation on adherent conditions, but played a role in the specification of cholinergic neurons derived from hippocampal neural stem/progenitor cells in vitro.
ESTHER : Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
PubMedSearch : Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
PubMedID: 23150137

Title : Complete genome sequences of Brucella melitensis strains M28 and M5-90, with different virulence backgrounds - Wang_2011_J.Bacteriol_193_2904
Author(s) : Wang F , Hu S , Gao Y , Qiao Z , Liu W , Bu Z
Ref : Journal of Bacteriology , 193 :2904 , 2011
Abstract : Brucella melitensis is a Gram-negative coccobacillus bacteria belonging to the Alphaproteobacteria subclass. It is an important zoonotic pathogen that causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. The B. melitensis strain M5-90, a live attenuated vaccine cultured from the B. melitensis virulent strain M28, has been an effective tool to control brucellosis in goats and sheep in China. Here we report the complete genome sequences of B. melitensis M28 and M5-90, strains with different virulence backgrounds, which will serve as a valuable reference for future studies.
ESTHER : Wang_2011_J.Bacteriol_193_2904
PubMedSearch : Wang_2011_J.Bacteriol_193_2904
PubMedID: 21478357
Gene_locus related to this paper: brume-BMEI0552 , brume-BMEI1119 , brume-BMEI1365 , brume-BMEI1594 , brume-BMEI1608 , brume-BMEII0047 , brume-BMEII0681 , brume-BMEII0989 , brume-PCAD , brusu-BR1327

Title : Severity of diabetes governs vascular lipoprotein lipase by affecting enzyme dimerization and disassembly - Wang_2011_Diabetes_60_2041
Author(s) : Wang Y , Puthanveetil P , Wang F , Kim MS , Abrahani A , Rodrigues B
Ref : Diabetes , 60 :2041 , 2011
Abstract : OBJECTIVE: In diabetes, when glucose consumption is restricted, the heart adapts to use fatty acid (FA) exclusively. The majority of FA provided to the heart comes from the breakdown of circulating triglyceride (TG), a process catalyzed by lipoprotein lipase (LPL) located at the vascular lumen. The objective of the current study was to determine the mechanisms behind LPL processing and breakdown after moderate and severe diabetes. RESEARCH DESIGN AND METHODS: To induce acute hyperglycemia, diazoxide, a selective, ATP-sensitive K(+) channel opener was used. For chronic diabetes, streptozotocin, a beta-cell-specific toxin was administered at doses of 55 or 100 mg/kg to generate moderate and severe diabetes, respectively. Cardiac LPL processing into active dimers and breakdown at the vascular lumen was investigated. RESULTS: After acute hyperglycemia and moderate diabetes, more LPL is processed into an active dimeric form, which involves the endoplasmic reticulum chaperone calnexin. Severe diabetes results in increased conversion of LPL into inactive monomers at the vascular lumen, a process mediated by FA-induced expression of angiopoietin-like protein 4 (Angptl-4). CONCLUSIONS: In acute hyperglycemia and moderate diabetes, exaggerated LPL processing to dimeric, catalytically active enzyme increases coronary LPL, delivering more FA to the heart when glucose utilization is compromised. In severe chronic diabetes, to avoid lipid oversupply, FA-induced expression of Angptl-4 leads to conversion of LPL to inactive monomers at the coronary lumen to impede TG hydrolysis. Results from this study advance our understanding of how diabetes changes coronary LPL, which could contribute to cardiovascular complications seen with this disease.
ESTHER : Wang_2011_Diabetes_60_2041
PubMedSearch : Wang_2011_Diabetes_60_2041
PubMedID: 21646389

Title : Expression and characterization of recombinant Rhizopus oryzae lipase for enzymatic biodiesel production - Li_2011_Bioresour.Technol_102_9810
Author(s) : Li Z , Li X , Wang Y , Wang F , Jiang J
Ref : Bioresour Technol , 102 :9810 , 2011
Abstract : The Rhizopus oryzae lipase containing prosequence was expressed in Pichia pastoris. Recombinant lipase subunit showed a molecular mass of 32 kDa. The maximum activity of recombinant lipase obtained from Mut(s) recombinant was 90 IU/ml. The enzyme was stable in broad ranges of temperatures and pH, with the optimal temperature at 35 degrees C and pH 7.0. The crude recombinant R. oryzae lipase can be directly used for the transesterification of plant oils at high-water content of 60-100% (w/w) based on oil weight. The addition of 80% water to the transesterification systems resulted in the yield of methyl ester of 95%, 94% and 92% after 72 h using soybean oil, Jatropha curcas seed raw oil and Pistacia chinensis seed raw oil as raw material, respectively. These results indicate that the recombinant lipase is an effective biocatalyst for enzymatic biodiesel production.
ESTHER : Li_2011_Bioresour.Technol_102_9810
PubMedSearch : Li_2011_Bioresour.Technol_102_9810
PubMedID: 21852124

Title : Dynamic alterations of gene expression of nicotinic acetylcholine receptor alpha7, alpha4 and beta2 subunits in an acute MPTP-lesioned mouse model - Hu_2011_Neurosci.Lett_494_232
Author(s) : Hu J , Zhu C , Liu Y , Wang F , Huang Z , Fan W , Wu J
Ref : Neuroscience Letters , 494 :232 , 2011
Abstract : Epidemiologic studies show that the prevalence of Parkinson's disease (PD) is lower in smokers than in nonsmokers. Nicotine, a potent agonist of nicotinic acetylcholine receptors (nAChRs), excites midbrain dopaminergic neurons and this may contribute to the anti-parkinsonian effects. However, the alterations in gene expression of nAChR subunits using an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model remain unclear. In the present study, we profile the time course of nAChR alpha7, alpha4 and beta2 subunit expression levels using a comparative RT-PCR approach after acute MPTP injection. The results fall into four categories. (1) MPTP treatment transiently increased nAChR alpha7 (after last injection of MPTP 3 and 24 h), alpha4 and beta2 (24 h) mRNA expression in the substantia nigra (SN) and striatum. (2) Compared to cortical and hippocampal tissues, this transient increase of nAChR subunit expression specifically occurred in the SN and striatum. (3) In the acute MPTP model, time-courses of altered expression for nAChR alpha7, alpha4 and beta2 subunits closely mirrored the deficits observed in animal motor activity. (4) Stereological data showed that after administration of MPTP for 24h, there was a robust astrogliosis in the SN associated with significant dopaminergic neurodegeneration. These changes followed or paralleled MPTP-induced elevation in the levels of alpha7, alpha4 and beta2 mRNAs. Collectively, our results demonstrate that nAChRs are important targets in the MPTP neurotoxic process. These data suggest that therapeutic strategies targeted toward nAChR alpha7, alpha4 and beta2 subunits may have potential for developing new treatments for PD.
ESTHER : Hu_2011_Neurosci.Lett_494_232
PubMedSearch : Hu_2011_Neurosci.Lett_494_232
PubMedID: 21406211

Title : Biodiesel production with immobilized lipase: A review - Tan_2010_Biotechnol.Adv_28_628
Author(s) : Tan T , Lu J , Nie K , Deng L , Wang F
Ref : Biotechnol Adv , 28 :628 , 2010
Abstract : Fatty acid alkyl esters, also called biodiesel, are environmentally friendly and show great potential as an alternative liquid fuel. Biodiesel is produced by transesterification of oils or fats with chemical catalysts or lipase. Immobilized lipase as the biocatalyst draws high attention because that process is "greener". This article reviews the current status of biodiesel production with immobilized lipase, including various lipases, immobilization methods, various feedstocks, lipase inactivation caused by short chain alcohols and large scale industrialization. Adsorption is still the most widely employed method for lipase immobilization. There are two kinds of lipase used most frequently especially for large scale industrialization. One is Candida antartica lipase immobilized on acrylic resin, and the other is Candida sp. 99-125 lipase immobilized on inexpensive textile membranes. However, to further reduce the cost of biodiesel production, new immobilization techniques with higher activity and stability still need to be explored.
ESTHER : Tan_2010_Biotechnol.Adv_28_628
PubMedSearch : Tan_2010_Biotechnol.Adv_28_628
PubMedID: 20580809

Title : BZYX, a novel acetylcholinesterase inhibitor, significantly improved chemicals-induced learning and memory impairments on rodents and protected PC12 cells from apoptosis induced by hydrogen peroxide - Zhang_2009_Eur.J.Pharmacol_613_1
Author(s) : Zhang J , Zhu D , Sheng R , Wu H , Hu Y , Wang F , Cai T , Yang B , He Q
Ref : European Journal of Pharmacology , 613 :1 , 2009
Abstract : BZYX was designed as a dual-binding-site acetylcholinesterase (AChE) inhibitor and selected from series of indanone derivatives. The present study was designed to examine the cognition-enhanced, anti-cholinesterase, and neuroprotective effects of BZYX. In the passive avoidance performance and radial arm maze, BZYX showed a comparable effect to donepezil and rivastigmine on memory deficits in different stages induced by scopolamine, NaNO(2) and ethanol, respectively. Ellman's assay indicated BZYX exhibited high inhibition on AChE activity. IC(50) values for BZYX: 0.058+/-0.022 microM; donepezil: 0.019+/-0.004 microM; rivastigmine: 3.81+/-2.81 microM; glantamine: 3.01+/-1.85 microM and huperzine A: 0.053+/-0.016 microM. BZYX also presented great neuroprotecive function from apoptosis induced by hydrogen peroxide(H(2)O(2)) in PC12 cells. MTT assay and Annexin V-FITC Apoptosis Detection showed the viability of PC12 cells remarkably decreased with 400 microM H(2)O(2), while it significantly increased when the cells were pretreated with 0.1-1.0 microM BZYX. BZYX pretreatment remarkably reversed the loss of mitochondria membrane potential (DeltaPsim), scavenged reactive oxygen species formation induced by H(2)O(2) and resulted in up-regulation of procaspase3 and xIAP protein level and down-regulation of phosphorylated JNK protein, p53 protein level and cleavage of caspase 3. It is speculated that the mitochondrial pathway, mediated by Bcl-2 family and Mitogen-Activated Protein Kinases (MAPKs), might involved in the neuroprotection of BZYX. These results first demonstrated that BZYX had neuroprotective effects as well as cognition enhancement and acetylcholinesterase inhibition. It is hopeful that BZYX becomes a potential candidate for use in the intervention for neurodegenerative diseases.
ESTHER : Zhang_2009_Eur.J.Pharmacol_613_1
PubMedSearch : Zhang_2009_Eur.J.Pharmacol_613_1
PubMedID: 19345205

Title : Analysis of a Blumeria graminis-secreted lipase reveals the importance of host epicuticular wax components for fungal adhesion and development - Feng_2009_Mol.Plant.Microbe.Interact_22_1601
Author(s) : Feng J , Wang F , Liu G , Greenshields D , Shen W , Kaminskyj S , Hughes GR , Peng Y , Selvaraj G , Zou J , Wei Y
Ref : Mol Plant Microbe Interact , 22 :1601 , 2009
Abstract : The biotrophic powdery mildew fungus Blumeria graminis releases extracellular materials to the surface of fungal infection structures that facilitate anchoring them to hydrophobic plant surfaces prior to infection; however, the chemistry of fungal adhesives and the mechanism of adhesion remain largely unclear. Expressed sequence tag analysis led to identification of a secreted lipase, Lip1, from B. graminis. Expression of LIP1 is dramatically upregulated during the early stages of fungal development. Lip1, secreted to the surface of fungal cell walls, possesses lipolytic activity against a broad range of glycerides and releases alkanes and primary fatty alcohols from the epicuticular wax of wheat leaves. Of the epicuticular wax components released by Lip1 activity, long-chain alkanes are the most efficient cues for triggering appressorium formation. Pretreatment of wheat leaves with Lip1, thereby removing leaf surface wax, severely compromises components of fungal pathogenicity, including conidial adhesion, appressorium formation, and secondary hypha growth. Our data suggest that Lip1 activity releases cues from the host surface to promote pathogen development and infection.
ESTHER : Feng_2009_Mol.Plant.Microbe.Interact_22_1601
PubMedSearch : Feng_2009_Mol.Plant.Microbe.Interact_22_1601
PubMedID: 19888825
Gene_locus related to this paper: blugr-d2cql4

Title : Study on acetylcholinesterase inhibition induced by endogenous neurotoxin with an enzyme-semiconductor photoelectrochemical system - Zhu_2009_Chem.Commun.(Camb)__2682
Author(s) : Zhu W , An YR , Luo XM , Wang F , Zheng JH , Tang LL , Wang QJ , Zhang ZH , Zhang W , Jin LT
Ref : Chem Commun (Camb) , :2682 , 2009
Abstract : The integration of Au-doped TiO(2) nanotubes with biomolecule acetylcholinesterase (AChE) yields a novel AChE-Au-TiO(2) hybrid system, which provides a new rapid and valid photoelectrochemical approach to the determination of AChE inhibition induced by endogenous neurotoxin.
ESTHER : Zhu_2009_Chem.Commun.(Camb)__2682
PubMedSearch : Zhu_2009_Chem.Commun.(Camb)__2682
PubMedID: 19532920

Title : Cyclic resolution of racemic ibuprofen via coupled efficient lipase and acid-base catalysis - Liu_2009_Chirality_21_349
Author(s) : Liu Y , Wang F , Tan T
Ref : Chirality , 21 :349 , 2009
Abstract : Extracellular lipase LIP prepared in our lab from the yeast Yarrowia lipolytica was used for the resolution of racemic ibuprofen. The (S)-enantiomer was preferred by lipase LIP, and the unreacted (R)-enantiomer was extracted and racemized in basic solvent-water medium to be re-resolved. Solvent, content of solvent, base concentration, and temperature have a strong effect on racemization. The (S)-ester was separated and hydrolyzed to (S)-ibuprofen in acidic dimethyl sulfoxide-water mixture containing 70% dimethyl sulfoxide. The high purity (S)-ibuprofen (ee = 0.98) was obtained using lipase LIP to catalyze hydrolysis of (S)-ester in 0.1 M phosphate buffer (pH = 8).
ESTHER : Liu_2009_Chirality_21_349
PubMedSearch : Liu_2009_Chirality_21_349
PubMedID: 18571801

Title : Cleavage of protein kinase D after acute hypoinsulinemia prevents excessive lipoprotein lipase-mediated cardiac triglyceride accumulation - Kim_2009_Diabetes_58_2464
Author(s) : Kim MS , Wang F , Puthanveetil P , Kewalramani G , Innis S , Marzban L , Steinberg SF , Webber TD , Kieffer TJ , Abrahani A , Rodrigues B
Ref : Diabetes , 58 :2464 , 2009
Abstract : OBJECTIVE: During hypoinsulinemia, when cardiac glucose utilization is impaired, the heart rapidly adapts to using more fatty acids. One means by which this is achieved is through lipoprotein lipase (LPL). We determined the mechanisms by which the heart regulates LPL after acute hypoinsulinemia. RESEARCH DESIGN AND METHODS: We used two different doses of streptozocin (55 [D-55] and 100 [D-100] mg/kg) to induce moderate and severe hypoinsulinemia, respectively, in rats. Isolated cardiomyocytes were also used for transfection or silencing of protein kinase D (PKD) and caspase-3. RESULTS: There was substantial increase in LPL in D-55 hearts, an effect that was absent in severely hypoinsulinemic D-100 animals. Measurement of PKD, a key element involved in increasing LPL, revealed that only D-100 hearts showed an increase in proteolysis of PKD, an effect that required activation of caspase-3 together with loss of 14-3-3zeta, a binding protein that protects enzymes against degradation. In vitro, phosphomimetic PKD colocalized with LPL in the trans-golgi. PKD, when mutated to prevent its cleavage by caspase-3 and silencing of caspase-3, was able to increase LPL activity. Using a caspase inhibitor (Z-DEVD) in D-100 animals, we effectively lowered caspase-3 activity, prevented PKD cleavage, and increased LPL vesicle formation and translocation to the vascular lumen. This increase in cardiac luminal LPL was associated with a striking accumulation of cardiac triglyceride in Z-DEVD-treated D-100 rats. CONCLUSIONS After severe hypoinsulinemia, activation of caspase-3 can restrict LPL translocation to the vascular lumen. When caspase-3 is inhibited, this compensatory response is lost, leading to lipid accumulation in the heart.
ESTHER : Kim_2009_Diabetes_58_2464
PubMedSearch : Kim_2009_Diabetes_58_2464
PubMedID: 19875622

Title : Acute dexamethasone-induced increase in cardiac lipoprotein lipase requires activation of both Akt and stress kinases - Kewalramani_2008_Am.J.Physiol.Endocrinol.Metab_295_E137
Author(s) : Kewalramani G , Puthanveetil P , Kim MS , Wang F , Lee V , Hau N , Beheshti E , Ng N , Abrahani A , Rodrigues B
Ref : American Journal of Physiology Endocrinol Metab , 295 :E137 , 2008
Abstract : Following dexamethasone (DEX), cardiac energy generation is mainly through utilization of fatty acids (FA), with DEX animals demonstrating an increase in coronary lipoprotein lipase (LPL), an enzyme that hydrolyzes lipoproteins to FA. We examined the mechanisms by which DEX augments cardiac LPL. DEX was injected in rats, and hearts were removed, or isolated cardiomyocytes were incubated with DEX (0-8 h), for measurement of LPL activity and Western blotting. Acute DEX induced whole body insulin resistance, likely an outcome of a decrease in insulin signaling in skeletal muscle, but not cardiac tissue. The increase in luminal LPL activity after DEX was preceded by rapid nongenomic alterations, which included phosphorylation of AMPK and p38 MAPK, that led to phosphorylation of heat shock protein (HSP)25 and actin cytoskeleton rearrangement, facilitating LPL translocation to the myocyte cell surface. Unlike its effects in vivo, although DEX activated AMPK and p38 MAPK in cardiomyocytes, there was no phosphorylation of HSP25, nor was there any evidence of F-actin polymerization or an augmentation of LPL activity up to 8 h after DEX. Combining DEX with insulin appreciably enhanced cardiomyocyte LPL activity, which closely mirrored a robust elevation in phosphorylation of HSP25 and F-actin polymerization. Silencing of p38 MAPK, inhibition of PI 3-kinase, or preincubation with cytochalasin D prevented the increases in LPL activity. Our data suggest that, following DEX, it is a novel, rapid, nongenomic phosphorylation of stress kinases that, together with insulin, facilitates LPL translocation to the myocyte cell surface.
ESTHER : Kewalramani_2008_Am.J.Physiol.Endocrinol.Metab_295_E137
PubMedSearch : Kewalramani_2008_Am.J.Physiol.Endocrinol.Metab_295_E137
PubMedID: 18460599

Title : Immobilized lipase Candida sp. 99-125 catalyzed methanolysis of glycerol trioleate: solvent effect - Lu_2008_Bioresour.Technol_99_6070
Author(s) : Lu J , Nie K , Wang F , Tan T
Ref : Bioresour Technol , 99 :6070 , 2008
Abstract : The immobilized lipase Candida sp. 99-125 catalyzed methanolysis of glycerol trioleate was studied in twelve different solvents in order to deduce the solvent effect through an attempt to correlate the highest yield with such solvent properties as hydrophobicity (log P), dielectric constant (epsilon), and Hildebrand solubility parameter (delta). The results showed that the conversion of glycerol trioleate and yield of oleic acid methyl ester were quite dependent on the solvent. The catalyst lipase in various solvents also needed different optimum amount of water to keep its maximum activity, and generally this lipase in more hydrophobic solvents required more water. The correlation between the highest yield and log P value was found to be reasonable except deviation of data points of certain solvents, while no obvious correlation existed between the other two parameters, dielectric constant (epsilon) and Hildebrand solubility parameter (delta), and the enzyme activity. The study revealed that more hydrophobic solvents such as n-hexane or cyclohexane were more suitable solvents for Candida sp. 99-125 catalyzed transesterification of glycerol trioleate to oleic acid methyl ester.
ESTHER : Lu_2008_Bioresour.Technol_99_6070
PubMedSearch : Lu_2008_Bioresour.Technol_99_6070
PubMedID: 18255281

Title : Environmental adaptation: genomic analysis of the piezotolerant and psychrotolerant deep-sea iron reducing bacterium Shewanella piezotolerans WP3 - Wang_2008_PLoS.One_3_e1937
Author(s) : Wang F , Wang J , Jian H , Zhang B , Li S , Zeng X , Gao L , Bartlett DH , Yu J , Hu S , Xiao X
Ref : PLoS ONE , 3 :e1937 , 2008
Abstract : Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature.
ESTHER : Wang_2008_PLoS.One_3_e1937
PubMedSearch : Wang_2008_PLoS.One_3_e1937
PubMedID: 18398463
Gene_locus related to this paper: shepw-b8ci75 , shepw-b8cib3 , shepw-b8ciu7 , shepw-b8cld5 , shepw-b8cll2 , shepw-b8clm3 , shepw-b8cls4 , shepw-b8ct86 , shepw-b8ctf0 , shepw-b8ctt3 , shepw-b8cuq7 , shepw-b8cuu6 , shepw-b8cuz1 , shepw-b8cvm0 , shepw-b8cqh1 , shepw-b8cgv9 , shepw-b8chj5 , shepw-b8cpv3 , shepw-b8civ4 , shepw-b8cn18

Title : Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters - Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
Author(s) : Wang F , Wang W , Wahala K , Adlercreutz H , Ikonen E , Tikkanen MJ
Ref : American Journal of Physiology Endocrinol Metab , 295 :E1455 , 2008
Abstract : Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) belong to a unique family of naturally occurring hydrophobic steroid hormone derivatives that are transported in circulating lipoproteins and may act as a source of dehydroepiendrosterone (DHEA) and other biologically active steroid hormones in cells. Here, we studied the metabolic fate of low-density lipoprotein-associated [(3)H]DHEA-FAE ([(3)H]DHEA-FAE-LDL) and the possible role of lysosomal acid lipase (LAL) in the hydrolysis of DHEA-FAE in cultured human cells. When HeLa cells were incubated with [(3)H]DHEA-FAE-LDL, the accumulation of label in the cellular fraction increased with incubation time and could be inhibited by excess unlabeled LDL, suggesting LDL receptor or LDL receptor-related receptor-dependent uptake. During 48 h of chase, decreasing amounts of [(3)H]DHEA-FAE were found in the cellular fraction, while in the medium increasing amounts of unesterified [(3)H]DHEA and its two metabolites, [(3)H]-5alpha-androstanedione (5alpha-adione) and [(3)H]androstenedione (4-adione), appeared. As LDL-cholesteryl ester hydrolysis is dependent on LAL activity, we depleted LAL from HeLa cells using small interfering RNAs and compared the hydrolysis of [(3)H]DHEA-FAE-LDL and [(3)H]cholesteryl-FAE-LDL. The results demonstrated a more modest but significant reducing effect on the hydrolysis of [(3)H]DHEA-FAE compared with [(3)H]cholesteryl-FAE. Moreover, experiments in LAL-deficient human fibroblasts (Wolman disease patient cells) showed that [(3)H]DHEA-FAE hydrolysis was not completely dependent on LAL activity. In summary, LDL-transported [(3)H]DHEA-FAE entered cells via LDL receptor or LDL receptor-related receptor-mediated uptake, followed by intracellular hydrolysis and further metabolism into 5alpha-adione and 4-adione that were excreted from cells. Although LAL contributed to the deesterification of DHEA-FAE, it was not solely responsible for the hydrolysis.
ESTHER : Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
PubMedSearch : Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
PubMedID: 18796546

Title : Derivatives of vibralactone from cultures of the basidiomycete Boreostereum vibrans - Jiang_2008_Chem.Pharm.Bull.(Tokyo)_56_1286
Author(s) : Jiang MY , Wang F , Yang XL , Fang LZ , Dong ZJ , Zhu HJ , Liu JK
Ref : Chem Pharm Bull (Tokyo) , 56 :1286 , 2008
Abstract : Four new natural products possessing vibralactone skeleton, 1,5-secovibralactone (1), vibralactone B (2), vibralactone C (3) and acetylated vibralactone (4), together with known compound vibralactone (5), had been isolated from cultures of the basidiomycete Boreostereum vibrans. The structures of 1-4 were elucidated on the basis of spectroscopic methods. The absolute configuration of 1 was suggested to be S by computational methods.
ESTHER : Jiang_2008_Chem.Pharm.Bull.(Tokyo)_56_1286
PubMedSearch : Jiang_2008_Chem.Pharm.Bull.(Tokyo)_56_1286
PubMedID: 18758102

Title : Protein kinase D is a key regulator of cardiomyocyte lipoprotein lipase secretion after diabetes - Kim_2008_Circ.Res_103_252
Author(s) : Kim MS , Wang F , Puthanveetil P , Kewalramani G , Hosseini-Beheshti E , Ng N , Wang Y , Kumar U , Innis S , Proud CG , Abrahani A , Rodrigues B
Ref : Circulation Research , 103 :252 , 2008
Abstract : The diabetic heart switches to exclusively using fatty acid (FA) for energy supply and does so by multiple mechanisms including hydrolysis of lipoproteins by lipoprotein lipase (LPL) positioned at the vascular lumen. We determined the mechanism that leads to an increase in LPL after diabetes. Diazoxide (DZ), an agent that decreases insulin secretion and causes hyperglycemia, induced a substantial increase in LPL activity at the vascular lumen. This increase in LPL paralleled a robust phosphorylation of Hsp25, decreasing its association with PKCdelta, allowing this protein kinase to phosphorylate and activate protein kinase D (PKD), an important kinase that regulates fission of vesicles from the golgi membrane. Rottlerin, a PKCdelta inhibitor, prevented PKD phosphorylation and the subsequent increase in LPL. Incubating control myocytes with high glucose and palmitic acid (Glu+PA) also increased the phosphorylation of Hsp25, PKCdelta, and PKD in a pattern similar to that seen with diabetes, in addition to augmenting LPL activity. In myocytes in which PKD was silenced or a mutant form of PKCdelta was expressed, high Glu+PA were incapable of increasing LPL. Moreover, silencing of cardiomyocyte Hsp25 allowed phorbol 12-myristate 13-acetate to elicit a significant phosphorylation of PKCdelta, an appreciable association between PKCdelta and PKD, and a vigorous activation of PKD. As these cells also demonstrated an additional increase in LPL, our data imply that after diabetes, PKD control of LPL requires dissociation of Hsp25 from PKCdelta, association between PKCdelta and PKD, and vesicle fission. Results from this study could help in restricting cardiac LPL translocation, leading to strategies that overcome contractile dysfunction after diabetes.
ESTHER : Kim_2008_Circ.Res_103_252
PubMedSearch : Kim_2008_Circ.Res_103_252
PubMedID: 18583709

Title : [Immobilization of lipase by chemical modification of chitosan] - Hu_2007_Sheng.Wu.Gong.Cheng.Xue.Bao_23_667
Author(s) : Hu WJ , Tan TW , Wang F , Gao Y
Ref : Sheng Wu Gong Cheng Xue Bao , 23 :667 , 2007
Abstract : Lipase (EC3.1.1.3) from Candida sp. 99-125 was immobilized on chitosan by chemical covalence. Lipase was first immobilized to chitosan beads by activating its hydroxyl groups with carbodiimide followed by cross-linking more lipase to the amino groups with glutaraldehyde. In this article, different factors that influenced the immobilization were investigated, and the optimum conditions were ascertained. Comparative studies of organic solvent and thermal stability between free lipase and immobilized lipase were conducted. Immobilization enhanced the lipase stability against changes of temperature and organic solvent. Immobilization lipase can be reused in the synthesis system of palmitate hexadecyl. Operational stability tests indicated that the immobilized lipase occurs after 16 consecutive batches, the conversion rate remained 85%. Such results revealed good potential for recycling under esterification system.
ESTHER : Hu_2007_Sheng.Wu.Gong.Cheng.Xue.Bao_23_667
PubMedSearch : Hu_2007_Sheng.Wu.Gong.Cheng.Xue.Bao_23_667
PubMedID: 17822041

Title : Production of biodiesel by immobilized Candida sp. lipase at high water content - Tan_2006_Appl.Biochem.Biotechnol_128_109
Author(s) : Tan T , Nie K , Wang F
Ref : Appl Biochem Biotechnol , 128 :109 , 2006
Abstract : A new process for enzymatic synthesis of biodiesel at high water content (10-20%) with 96% conversion by lipase from Candida sp. 99-125 was studied. The lipase, a no-position-specific lipase, was immobilized by a cheap cotton membrane and the membrane-immobilized lipase could be used at least six times with high conversion. The immobilized lipase could be used for different oil conversion and preferred unsaturated fatty acids such as oleic acid to saturated fatty acids such as palmitic acid. The changes in concentration of fatty acids, diglycerides, and methyl esters in the reaction were studied and a mechanism of synthesis of biodiesel was suggested: the triglycerides are first enzymatically hydrolyzed into fatty acids, and then these fatty acids are further converted into methyl esters.
ESTHER : Tan_2006_Appl.Biochem.Biotechnol_128_109
PubMedSearch : Tan_2006_Appl.Biochem.Biotechnol_128_109
PubMedID: 16484720

Title : Vibralactone: a lipase inhibitor with an unusual fused beta-lactone produced by cultures of the basidiomycete Boreostereum vibrans - Liu_2006_Org.Lett_8_5749
Author(s) : Liu DZ , Wang F , Liao TG , Tang JG , Steglich W , Zhu HJ , Liu JK
Ref : Org Lett , 8 :5749 , 2006
Abstract : The structure and absolute configuration of vibralactone (1) from the cultures of the Basidiomycete Boreostereum vibrans were established by spectroscopic methods and computational methods. Vibralactone, an unusual fused beta-lactone-type metabolite, was found to inhibit pancreatic lipase with an IC50 of 0.4 microg/mL. [structure: see text]
ESTHER : Liu_2006_Org.Lett_8_5749
PubMedSearch : Liu_2006_Org.Lett_8_5749
PubMedID: 17134263

Title : Presynaptic glycine receptors on GABAergic terminals facilitate discharge of dopaminergic neurons in ventral tegmental area - Ye_2004_J.Neurosci_24_8961
Author(s) : Ye JH , Wang F , Krnjevic K , Wang W , Xiong ZG , Zhang J
Ref : Journal of Neuroscience , 24 :8961 , 2004
Abstract : GABA-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic (DA) neurons of the ventral tegmental area (VTA) of rats, in acute brain slices, and from enzymatically or mechanically dissociated neurons. In young rats (3-10 d of age), where GABA is excitatory, glycine (1-3 microm) and taurine (10-30 microm) increased the amplitude of evoked IPSCs (eIPSCs) and the frequency of spontaneous IPSCs (sIPSCs) but had minimal postsynaptic effects. Strychnine (1 microm) blocked the action of glycine; when applied alone, it reduced the amplitude of eIPSCs and the frequency of sIPSCs, indicating a tonic facilitation of GABAergic excitation by some endogenous glycine agonist(s). In medium containing no Ca2+, or with Cd2+ or tetrodotoxin added, the amplitude and especially the frequency of sIPSCs greatly diminished. In many cells, glycine had no effect on remaining miniature IPSCs, suggesting a preterminal site of glycine receptors (GlyRs). Fura-2 fluorescent imaging showed a glycine-induced increase of [Ca2+] in nerve terminals (on DA neurons), which was suppressed by strychnine or 3 microm omega-conotoxin MVIIA. Therefore, the presynaptic GlyR-mediated facilitation of GABAergic transmission seems to be mediated by N- and/or P/Q-type Ca2+ channels. In older rats (22-30 d of age), where GABA causes inhibition, the effect of strychnine on GABAergic IPSCs was reversed to facilitation, indicating a tonic glycinergic inhibition of GABA release. Furthermore, glycine (1-3 microm) reduced the amplitude of eIPSCs and the frequency of sIPSCs. Hence, the overall effect of the presynaptic action of glycine is to enhance the firing of DA cells, both in very young and older rats.
ESTHER : Ye_2004_J.Neurosci_24_8961
PubMedSearch : Ye_2004_J.Neurosci_24_8961
PubMedID: 15483115

Title : Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm - Wang_2004_World.J.Gastroenterol_10_550
Author(s) : Wang Z , Wang F , Wang WQ , Gao Q , Wei WL , Yang Y , Wang GY
Ref : World J Gastroenterol , 10 :550 , 2004
Abstract : AIM: To study the function of N-myc downstream-regulated gene 1 (NDRG1) in colorectal carcinogenesis and its correlation with tumor lymph node metastasis.
METHODS: NDRG1 was detected at its protein level by immunohistochemistry (IHC) and image analysis (IA), and NDRG1 mRNA was detected by in situ hybridization (ISH) in formalin-fixed and paraffin-embedded sections with a total of 190 specimens including 38 normal colorectal mucosae, 31 colorectal adenomas, 45 non-metastatic colorectal carcinomas (CRCs), 38 metastatic primary CRC and subsequently regional lymph nodes respectively. At the same time, the correlations of NDRG1 with sex, age of patients and histological types of colorectal carcinomas were observed.
RESULTS: NDRG1 proteins were gradually increased in colorectal carcinogenesis (P<0.05 or P<0.01). There was a significant difference in the expression of NDRG1 between non-metastatic and metastatic CRCs (P<0.05), and the correlation was positive (P<0.01, r(s)=0.329). However, there was no obvious difference in the expression of NDRG1 between the primary sites of CRCs and that in the metastatic sites of corresponding regional lymph nodes, nor was there an apparent difference in sex, age, and histological types. The expression of NDRG1 mRNA was generally in concordance with that of NDRG1 protein. CONCLUSION: NDRG1 gene may play an important role in colorectal carcinogenesis. In addition, NDRG1 may be a putative tumor metastasis promoter gene and is regarded as one of the molecular biological markers that can forecast early metastasis of CRCs. NDRG1 gene in the metastatic sites of regional lymph nodes may preserve its expression characteristics in the primary sites of CRCs to some extent. The expression of NDRG1 is not affected by sex, age and histological types. The role of NDRG1 in tumor metastatic process can be demonstrated by in vivo and in vitro.
ESTHER : Wang_2004_World.J.Gastroenterol_10_550
PubMedSearch : Wang_2004_World.J.Gastroenterol_10_550
PubMedID: 14966915
Gene_locus related to this paper: human-NDRG1

Title : Taurine activates strychnine-sensitive glycine receptors in neurons freshly isolated from nucleus accumbens of young rats - Jiang_2004_J.Neurophysiol_91_248
Author(s) : Jiang Z , Krnjevic K , Wang F , Ye JH
Ref : Journal of Neurophysiology , 91 :248 , 2004
Abstract : Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12- to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (IGly and ITau) with an EC50 of 0.12 and 1.25 mM, respectively. The reversal potential of IGly or ITau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations <1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC50 of 60 nM and 36.5 microM for IGly, and 40 nM and 42.2 microM for ITau) but were insensitive to 10 microM bicuculline. The currents elicited by taurine (< or =1 mM) showed complete cross-desensitization with IGly, but none with gamma-aminobutyric acid (GABA)-induced currents (IGABA). However, ITau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with IGABA, and it was substantially antagonized by 10 microM bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABAA receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.
ESTHER : Jiang_2004_J.Neurophysiol_91_248
PubMedSearch : Jiang_2004_J.Neurophysiol_91_248
PubMedID: 12878709

Title : Sequence of Plasmodium falciparum chromosome 12 - Hyman_2002_Nature_419_534
Author(s) : Hyman RW , Fung E , Conway A , Kurdi O , Mao J , Miranda M , Nakao B , Rowley D , Tamaki T , Wang F , Davis RW
Ref : Nature , 419 :534 , 2002
Abstract : The human malaria parasite Plasmodium falciparum is responsible for the death of more than a million people every year. To stimulate basic research on the disease, and to promote the development of effective drugs and vaccines against the parasite, the complete genome of P. falciparum clone 3D7 has been sequenced, using a chromosome-by-chromosome shotgun strategy. Here we report the nucleotide sequence of the third largest of the parasite's 14 chromosomes, chromosome 12, which comprises about 10% of the 23-megabase genome. As the most (A + T)-rich (80.6%) genome sequenced to date, the P. falciparum genome presented severe problems during the assembly of primary sequence reads. We discuss the methodology that yielded a finished and fully contiguous sequence for chromosome 12. The biological implications of the sequence data are more thoroughly discussed in an accompanying Article (ref. 3).
ESTHER : Hyman_2002_Nature_419_534
PubMedSearch : Hyman_2002_Nature_419_534
PubMedID: 12368869

Title : A clinical analysis of 104 cases of acute pure and mixed organophosphate poisoning - Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
Author(s) : Zhang J , Zhao J , Sun S , Ma H , Zhao C , Guo Z , Wang F
Ref : Zhonghua Nei Ke Za Zhi , 41 :544 , 2002
Abstract : OBJECTIVE To study the difference of the clinical manifestations between single and mixed acute organophosphate (OP) poisoning. METHODS: The clinical signs and symptoms, the activity of cholinesterase (ChE) in erythrocytes, plasma and whole blood, and the level of AST, CK, LDH and ALT were compared between a single OP poisoning group (Group S) and a mixed OP poisoning group (Group C). RESULTS: Group S and Group C compare with: (1) Symptoms and signs on arrival at hospital: Group C was found to have more cases showing, nausea and vomiting than group S with obvious difference (P < 0.05). (2) The rates of other symptoms and signs were of no significant difference between the 2 groups. The activity of cholinesterase of the 2 groups on arrival at hospital: Whole blood ChE < 0.30: 16 cases and 14 cases; > 0.30 approximately : 24 cases and 19 cases; 0.50 approximately 0.70: 14 cases and 17 cases; erythrocyte ChE < 0.30: 18 cases and 14 cases; > 0.30 approximately : 22 cases and 21 cases; 0.50 approximately 0.70: 14 cases and 15 cases; plasma ChE < 0.30: 28 cases and 25 cases; > 0.30 approximately : 10 cases and 12 cases; 0.50 approximately 0.70: 16 cases and 13 cases; chi(2) = 0.852, 1.444, 0.509. There was no obvious difference (P > 0.05). (3) Positive rates of serum biochemical parameters between the 2 groups within 72 hours after arrival at hospital: Group S AST 24 cases, ALT 18 cases, CK 42 cases, LDH 22 cases, Tbil 21 cases; Group C AST 20 cases, ALT 11 cases, CK 32 cases, LDH 18 cases, Tbil 17 cases. There was also no obvious difference (P > 0.05). (4) Positive rate of ECG: between the 2 group on arrival at hospital Group S 24 cases, Group C 19 cases. No obvious difference was shown (P > 0.05). (5) Fatality rates between the 2 groups: Group S 7.41% (4/54), Group C 6.00% (3/50), chi(2) = 0.082, P > 0.05. CONCLUSION: Acute mixed OP poisoning and single OP poisoning show no significant difference in clinical manifestations. The treatment measures for single OP poisoning also has good effect fo mixed OP poisoning.
ESTHER : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedSearch : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedID: 12421504

Title : Amacrine, ganglion, and displaced amacrine cells in the rabbit retina express nicotinic acetylcholine receptors - Keyser_2000_Vis.Neurosci_17_743
Author(s) : Keyser KT , MacNeil MA , Dmitrieva N , Wang F , Masland RH , Lindstrom JM
Ref : Vis Neurosci , 17 :743 , 2000
Abstract : Acetylcholine (ACh) in the vertebrate retina affects the response properties of many ganglion cells, including those that display directional selectivity. Three beta and eight alpha subunits of neuronal nicotinic acetylcholine receptors (nAChRs) have been purified and antibodies have been raised against many of them. Here we describe biochemical and immunocytochemical studies of nAChRs in the rabbit retina. Radioimmunoassay and Western blot analysis demonstrated that many of the nAChRs recognized by a monoclonal antibody (mAb210) contain beta2 subunits, some of which are in combination with alpha3 and possibly other subunits. MAb210-immunoreactive cells in the inner nuclear layer (INL) were 7-14 microm in diameter and were restricted to the innermost one or two tiers of cells, although occasional cells were found in the middle of the INL. At least 60% of the cells in the ganglion cell layer (GCL) in the visual streak displayed mAb210 immunoreactivity; these neurons ranged from 7-18 microm in diameter. The dendrites of cells in both the INL and GCL could sometimes be followed until they entered one of two dense, poorly defined, bands of processes in the inner plexiform layer (IPL) that overlap the arbors of the cholinergic starburst cells. Parvalbumin and serotonin-positive neurons did not exhibit nAChR immunoreactivity. Although the level of receptor expression appeared to be low, mAb210 immunoreactivity was observed in some of the ChAT-positive (starburst) amacrine cells.
ESTHER : Keyser_2000_Vis.Neurosci_17_743
PubMedSearch : Keyser_2000_Vis.Neurosci_17_743
PubMedID: 11153654

Title : Ion channel modulation as the basis for general anesthesia - Narahashi_1998_Toxicol.Lett_100-101_185
Author(s) : Narahashi T , Aistrup GL , Lindstrom JM , Marszalec W , Nagata K , Wang F , Yeh JZ
Ref : Toxicol Lett , 100-101 :185 , 1998
Abstract : (1) Modulation of the function of the GABA(A) and neuronal nicotinic acetylcholine receptor channels caused by general anesthetics and modulation of the GABA(A) receptor-channel by halothane, enflurane, isoflurane, and n-octanol was channel state-dependent. (3) Halothane modulation of the GABA(A) receptor was independent of subunits, but n-octanol modulation was subunit-dependent. (4) Ethanol at 30-100 microM was very potent in accelerating the desensitization of currents induced by acetylcholine. (5) The ethanol modulation was subunit- and state-dependent, occurring in the alpha3beta4 combination but only weakly in the alpha3beta2 combination. (6) In contrast, halothane at 430 microM (approximately 1 MAC) potently suppressed ACh-induced currents in the alpha3beta2 subunit combination.
ESTHER : Narahashi_1998_Toxicol.Lett_100-101_185
PubMedSearch : Narahashi_1998_Toxicol.Lett_100-101_185
PubMedID: 10049141

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

Title : Structure and function of neuronal nicotinic acetylcholine receptors -
Author(s) : Lindstrom JM , Anand R , Gerzanich V , Peng X , Wang F , Wells G
Ref : Prog Brain Res , 109 :125 , 1996
PubMedID: 9009699

Title : Rings of anionic amino acids as structural determinants of ion selectivity in the acetylcholine receptor channel - Konno_1991_Proc.Biol.Sci_244_69
Author(s) : Konno T , Busch C , Von Kitzing E , Imoto K , Wang F , Nakai J , Mishina M , Numa S , Sakmann B
Ref : Proc Biol Sci , 244 :69 , 1991
Abstract : To gain an insight into the molecular basis of the weak but significant selectivity among alkali metal cations of the nicotinic acetylcholine receptor (AChR) channel, we have determined single-channel conductance and permeability ratios for alkali metal cations on specifically mutated Torpedo californica AChR channels expressed in Xenopus oocytes. The mutations involved charged and polar side chains in the three anionic rings (extracellular, intermediate and cytoplasmic ring) which have previously been found to determine the rate of K+ transport through the AChR channel. The results obtained reveal that mutations in the intermediate ring exert much stronger effects on ion selectivity than do mutations in the extracellular and the cytoplasmic ring. The experimental results, together with simulations of the channel's energy profile, suggest that the amino acid residues forming the intermediate ring come into close contact with permeating cations and possibly represent part of the physical correlate of the postulated selectivity filter in the AChR channel.
ESTHER : Konno_1991_Proc.Biol.Sci_244_69
PubMedSearch : Konno_1991_Proc.Biol.Sci_244_69
PubMedID: 1679551

Title : A ring of uncharged polar amino acids as a component of channel constriction in the nicotinic acetylcholine receptor - Imoto_1991_FEBS.Lett_289_193
Author(s) : Imoto K , Konno T , Nakai J , Wang F , Mishina M , Numa S
Ref : FEBS Letters , 289 :193 , 1991
Abstract : The channel pore of the nicotinic acetylcholine receptor (AChR) has been investigated by analysing single-channel conductances of systematically mutated Torpedo receptors expressed in Xenopus oocytes. The mutations mainly alter the size and polarity of uncharged polar amino acid residues of the acetylcholine receptor subunits positioned between the cytoplasmic ring and the extracellular ring. From the results obtained, we conclude that a ring of uncharged polar residues comprising threonine 244 of the alpha-subunit (alpha T244), beta S250, gamma T253 and delta S258 (referred to as the central ring) and the anionic intermediate ring, which are adjacent to each other in the assumed alpha-helical configuration of the M2-containing transmembrane segment, together form a narrow channel constriction of short length, located close to the cytoplasmic side of the membrane. Our results also suggest that individual subunits, particularly the gamma-subunit, are asymmetrically positioned at the channel constriction.
ESTHER : Imoto_1991_FEBS.Lett_289_193
PubMedSearch : Imoto_1991_FEBS.Lett_289_193
PubMedID: 1717313