Li J

References (473)

Title : Integrating Enzymes with Supramolecular Polymers for Recyclable Photobiocatalytic Catalysis - Ouyang_2024_Angew.Chem.Int.Ed.Engl__e202400105
Author(s) : Ouyang J , Zhang Z , Li J , Wu C
Ref : Angew Chem Int Ed Engl , :e202400105 , 2024
Abstract : Chemical modifications of enzymes excel in the realm of enzyme engineering due to its directness, robustness, and efficiency; however, challenges persist in devising versatile and effective strategies. In this study, we introduce a supramolecular modification methodology that amalgamates a supramolecular polymer with Candida antarctica lipase B (CalB) to create supramolecular enzymes (SupEnzyme). This approach features the straightforward preparation of a supramolecular amphiphilic polymer (beta-CD@SMA), which was subsequently conjugated to the enzyme, resulting in a SupEnzyme capable of self-assembly into supramolecular nanoparticles. The resulting SupEnzyme nanoparticles can form micron-scale supramolecular aggregates via supramolecular and electrostatic interactions with guest entities, thus enhancing catalyst recycling. Remarkably, these aggregates maintain 80% activity after seven cycles, outperforming Novozym 435. Additionally, they can effectively initiate photobiocatalytic cascade reactions using guest photocatalysts. As a consequence, our SupEnzyme methodology exhibits noteworthy adaptability in enzyme modification, presenting a versatile platform for various polymer, enzyme, and biocompatible catalyst pairings, with potential applications in the fields of chemistry and biology.
ESTHER : Ouyang_2024_Angew.Chem.Int.Ed.Engl__e202400105
PubMedSearch : Ouyang_2024_Angew.Chem.Int.Ed.Engl__e202400105
PubMedID: 38386281

Title : Aquatic photolysis of high-risk fluorinated liquid crystal monomers: Kinetics, toxicity evaluation, and mechanisms - Wu_2024_Water.Res_255_121510
Author(s) : Wu J , Ye W , Feng Y , Lao W , Li J , Lu H , Liu G , Su G , Deng Y
Ref : Water Res , 255 :121510 , 2024
Abstract : Despite the frequent detection of fluorinated liquid-crystal monomers (FLCMs) in the environment, the level of understanding of their fate, toxicity, and transformation remains insufficient. Herein, we investigated the degradation kinetics and mechanism of an FLCM (4-cyano-3-fluorophenyl 4-ethylbenzoate, CEB-F) under ultraviolet (UV) photolysis in aquatic environment. Our findings demonstrated that the UV photolysis of CEB-F followed first-order kinetics. Photodegradation products were identified using liquid chromatography with mass spectrometry, and detailed reaction pathways were proposed. It is postulated that through the attack of reactive oxygen species, hydroxylation, and CO/C-F bond cleavage, CEB-F gradually degraded into small molecular compounds, releasing fluorine ions. Acute immobilization tests with Daphnia magna (D. magna) revealed significant acute toxicity of CEB-F, with LC(50) values ranging from 1.023 to 0.0536 microM over 24 to 96 h, emphasizing the potential high risk of FLCMs in aquatic ecosystems if inadvertently discharged. Interestingly, we found that the toxicity of CEB-F photolysis reaction solutions was effectively reduced. Through catalase and acetylcholinesterase activities analysis along with molecular docking simulation, we proposed differences in the underlying toxicity mechanisms of CEB-F and its photolysis products to D. magna. These findings highlight the potential harmful effects of FLCMs on aquatic ecosystems and enrich our understanding of the photolysis behavior of FLCMs.
ESTHER : Wu_2024_Water.Res_255_121510
PubMedSearch : Wu_2024_Water.Res_255_121510
PubMedID: 38555780

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

Title : Improved lipase performance by covalent immobilization of Candida antarctica lipase B on amino acid modified microcrystalline cellulose as green renewable support - Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
Author(s) : Li J , Shi X , Qin X , Liu M , Wang Q , Zhong J
Ref : Colloids Surf B Biointerfaces , 235 :113764 , 2024
Abstract : Development of immobilized lipase with excellent catalytic performance and low cost is the major challenge for large-scale industrial applications. In this study, green renewable microcrystalline cellulose (MCC) that was hydrophobically modified with D-alanine (Ala) or L-lysine (Lys) was used for immobilizing Candida antarctica lipase B (CALB). The improved catalytic properties were investigated by experimental and computational methods. CALB immobilized on MCC-Ala with higher hydrophobicity showed better catalytic activity than CALB@MCC-Lys because the increased flexibility of the lid region of CALB@MCC-Ala favored the formation of open conformation. Additionally, the low root mean square deviation and the high beta-sheet and alpha-helix contents of CALB@MCC-Ala indicated that the structure became more stable, leading to a significantly enhanced stability (54.80% and 90.90% relative activity at 70 degreesC and pH 9.0, respectively) and good reusability (48.92% activity after 5 cycles). This study provides a promising avenue to develop immobilized lipase with high catalytic properties for industry applications.
ESTHER : Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
PubMedSearch : Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
PubMedID: 38301428

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 : A MOF nanozyme-mediated acetylcholinesterase-free colorimetric strategy for direct detection of organophosphorus pesticides - Xiao_2024_Chem.Commun.(Camb)__
Author(s) : Xiao J , Shi F , Zhang Y , Peng M , Xu J , Li J , Chen Z , Yang Z
Ref : Chem Commun (Camb) , : , 2024
Abstract : Although some simple and rapid colorimetric methods have been developed to detect organophosphorus pesticides (OPs), the difficult extraction and easy denaturation of acetylcholinesterase (AChE) are still drawbacks needing to be overcome. Here, we propose a MOF nanozyme-mediated AChE-free colorimetric strategy for the direct detection of OPs. In the presence of OPs (pirimiphos-methyl as a model), the intense blue of oxidized 3,3',5,5'-tetramethylbenzidine (TMB) becomes light due to the quenching effect of OPs towards hydroxyl radicals (OH) that are generated by the decomposition of H(2)O(2) catalyzed by the Cu(4)Co(6) ZIF nanozyme with excellent peroxidase (POD)-like activity. The developed colorimetric sensor exhibits assay performance and offers a universal and promising analysis strategy for detecting OPs in practical samples.
ESTHER : Xiao_2024_Chem.Commun.(Camb)__
PubMedSearch : Xiao_2024_Chem.Commun.(Camb)__
PubMedID: 38168820

Title : LET-767 determines lipid droplet protein targeting and lipid homeostasis - Fu_2024_J.Cell.Biol_223_
Author(s) : Fu L , Zhang J , Wang Y , Wu H , Xu X , Li C , Li J , Liu J , Wang H , Jiang X , Li Z , He Y , Liu P , Wu Y , Zou X , Liang B
Ref : Journal of Cell Biology , 223 : , 2024
Abstract : Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.
ESTHER : Fu_2024_J.Cell.Biol_223_
PubMedSearch : Fu_2024_J.Cell.Biol_223_
PubMedID: 38551495

Title : Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review - Liu_2024_Expert.Opin.Drug.Metab.Toxicol__1
Author(s) : Liu Y , Li J , Zhu HJ
Ref : Expert Opin Drug Metab Toxicol , :1 , 2024
Abstract : INTRODUCTION: Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs. AREAS COVERED: This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024. EXPERT OPINION: Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.
ESTHER : Liu_2024_Expert.Opin.Drug.Metab.Toxicol__1
PubMedSearch : Liu_2024_Expert.Opin.Drug.Metab.Toxicol__1
PubMedID: 38706437

Title : Microneedle-mediated nose-to-brain drug delivery for improved Alzheimer's disease treatment - Ruan_2024_J.Control.Release__
Author(s) : Ruan S , Li J , Ruan H , Xia Q , Hou X , Wang Z , Guo T , Zhu C , Feng N , Zhang Y
Ref : J Control Release , : , 2024
Abstract : Conventional transnasal brain-targeted drug delivery strategies are limited by nasal cilia clearance and the nasal mucosal barrier. To address this challenge, we designed dissolving microneedles combined with nanocarriers for enhanced nose-to-brain drug delivery. To facilitate transnasal administration, a toothbrush-like microneedle patch was fabricated with hyaluronic acid-formed microneedles and tannic acid-crosslinked gelatin as the base, which completely dissolved in the nasal mucosa within seconds leaving only the base, thereby releasing the loaded cyclodextrin-based metal-organic frameworks (CD-MOFs) without affecting the nasal cilia and nasal microbial communities. As nanocarriers for high loading of huperzine A, these potassium-structured CD-MOFs, reinforced with stigmasterol and functionalized with lactoferrin, possessed improved physical stability and excellent biocompatibility, enabling efficient brain-targeted drug delivery. This delivery system substantially attenuated H(2)O(2)- and scopolamine-induced neurocyte damage. The efficacy of huperzine A on scopolamine- and D-galactose & AlCl(3)-induced memory deficits in rats was significantly improved, as evidenced by inhibiting acetylcholinesterase activity, alleviating oxidative stress damage in the brain, and improving learning function, meanwhile activating extracellular regulated protein kinases-cyclic AMP responsive element binding protein-brain derived neurotrophic factor pathway. Moreover, postsynaptic density protein PSD-95, which interacts with two important therapeutic targets Tau and beta-amyloid in Alzheimer's disease, was upregulated. This fruitful treatment was further shown to significantly ameliorate Tau hyperphosphorylation and decrease beta-amyloid by ways including modulating beta-site amyloid precursor protein cleaving enzyme 1 and a disintegrin and metalloproteinase 10. Collectively, such a newly developed strategy breaks the impasse for efficient drug delivery to the brain, and the potential therapeutic role of huperzine A for Alzheimer's disease is further illustrated.
ESTHER : Ruan_2024_J.Control.Release__
PubMedSearch : Ruan_2024_J.Control.Release__
PubMedID: 38219911

Title : Biotransformation of HBCDs by the microbial communities enriched from mangrove sediments - Yu_2024_J.Hazard.Mater_469_134036
Author(s) : Yu F , Zhang B , Liu Y , Luo W , Chen H , Gao J , Ye X , Li J , Xie Q , Peng T , Wang H , Huang T , Hu Z
Ref : J Hazard Mater , 469 :134036 , 2024
Abstract : 1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are a sort of persistent organic pollutants (POPs). This research investigated 12 microbial communities enriched from sediments of four mangroves in China to transform HBCDs. Six microbial communities gained high transformation rates (27.5-97.7%) after 12 generations of serial transfer. Bacteria were the main contributors to transform HBCDs rather than fungi. Analyses on the bacterial compositions and binning genomes showed that Alcanivorax (55.246-84.942%) harboring haloalkane dehalogenase genes dadAH and dadBH dominated the microbial communities with high transformation rates. Moreover, expressions of dadAH and dadBH in the microbial communities and Alcanivorax isolate could be induced by HBCDs. Further, it was found that purified proteins DadAH and DadBH showed high conversion rates on HBCDs in 36 h (91.9 +/- 7.4 and 101.0 +/- 1.8%, respectively). The engineered Escherichia coli BL21 strains harbored two genes could convert 5.7 +/- 0.4 and 35.1 +/- 0.1% HBCDs, respectively, lower than their cell-free crude extracts (61.2 +/- 5.2 and 56.5 +/- 8.7%, respectively). The diastereoisomer-specific transforming trend by both microbial communities and enzymes were gamma- > alpha- > beta-HBCD, differed from alpha- > beta- > gamma-HBCD by the Alcanivorax isolate. The identified transformation products indicated that HBCDs were dehalogenated via HBr elimination (dehydrobromination), hydrolytic and reductive debromination pathways in the enriched cultures. Two enzymes converted HBCDs via hydrolytic debromination. The present research provided theoretical bases for the biotransformation of HBCDs by microbial community and the bioremediation of HBCDs contamination in the environment.
ESTHER : Yu_2024_J.Hazard.Mater_469_134036
PubMedSearch : Yu_2024_J.Hazard.Mater_469_134036
PubMedID: 38493623

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

Title : Synthesis and evaluation of a highly selective cannabidiol amide cholinesterase inhibitor - Zhang_2024_Results.Chem_7_101492
Author(s) : Zhang R , Zhao M , Wang D , Zhao Y , Li J , Zhang S , Zhang W , Shi Z
Ref : Results in Chemistry , 7 :101492 , 2024
Abstract : The therapeutic mechanism for the treatment of Alzheimer's disease (AD) is mainly by inhibiting the activity of cholinesterase (ChE) and increasing the transmission of choline and the function of neurons. In this study, two series of ChE inhibitors (CA1CA8 and CB1CB7) were designed and synthesized by the acylation of a cannabinoid (CBD) with bromoacetyl bromide, or the esterification of a CBD with an amino acid. All the synthesized compounds were tested for in vitro activity to evaluate the compounds as AD therapies. Compound CB7 was identified as a potential butyrylcholinesterase (BuChE) inhibitor (IC50=0.310.09microM), which did not display toxicity against HepG2 or PC12 cells at 6.25microM. Compound CB7 showed good antioxidant behavior, effective anti-tyrosinase activity (IC50=0.0370.003microM), and anti-acetylcholinesterase (AChE) activity (IC50=19.730.79microM). Kinetic studies also showed that CB7 can act as a dual inhibitor. These results provide a theoretical basis for the use of the natural product CBD in the design and development of anti-AD drugs.
ESTHER : Zhang_2024_Results.Chem_7_101492
PubMedSearch : Zhang_2024_Results.Chem_7_101492

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : Alteration of the intestinal microbiota and serum metabolites in a mouse model of Pon1 gene ablation - Li_2024_Faseb.j_38_e23611
Author(s) : Li J , Yan K , Wang S , Wang P , Jiao J , Dong Y
Ref : Faseb j , 38 :e23611 , 2024
Abstract : Mutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.
ESTHER : Li_2024_Faseb.j_38_e23611
PubMedSearch : Li_2024_Faseb.j_38_e23611
PubMedID: 38597925

Title : 1,3-Dioleoyl-2-palmitoyl-glycerol and 1-oleoyl-2-palmitoyl-3-linoleoyl-glycerol: Structure-function relationship, triacylglycerols preparation, nutrition value - Wei_2024_Food.Chem_443_138560
Author(s) : Wei T , Mueed A , Luo T , Sun Y , Zhang B , Zheng L , Deng Z , Li J
Ref : Food Chem , 443 :138560 , 2024
Abstract : Based on multivariate statistics, this review compared major triacylglycerols (TAGs) in animal milk and human milk fat from China and other countries. Human milk fat differs from animal milk fat in that it has longer acyl chains and higher concentrations of 1,3-dioleoyl-2-palmitoyl-glycerol (O-P-O) and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (O-P-L). O-P-L is a significant and distinct TAG in human milk fat, particularly in China. 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) is human milk's major triglyceride molecule of O-P-L, accounting for more than 70%. As a result, OPL has piqued the interest of Chinese academics. The synthesis process and nutritional outcomes of OPL have been studied, including changes in gut microbiota, serum lipid composition, improved fatty acid and calcium absorption, and increased total bile acid levels. However, current OPL research is limited. Therefore, this review discussed enzymatic preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and OPL and their nutritional and physiological activity to direct future research direction for sn-2 palmitate and OPL.
ESTHER : Wei_2024_Food.Chem_443_138560
PubMedSearch : Wei_2024_Food.Chem_443_138560
PubMedID: 38295563

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Evaluation of antioxidant, antidiabetic and antiobesity potential of phenylpropanoids (PPs): Structure-activity relationship and insight into action mechanisms against dual digestive enzymes by comprehensive technologies - Li_2024_Bioorg.Chem_146_107290
Author(s) : Li J , Qin CF , Chen ND
Ref : Bioorg Chem , 146 :107290 , 2024
Abstract : Phenylpropanoids (PPs), a group of natural compounds characterized by one or more C6-C3 units, have exhibited considerable potential in addressing metabolic disease. However, the comprehensive investigation on the relationship of compound structures and involved activity, along with the action mechanisms on the drug target is absent. This study aimed to evaluate the antioxidant and inhibitory activities of 16 PPs against two digestive enzymes, including alpha-glucosidase and pancreatic lipase, explore the structure-activity relationships and elucidate the mechanisms underlying enzyme inhibition. The findings revealed the similarities in the rules governing antioxidant and enzyme inhibitory activities of PPs. Specifically, the introduction of hydroxyl groups generally exerted positive effects on the activities, while the further methoxylation and glycosylation were observed to be unfavorable. Among the studied PPs, esculetin exhibited the most potent antioxidant activity and dual enzymes inhibition potential, displaying IC(50) values of 0.017 and 0.0428 mM for DPPH and ABTS radicals scavenging, as well as 1.36 and 6.67 mM for alpha-glucosidase and lipase inhibition, respectively. Quantification analysis indicated esculetin bound on both alpha-glucosidase and lipase successfully by a mixed-type mode. Further analyses by UV-Vis, FT-IR, fluorescence spectra, surface hydrophobicity, SEM, and molecular docking elucidated that esculetin could bind on the catalytic or non-catalytic sites of enzymes to form complex, impacting the normal spatial conformation for hydrolyzing the substrate, thus exhibiting the weakened activity. These results may shed light on the utilization value of natural PPs for the management of hyperglycemia and hyperlipemia, and afford the theoretical basis for designing drugs with stronger inhibition against the dual digestive enzymes based on esculetin.
ESTHER : Li_2024_Bioorg.Chem_146_107290
PubMedSearch : Li_2024_Bioorg.Chem_146_107290
PubMedID: 38507999

Title : Extraction and characterization of polysaccharides from blackcurrant fruits and its inhibitory effects on acetylcholinesterase - Yang_2024_Int.J.Biol.Macromol_262_130047
Author(s) : Yang Y , Zou J , Li M , Yun Y , Li J , Bai J
Ref : Int J Biol Macromol , 262 :130047 , 2024
Abstract : Microwave assisted aqueous two-phase system (MA-ATPS) was used to simultaneously extract two polysaccharides from blackcurrant. Under the suitable ATPS (ethanol/(NH(4))(2)SO(4), 26.75 %/18.98 %) combining with the optimal MA conditions (liquid-to-material ratio 58.5 mL/g, time 9.5 min, temperature 60.5 degreesC, power 587 W) predicted by response surface methodology, the yields of the top/bottom phase polysaccharides were 13.08 +/- 0.37 % and 42.65 +/- 0.89 %, respectively. After purification through column chromatography, the top phase polysaccharide (PRTP) and bottom phase polysaccharide (PRBP) were obtained. FT-IR, methylation and NMR analyses confirmed that the repeating unit in the backbone of PRTP was 2, 5)-alpha-L-Araf-(1 3)-alpha-D-Manp-(1 6)-beta-D-Galp-(1 6)-alpha-D-Glcp-(1 4)-alpha-L-Rhap-(1 4)-alpha-D-GalAp-(1, while the possible unit in PRBP was 4)-alpha-L-Rhap-(1 3)-alpha-D-Manp-(1 6)-beta-D-Galp-(1 6)-alpha-D-Glcp-(1 2, 5)-alpha-L-Araf-(1 4)-alpha-D-GalAp-(1. PRBP with relatively low molecular weight exhibited better stability, rheological property, free radical scavenging and acetylcholinesterase (AChE) inhibitory activities than PRTP. PRTP and PRBP were reversible mixed-type inhibitors for AChE, and the conformation of AChE was changed after binding with the polysaccharides. Molecular docking, fluorescence and isothermal titration calorimetry assays revealed that PRTP and PRBP quenched the fluorescence through static quenching mechanism, and the van der Waals interactions and hydrogen bonding played key roles in the stability of polysaccharide-enzyme complexes. This study provided a theoretical basis for blackcurrant polysaccharides as AChE inhibitors to treat Alzheimer's disease.
ESTHER : Yang_2024_Int.J.Biol.Macromol_262_130047
PubMedSearch : Yang_2024_Int.J.Biol.Macromol_262_130047
PubMedID: 38336315

Title : Neuroprotective effects of dipeptidyl peptidase 4 inhibitor on Alzheimer's disease: a narrative review - Jiang_2024_Front.Pharmacol_15_1361651
Author(s) : Jiang X , Li J , Yao X , Ding H , Gu A , Zhou Z
Ref : Front Pharmacol , 15 :1361651 , 2024
Abstract : Insulin resistance in brain and amyloidogenesis are principal pathological features of diabetes-related cognitive decline and development of Alzheimer's disease (AD). A growing body of evidence suggests that maintaining glucose under control in diabetic patients is beneficial for preventing AD development. Dipeptidyl peptidase 4 inhibitors (DDP4is) are a class of novel glucose-lowering medications through increasing insulin excretion and decreasing glucagon levels that have shown neuroprotective potential in recent studies. This review consolidates extant evidence from earlier and new studies investigating the association between DPP4i use, AD, and other cognitive outcomes. Beyond DPP4i's benefits in alleviating insulin resistance and glucose-lowering, underlying mechanisms for the potential neuroprotection with DPP4i medications were categorized into the following sections: (Ferrari et al., Physiol Rev, 2021, 101, 1,047-1,081): the benefits of DPP4is on directly ameliorating the burden of beta-amyloid plaques and reducing the formation of neurofibrillary tangles; DPP4i increasing the bioactivity of neuroprotective DPP4 substrates including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and stromal-derived factor-1alpha (SDF-1alpha) etc.; pleiotropic effects of DPP4is on neuronal cells and intracerebral structure including anti-inflammation, anti-oxidation, and anti-apoptosis. We further revisited recently published epidemiological studies that provided supportive data to compliment preclinical evidence. Given that there remains a lack of completed randomized trials that aim at assessing the effect of DPP4is in preventing AD development and progression, this review is expected to provide a useful insight into DPP4 inhibition as a potential therapeutic target for AD prevention and treatment. The evidence is helpful for informing the rationales of future clinical research and guiding evidence-based clinical practice.
ESTHER : Jiang_2024_Front.Pharmacol_15_1361651
PubMedSearch : Jiang_2024_Front.Pharmacol_15_1361651
PubMedID: 38405664

Title : Determination of Acetylcholinesterase Activity Based on Ratiometric Fluorescence Signal Sensing - Zhao_2024_J.Fluoresc__
Author(s) : Zhao F , Guo H , Yang W , Guo L , Li J , Chen H
Ref : J Fluoresc , : , 2024
Abstract : Acetylcholinesterase (AChE) plays an important role in the treatment of human diseases, environmental security and global food supply. In this study, the simple fluorescent indicators and MnO(2) nanosheets were developed and integrated to establish a ratiometric fluorescence sensing system for the detection of AChE activity. Two fluorescence signals could be recorded independently at the same excitation wavelength, which extended the detection range and enhanced the visibility of results. Fluorescence of F-PDA was quenched by MnO(2) nanosheets on account of inner filtering effect. Meanwhile, the nonfluorescent OPD was catalytically oxidized to 2,3-diaminophenazine by MnO(2) nanosheets. The acetylcholine (ATCh) was catalytically hydrolyzed by AChE to enzymatic thiocholine, which decomposed MnO(2) to Mn(2+), recovered the fluorescence of F-PDA and reduced the emission of ox-OPD. Utilizing the fluorescence intensity ratio F(468)/F(558) as the signal readout, the ratiometric fluorescence method was established to detect AChE activity. Under the excitation wavelength of 410 nm, the ratio F(460)/F(558) against the AChE concentration demonstrated two linear relationships in the range 0.05 -1.0 and 1.0-50 U.L(- 1) with a limit of detection (LOD) of 0.073 U.L(- 1). The method was applied to the detection of AChE activity and the analysis of the inhibitor Huperzine-A. Due to the advantages of high sensitivity and favorable selectivity, the method possesses an application prospect in the activity deteceion of AChE and the screening of inhibitors.
ESTHER : Zhao_2024_J.Fluoresc__
PubMedSearch : Zhao_2024_J.Fluoresc__
PubMedID: 38613708

Title : Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430 - Wu_2024_J.Nat.Prod__
Author(s) : Wu Z , Wang W , Li J , Ma C , Chen L , Che Q , Zhang G , Zhu T , Li D
Ref : Journal of Natural Products , : , 2024
Abstract : Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster (sla) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key alpha,beta-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin (1), characterized by an N-acylated amino acid structure and demonstrating weak anti-Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.
ESTHER : Wu_2024_J.Nat.Prod__
PubMedSearch : Wu_2024_J.Nat.Prod__
PubMedID: 38447096

Title : Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis - Guo_2023_Mil.Med.Res_10_24
Author(s) : Guo LK , Su Y , Zhang YY , Yu H , Lu Z , Li WQ , Yang YF , Xiao X , Yan H , Lu TL , Li J , Liao YD , Kang ZW , Wang LF , Li Y , Li M , Liu B , Huang HL , Lv LX , Yao Y , Tan YL , Breen G , Everall I , Wang HX , Huang Z , Zhang D , Yue WH
Ref : Mil Med Res , 10 :24 , 2023
Abstract : BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R(2) for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R(2) = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R(2) = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( ), CAPEC-ChiCTR-RNC-09000522 ( ).
ESTHER : Guo_2023_Mil.Med.Res_10_24
PubMedSearch : Guo_2023_Mil.Med.Res_10_24
PubMedID: 37269009

Title : Visualization of production and remediation of acetaminophen-induced liver injury by a carboxylesterase-2 enzyme-activatable near-infrared fluorescent probe - Yang_2023_Talanta_269_125418
Author(s) : Yang B , Ding X , Zhang Z , Li J , Fan S , Lai J , Su R , Wang X , Wang B
Ref : Talanta , 269 :125418 , 2023
Abstract : Acetaminophen (APAP) overdose, also known as APAP poisoning, may directly result in hepatic injury, acute liver failure and even death. Nowadays, APAP-induced liver injury (AILI) has become an urgent public health issue in the developing world so the early accurate diagnosis and the revelation of underlying molecular mechanism of AILI are of great significance. As a major detoxifying organ, liver is responsible for metabolizing chemical substances, in which human carboxylesterase-2 (CES2) is present. Hence, we chose CES2 as an effective biomarker for evaluating AILI. By developing a CES2-activatable and water-soluble fluorescent probe PFQ-E with superior affinity (K(m) = 5.9 microM), great sensitivity (limit of detection = 1.05 ng/mL), near-infrared emission (655 nm) and large Stokes shift (135 nm), activity and distribution of CES2 in cells were determined or imaged effectively. More importantly, the APAP-induced hepatotoxicity and the underlying molecular mechanism of pathogenesis of AILI were investigated by measuring the "light-up" response of PFQ-E towards endogenous CES2 in vivo for the first time. Based on the superior performance of the probe PFQ-E for sensing CES2, we believe that it has broad potential in clinical diagnosis and therapy response evaluation of AILI.
ESTHER : Yang_2023_Talanta_269_125418
PubMedSearch : Yang_2023_Talanta_269_125418
PubMedID: 37988783

Title : Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies - Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
Author(s) : Liu Y , Sun S , Li J , Wang W , Zhu HJ
Ref : ACS Pharmacol Transl Sci , 6 :1340 , 2023
Abstract : The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that the activation of ProTide prodrugs varied in different cell lines. In the present study, we investigated the activation profiles of two antiviral prodrugs tenofovir alafenamide (TAF) and sofosbuvir (SOF) in five cell lines commonly used in antiviral research, namely, Vero E6, Huh-7, Calu-3, A549, and Caco-2. We found that TAF and SOF were activated in a cell-dependent manner with Vero E6 being the least efficient and Huh-7 being the most efficient cell line for activating the prodrugs. We also demonstrated that TAF was activated at a significantly higher rate than SOF. We further analyzed the protein expressions of the activating enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding protein 1, and the relevant drug transporters P-glycoprotein and organic anion-transporting polypeptides 1B1 and 1B3 in the cell lines using the proteomics data extracted from the literature and proteome database. The results revealed significant differences in the expression patterns of the enzymes and transporters among the cell lines, which might partially contribute to the observed cell-dependent activation of TAF and SOF. These findings highlight the variability of the abundance of activating enzymes and transporters between cell lines and emphasize the importance of selecting appropriate cell lines for assessing the antiviral efficacy of nucleoside/nucleotide prodrugs.
ESTHER : Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
PubMedSearch : Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
PubMedID: 37854623

Title : Molecular identification of carboxylesterase genes and their potential roles in the insecticides susceptibility of Grapholita molesta - Li_2023_Insect.Mol.Biol__
Author(s) : Li J , Jia Y , Zhang D , Li Z , Zhang S , Liu X
Ref : Insect Molecular Biology , : , 2023
Abstract : Grapholita molesta is one of the most damaging pests worldwide in stone and pome fruits. Application of chemical pesticides is still the main method to control this pest, and results in resistance to several types of insecticides. Carboxylesterase (CarE) is one kind of the important enzymes involved in the detoxification metabolism and tolerance of xenobiotics and insecticides. However, the roles of CarEs in insecticides susceptibility of G. molesta are still unclear. In the present study, the enzyme activity of CarEs and mRNA expression of six CarE genes were consistently elevated after treatment with three insecticides (emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole). According to spatio-temporal expression profiles, 6 CarE genes expressed differently in different developmental stages, and highly expressed in some detoxification metabolic organs. RNAi-mediated knockdown of these six CarE genes indicated that the susceptibility of G. molesta to all these three insecticides were obviously raised after GmCarE9, GmCarE14, GmCarE16, and GmCarE22 knockdown, respectively. Overall, these results demonstrated that GmCarE9, GmCarE14, GmCarE16, and GmCarE22 play a role in the susceptibility of G. molesta to emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole treatment. This study expands our understanding of CarEs in insects, that the same CarE gene could participate in the susceptibility of different insecticides. This article is protected by copyright. All rights reserved.
ESTHER : Li_2023_Insect.Mol.Biol__
PubMedSearch : Li_2023_Insect.Mol.Biol__
PubMedID: 36661850

Title : Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms - Liu_2023_Molecules_28_
Author(s) : Liu C , Zheng P , Wang H , Wei Y , Wang C , Hao S , Liu S , Chen W , Zhao Y , Zong Y , Li J , He Z
Ref : Molecules , 28 : , 2023
Abstract : Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.
ESTHER : Liu_2023_Molecules_28_
PubMedSearch : Liu_2023_Molecules_28_
PubMedID: 36677589 || 38067664

Title : Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93 - Li_2023_Front.Microbiol_13_1081094
Author(s) : Li Y , Rong Z , Li Z , Cui H , Li J , Xu XW
Ref : Front Microbiol , 13 :1081094 , 2023
Abstract : Introduction: CPT11 (Irinotecan; 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) is an important camptothecin-based broad-spectrum anticancer prodrug. The activation of its warhead, SN38 (7-ethyl-10-hydroxycamptothecin), requires hydrolysis by carboxylesterases. NPC (7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin) is a metabolic derivative of CPT11 and is difficult to be hydrolyzed by human carboxylesterase. Microbial carboxylesterase with capability on both CPT11 and NPC hydrolysis is rarely reported. A marine microbial carboxylesterase, E93, was identified to hydrolyze both substrates in this study. This enzyme was an appropriate subject for uncovering the catalytic mechanism of carboxylesterases to CPT11 and NPC hydrolysis. Methods: X-ray diffraction method was applied to obtain high-resolution structure of E93. Molecular docking was adopted to analyze the interaction of E93 with p -NP ( p -nitrophenyl), CPT11, and NPC substrates. Mutagenesis and enzymatic assay were adopted to verify the binding pattern of substrates. Results: Three core regions (Region A, B, and C) of the catalytic pocket were identified and their functions on substrates specificity were validated via mutagenesis assays. The Region A was involved in the binding with the alcohol group of all tested substrates. The size and hydrophobicity of the region determined the binding affinity. The Region B accommodated the acyl group of p -NP and CPT11 substrates. The polarity of this region determined the catalytic preference to both substrates. The Region C specifically accommodated the acyl group of NPC. The interaction from the acidic residue, E428, contributed to the binding of E93 with NPC. Discussion: The study analyzed both unique and conserved structures of the pocket in E93, for the first time demonstrating the discrepancy of substrate-enzyme interaction between CPT11 and NPC. It also expanded the knowledge about the substrate specificity and potential application of microbial Family VII carboxylesterases.
ESTHER : Li_2023_Front.Microbiol_13_1081094
PubMedSearch : Li_2023_Front.Microbiol_13_1081094
PubMedID: 36756200
Gene_locus related to this paper: 9sphn-E93

Title : Lycopodiastrum casuarinoides: An overview of their phytochemicals, biological activities, structure-activity relationship, biosynthetic pathway and (13)C NMR data - Liu_2023_Fitoterapia__105425
Author(s) : Liu Y , Wang Q , Xie Z , Zheng DK , Li J , Tan GS
Ref : Fitoterapia , :105425 , 2023
Abstract : Huperzine A, a lycodine-type alkaloid, exhibits potent inhibitory activity against acetylcholinesterase (AChE) and has been utilized to treat neurodegenerative diseases' symptoms. Lycopodiastrum casuarinoides, a member of the family Lycopodiaceae, is renowned for its lycodine-type alkaloids. Some of these alkaloids show various pharmacological benefits, such as anti-cholinesterase, neuroprotective, and cytotoxic effects. To date, 113 chemical compounds, including seventy-four lycodine-type alkaloids, ten terpenoids, eleven aliphatics, and eighteen other compounds, have been isolated from this plant. In this review, we have discussed phytochemicals and biological activities of the reported compounds of L. casuarinoides. Moreover, structure-activity relationship (SAR), plausible biosynthetic pathways, and (13)C nuclear magnetic resonance spectroscopy ((13)C NMR) data of the lycodine-type alkaloids are also summarized.
ESTHER : Liu_2023_Fitoterapia__105425
PubMedSearch : Liu_2023_Fitoterapia__105425
PubMedID: 36608712

Title : Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies - Fu_2023_J.Transl.Med_21_261
Author(s) : Fu W , Ge M , Li J
Ref : J Transl Med , 21 :261 , 2023
Abstract : BACKGROUND: Acute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms. METHODS: 10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot. RESULTS: Proteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis. CONCLUSIONS: Comprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis.
ESTHER : Fu_2023_J.Transl.Med_21_261
PubMedSearch : Fu_2023_J.Transl.Med_21_261
PubMedID: 37069596

Title : The miRNAs let-7b and miR-141 Coordinately Regulate Vitellogenesis by Modulating Methyl Farnesoate Degradation in the Swimming Crab Portunus trituberculatus - Yu_2023_Int.J.Mol.Sci_25_279
Author(s) : Yu X , Zhang M , Liu P , Li J , Gao B , Meng X
Ref : Int J Mol Sci , 25 : , 2023
Abstract : Methyl farnesoate (MF), a crucial sesquiterpenoid hormone, plays a pivotal role in the reproduction of female crustaceans, particularly in the vitellogenesis process. Despite extensive research on its functions, the molecular mechanisms that regulate MF levels during the vitellogenic phase remain largely elusive. This study investigates the roles of microRNAs (miRNAs), significant post-transcriptional regulators of gene expression, in controlling MF levels in the swimming crab Portunus trituberculatus. Through bioinformatic analysis, four miRNAs were identified as potential regulators targeting two genes encoding Carboxylesterases (CXEs), which are key enzymes in MF degradation. Dual luciferase reporter assays revealed that let-7b and miR-141 suppress CXE1 and CXE2 expression by directly binding to their 3' UTRs. In vivo overexpression of let-7b and miR-141 significantly diminished CXE1 and CXE2 levels, consequently elevating hemolymph MF and enhancing vitellogenin expression. Spatiotemporal expression profile analysis showed that these two miRNAs and their targets exhibited generally opposite patterns during ovarian development. These findings demonstrate that let-7b and miR-141 collaboratively modulate MF levels by targeting CXEs, thus influencing vitellogenesis in P. trituberculatus. Additionally, we found that the expression of let-7b and miR-141 were suppressed by MF, constituting a regulatory loop for the regulation of MF levels. The findings contribute novel insights into miRNA-mediated ovarian development regulation in crustaceans and offer valuable information for developing innovative reproduction manipulation techniques for P. trituberculatus.
ESTHER : Yu_2023_Int.J.Mol.Sci_25_279
PubMedSearch : Yu_2023_Int.J.Mol.Sci_25_279
PubMedID: 38203450
Gene_locus related to this paper: portr-a0a1i9kj57 , portr-a0a1i9ky23

Title : Visualizing Dipeptidyl Peptidase-IV with an Advanced Non--Conjugated Fluorescent Probe for Early Thyroid Disease Diagnosis - Li_2023_Anal.Chem_95_17577
Author(s) : Li J , Ma M , Xu L , Song D , Ma P , Fei Q
Ref : Analytical Chemistry , 95 :17577 , 2023
Abstract : Early detection and effective treatment of thyroid cancer are vital due to the aggressiveness and high mortality rate of the cancer. Nevertheless, the exploration of dipeptidyl peptidase-IV (DPP-IV) as a biomarker for thyroid diseases has not been widely conducted. In this study, we developed a novel non-Pi-conjugated near-infrared fluorescent probe, MB-DPP4, specifically designed to visualize and detect endogenous DPP-IV. Traditional DPP-IV-specific fluorescent probes rely primarily on the intramolecular charge transfer mechanism. For this reason, these probes are often hampered by high background levels that can inhibit their ability to achieve a fluorescence turn-on effect. MB-DPP4 successfully surmounts several drawbacks of traditional DPP-IV probes, boasting unique features such as exceptional selectivity, ultrahigh sensitivity (0.29 ng/mL), innovative structure, low background, and long-wavelength fluorescence. MB-DPP4 is an "off-on" chemosensor that exhibits strong fluorescence at 715 nm and releases a methylene blue (MB) fluorophore upon interacting with DPP-IV, resulting in a visible color change from colorless to blue. Given these remarkable attributes, MB-DPP4 shows great promise as a versatile tool for advancing research on biological processes and for evaluating the physiological roles of DPP-IV in living systems. Finally, we conducted a comprehensive investigation of DPP-IV expression in human serum, urine, thyroid cells, and mouse thyroid tumor models. Our findings could potentially establish a foundation for the early diagnosis and treatment of thyroid diseases.
ESTHER : Li_2023_Anal.Chem_95_17577
PubMedSearch : Li_2023_Anal.Chem_95_17577
PubMedID: 38050673

Title : PI3K-Akt signaling pathway based on network pharmacology for the anti-Alzheimer's disease effect of licorice stem flavonoids - Pei_2023_Aging.(Albany.NY)_15_
Author(s) : Pei H , He L , Shi M , Guo X , Chen W , Li J , He Z , Du R
Ref : Aging (Albany NY) , 15 : , 2023
Abstract : Active ingredients were screened by TCMSP and swissADME, meanwhile, PharmMapper combined with UniProt database was used to predict the active ingredient target information, GeneCard database was employed to obtain Alzheimer's disease (AD)-related genes, Cytoscapes 3.7.2 software was utilized to map the active ingredient-target effect. Besides, Cytoscapes 3.7.2 software Bisogenet and Cyto NCA plug-in combined with STRING platform were utilized to map the protein-protein interaction (PPI) network, DAVID was employed for GO annotation, while KEGG plug-in was used for KEGG pathway enrichment. Mice were tested for inflammatory damage induced by intracerebral injection of lipopolysaccharide (LPS), as well as learning memory and anxiety by water maze and open field tests. In addition, the expression of Caspase-3 and Caspase-9, together with inflammatory factors TNF-alpha, IL-6, and IL-1beta was analyzed in serum. The expression levels of proteins related to PI3K-Akt signaling pathway in the brain were detected by Western blot (WB) assay. According to the results of network pharmacology, there were 35 active ingredients of licorice stem and leaf flavonoids screened, which exerted the anti-Alzheimer's disease (AD) effects via 67 targets and activated 41 signaling pathways including the PI3K-Akt pathway. Furthermore, Behavioural results revealed that Licorice stem and leaf flavonoids improved the learning and memory abilities of model mice and significantly improved the anxiety caused by inflammatory brain damage. Moreover, as suggested by HE staining and TUNEL staining of brain sections, Glycyrrhiza glabra stem and leaf flavonoids alleviated morphological lesions and cell nuclear damage in brain tissue. Results: of brain homogenate supernatant assay demonstrated that Glycyrrhiza glabra stem and leaf flavonoids had a significant effect on the levels of oxidative indicators superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), acetylcholine (Ach), acetylcholinesterase (AchE), Caspase-3, Caspase-9 and serum inflammatory factors TNF-alpha, IL-6 and IL-1beta. Additionally, WB assay results indicated that the PI3K-Akt signaling pathway was activated.
ESTHER : Pei_2023_Aging.(Albany.NY)_15_
PubMedSearch : Pei_2023_Aging.(Albany.NY)_15_
PubMedID: 37166431

Title : Maize resistance to witchweed through changes in strigolactone biosynthesis - Li_2023_Science_379_94
Author(s) : Li C , Dong L , Durairaj J , Guan JC , Yoshimura M , Quinodoz P , Horber R , Gaus K , Li J , Setotaw YB , Qi J , De Groote H , Wang Y , Thiombiano B , Flokova K , Walmsley A , Charnikhova TV , Chojnacka A , Correia de Lemos S , Ding Y , Skibbe D , Hermann K , Screpanti C , De Mesmaeker A , Schmelz EA , Menkir A , Medema M , van Dijk ADJ , Wu J , Koch KE , Bouwmeester HJ
Ref : Science , 379 :94 , 2023
Abstract : Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga-resistant maize.
ESTHER : Li_2023_Science_379_94
PubMedSearch : Li_2023_Science_379_94
PubMedID: 36603079

Title : Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta - Li_2023_Front.Plant.Sci_14_1074184
Author(s) : Li J , Li F , Wu G , Gui F , Li H , Xu L , Hao X , Zhao Y , Ding X , Qin X
Ref : Front Plant Sci , 14 :1074184 , 2023
Abstract : Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3-8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 +/- 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.
ESTHER : Li_2023_Front.Plant.Sci_14_1074184
PubMedSearch : Li_2023_Front.Plant.Sci_14_1074184
PubMedID: 36844064

Title : Nickel Single-Atom Catalyst-Mediated Efficient Redox Cycle Enables Self-Checking Photoelectrochemical Biosensing with Dual Photocurrent Readouts - Tan_2023_ACS.Sens__
Author(s) : Tan R , Qin Y , Liu M , Wang H , Li J , Luo Z , Hu L , Gu W , Zhu C
Ref : ACS Sens , : , 2023
Abstract : Developing a self-checking photoelectrochemical biosensor with dual photocurrent signals could efficiently eliminate false-positive or false-negative signals. Herein, a novel biosensor with dual photocurrent responses was established for the detection of acetylcholinesterase activity. To achieve photocurrent polarity-switchable behavior, the iodide/tri-iodide redox couple was innovatively introduced to simultaneously consume the photoexcited electrons and holes, which circumvents the inconvenience caused by the addition of different hole- and electron-trapping agents in the electrolyte. Importantly, benefiting from the high catalytic activity, the enhanced photoelectric responsivity can be realized after decorating the counter electrode with nickel single-atom catalysts, which promotes a more efficient iodide/tri-iodide redox reaction under low applied voltages. It is envisioned that the proposed photocurrent polarity switching system offers new routes to sensitive and reliable biosensing.
ESTHER : Tan_2023_ACS.Sens__
PubMedSearch : Tan_2023_ACS.Sens__
PubMedID: 36624088

Title : Insecticidal Effect of the Entomopathogenic Fungus Lecanicillium araneicola HK-1 in Aphis craccivora (Hemiptera: Aphididae) - Liu_2023_Insects_14_
Author(s) : Liu S , Li J , Feng Q , Chu L , Tan Z , Ji X , Jin P
Ref : Insects , 14 : , 2023
Abstract : Aphis craccivora (Hemiptera: Aphididae) is an important pest affecting various crops worldwide. However, only few studies have been conducted on the infection of A. craccivora by Lecanicillium and related insecticidal mechanisms. We investigated the infection process of A. craccivora by Lecanicillium araneicola HK-1 using fluorescence microscopy and scanning electron microscopy (SEM), and our results indicated that the conidia of strain HK-1 easily attached to the feet and dorsum of A. craccivora. The activities of chitinase and extracellular protease were induced in the aphid after treatment with HK-1. A bioassay on A. craccivora showed that the median lethal concentration (LC(50)) of the fungus crude extract was 24.00 mg mL(-1) for 24 h of treatment. Additionally, the results showed that the crude extract disrupted the enzyme system of A. craccivora, inducing the inhibition of carboxylesterase (CarE) and the induction of glutathione S-transferase (GST) and acetylcholinesterase (AChE). Combining these results with those of a gas chromatography-mass spectrometry (GC-MS) analysis, it is suggested that p-cymene, hymecromone, 9,12-octadecadienoic acid (Z, Z) methyl ester, and 9,12-octadecadienoic acid (Z, Z) may be connected to the insecticidal effects we observed. This study provides a theoretical basis for the use of L. araneicola HK-1 as a potential biological control agent.
ESTHER : Liu_2023_Insects_14_
PubMedSearch : Liu_2023_Insects_14_
PubMedID: 37999059

Title : Novel Sophoridine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, Acetylcholinesterase Inhibition, and Morphological Study - Ang_2023_Insects_14_
Author(s) : Ang S , Cao N , Zheng W , Zhang Z , Li J , Yan Z , Su K , Wong WL , Zhang K , Hong WD , Wu P
Ref : Insects , 14 : , 2023
Abstract : Two series of novel sophoridine derivatives were designed, synthesized, and evaluated for their anti-mosquito activity. SOP-2g, SOP-2q, and SOP-2r exhibited potential larvicidal activity against Aedes albopictus larva with LC(50) values of 330.98, 430.53, and 411.09 ppm, respectively. Analysis of structure-activity relationships indicated that the oxime ester group was beneficial for improving the larvicidal biological activity, whereas the long-chain aliphatic group and fused-ring group were introduced. Furthermore, the larvicidal mechanism was also investigated based on the inhibition assay of acetylcholinesterase (AChE) and the morphological observation of dead larva treated with derivatives. Results indicated that the AChE inhibitory activity of the preferred three derivatives were 63.16%, 46.67%, and 35.11%, respectively, at 250 ppm concentration. Additionally, morphological evidence demonstrated that SOP-2q and SOP-2r induced changes in the larva's intestinal cavity, caudal gill, and tail, thereby displaying larvicidal action against Ae. albopictus together with AChE inhibition. Therefore, this study implied that sophoridine and its novel derivatives could be used to control the population of mosquito larva, which may also be effective alkaloids to reduce the mosquito population density.
ESTHER : Ang_2023_Insects_14_
PubMedSearch : Ang_2023_Insects_14_
PubMedID: 37103214

Title : Customized fluorescent probe for peering into the expression of butyrylcholinesterase in thyroid cancer - Kang_2023_Anal.Chim.Acta_1282_341932
Author(s) : Kang W , Ma M , Xu L , Tang S , Li J , Ma P , Song D , Sun Y
Ref : Anal Chim Acta , 1282 :341932 , 2023
Abstract : BACKGROUND: Thyroid cancer has been increasingly prevalent in recent years. The main diagnostic methods for thyroid are B-ultrasound scan, serum detection and puncture detection. However, these methods are invasive and complex. It is a pressing need to develop non-invasive or minimally invasive methods for thyroid cancer diagnosis. Fluorescence method as a non-invasive detection method has attracted much attention. Butyrylcholinesterase (BChE) is a common enzyme in the human body, and many diseases affect its reduction. We found that BChE is also a marker for thyroid cancer. Therefore, it is of certain clinical value to explore the expression of BChE in thyroid cancer cells through a customized fluorescent probe to provide valuable experimental data and clues for studying the expression of thyroid cancer marker to reflect thyroid status. RESULTS: In this study, we customized a fluorescent probe named Kang-BChE, which is easy to synthesize with a high yield. The experimental results show that the probe Kang-BChE can detect BChE in the linear range of 0-900 U L(-1) (R(2) = 0.9963), and the detection limit is as low as 3.93 U L(-1) (lambda(ex/em) = 550/689 nm). In addition, Kang-BChE probes have low cytotoxicity, good specificity, and can completely eliminate interference from acetylcholinesterase (AChE). Kang-BChE showed excellent stability in the detection of complex biological samples in serum recovery experiments (95.64-103.12 %). This study was the first time using Kang-BChE to study the low expression of BChE in thyroid cancer cells (Tpc-1 cells). In addition, we observed that H(2)O(2) concentration in Tpc-1 cells was positively correlated with BChE activity. SIGNIFICANCE: Kang-BChE is expected to be an important tool for monitoring the change of BChE content in complex biological environments due to its excellent performance. Kang-BChE can also be used to explore the influence of molecules in more organisms on the change of BChE content due to its excellent anti-interference ability. We expect that Kang-BChE can play a significant role in the clinical diagnosis and treatment of thyroid cancer.
ESTHER : Kang_2023_Anal.Chim.Acta_1282_341932
PubMedSearch : Kang_2023_Anal.Chim.Acta_1282_341932
PubMedID: 37923409

Title : Strategy of In Situ Electrochemical Regulation for Highly Enhanced Nonenzymatic Sensing of Carbaryl - Lv_2023_Anal.Chem__
Author(s) : Lv Y , Zhang Y , Yang Y , Li J , Wang J , Xiao X , Zhang M
Ref : Analytical Chemistry , : , 2023
Abstract : Specific and sensitive sensing of most pesticide residues relies on enzymes such as acetylcholinesterase and advanced materials, which need to be loaded on the surface of working electrodes, leading to instability, uneven surface, tedious process, and high cost. Meanwhile, employing certain potential or current in electrolyte solution could also modify the surface in situ and overcome these drawbacks. However, this method is only regarded as electrochemical activation widely applied in the pretreatment of electrodes. In this paper, by means of regulating the electrochemical technique and its parameters, we prepared a proper sensing interface and derivatized the carbaryl (a carbamate pesticide) hydrolyzed form (1-naphthol) to enhance sensing by 100 times within several minutes. After regulation I by chronopotentiometry with 0.2 mA for 20 s or chronoamperometry with 2 V for 10 s, abundant oxygen-containing groups form and the ordered carbon structure is destroyed. Sweeping from -0.5 to 0.9 V through cyclic voltammetry for only one segment, following regulation II, the composition of oxygen-containing groups changes and the disordered structure is alleviated. Finally, on the constructed sensing interface, test by regulation III through differential pulse voltammetry from 0.8 to -0.4 V, resulting in derivatization of 1-naphthol during 0.8-0 V, followed by electroreduction of the derivative at around -0.17 V. Compared with the electro-oxidation peak at 0.5 V in previous reports, it is essential to improve specificity, even toward several other carbamate pesticides with similar structures. Hence, the in situ electrochemical regulation strategy has demonstrated great potential for effective sensing of electroactive molecules.
ESTHER : Lv_2023_Anal.Chem__
PubMedSearch : Lv_2023_Anal.Chem__
PubMedID: 36802553

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : An overview of microbial enzymatic approaches for pectin degradation - Li_2023_Int.J.Biol.Macromol_254_127804
Author(s) : Li J , Peng C , Mao A , Zhong M , Hu Z
Ref : Int J Biol Macromol , 254 :127804 , 2023
Abstract : Pectin, a complex natural macromolecule present in primary cell walls, exhibits high structural diversity. Pectin is composed of a main chain, which contains a high amount of partly methyl-esterified galacturonic acid (GalA), and numerous types of side chains that contain almost 17 different monosaccharides and over 20 different linkages. Due to this peculiar structure, pectin exhibits special physicochemical properties and a variety of bioactivities. For example, pectin exhibits strong bioactivity only in a low molecular weight range. Many different degrading enzymes, including hydrolases, lyases and esterases, are needed to depolymerize pectin due to its structural complexity. Pectin degradation involves polygalacturonases/rhamnogalacturonases and pectate/pectin lyases, which attack the linkages in the backbone via hydrolytic and beta-elimination modes, respectively. Pectin methyl/acetyl esterases involved in the de-esterification of pectin also play crucial roles. Many alpha-L-rhamnohydrolases, unsaturated rhamnogalacturonyl hydrolases, arabinanases and galactanases also contribute to heterogeneous pectin degradation. Although numerous microbial pectin-degrading enzymes have been described, the mechanisms involved in the coordinated degradation of pectin through these enzymes remain unclear. In recent years, the degradation of pectin by Bacteroides has received increasing attention, as Bacteroides species contain a unique genetic structure, polysaccharide utilization loci (PULs). The specific PULs of pectin degradation in Bacteroides species are a new field to study pectin metabolism in gut microbiota. This paper reviews the scientific information available on pectin structural characteristics, pectin-degrading enzymes, and PULs for the specific degradation of pectin.
ESTHER : Li_2023_Int.J.Biol.Macromol_254_127804
PubMedSearch : Li_2023_Int.J.Biol.Macromol_254_127804
PubMedID: 37913880

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 : 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 : Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities - Zang_2023_Eur.J.Med.Chem_265_116070
Author(s) : Zang WB , Wei HL , Zhang WW , Ma W , Li J , Yao Y
Ref : Eur Journal of Medicinal Chemistry , 265 :116070 , 2023
Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. Contemporary treatments can only relieve symptoms but fail to delay disease progression. Curcumin is a naturally derived compound that has demonstrated significant therapeutic effects in AD treatment. Recently, molecular hybridization has been utilized to combine the pharmacophoric groups present in curcumin with those of other AD drugs, resulting in a series of novel compounds that enhance the therapeutic efficacy through multiple mechanisms. In this review, we firstly provide a concise summary of various pathogenetic hypotheses of AD and the mechanism of action of curcumin in AD, as well as the concept of molecular hybridization. Subsequently, we focus on the recent development of hybrid molecules derived from curcumin, summarizing their structures and pharmacological activities, including cholinesterase inhibitory activity, Abeta aggregation inhibitory activity, antioxidant activity, and other activities. The structure-activity relationships were further discussed.
ESTHER : Zang_2023_Eur.J.Med.Chem_265_116070
PubMedSearch : Zang_2023_Eur.J.Med.Chem_265_116070
PubMedID: 38134747

Title : A molecular imaging tool for monitoring carboxylesterase 2 during early diagnosis of liver-related diseases - Li_2023_Sens.Actuators.B.Chem_377_133122
Author(s) : Li J , Cao J , Wu W , Xu L , Zhang S , Ma P , Wu Q , Song D
Ref : Sensors and Actuators B: Chemical , 377 :133122 , 2023
Abstract : Early disease diagnosis is crucial for human health and successful therapy. Carboxylesterase 2 (CES2), the main enzyme found in many tumor tissues, is closely associated with many malignant diseases. Therefore, the ability to detect endogenous CES2-associated diseases can be of therapeutic significance. In this study, we designed a novel mitochondria-targeting near-infrared (NIR) chemosensor (YDT) to visualize the endogenous CES2. This is the first study to track CES2 at the mitochondrial level and present the currently most sensitive CES2 detection sensor. With various features including large Stokes shift, quick response time, excellent selectivity, and ultrahigh sensitivity, the sensor can overcome numerous limitations faced by traditional CES2 probes. YDT is an "off-on" chemosensor that releases fluorophore YD-1 upon interacting with CES2, emits strong fluorescence at 660 nm. Importantly, YDT can dynamically monitor immediate changes in CES2 level under external stimuli. Moreover, we used YDT to systematically study the CES2 expression in drug-induced liver injury and its remediation model, as well as in an inflammation model. With these outstanding characteristics, YDT is a considerably promising tool for further research on biological processes and for examining the physiological roles of CES2 in living systems
ESTHER : Li_2023_Sens.Actuators.B.Chem_377_133122
PubMedSearch : Li_2023_Sens.Actuators.B.Chem_377_133122
Gene_locus related to this paper: human-CES2

Title : Comprehensive in-silico analysis of deleterious SNPs in APOC2 and APOA5 and their differential expression in cancer and cardiovascular diseases conditions - Deng_2023_Genomics_115_110567
Author(s) : Deng H , Li J , Shah AA , Ge L , Ouyang W
Ref : Genomics , 115 :110567 , 2023
Abstract : Genetic variations in APOC2 and APOA5 genes involve activating lipoprotein lipase (LPL), responsible for the hydrolysis of triglycerides (TG) in blood and whose impaired functions affect the TG metabolism and are associated with metabolic diseases. In this study, we investigate the biological significance of genetic variations at the DNA sequence and structural level using various computational tools. Subsequently, 8 (APOC2) and 17 (APOA5) non-synonymous SNPs (nsSNPs) were identified as high-confidence deleterious SNPs based on the effects of the mutations on protein conservation, stability, and solvent accessibility. Furthermore, based on our docking results, the interaction of native and mutant forms of the corresponding proteins with LPL depicts differences in root mean square deviation (RMSD), and binding affinities suggest that these mutations may affect their function. Furthermore, in vivo, and in vitro studies have shown that differential expression of these genes in disease conditions due to the influence of nsSNPs abundance may be associated with promoting the development of cancer and cardiovascular diseases. Preliminary screening using computational methods can be a helpful start in understanding the effects of mutations in APOC2 and APOA5 on lipid metabolism; however, further wet-lab experiments would further strengthen the conclusions drawn from the computational study.
ESTHER : Deng_2023_Genomics_115_110567
PubMedSearch : Deng_2023_Genomics_115_110567
PubMedID: 36690263

Title : Genome-wide identification and analysis of the SUPPRESSOR of MAX2 1-LIKE gene family and its interaction with DWARF14 in poplar - Sun_2023_BMC.Plant.Biol_23_105
Author(s) : Sun M , Wang D , Liu C , Liu Y , Niu M , Wang J , Li J
Ref : BMC Plant Biol , 23 :105 , 2023
Abstract : BACKGROUND: Strigolactones (SLs) are important phytohormones that can regulate branch development in plants. Although SUPPRESSOR of MAX2 1-LIKE proteins (SMXLs) play a crucial role in SL signaling transduction, the SMXL gene family has not been well characterized in poplar. RESULTS: In this study, 12 members of the poplar SMXL gene family were identified and phylogenetically classified into four clades. Motif and 3D structural analyses revealed that PtSMXL proteins are structurally very conserved; however, the P-loop NTPase domain at the C-terminal was found to vary substantially among clades. A genomic collinearity analysis indicated that PtSMXL gene family members have expanded during recent genome doubling events in poplar, with all gene pairs subsequently undergoing purifying selection. According to a Cis-element analysis, PtSMXL promoters contain many light-responsive elements. In an expression pattern analysis, all 12 PtSMXL genes displayed tissue-specific expression, especially PtSMXL8a. PtSMXL7b expression was significantly downregulated after axillary bud growth begins. In addition, the expressions of PtSMXL7b and PtSMXL8a were highly induced by 2 microM GR24, a synthetic SL analog, thus suggesting that these genes are involved in SL-regulated axillary bud growth. In a yeast two-hybrid assay, only PtSMXL7b in clade II was able to interact with the SL receptor PtD14a in an SL dependent manner, which indicates that PtSMXL7b may be the functional homolog of D53/SMXL6/7/8 in poplar. Finally, we established its ability to affect axillary bud growth by constructing poplar overexpressing the PtSMXL7b gene. CONCLUSIONS: Our findings may inform future research on the functions of SMXLs in poplar, especially with respect to branch development.
ESTHER : Sun_2023_BMC.Plant.Biol_23_105
PubMedSearch : Sun_2023_BMC.Plant.Biol_23_105
PubMedID: 36814183

Title : Effect of the sEH inhibitor AUDA on arachidonic acid metabolism and NF-B signaling of rats with postpartum depression-like behavior - Duan_2023_J.Neuroimmunol_385_578250
Author(s) : Duan L , Song L , Qiu C , Li J
Ref : Journal of Neuroimmunology , 385 :578250 , 2023
Abstract : OBJECTIVE: To investigate whether sEH inhibitor AUDA can mitigate postpartum depression (PPD)-like symptoms in the rat model and regulate the AA/NF-kappaB pathway to suppress the inflammatory response in the prefrontal lobes of PPD rats. METHODS: Five groups of Sprague Dawley rats were used: normal, sham operated, PPD model, AUDA, and paroxetine hydrochloride. During the 21-day treatment period, animals in all groups underwent assessments (open field test, forced swimming test, and sucrose consumption) for depression-like behavior. At the conclusion of the treatment period, animals in all study groups were euthanized and various proteins in the prefrontal lobes were measured. RESULTS: Depression-like behavior in rats was attenuated by AUDA. In the prefrontal lobes of PPD rats, levels of 5-LOX, COX-2, sEH, IL-1beta, IL- 6, p65, p-p65, P-IkappaBalpha, NF-kappaB p65, and GFAP were increased while levels of epoxyeicosatrienoic acids and 5-HT were decreased. AUDA reversed these changes, thus having a similar effect as the classic antidepressant paroxetine hydrochloride. CONCLUSION: AUDA may constrain AA/NF-kappaB in the prefrontal cortex of PPD rats, thus inhibiting the inflammatory response and ultimately attenuating postpartum depression-like behavior.
ESTHER : Duan_2023_J.Neuroimmunol_385_578250
PubMedSearch : Duan_2023_J.Neuroimmunol_385_578250
PubMedID: 38029646

Title : Alveolar macrophage-derived gVPLA2 promotes ventilator-induced lung injury via the cPLA2\/PGE2 pathway - Han_2023_BMC.Pulm.Med_23_494
Author(s) : Han H , Xie Q , Shao R , Li J , Du X
Ref : BMC Pulm Med , 23 :494 , 2023
Abstract : BACKGROUND: Ventilator-induced lung injury (VILI) is a clinical complication of mechanical ventilation observed in patients with acute respiratory distress syndrome. It is characterized by inflammation mediated by inflammatory cells and their secreted mediators. METHODS: To investigate the mechanisms underlying VILI, a C57BL/6J mouse model was induced using high tidal volume (HTV) mechanical ventilation. Mice were pretreated with Clodronate liposomes to deplete alveolar macrophages or administered normal bone marrow-derived macrophages or Group V phospholipase A2 (gVPLA2) intratracheally to inhibit bone marrow-derived macrophages. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to assess lung injury and measure Ca2+ concentration, gVPLA2, downstream phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), prostaglandin E2 (PGE2), protein expression related to mitochondrial dynamics and mitochondrial damage. Cellular experiments were performed to complement the animal studies. RESULTS: Depletion of alveolar macrophages attenuated HTV-induced lung injury and reduced gVPLA2 levels in alveolar lavage fluid. Similarly, inhibition of alveolar macrophage-derived gVPLA2 had a similar effect. Activation of the cPLA2/PGE2/Ca2 + pathway in alveolar epithelial cells by gVPLA2 derived from alveolar macrophages led to disturbances in mitochondrial dynamics and mitochondrial dysfunction. The findings from cellular experiments were consistent with those of animal experiments. CONCLUSIONS: HTV mechanical ventilation induces the secretion of gVPLA2 by alveolar macrophages, which activates the cPLA2/PGE2/Ca2 + pathway, resulting in mitochondrial dysfunction. These findings provide insights into the pathogenesis of VILI and may contribute to the development of therapeutic strategies for preventing or treating VILI.
ESTHER : Han_2023_BMC.Pulm.Med_23_494
PubMedSearch : Han_2023_BMC.Pulm.Med_23_494
PubMedID: 38057837

Title : Nanoclusterzyme for Dual Colorimetric Sensings: A Case Study on [Au(14) (Dppp)(5) I(4) ](2) - Zhao_2023_Small__e2207936
Author(s) : Zhao H , You Q , Zhu W , Li J , Deng H , Li MB , Zhao Y , Wu Z
Ref : Small , :e2207936 , 2023
Abstract : The enzymatic activity of atomically precise metal nanoclusters has recently been recognized; however, the number of nanoclusterzymes is very small. Besides, the applications of nanoclusterzyme wait to be explored. Herein, a novel nanoclusterzyme is synthesized and its structure is majorly resolved by single-crystal X-ray diffraction and mass spectrometry, which reveal that the nanocluster consists of an Au(13) icosahedron capped by an exterior shell including four I, three Dppp (1,3-bis(diphenylphosphino) propane) ligands, and a rarely reported Dppp-Au-Dppp handle staple, which contributes a lot to the enzyme activity of [Au(14) (Dppp)(5) I(4) ](2+) nanocluster. The as-obtained nanocluster can catalyze oxygen to O(2) (-) under visible light irradiation with a specific activity up to 0.182 and lead to the blue color of 3,3',5,5'-tetramethylbenzidine (TMB) in both solution and solid states. With the addition of acetylcholinesterase (AChE), the blue color of (Au(14) + TMB) solution system disappears due to the nanoclusterzyme activity inhibition, but the further addition of organophosphorus pesticides (OPs) into the above mixture can restore the nanoclusterzyme and recover the blue color. Based on the color turn-off and on, the various nanoclusterzyme-containing systems are used to colorimetrically sense AChE and OPs with the detection limits reaching 0.04 mU.mL(-1) and 0.02 ng.mL(-1) , respectively.
ESTHER : Zhao_2023_Small__e2207936
PubMedSearch : Zhao_2023_Small__e2207936
PubMedID: 37060229

Title : Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase\/monoamine oxidase B inhibitors - Hu_2023_Future.Med.Chem__
Author(s) : Hu Z , Zhou S , Li J , Li X , Zhou Y , Zhu Z , Xu J , Liu J
Ref : Future Med Chem , : , 2023
Abstract : Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC(50) = 0.054 +/- 0.004 microM; MAO-B: IC(50) = 3.25 +/- 0.20 microM), moderate inhibitory effects on self-mediated amyloid-beta (Abeta) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.
ESTHER : Hu_2023_Future.Med.Chem__
PubMedSearch : Hu_2023_Future.Med.Chem__
PubMedID: 37902028

Title : Plant immune signaling network mediated by helper NLRs - Gong_2023_Curr.Opin.Plant.Biol_73_102354
Author(s) : Gong Y , Tian L , Kontos I , Li J , Li X
Ref : Curr Opin Plant Biol , 73 :102354 , 2023
Abstract : Plant nucleotide-binding leucine-rich repeat receptors (NLRs) are intracellular immune receptors for pathogen recognition and signaling. They include sensor NLRs (sNLRs) that detect pathogens, and helper NLRs, which transduce downstream immune signals. During immune responses, both membrane-localized pattern recognition receptors (PRRs) and sNLRs rely on helper NLRs for signal transduction. The Arabidopsis helper NLRs, ADR1s and NRG1s, along with their interacting lipase-like protein dimers, are differentially required by sNLRs. Recent structural and biochemical analyses suggest that they assemble into oligomeric resistosomes with lipase-like protein dimers upon perception of small molecules produced from enzymatic activities of upstream TIR-type sNLRs. As a result, ADR1s and NRG1s form membrane calcium channels to induce immune responses and cell death. In contrast, Solanaceous NRC clade helper NLRs transduce signals from many sNLRs and some PRRs. Here, we summarize the recent advances in plant helper NLR research, with a focus on their structural and biochemical mechanisms in immune signaling.
ESTHER : Gong_2023_Curr.Opin.Plant.Biol_73_102354
PubMedSearch : Gong_2023_Curr.Opin.Plant.Biol_73_102354
PubMedID: 37003229

Title : A New Brominated Isocoumarin from the Marine Starfish-Associated Fungus Aspergillus sp. WXF1904 - Li_2023_Chem.Biodivers__e202301706
Author(s) : Li C , Lin X , Wang S , Guan D , Wang X , Yang B , Zhou X , Li J , Xiong B , Liu Y , Sun Y
Ref : Chem Biodivers , :e202301706 , 2023
Abstract : Based on the one strain many compounds strategy, a new brominated isocoumarin, 5-bromo-6,8-dihydroxy-3,7-dimethylisocoumarin (1), along with four new natural products, methyl 3-bromo-2,4-dihydroxy-6-methylbenzoate (2), methyl 2-bromo-4,6-dihydroxybenzoate (3), (E)-3-(3-bromo-4-hydroxyphenyl) acrylic acid (4) and 4-hydroxy-3-methyl-6-phenyl-2H-pyran-2-one (5), and four known compounds, methyl orsellinate (6), 4-hydroxy-3-methyl-6-(1-methyl-1-propenyl)-2H-pyran-2-one (7), pilobolusate (8) and cis-ferulic acid (9), were isolated from the ethyl acetate extract of the fungus Aspergillus sp. WXF1904 under the condition of adding bromine salt to the production medium. The structures of the new compounds were established by analysis of NMR and MS data. Compounds (1-9) were evaluated for inhibitory activity of acetylcholinesterase and pancreatic lipase, the new compound 1, known compounds 6 and 7 displayed weak inhibitory activity against acetylcholinesterase, compounds 257 and 8 showed weak inhibitory activity against pancreatic lipase.
ESTHER : Li_2023_Chem.Biodivers__e202301706
PubMedSearch : Li_2023_Chem.Biodivers__e202301706
PubMedID: 38079052

Title : A Multifunctional (-)-Meptazinol-Serotonin Hybrid Ameliorates Oxidative Stress-Associated Apoptotic Neuronal Death and Memory Deficits via Activating the Nrf2\/Antioxidant Enzyme Pathway - Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
Author(s) : Zhao F , Zhao L , Zhou Y , Tan X , Yang Y , Ni W , Zheng W , Chen H , Qiu Y , Li J
Ref : Oxid Med Cell Longev , 2023 :6935947 , 2023
Abstract : The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H(2)O(2)-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H(2)O(2) through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H(2)O(2)-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and gamma-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.
ESTHER : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedSearch : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedID: 36819782

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

Title : Inducible Gut-Specific Carboxylesterase SlCOE030 in Polyphagous Pests of Spodoptera litura Conferring Tolerance between Nicotine and Cyantraniliprole - Li_2023_J.Agric.Food.Chem__
Author(s) : Li J , Lv Y , Liu Y , Bi R , Pan Y , Shang Q
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Insecticides tolerance in herbivorous arthropods is associated with preadaptation to host plant allelochemicals. However, how plant secondary metabolites activate detoxifying metabolic genes to develop tolerance remains unclear. Herein, the tolerance of Spodoptera litura larvae to cyantraniliprole was increased after nicotine exposure. An S. litura alpha esterase, SlCOE030, was predominantly expressed in the midgut and induced after exposure to cyantraniliprole, nicotine, and cyantraniliprole plus nicotine. Drosophila melanogaster with ectopically overexpressed SlCOE030 enhanced cyantraniliprole and nicotine tolerance by 4.91- and 2.12-fold, respectively. Compared to UAS-SlCOE030 and Esg-GAL4 lines, the Esg > SlCOE030 line laid more eggs after nicotine exposure. SlCOE030 knockdown decreased the sensitivity of nicotine-treated S. litura larvae to cyantraniliprole. Metabolism assays indicated that recombinant SlCOE030 protein metabolizes cyantraniliprole. Homology modeling and molecular docking analysis demonstrated that SlCOE030 exhibits effective affinities for cyantraniliprole and nicotine. Thus, insect CarEs may result in the development of cross-tolerance between synthetic insecticides and plant secondary metabolites.
ESTHER : Li_2023_J.Agric.Food.Chem__
PubMedSearch : Li_2023_J.Agric.Food.Chem__
PubMedID: 36877657
Gene_locus related to this paper: spolt-SlCOE030

Title : Plasminogen decreases Abeta42 and Tau deposition, and shows multi-beneficial effects on Alzheimer's disease in mice and humans - Guo_2023_Biochem.Biophys.Res.Commun_654_102
Author(s) : Guo C , Wang T , Zhang D , Ge X , Li J
Ref : Biochemical & Biophysical Research Communications , 654 :102 , 2023
Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Abeta) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. Using ex vivo, in vivo and clinical approaches, we investigated the functional effects of plasminogen on the widely used FAD, Abeta42 oligomer or Tau intracranial injection-induced AD mouse model and explored its therapeutic effects on patients with AD. The results show that intravenously injected plasminogen rapidly crosses the blood-brain barrier (BBB); increases plasmin activity in the brain; colocalizes with and effectively promotes the clearance of Abeta42 peptide and Tau protein deposits ex vivo and in vivo; increases the choline acetyltransferase (ChAT) level and decreases the acetylcholinesterase (AChE) activity; and improves the memory functions. Clinically, when GMP-level plasminogen was administered to 6 AD patients for 1-2 weeks, their average scores on the Minimum Mental State Examination (MMSE), which is a standard scoring system used to measure the memory loss and cognitive deficits, were extremely significantly improved by 4.2 +/- 2.23 points, e.g., an average increase from 15.5 +/- 8.22 before treatment to 19.7 +/- 7.09 after treatment. The preclinical study and pilot clinical study suggest that plasminogen is effective in treating AD and may be a promising drug candidate.
ESTHER : Guo_2023_Biochem.Biophys.Res.Commun_654_102
PubMedSearch : Guo_2023_Biochem.Biophys.Res.Commun_654_102
PubMedID: 36905760

Title : Gut microbiome helps honeybee (Apis mellifera) resist the stress of toxic nectar plant (Bidens pilosa) exposure: Evidence for survival and immunity - Tang_2023_Environ.Microbiol__
Author(s) : Tang Q , Li W , Wang Z , Dong Z , Li X , Li J , Huang Q , Cao Z , Gong W , Zhao Y , Wang M , Guo J
Ref : Environ Microbiol , : , 2023
Abstract : Honeybee (Apis mellifera) ingestion of toxic nectar plants can threaten their health and survival. However, little is known about how to help honeybees mitigate the effects of toxic nectar plant poisoning. We exposed honeybees to different concentrations of Bidens pilosa flower extracts and found that B. pilosa exposure significantly reduced honeybee survival in a dose-dependent manner. By measuring changes in detoxification and antioxidant enzymes and the gut microbiome, we found that superoxide dismutase, glutathione-S-transferase and carboxylesterase activities were significantly activated with increasing concentrations of B. pilosa and that different concentrations of B. pilosa exposure changed the structure of the honeybee gut microbiome, causing a significant reduction in the abundance of Bartonella (p < 0.001) and an increase in Lactobacillus. Importantly, by using Germ-Free bees, we found that colonization by the gut microbes Bartonella apis and Apilactobacillus kunkeei (original classification as Lactobacillus kunkeei) significantly increased the resistance of honeybees to B. pilosa and significantly upregulated bee-associated immune genes. These results suggest that honeybee detoxification systems possess a level of resistance to the toxic nectar plant B. pilosa and that the gut microbes B. apis and A. kunkeei may augment resistance to B. pilosa stress by improving host immunity.
ESTHER : Tang_2023_Environ.Microbiol__
PubMedSearch : Tang_2023_Environ.Microbiol__
PubMedID: 37291689

Title : Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis - Ang_2023_Molecules_28_
Author(s) : Ang S , Liang J , Zheng W , Zhang Z , Li J , Yan Z , Wong WL , Zhang K , Chen M , Wu P
Ref : Molecules , 28 : , 2023
Abstract : A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC(50) values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 microg/mL, respectively, whereas the LC(50) value of MA was 659.34 microg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 microg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.
ESTHER : Ang_2023_Molecules_28_
PubMedSearch : Ang_2023_Molecules_28_
PubMedID: 37049799

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

Title : Therapeutic targets and functions of curcumol against COVID-19 and colon adenocarcinoma - Li_2022_Front.Nutr_9_961697
Author(s) : Li J , Peng P , Lai KP
Ref : Front Nutr , 9 :961697 , 2022
Abstract : Since 2019, the coronavirus disease (COVID-19) has caused 6,319,395 deaths worldwide. Although the COVID-19 vaccine is currently available, the latest variant of the virus, Omicron, spreads more easily than earlier strains, and its mortality rate is still high in patients with chronic diseases, especially cancer patients. So, identifying a novel compound for COVID-19 treatment could help reduce the lethal rate of the viral infection in patients with cancer. This study applied network pharmacology and systematic bioinformatics analysis to determine the possible use of curcumol for treating colon adenocarcinoma (COAD) in patients infected with COVID-19. Our results showed that COVID-19 and COAD in patients shared a cluster of genes commonly deregulated by curcumol. The clinical pathological analyses demonstrated that the expression of gamma-aminobutyric acid receptor subunit delta (GABRD) was associated with the patients' hazard ratio. More importantly, the high expression of GABRD was associated with poor survival rates and the late stages of COAD in patients. The network pharmacology result identified seven-core targets, including solute carrier family 6 member 3, gamma-aminobutyric acid receptor subunit pi, butyrylcholinesterase, cytochrome P450 3A4, 17-beta-hydroxysteroid dehydrogenase type 2, progesterone receptor, and GABRD of curcumol for treating patients with COVID-19 and COAD. The bioinformatic analysis further highlighted their importance in the biological processes and molecular functions in gland development, inflammation, retinol, and steroid metabolism. The findings of this study suggest that curcumol could be an alternative compound for treating patients with COVID-19 and COAD.
ESTHER : Li_2022_Front.Nutr_9_961697
PubMedSearch : Li_2022_Front.Nutr_9_961697
PubMedID: 35967794

Title : Protective effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in aging mice - Guo_2022_Front.Pharmacol_13_992269
Author(s) : Guo Y , Qu Y , Li W , Shen H , Cui J , Liu J , Li J , Wu D
Ref : Front Pharmacol , 13 :992269 , 2022
Abstract : The aging process of human beings is accompanied by the decline of learning and memory ability and progressive decline of brain function, which induces Alzheimer's Disease (AD) in serious cases and seriously affects the quality of patient's life. In recent years, more and more studies have found that natural plant antioxidants can help to improve the learning and memory impairment, reduce oxidative stress injury and aging lesions in tissues. This study aimed to investigate the effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in D-galactose-induced aging mice and its molecular mechanism. The composition of Monarda didymaL. essential oil was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). A mouse aging model was established by the subcutaneous injection of D-galactose in mice. The behavior changes of the mice were observed by feeding the model mice with essential oil, thymol and donepezil, and the histopathological changes of the hippocampus were observed by HE staining. And the changes of acetylcholinesterase (AchE), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and the content of malondialdehyde (MDA) in hippocampal tissues were detected by corresponding kits. The expression of mitogen activated protein kinase (MAPK) and nuclear factor E2 related factor 2 (Nrf2) pathways related proteins were detected by western blot. Animal experimental results showed that compared with model group, the above indexes in Monarda didymaL. essential oil and thymol groups improved significantly in a dose-dependent manner. Monarda didymaL. essential oil and its main active component thymol can improve the learning and memory impairment of aging mice to some extent, and Nrf2 and MAPK pathways may be involved in its action process.
ESTHER : Guo_2022_Front.Pharmacol_13_992269
PubMedSearch : Guo_2022_Front.Pharmacol_13_992269
PubMedID: 36105199

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

Title : Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus - Gao_2022_Parasit.Vectors_15_353
Author(s) : Gao H , Gu Z , Xing D , Yang Q , Li J , Zhou X , Zhao T , Li C
Ref : Parasit Vectors , 15 :353 , 2022
Abstract : BACKGROUND: Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. METHODS: Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. RESULTS: Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. CONCLUSION: The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences.
ESTHER : Gao_2022_Parasit.Vectors_15_353
PubMedSearch : Gao_2022_Parasit.Vectors_15_353
PubMedID: 36182902

Title : A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells - Moore_2022_ACS.Chem.Biol_17_2595
Author(s) : Moore KP , Schwaid AG , Tudor M , Park S , Beshore DC , Converso A , Shipe WD , Anand R , Lan P , Moningka R , Rothman DM , Sun W , Chi A , Cornella-Taracido I , Adam GC , Bahnck-Teets C , Carroll SS , Fay JF , Goh SL , Lusen J , Quan S , Rodriguez S , Xu M , Andrews CL , Song C , Filzen T , Li J , Hollenstein K , Klein DJ , Lammens A , Lim UM , Fang Z , McHale C , Li Y , Lu M , Diamond TL , Howell BJ , Zuck P , Balibar CJ
Ref : ACS Chemical Biology , 17 :2595 , 2022
Abstract : Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells. Tool compounds ICeD-1 and ICeD-2 ("inducer of cell death-1 and 2"), optimized for potency and selectivity from screening hits, were used to deconvolute the mechanism of action using a combination of chemoproteomic, biochemical, pharmacological, and genetic approaches. We determined that these compounds function by modulating dipeptidyl peptidase 9 (DPP9) and activating the caspase recruitment domain family member 8 (CARD8) inflammasome. Efficacy of ICeD-1 and ICeD-2 was dependent on HIV-1 protease activity and synergistic with efavirenz, which promotes premature activation of HIV-1 protease at high concentrations in infected cells. This in vitro synergy lowers the efficacious cell kill concentration of efavirenz to a clinically relevant dose at concentrations of ICeD-1 or ICeD-2 that do not result in complete DPP9 inhibition. These results suggest engagement of the pyroptotic pathway as a potential approach to eliminate HIV-1 infected cells.
ESTHER : Moore_2022_ACS.Chem.Biol_17_2595
PubMedSearch : Moore_2022_ACS.Chem.Biol_17_2595
PubMedID: 36044633
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Genome-Wide Identification and Analysis of Lipases in Fig Wasps (Chalcidoidea, Hymenoptera) - Wei_2022_Insects_13_
Author(s) : Wei X , Li J , Wang T , Xiao J , Huang D
Ref : Insects , 13 : , 2022
Abstract : Lipases are the main enzymes involved in lipid metabolism. However, the characteristics of lipases in insects were scarcely investigated. Here, we screened the recently sequenced genomes of 12 fig wasp species consisting of seven pollinator fig wasps (PFWs) and five non-pollinating fig wasps (NPFWs) for the six major lipase gene families. In total, 481 lipase genes were identified, and the two most numerous families were the neutral and acid lipases. Tandem duplication accounted for the expansion of the gene family. NPFWs had significantly more lipases than PFWs. A significant gene family contraction occurred in the clade of PFWs. The difference of lipases between NPFWs and PFWs might contribute to their distinction in life histories and feeding regimes. Phylogenetic analysis showed that the lipase genes of each fig wasp species was almost equally distributed in each clade, indicating that the lipase genes were conserved. The gene structures were similar within each clade, while they were different among clades. Most of the neutral and acid lipases were signal peptides and located extracellularly. The pathways of lipases involved were predicted. This genome-wide study provides a systematic analysis of lipase gene families in 12 hymenopteran insects and further insights towards understanding the potential functions of lipases.
ESTHER : Wei_2022_Insects_13_
PubMedSearch : Wei_2022_Insects_13_
PubMedID: 35621743

Title : Cymbopogon citratus (DC.) Stapf aqueous extract ameliorates loperamide-induced constipation in mice by promoting gastrointestinal motility and regulating the gut microbiota - Gao_2022_Front.Microbiol_13_1017804
Author(s) : Gao X , Hu Y , Tao Y , Liu S , Chen H , Li J , Zhao Y , Sheng J , Tian Y , Fan Y
Ref : Front Microbiol , 13 :1017804 , 2022
Abstract : Slow transit constipation (STC) is the most common type of functional constipation. Drugs with good effects and few side effects are urgently needed form the treatment of STC. Cymbopogon citratus (DC.) Stapf (CC) is an important medicinal and edible spice plant. The wide range of biological activities suggested that CC may have laxative effects, but thus far, it has not been reported. In this study, the loperamide-induced STC mouse model was used to evaluate the laxative effect of the aqueous extract of CC (CCAE), and the laxative mechanism was systematically explored from the perspectives of the enteric nervous system (ENS), neurotransmitter secretion, gastrointestinal motility factors, intestinal inflammation, gut barrier and gut microbiota. The results showed that CCAE not only decreased the serum vasoactive intestinal polypeptide (VIP), induced nitric oxide synthases (iNOS), and acetylcholinesterase (AchE) in STC mice but also increased the expression of gastrointestinal motility factors in colonic interstitial cells of Cajal (ICCs) and smooth muscle cells (SMCs), thereby significantly shortening the defecation time and improving the gastrointestinal transit rate. The significantly affected gastrointestinal motility factors included stem cell factor receptor (c-Kit), stem cell factor (SCF), anoctamin 1 (Ano1), ryanodine receptor 3 (RyR3), smooth muscle myosin light chain kinase (smMLCK) and Connexin 43 (Cx43). Meanwhile, CCAE could repair loperamide-induced intestinal inflammation and intestinal barrier damage by reducing the expression of the pro-inflammatory factor IL-1beta and increasing the expression of the anti-inflammatory factor IL-10, chemical barrier (Muc-2) and mechanical barrier (Cldn4, Cldn12, Occludin, ZO-1, and ZO-2). Interestingly, CCAE could also partially restore loperamide-induced gut microbial dysbiosis in various aspects, such as microbial diversity, community structure and species composition. Importantly, we established a complex but clear network between gut microbiota and host parameters. Muribaculaceae, Lachnospiraceae and UCG-010 showed the most interesting associations with the laxative phenotypes; several other specific taxa showed significant associations with serum neurotransmitters, gastrointestinal motility factors, intestinal inflammation, and the gut barrier. These findings suggested that CCAE might promote intestinal motility by modulating the ENS-ICCs-SMCs network, intestinal inflammation, intestinal barrier and gut microbiota. CC may be an effective and safe therapeutic choice for STC.
ESTHER : Gao_2022_Front.Microbiol_13_1017804
PubMedSearch : Gao_2022_Front.Microbiol_13_1017804
PubMedID: 36267178

Title : Antifeedant Mechanism of Dodonaea viscosa Saponin A Isolated from the Seeds of Dodonaea viscosa - Yu_2022_Molecules_27_4464
Author(s) : Yu H , Li J , Wu G , Tang Q , Duan X , Liu Q , Lan M , Zhao Y , Hao X , Qin X , Ding X
Ref : Molecules , 27 :4464 , 2022
Abstract : Dodonaea viscosa is a medicinal plant which has been used to treat various diseases in humans. However, the anti-insect activity of extracts from D. viscosa has not been evaluated. Here, we found that the total saponins from D. viscosa (TSDV) had strong antifeedant and growth inhibition activities against 4th-instar larvae of Spodoptera litura. The median antifeeding concentration (AFC(50)) value of TSDV on larvae was 1621.81 microg/mL. TSDV affected the detoxification enzyme system of the larvae and also exerted antifeedant activity possibly through targeting the gamma-aminobutyric acid (GABA) system. The AFC(50) concentration, the carboxylesterase activity, glutathione S-transferases activity, and cytochrome P450 content increased to 258%, 205%, and 215%, respectively, and likewise the glutamate decarboxylase activity and GABA content to 195% and 230%, respectively, in larvae which fed on TSDV. However, D. viscosa saponin A (DVSA) showed better antifeedant activity and growth inhibition activity in larvae, compared to TSDV. DVSA also exerted their antifeedant activity possibly through targeting the GABA system and subsequently affected the detoxification enzyme system. Further, DVSA directly affected the medial sensillum and the lateral sensillum of the 4th-instar larvae. Stimulation of Spodoptera litura. with DVSA elicited clear, consistent, and robust excitatory responses in a single taste cell.
ESTHER : Yu_2022_Molecules_27_4464
PubMedSearch : Yu_2022_Molecules_27_4464
PubMedID: 35889337

Title : Mechanism and Structural Insights Into a Novel Esterase, E53, Isolated From Erythrobacter longus - Ding_2022_Front.Microbiol_12_798194
Author(s) : Ding Y , Nie L , Yang XC , Li Y , Huo YY , Li Z , Gao Y , Cui HL , Li J , Xu XW
Ref : Front Microbiol , 12 :798194 , 2022
Abstract : Esterases are a class of enzymes that split esters into an acid and an alcohol in a chemical reaction with water, having high potential in pharmaceutical, food and biofuel industrial applications. To advance the understanding of esterases, we have identified and characterized E53, an alkalophilic esterase from a marine bacterium Erythrobacter longus. The crystal structures of wild type E53 and three variants were solved successfully using the X-ray diffraction method. Phylogenetic analysis classified E53 as a member of the family IV esterase. The enzyme showed highest activity against p-nitrophenyl butyrate substrate at pH 8.5 9.5 and 40 C. Based on the structural feature, the catalytic pocket was defined as R1 (catalytic center), R2 (pocket entrance), and R3 (end area of pocket) regions. Nine variants were generated spanning R1-R3 and thorough functional studies were performed. Detailed structural analysis and the results obtained from the mutagenesis study revealed that mutations in the R1 region could regulate the catalytic reaction in both positive and negative directions; expanding the bottleneck in R2 region has improved the enzymatic activity; and R3 region was associated with the determination of the pH pattern of E53. N166A in R3 region showed reduced activity only under alkaline conditions, and structural analysis indicated the role of N166 in stabilizing the loop by forming a hydrogen bond with L193 and G233. In summary, the systematic studies on E53 performed in this work provide structural and functional insights into alkaliphilic esterases and further our knowledge of these enzymes.
ESTHER : Ding_2022_Front.Microbiol_12_798194
PubMedSearch : Ding_2022_Front.Microbiol_12_798194
PubMedID: 35069500
Gene_locus related to this paper: erylo-E53

Title : Design of 2,5-furandicarboxylic based polyesters degraded in different environmental conditions: Comprehensive experimental and theoretical study - Hu_2022_J.Hazard.Mater_425_127752
Author(s) : Hu H , Li J , Luo S , Tian Y , Wang J , Zhao YL , Zhang R , Zhu J
Ref : J Hazard Mater , 425 :127752 , 2022
Abstract : Nowadays, the promotion and application of aliphatic-aromatic copolyesters, such as poly (butylene adipate-co-terephthalate) (PBAT), are growing into a general trend. Although the structures of diacids exerted substantial impacts on degradation behavior, the underlying mechanisms have rarely been studied. In this work, 2,5-Furandicarboxylic acid was combined with succinic acid (PBSF), adipic acid (PBAF) and diglycolic acid (PBDF) to prepare three kinds of copolyesters. They showed unique degradation behaviors in buffer, enzyme environment and artificial seawater. These characteristics are closely related to the structural compositions of diacids. PBAFs displayed impressive biodegradability when catalyzed by Candida antarctica lipase B (CALB), while the more hydrophilic PBDFs exhibited faster hydrolysis in both buffer and artificial seawater. PBSFs, with hydrophobic and short segments, obtained a relatively slower rate of hydrolysis and enzymatic degradation. The reactivity sites and hydrolytic pathway were revealed by the combination of DFT calculation and Fukui function analysis. MD simulations, QM/MM optimizations and theozyme calculations showed that PBAF-CALB was prone to form a pre-reaction state, leading to the reduced energy barrier in the acylation process. This work revealed the effects of different structural features of diacids on polymer degradation and paved a way to design target biodegradable polymers in different degradation conditions.
ESTHER : Hu_2022_J.Hazard.Mater_425_127752
PubMedSearch : Hu_2022_J.Hazard.Mater_425_127752
PubMedID: 34906869
Gene_locus related to this paper: canar-LipB

Title : Overexpression of ATGL impairs lipid droplet accumulation by accelerating lipolysis in goat mammary epithelial cells - Li_2022_Anim.Biotechnol__1
Author(s) : Li J , Wang Y , Yang P , Han H , Zhang G , Xu H , Quan K
Ref : Anim Biotechnol , :1 , 2022
Abstract : Adipose triglyceride lipase (ATGL) is the key enzyme for the degradation of triacylglycerols (TAGs). It functions in concert with other enzymes to mobilize TAG and supply fatty acids (FAs) for energy production. Dysregulated lipolysis leads to excess concentrations of circulating FAs, which may lead to destructive and lipotoxic effects to the organism. To understand the role of ATGL in mammary lipid metabolism, ATGL was overexpressed in goat mammary epithelial cells (GMECs) by using a recombinant adenovirus system. ATGL overexpression decreased lipid droplet (LD) accumulation and cellular TG content (p< 0.05) along with a decrease in the expression of the key enzyme that catalyzes the final step of TG synthesis (DGAT). Significant increases were observed in the expression of genes related to lipolysis (hormone-sensitive lipase [HSL]) and FA desaturation (SCD) by ATGL overexpression. Genes responsible for FA oxidation (PPARalpha), LD formation and secretion (ADRP and BTN1A1), and long-chain FA uptake (CD36) were all decreased by ATGL overexpression (p < 0.05). The primary products of TAG lipolysis, free FAs (FFAs), were notably increased in the ATGL-overexpressing cells. Taken together, our results demonstrated that ATGL activation impairs lipid formation partially through accelerating lipolysis in GMECs.
ESTHER : Li_2022_Anim.Biotechnol__1
PubMedSearch : Li_2022_Anim.Biotechnol__1
PubMedID: 36306180

Title : Construction of a Novel Lipase Catalytic System Based on Hybrid Membranes with Interwoven Electrospun Polyacrylic Acid and Polyvinyl Pyrrolidone Gel Fibers - Wang_2022_Gels_8_
Author(s) : Wang Z , Lin S , Zhang Q , Li J , Yin S
Ref : Gels , 8 : , 2022
Abstract : Efficient lipase catalysis requires sufficient oil-water interface engineered through structural design. Inspired by the architectural features of fabrics, a novel lipase-membrane catalytic system with interwoven polyacrylic acid (PAA) gel fibers and polyvinyl pyrrolidone (PVP) gel fibers was developed in this study by using double-needle electrospinning and gelation. It has been demonstrated that PAA/PVP hybrid gel fiber membranes (HGFMs) have a high swelling capacity for both water and oil phases, which created numerous discontinuous oil-water contact surface units in limited space of HGFMs, consequently forming effective interfacial catalytic systems. Volume competition between the water and oil phases suggests that balancing the proportions of these phases is very important for effective construction of oil-water interfaces and conditioning catalysis. Regulation of multiple factors of PAA/PVP HGFMs resulted in a catalytic efficiency of up to 2.1 times that of a macroscopic 'oil-up/water-down' system (room temperature, pH = 7), and 2.9 times when three membranes are superimposed, as well as excellent pH and temperature stability. HGFMs were stacked to build a high-performing catalytic performance reactor. We expect that this study will be a beneficial exploration for expanding the lipase catalytic system.
ESTHER : Wang_2022_Gels_8_
PubMedSearch : Wang_2022_Gels_8_
PubMedID: 36547336

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

Title : LC-MS\/MS assay of fluoropezil and its two major metabolites in human plasma: an application to pharmacokinetic studies - Guo_2022_Bioanalysis_14_817
Author(s) : Guo R , Hu J , Jing J , Liu Y , Li J , Zhou Y , Liu H , Zhou L , Chen X
Ref : Bioanalysis , 14 :817 , 2022
Abstract : Background: LC-MS/MS methods were developed for pharmacokinetic analysis and verified to measure fluoropezil, a new AchE inhibitor for Alzheimer's disease treatment, and its two primary metabolites (N-debenzyl fluoride fluoropezil [M1] and N-oxidized fluoropezil [M11]) in human plasma. Methods & results: Analytes were extracted from 50 microl plasma using protein precipitation and separated by HPLC using a bridged ethyl hybrid column and gradient elution procedure. Analytical detection was performed with a triple quadrupole mass spectrometer and electrospray ionization source in multiple reaction monitoring mode. The LC-MS/MS method was fully validated. The quantification linear ranges were 0.100-50.0 ng/ml (fluoropezil), 0.0500-25.0 ng/ml (M1) and 0.0500-25.0 ng/ml (M11). Conclusion: A sensitive, reliable LC-MS/MS method was established and used successfully to explore the pharmacokinetics of fluoropezil.
ESTHER : Guo_2022_Bioanalysis_14_817
PubMedSearch : Guo_2022_Bioanalysis_14_817
PubMedID: 35735138

Title : A network pharmacology-based approach to explore the therapeutic potential of Sceletium tortuosum in the treatment of neurodegenerative disorders - Luo_2022_PLoS.One_17_e0273583
Author(s) : Luo Y , Shan L , Xu L , Patnala S , Kanfer I , Li J , Yu P , Jun X
Ref : PLoS ONE , 17 :e0273583 , 2022
Abstract : Sceletium tortuosum (SCT) has been utilized medicinally by indigenous Koi-San people purportedly for mood elevation. SCT extracts are reported to be neuroprotective and have efficacy in improving cognition. However, it is still unclear which of the pharmacological mechanisms of SCT contribute to the therapeutic potential for neurodegenerative disorders. Hence, this study investigated two aspects-firstly, the abilities of neuroprotective sub-fractions from SCT on scavenging radicals, inhibiting some usual targets relevant to Alzheimer's disease (AD) or Parkinson's disease (PD), and secondly utilizing the network pharmacology related methods to search probable mechanisms using Surflex-Dock program to show the key targets and corresponding SCT constituents. The results indicated sub-fractions from SCT could scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, inhibit acetylcholinesterase (AChE), monoamine oxidase type B (MAO-B) and N-methyl-D-aspartic acid receptor (NMDAR). Furthermore, the results of gene ontology and docking analyses indicated the key targets involved in the probable treatment of AD or PD might be AChE, MAO-B, NMDAR subunit2B (GluN2B-NMDAR), adenosine A2A receptor and cannabinoid receptor 2, and the corresponding constituents in Sceletium tortuosum might be N-trans-feruloyl-3-methyldopamine, dihydrojoubertiamine and other mesembrine type alkaloids. In summary, this study has provided new evidence for the therapeutic potential of SCT in the treatment of AD or PD, as well as the key targets and notable constituents in SCT. Therefore, we propose SCT could be a natural chemical resource for lead compounds in the treatment of neurodegenerative disorders.
ESTHER : Luo_2022_PLoS.One_17_e0273583
PubMedSearch : Luo_2022_PLoS.One_17_e0273583
PubMedID: 36006974

Title : Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer's disease - Liu_2022_Bioorg.Med.Chem_58_116660
Author(s) : Liu Z , Shi Y , Zhang X , Yu G , Li J , Cong S , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 58 :116660 , 2022
Abstract : Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC(50) = 0.087 microM), HuAChE (IC(50) = 0.041 microM) and MAO-B (IC(50) = 0.30 microM). Furthermore, molecular docking studies were conducted to investigate the interaction mode with enzymes. Besides, 7d also possessed good effects of Cu(2+) chelation, ameliorate oxidative stress, and anti-neuroinflammation, desirable BBB permeability and eligible drug-like properties. Altogether, the multifunctional profiles of 7d prove that it deserves further investigation as a novel drug candidate for AD treatment.
ESTHER : Liu_2022_Bioorg.Med.Chem_58_116660
PubMedSearch : Liu_2022_Bioorg.Med.Chem_58_116660
PubMedID: 35183029

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

Title : Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection - Cai_2022_Enzyme.Microb.Technol_155_109992
Author(s) : Cai J , Romao E , Wu G , Li J , Li L , Wang Z , Li Y , Yang J , Shen Y , Xu Z , Muyldermans S , Wang H
Ref : Enzyme Microb Technol , 155 :109992 , 2022
Abstract : In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE.
ESTHER : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedSearch : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedID: 35114480

Title : Nematicidal activity of tirotundin and parthenolide isolated from Tithonia diversifolia and Chrysanthemum parthenium - Lan_2022_J.Environ.Sci.Health.B__1
Author(s) : Lan M , Gao X , Duan X , Li H , Yu H , Li J , Zhao Y , Hao X , Ding X , Wu G
Ref : J Environ Sci Health B , :1 , 2022
Abstract : Acetylcholinesterase (AChE) is an enzyme that catalyzes acetylcholine into choline and acetic acid. Conventional pesticides, including organophosphates and carbamates target and inhibit the activity of AChE. To obtain more pesticide precursors that meet the safety requirements, more than 200 compounds were screened. Tirotundin and parthenolide identified as potential neurotoxins to nematodes were isolated from Tithonia diversifolia and Chrysanthemum parthenium, respectively. Their IC(50) values were 6.89 +/- 0.30 and 5.51 +/- 0.23 microg/mL, respectively against the AChE isolated from Caenorhabditis elegans. AChE was inhibited in a dose-dependent manner using the two compounds. And the Lineweaver-Burk and Dixon plots indicated that tirotundin and parthenolide were reversible inhibitors against AChE, both inhibiting AChE in a mixed-type competitive manner and demonstrating these compounds may possess dual binding site AChE inhibitors. LC(50) values of tirotundin and parthenolide against C. elegans were 9.16 +/- 0.21 and 7.23 +/- 0.48 microg/mL, respectively. These results provide a certain theoretical basis for the development and utilization of novel pesticides.
ESTHER : Lan_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Lan_2022_J.Environ.Sci.Health.B__1
PubMedID: 34983315

Title : Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer's disease - Li_2022_Front.Pharmacol_13_940999
Author(s) : Li J , Zou B , Cheng XY , Yang XH , Zhao CH , Ma RX , Tian JX , Yao Y
Ref : Front Pharmacol , 13 :940999 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Abeta) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Abeta generation and senile plaque deposition via activating Nrf2 and downregulating the expression of beta-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-kappaB (NF-kappaB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Abeta, TS could significantly inhibit the aggregation of Abeta and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-kappaB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-kappaB through Nrf2, thereby reducing the generation of Abeta and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress.
ESTHER : Li_2022_Front.Pharmacol_13_940999
PubMedSearch : Li_2022_Front.Pharmacol_13_940999
PubMedID: 35935875

Title : Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles - Wu_2022_Heliyon_8_e11751
Author(s) : Wu MY , Shi XC , Shan J , Wang R , Wang Y , Li J , Tian DN , Xu HM
Ref : Heliyon , 8 :e11751 , 2022
Abstract : OBJECTIVE: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. METHODS: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-alpha), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. RESULTS: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-alpha increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (++), CHRM5 (++), CHRNA5 (++), CHRNA7 (++), CHRNA9 (- +), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. CONCLUSION: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.
ESTHER : Wu_2022_Heliyon_8_e11751
PubMedSearch : Wu_2022_Heliyon_8_e11751
PubMedID: 36468138

Title : Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions - Xu_2022_Molecules_27_7798
Author(s) : Xu Y , Li F , Ma J , Li J , Xie H , Wang C , Chen P , Wang L
Ref : Molecules , 27 :7798 , 2022
Abstract : Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted beta-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.
ESTHER : Xu_2022_Molecules_27_7798
PubMedSearch : Xu_2022_Molecules_27_7798
PubMedID: 36431898

Title : Identification and expression patterns of candidate carboxylesterases in Carposina sasakii Matsumura (Lepidoptera: Carposinidae), an important pest of fruit trees - Li_2022_Bull.Entomol.Res__1
Author(s) : Li J , Zhang L
Ref : Bull Entomol Res , :1 , 2022
Abstract : Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is an important pest of fruit trees in a large area of Asia. The adults mainly depend on olfaction to communicate with the environment, but the olfactory mechanism has not been well known. Odorant degrading enzymes (ODEs) are important olfactory proteins, which inactivate and degrade odorants to free odorant receptors for maintaining olfactory sensitivity. Carboxylesterases (CXEs) are considered to be a major group of moth ODEs. In this study, four candidate CXEs (CsasCXE1 ~ CsasCXE4) were identified by using head transcriptomic data from C. sasakii adult females and males. Sequence alignment showed conserved amino acid residues and their variations in C. sasakii CXEs. Phylogenetic analysis indicated the CXEs with the variations cluster well, and each C. sasakii CXE clusters in a clade with some of the other lepidopteran CXEs, with a high enough bootstrap value. Gene expression analysis revealed that CsasCXE2 and CsasCXE3 have similar tissue and sex expression patterns in C. sasakii adults. The two CXEs have relatively high expression levels in the heads and are expressed more abundantly in the female heads than male heads. CsasCXE1 and CsasCXE4 are expressed at higher levels in the male heads than female heads, but not dominantly expressed in the heads among the different tissues. Whether these CXEs function as ODEs remains to be further researched. This study laid the foundation for exploring functions of C. sasakii CXEs.
ESTHER : Li_2022_Bull.Entomol.Res__1
PubMedSearch : Li_2022_Bull.Entomol.Res__1
PubMedID: 35670157

Title : Integrated Strategy of Network Pharmacology and in vitro Screening to Identify Mechanism of Diazinon-induced Hippocampal Neurotoxicity - Li_2022_Neurotoxicol__
Author(s) : Li J , Bi H
Ref : Neurotoxicology , : , 2022
Abstract : Diazinon (DZN) is a commonly used organophosphorus pesticide that was recently found to cause hippocampal degeneration in rodents. In this study, we elucidated the underlying molecular mechanisms through integrated network pharmacology and in vitro toxicity screening. 37 potential molecular targets of DZN-induced hippocampal neurotoxicity were predicted. Identified targets were then included in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A preliminary protein-protein network (PPI) was constructed using STRING, and the top 10 network hub target genes (Akt1, Mapk3, Tnf, Il6, Ptgs2, Il10, Il2, Il4, Creb1, and Fgf2) were screened for expression changes under DZN treatment. Cell counting kit-8 (CCK8) and lactate dehydrogenase (LDH) assays revealed time- and dose-dependent toxicity of DZN against mouse hippocampus-derived HT22 cells. Acetylcholinesterase (AChE) activity assay suggested that DZN inhibited the AChE activity, and TUNEL staining revealed that DZN increased the apoptotic rate. The mRNA expression levels of 9 hub targets (all except Il10) showed significant changes during DZN treatment, and AChE activity inhibition correlated strongly with Akt1, Mapk3, Il6, Il2, and Fgf2. DZN-induced hippocampal neurotoxicity was associated with the altered activity of multiple signaling pathways (including PI3K-Akt, TNF, and apoptosis signaling). These results provided a theoretical basis for more precise elucidation of DZN neurotoxic mechanisms.
ESTHER : Li_2022_Neurotoxicol__
PubMedSearch : Li_2022_Neurotoxicol__
PubMedID: 35934178

Title : An efficient multi-enzyme cascade platform based on mesoporous metal-organic frameworks for the detection of organophosphorus and glucose - Cao_2022_Food.Chem_381_132282
Author(s) : Cao X , Guo Y , Zhao M , Li J , Wang C , Xia J , Zou T , Wang Z
Ref : Food Chem , 381 :132282 , 2022
Abstract : An efficient colorimetric detection platform based on multi-enzyme cascade has been developed for detection of organophosphorus. Firstly, the dual-enzyme platform was prepared and applied for sensitive glucose detection (detection limit 0.32 microM). And then three enzymes, including acetylcholinesterase, horseradish peroxidase and choline oxidase were encapsulated in cruciate flower-like zeolitic imidazolate framework-8 (CF-ZIF-8) through one-step co-precipitation to construct detection platform with acetylcholine chloride as substrate. The acephate inhibited the activity of acetylcholinesterase, obstructed the cascade reaction and reduced the production of H(2)O(2), resulting in the changes of color intensity for the colorimetric detection. With suitable size and porous structure, CF-ZIF-8 provided a good microenvironment for guaranteeing the activity and spatial proximity of enzymes. The multi-enzyme platform displayed great performances with the detection limit of 0.23 nM for acephate. It was applied to the detection of acephate in Chinese cabbage and romaine, verifying the practicability of this platform.
ESTHER : Cao_2022_Food.Chem_381_132282
PubMedSearch : Cao_2022_Food.Chem_381_132282
PubMedID: 35176684

Title : Cirrhosinones A-H, 24-hydroxy cevanine-type alkaloids from Fritillariacirrhosa - Dong_2022_Phytochemistry_197_113129
Author(s) : Dong H , Zhang Y , Wai Ming T , Wang S , Li J , Fu S , Zhang Q , Zeng K , Tu P , Liang H
Ref : Phytochemistry , 197 :113129 , 2022
Abstract : Eight undescribed isosteroidal alkaloids cirrhosinones A-H (1-8), along with six known isosteroidal alkaloids (9-14), were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were determined by HRESIMS and 2D NMR analysis, and their absolute configurations were established by X-ray analysis. Compounds 1-8 possessed a typical cevanine-type alkaloid skeleton with a hydroxyl group rarely substituted at C-24 and compounds 4-8 possessed rare 7alpha or 7beta-hydroxyl groups. This was the first report of both C-7 and C-24 hydroxyl groups substituted cevanine-type alkaloids. In addition, an approach for distinguishing D/E cis and trans conformations of cevanine-type alkaloids by (1)H NMR data was developed. Moreover, the correlations between the relative configurations of 3-OH, 7-OH, 22-C, 24-OH, and 25-Me and the (1)H NMR and (13)C NMR data were also summarized. Compounds 1-9 exhibited moderate NO inhibitory activities in LPS-stimulated BV-2 cells at the concentration of 40 microM. The acetylcholinesterase inhibitory activities of compounds 1-7 and 9-10 were also evaluated and none of them showed acetylcholinesterase inhibitory activities at the concentrations of 20-80 microM.
ESTHER : Dong_2022_Phytochemistry_197_113129
PubMedSearch : Dong_2022_Phytochemistry_197_113129
PubMedID: 35176308

Title : Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease - Li_2022_ACS.Chem.Neurosci__
Author(s) : Li X , Li T , Zhan F , Cheng F , Lu L , Zhang B , Li J , Hu Z , Zhou S , Jia Y , Allen S , White L , Phillips J , Zhu Z , Xu J , Yao H
Ref : ACS Chem Neurosci , : , 2022
Abstract : Based on a multitarget strategy, a series of novel chromanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). The optimal compound C10 possessed excellent dual AChE/MAO-B inhibition both in terms of potency and equilibrium (AChE: IC(50) = 0.58 0.05 M; MAO-B: IC(50) = 0.41 0.04 M). Further molecular modeling and kinetic investigations revealed that compound C10 was a dual-binding inhibitor bound to both the catalytic anionic site and peripheral anionic site of AChE. In addition, compound C10 exhibited low neurotoxicity and potently inhibited AChE enzymatic activity. Furthermore, compound C10 more effectively protected against mitochondrial dysfunction and oxidation than donepezil, strongly inhibited AChE-induced amyloid aggregation, and moderately reduced glutaraldehyde-induced phosphorylation of tau protein in SH-SY5Y cells. Moreover, compound C10 displayed largely enhanced improvements in cognitive behaviors and spatial memory in a scopolamine-induced AD mice model with better efficacy than donepezil. Overall, the multifunctional profiles of compound C10 suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
ESTHER : Li_2022_ACS.Chem.Neurosci__
PubMedSearch : Li_2022_ACS.Chem.Neurosci__
PubMedID: 36383455

Title : Identification and Validation of Reliable Reference Genes for Gene Expression Studies in Koelreuteria paniculata - Gao_2022_Genes.(Basel)_13_
Author(s) : Gao K , Khan WU , Li J , Huang S , Yang X , Guo T , Guo B , Wu R , An X
Ref : Genes (Basel) , 13 : , 2022
Abstract : RT-qPCR is considered a rapid and reliable technique for analyzing gene expression. This technique is commonly used to analyze the expression of various genes at diverse transcriptional levels in different samples. However, few studies have characterized ornamental Koelreuteria species for reliable reference genes. In this study, eight reference genes were evaluated as controls in RT-qPCR with SYBR green to quantify gene expression in different Koelreuteria paniculata samples. All selected reference genes showed a broad range of C(t) values in all samples, which was supportive of their variable expression. Our results showed significant variation in the stable expression of K. paniculata genes. Sample data, analyzed using geNorm, NormFinder, and BestKeeper, showed that phospholipase (PLA2) and beta-actin (ACT) were the most suitable and statistically reliable reference genes, whereas ribosomal protein L13 (RPL13) and elongation factor 1-alpha (EF1alpha) were less stable and unsuitable for use as internal controls. To compare gene expression levels, two or more reference genes should be used for data normalization. Thus, the stability and expression of both PLA2 and ACT were believed to provide better normalization and quantification of the transcript levels for gene expression studies in K. paniculata.
ESTHER : Gao_2022_Genes.(Basel)_13_
PubMedSearch : Gao_2022_Genes.(Basel)_13_
PubMedID: 35627099

Title : Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes-Related Cognitive Impairment: A Systematic Review and Meta-Analysis of Animal Studies - Hao_2022_Front.Pharmacol_13_917375
Author(s) : Hao Y , Li J , Yue S , Wang S , Hu S , Li B
Ref : Front Pharmacol , 13 :917375 , 2022
Abstract : Berberine, the main bioactive component of Coptis chinensis Franch., is widely used in the treatment of diabetes. Previous studies have reported that berberine supplementation may play a multitarget therapeutic role in diabetes-related cognitive impairment (DCI). This systematic review and meta-analysis evaluated the effect and possible mechanisms of berberine in animal models of DCI. Relevant studies were searched through PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and VIP) until March 2022. Twenty studies involving 442 animals were included, and SYRCLE's risk of bias tool was used to assess methodological quality. The statistical analysis was performed using STATA 15.0 to calculate the weighted standard mean difference (SMD) with a 95% confidence interval (CI). The fasting blood glucose (FBG) and Morris water maze test (MWM) were the main outcomes to be analyzed. The overall results showed that berberine could significantly improve FBG, escape latency, the times of crossing the platform, the time spent in the target quadrant, serum insulin, 2hBG of oral glucose tolerance test (OGTT), amyloid beta (Abeta), acetylcholinesterase (AChE), oxidative stress, and inflammation levels. The present meta-analysis demonstrated that berberine could not only lower blood glucose levels but also improve learning and memory in DCI animal models, which might involve regulating glucose and lipid metabolism, improving insulin resistance, anti-oxidation, anti-neuroinflammation, inhibiting endoplasmic reticulum (ER) stress; and improving the cholinergic system. However, additional attention should be paid to these outcomes due to the significant heterogeneity.
ESTHER : Hao_2022_Front.Pharmacol_13_917375
PubMedSearch : Hao_2022_Front.Pharmacol_13_917375
PubMedID: 35734409

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 : Acute effects of antimony exposure on adult zebrafish (Danio rerio): From an oxidative stress and intestinal microbiota perspective - Wang_2022_Fish.Shellfish.Immunol_123_1
Author(s) : Wang C , Yuan Z , Li J , Liu Y , Li R , Li S
Ref : Fish Shellfish Immunol , 123 :1 , 2022
Abstract : The rapid development of the textile industry has resulted in a large influx of wastewater production. The "national discharge standards of water pollutants for dyeing and finishing of textile industry (GB4287-2012)" stipulates that the discharge of total Sb from textile industry effluent must be < 0.10 mg/L, but it is difficult to meet the standard at present. Antimony is potentially carcinogenic, and the pathogenic mechanism of antimony is poorly understood. In this study, the acute toxic effects of various concentrations of antimony on adult zebrafish (Danio rerio) were investigated, including effects on oxidative stress, neurotransmitters and intestinal microbiota. The activities of catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and acetylcholinesterase (AChE) were measured in zebrafish muscle and intestine tissue samples. In addition, intestinal microbial community composition and diversity of zebrafish were also analyzed. The results demonstrated that SOD, CAT and GSH-Px activities in the zebrafish gut showed a decreasing and then increasing trend with antimony concentration increasing. SOD, CAT and MDA in zebrafish muscle decreased with increasing exposure time. GSH-Px activities increased with increasing exposure time. T-AOC increased and then decreased. In addition, antimony exposure was neurotoxic to zebrafish, and a significant decrease in AChE activity was found in the intestine with increased exposure time. The neurotoxicity caused by antimony in the high concentration group (40 mg/L) was stronger than that in low concentration groups (10 mg/L and 20 mg/L). Notably, antimony exposure caused increases in the relative abundance of phyla Fusobacteriota and Actinomycetes, but decreases in the relative abundance of the phyla Firmicutes and Proteobacteria in zebrafish intestine. These outcomes will advance our understanding of antimony-induced biotoxicity, environmental problems, and health hazards. In conclusion, this study shows that acute exposure of antimony to zebrafish induces host oxidative stress and neurotoxicity, dysregulates the intestinal microbiota, showing adverse effects on the health and gut microbiota of zebrafish.
ESTHER : Wang_2022_Fish.Shellfish.Immunol_123_1
PubMedSearch : Wang_2022_Fish.Shellfish.Immunol_123_1
PubMedID: 35219828

Title : The dark side of synaptic proteins in tumours - Li_2022_Br.J.Cancer__
Author(s) : Li J , Xu Y , Zhu H , Wang Y , Li P , Wang D
Ref : Br J Cancer , : , 2022
Abstract : Research in the past decade has uncovered the essential role of the nervous system in the tumour microenvironment. The recent advances in cancer neuroscience, especially the discovery of neuron-tumour synaptic/perisynaptic structures, have revealed the dark side of synaptic proteins in the progression of brain tumours. Here, we provide an overview of the synaptic proteins expressed by tumour cells and analyse their molecular functions and organisation by comparing them with neuronal synaptic proteins. We focus on the studies of neuroligin-3, the glutamate receptors AMPAR and NMDAR and the synaptic scaffold protein DLGAP1, for their newly discovered regulatory role in the proliferation and progression of tumours. Progress in cancer neuroscience has brought novel insights into the treatment of cancers. In the last part of this review, we discuss the therapeutical strategies targeting synaptic proteins and the current challenges and possible toolkits regarding their clinical application in cancer treatment. Our understanding of cancer neuroscience is still in its infancy; deeper investigation of how tumour cells co-opt synaptic signaling will help fulfil the therapeutical potential of the synaptic proteins as promising anti-tumour targets.
ESTHER : Li_2022_Br.J.Cancer__
PubMedSearch : Li_2022_Br.J.Cancer__
PubMedID: 35624299

Title : Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease - Zhang_2022_Bioorg.Chem_125_105844
Author(s) : Zhang H , Wang Y , Liu D , Li J , Feng Y , Lu Y , Yin G , Li Z , Shi T , Wang Z
Ref : Bioorg Chem , 125 :105844 , 2022
Abstract : A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC(50) > 100 microM; eqBChE IC(50) = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.
ESTHER : Zhang_2022_Bioorg.Chem_125_105844
PubMedSearch : Zhang_2022_Bioorg.Chem_125_105844
PubMedID: 35594720

Title : Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease from Natural (+\/-)-7,8-Dihydroxy-3-methyl-isochroman-4-one - Li_2022_Molecules_27_3090
Author(s) : Li X , Jia Y , Li J , Zhang P , Li T , Lu L , Yao H , Liu J , Zhu Z , Xu J
Ref : Molecules , 27 :3090 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (+/-)-7,8-dihydroxy-3-methyl-isochroman-4-one [(+/-)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Abeta aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood-brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.
ESTHER : Li_2022_Molecules_27_3090
PubMedSearch : Li_2022_Molecules_27_3090
PubMedID: 35630563

Title : Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_229_114044
Author(s) : Liu D , Zhang H , Wang Y , Liu W , Yin G , Wang D , Li J , Shi T , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 229 :114044 , 2022
Abstract : In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-alpha, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Abeta(1-42). Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.
ESTHER : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedSearch : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedID: 34923430

Title : Modulation of Trans-Synaptic Neurexin-Neuroligin Interaction in Pathological Pain - Li_2022_Cells_11_
Author(s) : Li H , Guo R , Guan Y , Li J , Wang Y
Ref : Cells , 11 : , 2022
Abstract : Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx-Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders. The present review provides an overview of the current understanding of the roles of Nrx-Nlg interaction in the regulation of trans-synaptic connections, with a specific focus on Nrx and Nlg structures, the dynamic shaping of synaptic function, and the dysregulation of Nrx-Nlg in pathological pain. Additionally, we discuss a range of proteins capable of modulating Nrx-Nlg interactions at the synaptic cleft, with the objective of providing a foundation to guide the future development of novel therapeutic agents for managing pathological pain.
ESTHER : Li_2022_Cells_11_
PubMedSearch : Li_2022_Cells_11_
PubMedID: 35741069

Title : Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study - Li_2022_J.Neuroinflammation_19_131
Author(s) : Li J , Lin J , Pan Y , Wang M , Meng X , Li H , Wang Y , Zhao X , Qin H , Liu L
Ref : J Neuroinflammation , 19 :131 , 2022
Abstract : OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.
ESTHER : Li_2022_J.Neuroinflammation_19_131
PubMedSearch : Li_2022_J.Neuroinflammation_19_131
PubMedID: 35761288

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

Title : Predictive value of serum cholinesterase in the mortality of acute pancreatitis: A retrospective cohort study - Wei_2022_Eur.J.Clin.Invest__e13741
Author(s) : Wei M , Xie X , Yu X , Lu Y , Ke L , Ye B , Zhou J , Li G , Li B , Tong Z , Lu G , Li W , Li J
Ref : European Journal of Clinical Investigation , :e13741 , 2022
Abstract : BACKGROUND: Severe acute pancreatitis has a high mortality of 20-40%, but there is lack of optimal prognostic biomarker for the severity of acute pancreatitis (AP) or mortality. This study is designed to investigate the relationship between serum cholinesterase (ChE) level and poor outcomes of AP. METHODS: A total of 1904 AP patients were screened in the study, and we finally got 692 patients eligible for analysis. Patients were divided into 2 groups based on serum ChE. The primary outcome was mortality, and multivariable logistic regression analysis for mortality was completed. Additionally, we used receiver operator characteristic (ROC) curve analysis to clarify the predictive value of serum ChE for mortality and organ failure. RESULTS: 378 patients and 314 patients were included in ChE low and normal group, respectively. Patients in ChE low group were older (46.68+/-12.70 vs 43.56+/-12.13 years old, p=0.001) and had a lower percentage of male (62.4% vs 71.0%, p=0.017) when compared with the ChE normal group. Mortality was significantly different in two groups (10.3% vs 0.0%, p<0.001). Moreover, organ failure also differed significantly in two groups (46.6% vs 8.6%, p<0.001). Decreased ChE level was independently associated with mortality in acute pancreatitis (odds ratio: 0.440; 95% confidence interval, 0.231, 0.838, p=0.013). The area under the curve of serum ChE was 0.875 and 0.803 for mortality and organ failure, respectively. CONCLUSIONS: Lower level of serum ChE was independently associated with the severity and mortality of AP.
ESTHER : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedSearch : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedID: 34981831

Title : Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer - Xu_2022_Ann.Transl.Med_10_169
Author(s) : Xu Y , Wang X , Chu Y , Li J , Wang W , Hu X , Zhou F , Zhang H , Zhou L , Kuai R , Jin Y , Yang D , Peng H
Ref : Ann Transl Med , 10 :169 , 2022
Abstract : BACKGROUND: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. METHODS: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). RESULTS: A total of 237 significantly differentially expressed genes (P(adj)<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. CONCLUSIONS: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
ESTHER : Xu_2022_Ann.Transl.Med_10_169
PubMedSearch : Xu_2022_Ann.Transl.Med_10_169
PubMedID: 35280417

Title : Anti-Alzheimer's disease active components screened out and identified from Hedyotis diffusa combining bioaffinity ultrafiltration LC-MS with acetylcholinesterase - Li_2022_J.Ethnopharmacol__115460
Author(s) : Li J , Yang G , Shi W , Fang X , Han L , Cao Y
Ref : J Ethnopharmacol , :115460 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa is a traditional ethnomedicinal plant in local communities in northeastern Asia and used to treat inflammation, nervous breakdown, among others. In recent years, it has been applied in the treatment of Alzheimer's disease (AD), while the specific chemical components responsible for the activity remain need to be explored. AIM OF THE STUDY: To prepare, screen and identify the potential anti-AD active components from Hedyotis diffusa. MATERIALS AND METHODS: The acetylcholinesterase (AChE) inhibitory activity of four different extracts of Hedyotis diffusa were initially assessed using a spectrophotometric Ellman's method. A more accurate LC-MS/MS screening method combining functional enzyme assay and affinity ultrafiltration (AU) screening assay was developed and applied for the screening of natural compound inhibitors of AChE from Hedyotis diffusa. The binding mode were further investigated between protein and ligands via molecular docking. Subsequently, CL4176, a transgenic nematode model for AD, was used for activity validation of one of these components. RESULTS: N-butanol extract of Hedyotis diffusa (NHD) appeared significant inhibitory activities on AChE, were chosen to delve deeper. Five bioactive components targeting AChE were screened out and identified using AU coupled to liquid chromatography-mass spectrometry. Molecular docking technique further confirmed the results of the screening assay. Finally, qurecetin-3-O-sophoroside (QS) was confirmed as a potent anti-AD agent by in vivo experiments in C. elegans. CONCLUSION: This study explores a new idea for screening anti-AD active components from traditional medicine. The findings provide a molecular structure and bioactivity basis for future potential applications of Hedyotis diffusa in medical industries.
ESTHER : Li_2022_J.Ethnopharmacol__115460
PubMedSearch : Li_2022_J.Ethnopharmacol__115460
PubMedID: 35714878

Title : A carboxylesterase-activatable near-infrared phototheranostic probe for tumor fluorescence imaging and photodynamic therapy - Li_2022_RSC.Adv_12_35477
Author(s) : Li L , Zhang Q , Li J , Tian Y , Liu W , Diao H
Ref : RSC Adv , 12 :35477 , 2022
Abstract : Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics.
ESTHER : Li_2022_RSC.Adv_12_35477
PubMedSearch : Li_2022_RSC.Adv_12_35477
PubMedID: 36540215

Title : Detoxification mechanism of vinegar-processed Kansui revealed by systematic phytochemical analysis using UPLC-DAD-MS\/MS, UPLC-HR-MS and in silico drug target identification - Liu_2022_Rapid.Commun.Mass.Spectrom__e9332
Author(s) : Liu L , Li J , Lv J , Jiang H , Chen FE
Ref : Rapid Commun Mass Spectrom , :e9332 , 2022
Abstract : RATIONALE: The dried roots of Euphorbia kansui L., known as Kansui, have been used to treat ascites and edema in Traditional Chinese Medicine. However, the toxicity of this herb had seriously restricted its clinical application. A unique vinegar-processing method has been used to reduce its toxicity since ancient China. However, the detoxification mechanism underlying such vinegar-processing has not been fully revealed, to find the answer, the processed-induced components change should be carefully investigated. METHODS: Here we performed systematic analysis of chemical components in raw and vinegar-processed Kansui by UPLC-DAD-MS/MS and UPLC-HR-MS, 31 chemical components in raw and vinegar processed Kansui were found, and the chemical structure of 28 components among them was proposed, and the processed-induced components change was then investigated. RESULTS: A comprehensive conclusion about the processed-induced chemical change was drew. It was found that jatrophane-type diterpenoids decreased markedly after the vinegar-processing, while ingenane-type diterpenoids retained in the vinegar-processing. In silico drug target identification gave hints that jatrophane-type diterpenoids, which decreased markedly during the vinegar-processing, maybe has more intense toxicity involved in cholinesterase and MAPKs, while ingenane-type diterpenoids, which retained in the vinegar-processing, maybe has more intense therapeutic effect involved in carbonic anhydrase. CONCLUSIONS: The possible detoxification mechanism of vinegar-processed Kansui was present. The research has significance on the therapeutic/toxic chemical basis of Kansui, besides, it has significance on drug discovery from terpenoids within the herb.
ESTHER : Liu_2022_Rapid.Commun.Mass.Spectrom__e9332
PubMedSearch : Liu_2022_Rapid.Commun.Mass.Spectrom__e9332
PubMedID: 35716385

Title : Lipase-catalyzed hydrazine insertion for the synthesis of N'-alkyl benzohydrazides - Yu_2022_Biotechnol.Appl.Biochem__
Author(s) : Yu Y , Li F , Li J , Zheng X , Tian H , Mahmut Z , Du Y , Dai Y , Wang L
Ref : Biotechnol Appl Biochem , : , 2022
Abstract : N'-alkyl benzohydrazides are classic organic compounds that have been widely utilized in organic chemistry. In this study, an efficient method was developed for the synthesis of N'-alkyl benzohydrazides by hydrazine insertion catalyzed by lipase. Under the optimal conditions (Morita-Baylis-Hillman ketone [1 mmol], phenylhydrazine [1.3 mmol], N,N-dimethylformamide [2 mL], lipase [20 mg], room temperature, 12 h), satisfactory yields (71%-97%) and substrate tolerance were obtained when porcine pancreatic lipase was used as biocatalyst. These findings imply the great potential for the lipase-catalyzed synthesis of N'-alkyl benzohydrazides and extend the utilization of lipase in organic chemistry. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2022_Biotechnol.Appl.Biochem__
PubMedSearch : Yu_2022_Biotechnol.Appl.Biochem__
PubMedID: 35285069

Title : Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93 - Li_2022_Front.Microbiol_13_1081094
Author(s) : Li Y , Rong Z , Li Z , Cui H , Li J , Xu XW
Ref : Front Microbiol , 13 :1081094 , 2022
Abstract : INTRODUCTION: CPT11 (Irinotecan; 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) is an important camptothecin-based broad-spectrum anticancer prodrug. The activation of its warhead, SN38 (7-ethyl-10-hydroxycamptothecin), requires hydrolysis by carboxylesterases. NPC (7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin) is a metabolic derivative of CPT11 and is difficult to be hydrolyzed by human carboxylesterase. Microbial carboxylesterase with capability on both CPT11 and NPC hydrolysis is rarely reported. A marine microbial carboxylesterase, E93, was identified to hydrolyze both substrates in this study. This enzyme was an appropriate subject for uncovering the catalytic mechanism of carboxylesterases to CPT11 and NPC hydrolysis. METHODS: X-ray diffraction method was applied to obtain high-resolution structure of E93. Molecular docking was adopted to analyze the interaction of E93 with p-NP (p-nitrophenyl), CPT11, and NPC substrates. Mutagenesis and enzymatic assay were adopted to verify the binding pattern of substrates. RESULTS: Three core regions (Region A, B, and C) of the catalytic pocket were identified and their functions on substrates specificity were validated via mutagenesis assays. The Region A was involved in the binding with the alcohol group of all tested substrates. The size and hydrophobicity of the region determined the binding affinity. The Region B accommodated the acyl group of p-NP and CPT11 substrates. The polarity of this region determined the catalytic preference to both substrates. The Region C specifically accommodated the acyl group of NPC. The interaction from the acidic residue, E428, contributed to the binding of E93 with NPC. DISCUSSION: The study analyzed both unique and conserved structures of the pocket in E93, for the first time demonstrating the discrepancy of substrate-enzyme interaction between CPT11 and NPC. It also expanded the knowledge about the substrate specificity and potential application of microbial Family VII carboxylesterases.
ESTHER : Li_2022_Front.Microbiol_13_1081094
PubMedSearch : Li_2022_Front.Microbiol_13_1081094
PubMedID: 36756200

Title : Magnetic COFs as satisfied support for lipase immobilization and recovery to effectively achieve the production of biodiesel by great maintenance of enzyme activity - Zhou_2021_Biotechnol.Biofuels_14_156
Author(s) : Zhou ZW , Cai CX , Xing X , Li J , Hu ZE , Xie ZB , Wang N , Yu XQ
Ref : Biotechnol Biofuels , 14 :156 , 2021
Abstract : BACKGROUND: Production of biodiesel from renewable sources such as inedible vegetable oils by enzymatic catalysis has been a hotspot but remains a challenge on the efficient use of an enzyme. COFs (Covalent Organic Frameworks) with large surface area and porosity can be applied as ideal support to avoid aggregation of lipase and methanol. However, the naturally low density limits its application. In this work, we reported a facile synthesis of core-shell magnetic COF composite (Fe(3)O(4)@COF-OMe) to immobilize RML (Rhizomucor miehei lipase), to achieve its utilization in biodiesel production. RESULT: This strategy gives extrinsic magnetic property, and the magnetic COFs is much heavier and could disperse in water medium well, facilitating the attachment with the enzyme. The resultant biocomposite exhibited an excellent capacity of RML due to its high surface area and fast response to the external magnetic field, as well as good chemical stability. The core-shell magnetic COF-OMe structure not only achieved highly efficient immobilization and recovery processes but also maintained the activity of lipase to a great extent. RML@Fe(3)O(4)@COF-OMe performed well in practical applications, while free lipase did not. The biocomposite successfully achieved the production of biodiesel from Jatropha curcas Oil with a yield of about 70% in the optimized conditions. CONCLUSION: Magnetic COFs (Fe(3)O(4)@COF-OMe) for RML immobilization greatly improved catalytic performance in template reaction and biodiesel preparation. The magneticity makes it easily recovered and separated from the system. This first successful attempt of COFs-based immobilized enzyme broadened the prospect of biodiesel production by COFs with some inspiration.
ESTHER : Zhou_2021_Biotechnol.Biofuels_14_156
PubMedSearch : Zhou_2021_Biotechnol.Biofuels_14_156
PubMedID: 34261529

Title : Odorant degrading carboxylesterases modulate foraging and mating behaviors of Grapholita molesta - Wei_2021_Chemosphere_270_128647
Author(s) : Wei H , Tan S , Li Z , Li J , Moural TW , Zhu F , Liu X
Ref : Chemosphere , 270 :128647 , 2021
Abstract : Odorant degrading carboxylesterases (CXEs) play key roles in the process of odor signal reception via degrading ester odorants. But the functional mechanisms of CXEs in modulating insect behaviors are unclear. Herein, we studied the roles that CXEs played in mating, foraging, and signal receptions of sex pheromones and host volatiles in Grapholita molesta. As a result, 23 candidate CXEs were identified by transcriptome analysis of G. molesta. The GmolCXE1 and 5 highly expressed in the antennae of male moths and GmolCXE14 and 21 abundantly expressed in larval heads, were significantly upregulated after exposure with odors from female adults or fresh ripe fruits respectively. After knockdown of GmolCXE1 and 5, or GmolCXE14 and 21 by RNA interference, the behavioral responses of G. molesta to ester sex pheromones or host volatiles were decreased, by exhibiting an inhibited searching behavior of G. molesta for females or fruits, respectively. Then evidence form GC-MS analysis, showed that the protein GmolCXE1 and GmolCXE5 could metabolize the sex pheromone components (Z/E)-8-dodecenyl acetate to their metabolites products (Z/E)-8-dodecenol, and that GmolCXE14 and GmolCXE21 could metabolize ethyl butanoate and ethyl hexanoate of ripe pears. In addition, fluorescent binding assays verified that GmolCXEs could degrade the free ester odor molecules, but not degrade the odor molecules protected by odorant-binding proteins. Our study not only demonstrated CXEs modulated the mating and foraging behaviors of G. molesta through inactivation of ester sex pheromone and host volatiles, but also discovered great potential molecular targets to develop behavioral inhibitors for pest management.
ESTHER : Wei_2021_Chemosphere_270_128647
PubMedSearch : Wei_2021_Chemosphere_270_128647
PubMedID: 33757271

Title : Activation of Tenofovir Alafenamide and Sofosbuvir in the Human Lung and Its Implications in the Development of Nucleoside\/Nucleotide Prodrugs for Treating SARS-CoV-2 Pulmonary Infection - Li_2021_Pharmaceutics_13_
Author(s) : Li J , Liu S , Shi J , Zhu HJ
Ref : Pharmaceutics , 13 : , 2021
Abstract : ProTide technology is a powerful tool for the design of nucleoside/nucleotide analog prodrugs. ProTide prodrug design improves cell permeability and enhances intracellular activation. The hydrolysis of the ester bond of a ProTide is a determinant of the intracellular activation efficiency and final antiviral efficacy of the prodrug. The hydrolysis is dictated by the catalytic activity and abundance of activating enzymes. The antiviral agents tenofovir alafenamide (TAF) and sofosbuvir (SBV) are typical ProTides. Both TAF and SBV have also been proposed to treat patients with COVID-19. However, the mechanisms underlying the activation of the two prodrugs in the lung remain inconclusive. In the present study, we profiled the catalytic activity of serine hydrolases in human lung S9 fractions using an activity-based protein profiling assay. We evaluated the hydrolysis of TAF and SBV using human lung and liver S9 fractions and purified enzymes. The results showed that CatA and CES1 were involved in the hydrolysis of the two prodrugs in the human lung. More specifically, CatA exhibited a nearly 4-fold higher hydrolytic activity towards TAF than SBV, whereas the CES1 activity on hydrolyzing TAF was slightly lower than that for SBV. Overall, TAF had a nearly 4-fold higher hydrolysis rate in human lung S9 than SBV. We further analyzed protein expression levels of CatA and CES1 in the human lung, liver, and primary cells of the two tissues using proteomics data extracted from the literature. The relative protein abundance of CatA to CES1 was considerably higher in the human lung and primary human airway epithelial cells than in the human liver and primary human hepatocytes. The findings demonstrated that the high susceptivity of TAF to CatA-mediated hydrolysis resulted in efficient TAF hydrolysis in the human lung, suggesting that CatA could be utilized as a target activating enzyme when designing antiviral ester prodrugs for the treatment of respiratory virus infection.
ESTHER : Li_2021_Pharmaceutics_13_
PubMedSearch : Li_2021_Pharmaceutics_13_
PubMedID: 34683949
Gene_locus related to this paper: human-CTSA

Title : Distal mutation V486M disrupts the catalytic activity of DPP4 by affecting the flap of the propeller domain - Li_2021_Acta.Pharmacol.Sin__1
Author(s) : Li TT , Peng C , Wang JQ , Xu ZJ , Su MB , Li J , Zhu WL , Li JY
Ref : Acta Pharmacol Sin , :1 , 2021
Abstract : Dipeptidyl peptidase-4 (DPP4) plays a crucial role in regulating the bioactivity of glucagon-like peptide-1 (GLP-1) that enhances insulin secretion and pancreatic beta-cell proliferation, making it a therapeutic target for type 2 diabetes. Although the crystal structure of DPP4 has been determined, its structure-function mechanism is largely unknown. Here, we examined the biochemical properties of sporadic human DPP4 mutations distal from its catalytic site, among which V486M ablates DPP4 dimerization and causes loss of enzymatic activity. Unbiased molecular dynamics simulations revealed that the distal V486M mutation induces a local conformational collapse in a beta-propeller loop (residues 234-260, defined as the flap) and disrupts the dimerization of DPP4. The "open/closed" conformational transitions of the flap whereby capping the active site, are involved in the enzymatic activity of DPP4. Further site-directed mutagenesis guided by theoretical predictions verified the importance of the conformational dynamics of the flap for the enzymatic activity of DPP4. Therefore, the current studies that combined theoretical modeling and experimental identification, provide important insights into the biological function of DPP4 and allow for the evaluation of directed DPP4 genetic mutations before initiating clinical applications and drug development.
ESTHER : Li_2021_Acta.Pharmacol.Sin__1
PubMedSearch : Li_2021_Acta.Pharmacol.Sin__1
PubMedID: 34907358

Title : m(6) A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer - Xue_2021_J.Cell.Physiol_236_2649
Author(s) : Xue L , Li J , Lin Y , Liu D , Yang Q , Jian J , Peng J
Ref : Journal of Cellular Physiology , 236 :2649 , 2021
Abstract : N(6) -methyladenosine (m(6) A) and long noncoding RNAs (lncRNAs) are both crucial regulators in non-small-cell lung cancer (NSCLC) tumorigenesis. However, the pathological roles of m(6) A and lncRNAs in NSCLC progression are still limited and undefined. Here, lncRNA ABHD11-AS1 was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients. Functionally, ABHD11-AS1 promoted the proliferation and Warburg effect of NSCLC. Mechanistically, m(6) A profile was analyzed by methylated RNA immunoprecipitation sequencing (MeRIP-Seq). MeRIP-Seq presented that there was m(6) A modification site in ABHD11-AS1. m(6) A methyltransferase-like 3 (METTL3) installed the m(6) A modification and enhanced ABHD11-AS1 transcript stability to increase its expression. In conclusion, our findings highlight the function and mechanism of METTL3-induced ABHD11-AS1 in NSCLC and inspire the understanding of m(6) A and lncRNA in cancer biology.
ESTHER : Xue_2021_J.Cell.Physiol_236_2649
PubMedSearch : Xue_2021_J.Cell.Physiol_236_2649
PubMedID: 32892348
Gene_locus related to this paper: human-ABHD11

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

Title : Risk Factors and a Nomogram Model Establishment for Postoperative Delirium in Elderly Patients Undergoing Arthroplasty Surgery: A Single-Center Retrospective Study - Chen_2021_Biomed.Res.Int_2021_6607386
Author(s) : Chen D , Li Y , Li Q , Gao W , Li J , Wang S , Cao J
Ref : Biomed Res Int , 2021 :6607386 , 2021
Abstract : OBJECTIVE: To explore the related risk factors of postoperative delirium (POD) after hip or knee arthroplasty in elderly orthopedic patients and the predictive value of related risk factors. Material and Methods. In total, 309 patients (<=60 years) who received knee and hip arthroplasty between January 2017 and May 2020 were consecutively selected into the POD and nonpostoperative delirium (NPOD) groups. Group bias was eliminated through propensity score matching. Univariate and multivariable logistic analysis was used to determine the risk factors for POD. The nomogram was made by R. RESULTS: 58 patients were included in each group after propensity score matching; multivariable analysis demonstrated that LDH (OR = 4.364, P = 0.017), CHE (OR = 4.640, P = 0.004), Cystatin C (OR = 5.283, P = 0.006), arrhythmia (OR = 5.253, P = 0.002), and operation duration (OR = 1.017, P = 0.050) were independent risk factors of POD. LDH, CHE, Cystatin C, and arrhythmia were used to construct a nomogram to predict the POD. The nomogram was well calibrated and had moderate discriminative ability (AUC = 0.821, 95% CI: 0.760~0.883). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Our study revealed that arrhythmia, operation duration, the increase of lactate dehydrogenase and Cystatin C, and the decrease of cholinesterase were reliable factors for predicting postoperative delirium after elderly hip and knee arthroplasty. Meanwhile, the nomogram we developed can assist the clinician to filtrate potential patients with postoperative delirium.
ESTHER : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedSearch : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedID: 34901277

Title : Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study - Mu_2021_Neurol.Res.Int_2021_6009342
Author(s) : Mu L , Chen J , Li J , Sobotka S , Nyirenda T
Ref : Neurol Res Int , 2021 :6009342 , 2021
Abstract : BACKGROUND: Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause "foot drop," a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). METHODS: As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. RESULTS: The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. CONCLUSION: NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.
ESTHER : Mu_2021_Neurol.Res.Int_2021_6009342
PubMedSearch : Mu_2021_Neurol.Res.Int_2021_6009342
PubMedID: 34925918

Title : Genome-Wide Selective Signature Analysis Revealed Insecticide Resistance Mechanisms in Cydia pomonella - Dai_2021_Insects_13_
Author(s) : Dai WT , Li J , Ban LP
Ref : Insects , 13 : , 2021
Abstract : The codling moth, Cydia pomonella L. (Lepidoptera, Tortricidae), is a serious invasive pest of pome fruits. Currently, C. pomonella management mainly relies on the application of insecticides, which have driven the development of resistance in the insect. Understanding the genetic mechanisms of insecticide resistance is of great significance for developing new pest resistance management techniques and formulating effective resistance management strategies. Using existing genome resequencing data, we performed selective sweep analysis by comparing two resistant strains and one susceptible strain of the insect pest and identified seven genes, among which, two (glycine receptor and glutamate receptor) were under strong insecticide selection, suggesting their functional importance in insecticide resistance. We also found that eight genes including CYP6B2, CYP307a1, 5-hydroxytryptamine receptor, cuticle protein, and acetylcholinesterase, are potentially involved in cross-resistance to azinphos-methyl and deltamethrin. Moreover, among several P450s identified as positively selected genes, CYP6B2, CYP4C1, and CYP4d2 showed the highest expression level in larva compared to other stages tested, and CYP6B2 also showed the highest expression level in midgut, supporting the roles they may play in insecticide metabolism. Our results provide several potential genes that can be studied further to advance understanding of complexity of insecticide resistance mechanisms in C. pomonella.
ESTHER : Dai_2021_Insects_13_
PubMedSearch : Dai_2021_Insects_13_
PubMedID: 35055845

Title : Using structural analysis to clarify the impact of single nucleotide variants in neurexin\/neuroligin revealed in clinical genomic sequencing - Xue_2021_J.Biomol.Struct.Dyn__1
Author(s) : Xue K , Hu Y , Gu S , Wang C , Kong R , Xie W , Li J
Ref : J Biomol Struct Dyn , :1 , 2021
Abstract : The synapse is a highly specialized and dynamic structure, which is involved in regulating neurotransmission. Nerve cell adhesion molecule is a kind of transmembrane protein that mediates the interaction between cells and cells, cells and extracellular matrix, and plays a role in cell recognition, metastasis, and transmembrane signal transduction. Among nerve cell adhesion molecules, Neurexins (NRXNs) and Neuroligins (NLGNs) have been focused due to the relation with autism and other neuropsychiatric diseases. The previous research discovered numerous variants in NRXNs and NLGNs reported in neurodevelopmental disorders by genomic sequencing. However, structural variants in synaptic molecules caused by genome variants still prevent us from understanding the molecular mechanism of diseases. Thus, we sought to conduct a comprehensive risk assessment of the known NRXN and NLGN gene variants by protein structure analysis. In this study, we analyzed the structural properties of the NRXN/NLGN complex by calculating free energy in residue scanning, in combination with existing risk evaluation tools to focus on candidate missense mutations. Our calculations show that five candidate missense mutations in NLGNs can reduce the stability of NLGNs and even prevent the formation of NRXN/NLGN complexes, namely R87W, R204H, R437H, R437C and R583W. In addition, we found that the affinity of the amino acid substitution (Leu593Phe) (deltadeltaG((affinity))) changes the affinity of the NLGN dimer. Overall, we have identified important potential pathological variants that provide clues to biomarkers.Communicated by Ramaswamy H. Sarma.
ESTHER : Xue_2021_J.Biomol.Struct.Dyn__1
PubMedSearch : Xue_2021_J.Biomol.Struct.Dyn__1
PubMedID: 33818307

Title : Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus - Liu_2021_Front.Neural.Circuits_15_638000
Author(s) : Liu X , Shi M , Ren H , Xie M , Zhang C , Wang D , Li J , Wang M
Ref : Front Neural Circuits , 15 :638000 , 2021
Abstract : Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme-DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, P < 0.05). Our findings demonstrated Vme-DMV circuit via which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level.
ESTHER : Liu_2021_Front.Neural.Circuits_15_638000
PubMedSearch : Liu_2021_Front.Neural.Circuits_15_638000
PubMedID: 33776655

Title : Enantioselective determination of phenthoate enantiomers in plant-origin matrices using reversed-phase high performance liquid chromatography-tandem mass spectrometry - Dong_2021_Biomed.Chromatogr__e5229
Author(s) : Dong C , Zhou J , Zuo W , Li Z , Li J , Jiao B
Ref : Biomedical Chromatography , :e5229 , 2021
Abstract : Phenthoate is a chiral organophosphate pesticide with a pair of enantiomers which differ in toxicity, behavior, and insecticidal activity, and its acute toxicity on human health due to the inhibition of acetylcholinesterase highlights the need for enantioselective detection of enantiomers. Therefore, this study is aimed to establish a simple rapid method for separation and detection of phenthoate enantiomers in fruits, vegetables, and grains. The enantiomers were separated using reversed-phase high performance liquid chromatography-tandem mass spectrometry (RP-HPLC-MS/MS) for the first time. Rapid chiral separation (within 9 min) of the target compound was achieved on a chiral OJ-RH column with the mobile phase of methanol/water=85/15(v/v), at a flow rate of 1 mL/min and column temperature of 30 degreesC. Acetonitrile and graphitized carbon black were used as the extractant and sorbent for pretreatment, respectively. This method provides excellent linearity (correlation coefficient no less than 0.9986), high sensitivity (limits of quantification at 5 microg/kg and limits of detection less than 0.25 microg/kg), satisfactory mean recoveries (76.2% to 91.0%) and relative standard deviations (intra-day RSDs ranged from 2.0% to 7.9% and inter-day RSDs ranged from 2.4% to 8.4%). In addition, field trial to explore the stereoselective degradation of phenthoate enantiomers in citrus showed that (-)-phenthoate degraded faster than its antipode, resulting in the relative accumulation of (+)-phenthoate.
ESTHER : Dong_2021_Biomed.Chromatogr__e5229
PubMedSearch : Dong_2021_Biomed.Chromatogr__e5229
PubMedID: 34414593

Title : Contributions of Cathepsin A and Carboxylesterase 1 to the hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis - Li_2021_Drug.Metab.Dispos__
Author(s) : Li J , Shi J , Xiao J , Tran L , Wang X , Zhu HJ
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitro incubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH-dependent manner. At their physiological pH environment, the activity of CatA (pH 5.2) was approximately 1,000-fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200-fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis-(p-nitrophenyl) phosphate. Moreover, an in vitro study revealed that the CES1 variant G143E (rs71647871) is a loss-of-function variant for CES1-mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation. Significance Statement Contrary to the general perception that carboxylesterase 1 (CES1) is the major enzyme responsible for tenofovir alafenamide (TAF) hydrolysis in the human liver, the present study demonstrated that cathepsin A (CatA) may play a more significant role in TAF hepatic hydrolysis. Furthermore, the CES1 variant G143E (rs71647871) was found to be a loss-of-function variant for CES1-mediated TAF hydrolysis.
ESTHER : Li_2021_Drug.Metab.Dispos__
PubMedSearch : Li_2021_Drug.Metab.Dispos__
PubMedID: 34933885
Gene_locus related to this paper: human-CES1 , human-CTSA

Title : Preparation of a Bombyx mori acetylcholinesterase enzyme reagent through chaperone protein disulfide isomerase co-expression strategy in Pichia pastoris for detection of pesticides - Li_2021_Enzyme.Microb.Technol_144_109741
Author(s) : Li J , Cai J , Ma M , Li L , Lu L , Wang Y , Wang C , Yang J , Xu Z , Yao M , Shen X , Wang H
Ref : Enzyme Microb Technol , 144 :109741 , 2021
Abstract : The cholinesterase-based spectrophotometric methods for detection of organophosphate pesticides (OPs) and carbamate pesticides (CPs) have been proposed as a good choice for their high efficiency, simplicity and low cost. The enzyme, as a core reagent, is of great importance for the developed method. In this study, a protein disulfide isomerase (PDI) co-expression strategy in Pichia pastoris was employed to enhance the yield of recombinant Bombyx mori acetylcholinesterase 2 (rBmAChE2). Subsequently, the prepared enzyme reagent was used to detect the pesticides in real samples. The results showed that the co-expression of rBmAChE2 with PDI increased the enzyme activity of the supernatant and the yield of purified rBmAChE2 up to 60 U/mL and 6 mg/L respectively, both almost 5-fold higher than those of original recombinant strain. In addition, 5 g/L gelatin reagent could help to preserve nearly 90% of the rBmAChE2 activity for 90 days in 4 degreesC and the limits of detections (LODs) of the rBmAChE2-based assay for 20 kinds of OPs or CPs ranged from 0.010 to 2.725 mg/kg, which were lower than most of indexes present in current Chinese National Standard (GB/T 5009.199-2003) or the maximum residue limits (GB 2763-2019). Furthermore, the detection results of 23 vegetable samples were verified by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, which indicated that the rBmAChE2-based assay in this work is suitable for pesticide residues rapid detection.
ESTHER : Li_2021_Enzyme.Microb.Technol_144_109741
PubMedSearch : Li_2021_Enzyme.Microb.Technol_144_109741
PubMedID: 33541576
Gene_locus related to this paper: boomi-ACHE2

Title : Accelerated biodegradation of polyethylene terephthalate by Thermobifida fusca cutinase mediated by Stenotrophomonas pavanii - Huang_2021_Sci.Total.Environ__152107
Author(s) : Huang QS , Yan ZF , Chen XQ , Du YY , Li J , Liu ZZ , Xia W , Chen S , Wu J
Ref : Sci Total Environ , :152107 , 2021
Abstract : Polyethylene terephthalate (PET) is a general plastic that produces a significant amount of waste due to its non-degradable properties. We obtained four bacteria (Stenotrophomonas pavanii JWG-G1, Comamonas thiooxydans CG-1, Comamonas koreensis CG-2 and Fulvimonas soli GM-1) that utilize PET as a sole carbon source through a novel stepwise screening and verification strategy. PET films pretreated with S. pavanii JWG-G1 exhibited weight loss of 91.4% following subsequent degradation by Thermobifida fusca cutinase (TfC). S. pavanii JWG-G1 was able to colonize the PET surface and maintain high cell viability (over 50%) in biofilm, accelerating PET degradation. Compared with PET films with no pretreatment, pretreatment with S. pavanii JWG-G1 caused the PET surface to be significantly rougher with greater hydrophilicity (contact angle of 86.3 +/- 2 degrees vs. 96.6 +/- 2 degrees), providing better opportunities for TfC to contact and act on PET. Our study indicates that S. pavanii JWG-G1 could be used as a novel pretreatment for efficiently accelerating PET biodegradation by TfC.
ESTHER : Huang_2021_Sci.Total.Environ__152107
PubMedSearch : Huang_2021_Sci.Total.Environ__152107
PubMedID: 34864034

Title : Enhanced Secretory Expression and Surface Display Level of Bombyx mori Acetylcholinesterase 2 by Pichia pastoris Based on Codon Optimization Strategy for Pesticides Setection - Li_2021_Appl.Biochem.Biotechnol__
Author(s) : Li J , Xie X , Cai J , Wang H , Yang J
Ref : Appl Biochem Biotechnol , : , 2021
Abstract : The cholinesterase-based spectrophotometric assay, also called enzyme inhibition method, is a good choice for rapid detection of organophosphate pesticides (OPs) and carbamate pesticides (CPs). Obviously, the cholinesterase is the core reagent in enzyme inhibition method. In our previous work, a recombinant acetylcholinesterase 2 from Bombyx mori (rBmAChE2) was expressed in yeast successfully and exhibited great sensitivity. However, the yield of rBmAChE2 is not desirable. In this study, a codon optimization strategy was employed to enhance the yield of rBmAChE2 in Pichia pastoris GS115. Results showed that by replacing 6 key rare codons and increasing the percentage of bases G and C up to 46.85%, codon adaptation index (CAI) of Bombyx mori acetylcholinesterase 2 (bmace2) gene was improved from 0.70 to 0.81. After being transformed into Pichia pastoris GS115 via electroporation, the expression transformant can produce 139.7 U/mL secretory codon-optimized rBmAChE2 (opt-rBmAChE2) in the culture supernatant, 3.62 times higher than that of strain bearing the wild-type bmace2 gene. Meanwhile, opt-rBmAChE2 displayed on the yeast surface was up to 2280.02 U/g, 2.8 times higher than wild-type displayed rBmAChE2. In addition, either secretory or surface-displayed opt-rBmAChE2 maintained the similar sensitivities to the wild-type rBmAChE2 for tested inhibitors. Furthermore, the detection limits of the opt-rBmAChE2-based enzyme inhibition method for 10 kinds of OPs or CPs (0.01-2.69 mg/kg) were lower than most of the indexes present in current standard method (GB/T 5009.199-2003) or the maximum residue limits (GB 2763-2019) in China. The results might contribute to the utilization of rBmAChE2 for pesticide residue screening detection in practice.
ESTHER : Li_2021_Appl.Biochem.Biotechnol__
PubMedSearch : Li_2021_Appl.Biochem.Biotechnol__
PubMedID: 34160750

Title : Complexation of caffeine and theophylline with epigallocatechin gallate in aqueous solution: Nuclear magnetic resonance, molecular docking and thermodynamics studies - Guo_2021_Food.Res.Int_148_110587
Author(s) : Guo C , Li J , Chen Y , Geng F , Li B
Ref : Food Res Int , 148 :110587 , 2021
Abstract : Epigallocatechin gallate (EGCg) and methylxanthines are representative bioactive compounds in tea leaves, the strong affinity between them will elicit destruction of tea quality. In order to elucidate the mechanism of complexation between EGCg and methylxanthines, we compared the bindings of theophylline and caffeine to EGCg by nuclear magnetic resonance (NMR), molecular docking and isothermal titration calorimetry (ITC). The results revealed that the stoichiometries of caffeine to EGCg and theophylline to EGCg were both 1:1. Caffeine and theophylline were captured in the hydrophobic space formed by aromatic rings of EGCg. The affinity between EGCg and caffeine was stronger than that between EGCg and theophylline, which could be partially attributed to the two extra CH-Pi interactions between N(7)-Me of caffeine and aromatic rings of EGCg. Furthermore, the results of ITC were agreed well with NMR and molecular docking, indicating that ITC was possible to accurately evaluate the complexation.
ESTHER : Guo_2021_Food.Res.Int_148_110587
PubMedSearch : Guo_2021_Food.Res.Int_148_110587
PubMedID: 34507732

Title : Biochemical and Structural Characterization of a Novel Bacterial Tannase From Lachnospiraceae bacterium in Ruminant Gastrointestinal Tract - Guan_2021_Front.Bioeng.Biotechnol_9_806788
Author(s) : Guan L , Wang K , Gao Y , Li J , Yan S , Ji N , Ren C , Wang J , Zhou Y , Li B , Lu S
Ref : Front Bioeng Biotechnol , 9 :806788 , 2021
Abstract : Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanA(Lb)) was characterized. The recombinant TanA(Lb) exhibited maximal activity at pH 7.0 and 50 degreesC, and it maintained more than 70% relative activity from 30 degreesC to 55 degreesC. The activity of TanA(Lb) was enhanced by Mg(2+) and Ca(2+), and was dramatically reduced by Cu(2+) and Mn(2+). TanA(Lb) is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (k (cat) /Km) of TanA(Lb) toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanA(Lb) contains an insertion loop (residues 341-450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanA(Lb) is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use.
ESTHER : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedSearch : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedID: 34976993
Gene_locus related to this paper: 9firm-TanALb

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

Title : Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model - Xiao_2021_Biomed.Res.Int_2021_5574207
Author(s) : Xiao Y , Wang X , Wang S , Li J , Xu X , Wang M , Li G , Shen W
Ref : Biomed Res Int , 2021 :5574207 , 2021
Abstract : Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-beta production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Abeta (25-35)-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Abeta (25-35)-microinjected rats attenuated hippocampal NF-kappaB activity; inhibited proinflammatory markers, namely, IL-1beta, IL-6, and TNF-alpha; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1beta, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Abeta (25-35)-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Abeta (25-35) through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.
ESTHER : Xiao_2021_Biomed.Res.Int_2021_5574207
PubMedSearch : Xiao_2021_Biomed.Res.Int_2021_5574207
PubMedID: 34350293

Title : Current insights into the microbial degradation for pyrethroids: strain safety, biochemical pathway, and genetic engineering - Zhao_2021_Chemosphere_279_130542
Author(s) : Zhao T , Hu K , Li J , Zhu Y , Liu A , Yao K , Liu S
Ref : Chemosphere , 279 :130542 , 2021
Abstract : As a biologically inspired insecticide, pyrethroids (PYRs) exert evident toxic side effects on non-target organisms. PYRs and their general toxic intermediate 3-phenoxybenzoic acid (3-PBA) have shown high detection rates/levels in human beings recently, for which diet was identified as the major exposure route. Microbial mineralization has emerged as a versatile strategy in addressing such escalating concern. Herein, PYRs and 3-PBA biodegradation with regards to strain safety, application and surfactant were summarized. Numerous PYRs-degrading microbes have been reported yet with a minority focused on 3-PBA. Most isolates were from contaminated sites while several microbial food cultures (MFCs) have been investigated. MFCs such as Bacillus spp. and Aspergillus spp. that dominate in PYRs-degrading microbial pools are applicable candidates for agricultural by-products detoxification during the postharvest process. Subsequently, we discussed committed degradation steps, wherein hydrolase responsible for PYRs ester linkage cleavage and oxygenase for 3-PBA diphenyl ether bond rupture play vital roles. Finally, comprehensive information of the key enzyme genes is outlined along with methodologies concerning gene cloning. Cytochrome P450 monooxygenases (CYP) is competent for diphenyl ether scission. Newly-developed omics has become a feasible gene and enzyme mining technology. To achieve PYRs mineralization in feed and food commodities, the screening of MFCs rich in related enzymes and the construction of MFCs-derived genetically modified microbes (GMMs) exhibit great potential considering the safety issues.
ESTHER : Zhao_2021_Chemosphere_279_130542
PubMedSearch : Zhao_2021_Chemosphere_279_130542
PubMedID: 33866100

Title : Inverting the Enantiopreference of Nitrilase-Catalyzed Desymmetric Hydrolysis of Prochiral Dinitriles by Reshaping the Binding Pocket with a Mirror-Image Strategy - Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
Author(s) : Yu S , Li J , Yao P , Feng J , Cui Y , Liu X , Wu Q , Lin J , Zhu D
Ref : Angew Chem Int Ed Engl , 60 :3679 , 2021
Abstract : A mirror-image strategy, that is, symmetry analysis of the substrate-binding pocket, was applied to identify two key amino acid residues W170 and V198 that possibly modulate the enantiopreference of a nitrilase from Synechocystis sp. PCC6803 towards 3-isobutyl glutaronitrile (1a). Exchange of these two residues resulted in the enantiopreference inversion (S, 90% ee to R, 47% ee). By further reshaping the substrate-binding pocket via routine site-saturation and combinatorial mutagenesis, variant E8 with higher activity and stereoselectivity (99% ee, R) was obtained. The mutant enzyme was applied in the preparation of optically pure (R)-3-isobutyl-4-cyanobutanoic acid ((R)-2a) and showed similar stereopreference inversion towards a series of 3-substituted glutaronitriles. This study may offer a general strategy to switch the stereopreference of other nitrilases and other enzymes toward the desymmetric reactions of prochiral substrates with two identical reactive functional groups.
ESTHER : Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
PubMedSearch : Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
PubMedID: 33141478

Title : Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit - Li_2021_Front.Aging.Neurosci_13_770948
Author(s) : Li L , Li J , Dai Y , Yang M , Liang S , Wang Z , Liu W , Chen L , Tao J
Ref : Front Aging Neurosci , 13 :770948 , 2021
Abstract : OBJECTIVES: To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 x FAD) mice. METHODS: Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. (1)H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-beta (Abeta). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 x FAD mice. RESULTS: Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 x FAD mice. Abeta deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG). CONCLUSION: Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 x FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment.
ESTHER : Li_2021_Front.Aging.Neurosci_13_770948
PubMedSearch : Li_2021_Front.Aging.Neurosci_13_770948
PubMedID: 35185516

Title : A photoelectrochemical sensor based on an acetylcholinesterase-CdS\/ZnO-modified extended-gate field-effect transistor for glyphosate detection - Yu_2021_Analyst__
Author(s) : Yu J , Lin J , Li J
Ref : Analyst , : , 2021
Abstract : A new photoelectrochemical enzyme biosensor based on an extended-gate field-effect transistor (EGFET) was constructed for the highly sensitive detection of glyphosate based on the inhibition of acetylcholinesterase (AChE) activity by glyphosate. First, a two-step hydrothermal method was used to introduce ZnO and CdS onto an activated indium tin oxide (ITO) electrode to prepare a CdS/ZnO/ITO electrode. Then, AChE was immobilized on CdS/ZnO/ITO with chitosan to obtain an AChE/CdS/ZnO EGFET sensor. Under optimal experimental conditions, the logarithmic value of glyphosate in the range of 1.0 x 10-15-1.0 x 10-11 mol L-1 exhibited a good linear relationship with the photo-drain current response. The detection limit was 3.8 x 10-16 mol L-1 (signal-to-noise ratio = 3). The results show that the AChE/CdS/ZnO EGFET sensor has extremely high sensitivity and good selectivity. Moreover, the sensor was used for the determination of glyphosate in vegetables, demonstrating its application for the real-time detection of samples.
ESTHER : Yu_2021_Analyst__
PubMedSearch : Yu_2021_Analyst__
PubMedID: 34160494

Title : Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate - Zhou_2021_J.Med.Chem_64_1844
Author(s) : Zhou Y , Fu Y , Yin W , Li J , Wang W , Bai F , Xu S , Gong Q , Peng T , Hong Y , Zhang D , Liu Q , Xu Y , Xu HE , Zhang H , Jiang H , Liu H
Ref : Journal of Medicinal Chemistry , 64 :1844 , 2021
Abstract : The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
ESTHER : Zhou_2021_J.Med.Chem_64_1844
PubMedSearch : Zhou_2021_J.Med.Chem_64_1844
PubMedID: 33570950
Gene_locus related to this paper: human-ACHE

Title : Stability comparison of four lipases and catalytic mechanism during the synthesis of 1,3-di-oleic-2-medium chain triacylglycerols in a trace water-in-oil system: Experimental analyses and computational simulations - Peng_2021_J.Food.Biochem__e13667
Author(s) : Peng B , Luo T , Chen F , Wang M , Fu JH , Zheng LF , Li J , Deng ZY
Ref : J Food Biochem , :e13667 , 2021
Abstract : In the present study, a kind of structured lipids, namely 1,3-di-oleic-2-medium chain (OMO) triacylglycerols, were synthesized through lipase-catalyzed reactions using coconut oil and rapeseed acid as materials in a trace water-in-oil system. Experimental analysis and computational simulations were undertaken to compare the stability of four lipases including Lipozyme RMIM, Lipozyme TLIM, Novozym 435, and Aspergillus oryzae immobilized lipase (AOIM), and illustrate catalytic mechanism of Novozym 435 during the synthesis of OMO. Fourier transform infrared and molecular dynamics simulation results demonstrated that a decrease in ordered structure (alpha-helix and beta-sheet) led to a reduction in enzyme activity. Compared with Lipozyme RMIM and Novozym 435, Lipozyme TLIM and AOIM exhibited better stability due to a short-chain lid in TLIM, which covers activity sites, and hydrogen bonds formed between activity center of AOIM and water. Among four lipases, AOIM exhibited best catalytic performance: a OMO yield of 30.7% at 3 hr and a good stability of long term (48 hr). Density functional theory results demonstrated that specifically, during the synthesis of OMO triacylglycerol, the addition of Novozym 435 (derived from Candida antarctica lipase B, CALB) substantially lowered reaction barriers (64.4 KJ/mol with CALB vs. 332.7 KJ/mol with no lipase), aiding in the generation of OMO because of the formations of transitional tetrahedral intermediates. A trace water-in-oil system was a green and efficient alternative for lipase-catalyzed production of OMO, and this study provided crucial insights into the stability/instability and catalytic mechanisms of lipase in the synthesis of structured lipids. PRACTICAL APPLICATIONS: We compared the stability of Lipozyme RMIM, Lipozyme 435, Lipozyme TLIM, and AOIM during the synthesis of the OMO triacylglycerols in a trace water-in-oil system, where exhibited a high catalytic activity of lipase in water-oil interface. AOIM had the highest stability and showed the best catalytic performance due to the formation of hydrogen bonds. Besides, for the first time, the transition tetrahedral structure was revealed in the enzymatic synthesis of medium- and long-chain triacylglycerols. This study provides a rational approach to compare lipase stability and a possible hint to choose appropriate enzyme in a specific catalytic condition.
ESTHER : Peng_2021_J.Food.Biochem__e13667
PubMedSearch : Peng_2021_J.Food.Biochem__e13667
PubMedID: 33837552

Title : Lipolytic Activity of a Carboxylesterase from Bumblebee (Bombus ignitus) Venom - Deng_2021_Toxins.(Basel)_13_
Author(s) : Deng Y , Kim BY , Lee KY , Yoon HJ , Wan H , Li J , Lee KS , Jin BR
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Bee venom is a complex mixture composed of peptides, proteins with enzymatic properties, and low-molecular-weight compounds. Although the carboxylesterase in bee venom has been identified as an allergen, the enzyme's role as a venom component has not been previously elucidated. Here, we show the lipolytic activity of a bumblebee (Bombus ignitus) venom carboxylesterase (BivCaE). The presence of BivCaE in the venom secreted by B. ignitus worker bees was confirmed using an anti-BivCaE antibody raised against a recombinant BivCaE protein produced in baculovirus-infected insect cells. The enzymatic activity of the recombinant BivCaE protein was optimal at 40 degreesC and pH 8.5. Recombinant BivCaE protein degrades triglycerides and exhibits high lipolytic activity toward long-chain triglycerides, defining the role of BivCaE as a lipolytic agent. Bee venom phospholipase A(2) binds to mammalian cells and induces apoptosis, whereas BivCaE does not affect mammalian cells. Collectively, our data demonstrate that BivCaE functions as a lipolytic agent in bee venom, suggesting that BivCaE will be involved in distributing the venom via degradation of blood triglycerides.
ESTHER : Deng_2021_Toxins.(Basel)_13_
PubMedSearch : Deng_2021_Toxins.(Basel)_13_
PubMedID: 33810599

Title : Hormetic Effects of Dimethachlone on Mycelial Growth and Virulence of Sclerotinia sclerotiorum - Hu_2021_Phytopathology_111_1166
Author(s) : Hu S , Li J , Wang P , Zhu F
Ref : Phytopathology , 111 :1166 , 2021
Abstract : Fungicide hormesis has implications for the application of fungicides to control plant diseases. We investigated the hormetic effects of the dicarboximide fungicide dimethachlone on mycelial growth and virulence of the necrotrophic plant pathogen Sclerotinia sclerotiorum. Dimethachlone at sublethal doses in potato dextrose agar (PDA) increased the mycelial growth of S. sclerotiorum. After the growth-stimulated mycelia were subcultured on fresh PDA and inoculated on rapeseed leaves, increased mycelial growth and virulence were observed, indicating that hormetic traits were passed down to the next generation. Dimethachlone applied to leaves at 0.002 to 500 microg/ml stimulated virulence, with a maximum stimulation amplitude (MSA) of 31.4% for the isolate HLJ4, which occurred at 2 microg/ml. Dimethachlone-resistant isolates and transformants had a mean virulence MSA of 30.4%, which was significantly higher (P = 0.008) than the MSA for sensitive isolates (16.2%). Negative correlations were detected between MSA and virulence in the absence of any fungicide (r = -0.872, P < 0.001) and between MSA and mycelial growth on PDA (r = -0.794, P = 0.002). Studies on hormetic mechanisms indicated that dimethachlone had no significant effects on expression levels of three virulence-associated genes, that is, a cutinase-encoding gene SsCut, a polygalacturonase gene SsPG1, or an oxaloacetate acetylhydrolase gene SsOah1. The results will contribute to understanding hormesis and have implications for the judicious application of fungicides to control plant diseases.
ESTHER : Hu_2021_Phytopathology_111_1166
PubMedSearch : Hu_2021_Phytopathology_111_1166
PubMedID: 33107780

Title : Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn - Ma_2021_Chin.J.Integr.Med_27_912
Author(s) : Ma LT , Bai Y , Li J , Qiao Y , Liu Y , Zheng J
Ref : Chin J Integr Med , 27 :912 , 2021
Abstract : OBJECTIVE: To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI). METHODS: Sixty-five rats were equally divided into 5 groups using a random number table: naive group, sham group, SNI group, SNI + elemene (40 group and naive + elemene (40 group. An SNI rat model was established and the intervention were given respectively for 14 consecutive days. Von Frey filament tests and elevated plus-maze (EPM) tests were used to evaluate the effect of elemene on the mechanical threshold and anxiety, respectively. Immunoblotting and immunostaining were used to measure the expression of glial fibrillary acidic protein (GFAP) and NMYC downstream-regulated gene 2 (NDRG2) within the lumbar spinal dorsal horn (SDH). RESULTS: The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (P<0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (P<0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (P<0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir), NDRG-ir, and GFAP/NDRG2 double-labelled cells within the SDH (P<0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (P<0.05). CONCLUSION: Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.
ESTHER : Ma_2021_Chin.J.Integr.Med_27_912
PubMedSearch : Ma_2021_Chin.J.Integr.Med_27_912
PubMedID: 33420586
Gene_locus related to this paper: human-NDRG2

Title : Two novel Mutations of the LPL Gene in two Chinese family cases with Familial Chylomicronemia Syndrome - Wang_2021_Clin.Chim.Acta__
Author(s) : Wang M , Zhou Y , He X , Deng C , Liu X , Li J , Zhou L , Li Y , Zhang Y , Liu H , Li L
Ref : Clinica Chimica Acta , : , 2021
Abstract : The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429+1G>T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.
ESTHER : Wang_2021_Clin.Chim.Acta__
PubMedSearch : Wang_2021_Clin.Chim.Acta__
PubMedID: 34324844
Gene_locus related to this paper: human-LPL

Title : Comprehensive profiling of phytochemical compounds, antioxidant activities, anti-HepG2 cell proliferation, and cholinesterase inhibitory potential of Elaeagnus mollis leaf extracts - Li_2020_PLoS.One_15_e0239497
Author(s) : Li J , Ma Y , Kong L , Liu Y
Ref : PLoS ONE , 15 :e0239497 , 2020
Abstract : The aim of this work was to enrich the knowledge on the potential applications of Elaeagnus mollis leaf extracts. For this purpose, the bioactive compounds (phenolic, flavonoid, alkaloid, proanthocyanidin, chlorophyll and carotene content), antioxidant activity, anti-HepG2 cell proliferation, and cholinesterase inhibitory potential (AChE and BChE) of E. mollis leaves which obtained from different habitats were quantitatively analyzed using various solvents (water, methanol, ethanol, and n-hexane). The results showed that the methanol extracts exhibited the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and the water extracts showed the best antioxidant activity in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging activity, ferric reducing antioxidant power (FRAP), and reducing power (RP) assays. Moreover, the methanol extracts showed the best inhibitory activity against cholinesterase and HepG2 cancer cells. Correlation analysis revealed that the high antioxidant and anti-HepG2 cell proliferation activities were mainly attributed to the total phenolics, flavonoids, and proanthocyanidins while AChE inhibition was attributed to the total alkaloid and carotene content. The statistical results showed that the effect of habitats was lower than that of different solvents used. Additionally, the metabolic profiles of E. mollis leaves were evaluated using HPLC-ESI-Q TRAP-MS/MS, and a total of 1,017 chemical components were detected and classified into 23 classes. The organic acids and derivatives ranked the first, followed by flavone, amino acid and derivatives, and so on. In conclusion, the effects of different solvents were more significant than the effects of different habitats and the methanol extracts of E. mollis leaves could be used as an effective source of functional active components, provide benefits to physical health care and be applied to the food and pharmaceutical industries.
ESTHER : Li_2020_PLoS.One_15_e0239497
PubMedSearch : Li_2020_PLoS.One_15_e0239497
PubMedID: 32966304

Title : Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure - Li_2020_Ecotoxicol.Environ.Saf_199_110751
Author(s) : Li W , Wang S , Li J , Wang X , Cui L , Chen J , Liu Z
Ref : Ecotoxicology & Environmental Safety , 199 :110751 , 2020
Abstract : Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 mug/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 mug/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 mug/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 mug/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 mug/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 mug/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 mug/L and 0.000395 mug/L, respectively, which were significantly lower than the PNEC of 2.636 mug/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.
ESTHER : Li_2020_Ecotoxicol.Environ.Saf_199_110751
PubMedSearch : Li_2020_Ecotoxicol.Environ.Saf_199_110751
PubMedID: 32446104

Title : GDSL lipase occluded stomatal pore 1 is required for wax biosynthesis and stomatal cuticular ledge formation - Tang_2020_New.Phytol_228_1880
Author(s) : Tang J , Yang X , Xiao C , Li J , Chen Y , Li R , Li S , Lu S , Hu H
Ref : New Phytol , 228 :1880 , 2020
Abstract : The plant leaf surface is coated with a waterproof cuticle layer. Cuticle facing the stomatal pore surface needs to be sculpted to form outer cuticular ledge (OCL) after stomatal maturation for efficient gas exchange. Here, we characterized the roles of Arabidopsis GDSL lipase, Occlusion of Stomatal Pore 1 (OSP1), in wax biosynthesis and stomatal OCL formation. OSP1 mutation results in significant reduction in leaf wax synthesis and occlusion of stomata, leading to increased epidermal permeability, decreased transpiration rate, and enhanced drought tolerance. We demonstrated that OSP1 activity is critical for its role in wax biosynthesis and stomatal function. In vitro enzymatic assays demonstrated that OSP1 possesses thioesterase activity, particularly on C22:0 and C26:0 acyl-CoAs. Genetic interaction analyses with CER1 (ECERIFERUM 1), CER3 (ECERIFERUM 3) and MAH1 (Mid-chain Alkane Hydroxylase 1) in wax biosynthesis and stomatal OCL formation showed that OSP1 may act upstream of CER3 in wax biosynthesis, and implicate that wax composition percentage changes and keeping ketones in a lower level play roles, at least partially, in forming stomatal ledges. Our findings provided insights into the molecular mechanism mediating wax biosynthesis and highlighted the link between wax biosynthesis and the process of stomatal OCL formation.
ESTHER : Tang_2020_New.Phytol_228_1880
PubMedSearch : Tang_2020_New.Phytol_228_1880
PubMedID: 32542680

Title : Preparation of Lipase-Electrospun SiO(2) Nanofiber Membrane Bioreactors and Their Targeted Catalytic Ability at the Macroscopic Oil-Water Interface - Kuang_2020_J.Agric.Food.Chem_68_8362
Author(s) : Kuang L , Zhang Q , Li J , Tian H
Ref : Journal of Agricultural and Food Chemistry , 68 :8362 , 2020
Abstract : Lipase is one of the most widely used enzymes in biocatalysis. Because of the special structure of the catalytic active center, lipases show high catalytic activity at oil-water interfaces. Hence, the interface plays a key role in activating and modulating lipase biocatalysis. Compared with traditional catalytic systems that offer interfaces, such as emulsions, a lipase-membrane bioreactor exhibits many obvious advantages when at the macroscopic oil-water system. In our current research, a series of new Burkholderia cepacia lipase (BCL)-SiO(2) nanofiber membrane (NFM) bioreactors prepared via combined electrospinning and immobilization strategies were reported. These SiO(2) NFMs assisted BCL in reaching the oil-water interface for efficient catalysis. The enzyme loading capacity and catalytic efficiency of BCL-SiO(2) NFMs varied with the surface hydrophobicity of the electrospun NFMs. As the hydrophobicity increased, the activity decreased from 2.43-fold to 0.74-fold that of free BCL. However, the lipase-loading capacity increased obviously when the hydrophobicity of the SiO(2) NFMs increased from 0 to 143 degrees, and no significant change was observed when the hydrophobicity of the SiO(2) NFMs increased from 143 to 153 degrees. The gel trapping technique proved that the hydrolytic activity of the different BCL-SiO(2) NFM bioreactors depends on the contact area of the membrane at the oil-water interface. BCL-SiO(2) NFM, BCL-SiO(2) NFM-C(12), and BCL-SiO(2) NFM-C(18) retained 32, 83, and 42% of activity, respectively, after five cycles of reuse. The current work was a useful exploration of the construction and modification of lipase-membrane reactors based on electrospun inorganic silicon.
ESTHER : Kuang_2020_J.Agric.Food.Chem_68_8362
PubMedSearch : Kuang_2020_J.Agric.Food.Chem_68_8362
PubMedID: 32649192

Title : Rapid biodegradation of polyphenylene sulfide plastic beads by Pseudomonas sp - Li_2020_Sci.Total.Environ_720_137616
Author(s) : Li J , Kim HR , Lee HM , Yu HC , Jeon E , Lee S , Kim DH
Ref : Sci Total Environ , 720 :137616 , 2020
Abstract : Pseudomonas sp. isolated from soil, are bioremediating microorganisms that are capable of degrading various types of plastics. Polyphenylene sulfide (PPS) has the most excellent structural stability among general plastics and thus is extremely difficult to break down using physical or chemical methods. This study demonstrates the efficient biodegradation of PPS by Pseudomonas sp., which exists in the gut of superworms. Compared with the conventional film-type of plastic, the degradation efficiencies to the bead form of plastic were significantly improved and thus the biodegradation time was dramatically shortened. Therefore, instead of film-type plastics, we used 300smicrom diameter plastic beads for the measurement of Pseudomonas sp.-mediated biodegradation of PPS during a 10-day period. This method not only can be used for comparison and verification of the biodegradation efficiency of different types of plastics within a short reaction time of 10sdays, but also provides the possibility to develop a new and more efficient screening system to rapidly identify the most efficient species of bacteria for the biodegradation of various types of plastics.
ESTHER : Li_2020_Sci.Total.Environ_720_137616
PubMedSearch : Li_2020_Sci.Total.Environ_720_137616
PubMedID: 32146401

Title : A safety type of genetically engineered bacterium that degrades chemical pesticides - Li_2020_AMB.Express_10_33
Author(s) : Li Q , Li J , Kang KL , Wu YJ
Ref : AMB Express , 10 :33 , 2020
Abstract : Chemical pesticides are used widely and their residues are found in the environment. Pesticide pollution has become a global problem. To find an economical, effective and safety way to degrade residues of pesticides in environment, we constructed a genetically engineered bacterium (GEB) having the ability to degrade pesticides, emit green fluorescence and has a containment system by using a dual plasmid expression system. One plasmid contains the genes of enhanced green fluorescent protein (EGFP) and carboxylesterase B1 (CarE B1), which were cloned downstream of lambda PL promoter and expressed constitutively. The gene of CarE B1 encodes an insect-detoxifying enzyme possessing the degradability to organochloride pesticides, organophosphorus pesticides, carbamates, and pyrethoid insecticides. The other is the conditional suicide plasmid for containment system, in which the lethal gene used was the nuclease gene of Serratia marcescens without the leader-coding sequence and was placed downstream of T7 promoter. The GEB has wide prospects of application on cleanup of pesticide residues with its degradability to several pesticides and containment system.
ESTHER : Li_2020_AMB.Express_10_33
PubMedSearch : Li_2020_AMB.Express_10_33
PubMedID: 32072335

Title : Ultra-highly sensitive organophosphorus biosensor based on chitosan\/tin disulfide and British housefly acetylcholinesterase - Liu_2020_Food.Chem_324_126889
Author(s) : Liu X , Sakthivel R , Liu WC , Huang CW , Li J , Xu C , Wu Y , Song L , He W , Chung RJ
Ref : Food Chem , 324 :126889 , 2020
Abstract : Pesticides have been extensively applied worldwide to protect crops from worms and insects; however, the continuous use of pesticides affects ecosystems, agricultural product safety, nontarget organisms, and human health. In this paper, we report a highly sensitive biosensor for the determination of pesticides based on tin sulfide (SnS2) and chitosan (CHIT) nanocomposites decorated with a unique British housefly acetylcholinesterase (AChE). The hydrothermally synthesized nano-SnS2 mixed with chitosan solution (CHIT-SnS2) was drop-casted onto a glassy carbon electrode (GCE). Subsequently, the British housefly AChE was immobilized on the CHIT/SnS2-coated GCE that was then employed for pesticide detection. The developed biosensor showed an ultra-high sensitivity and wide linear detection range from 0.02 nM to 20000 nM with a detection limit of 0.02 nM for the detection of chlorpyrifos as the model pesticide. Furthermore, the AChE/CHIT-SnS2/GCE exhibited acceptable storage stability, good reproducibility, and selectivity.
ESTHER : Liu_2020_Food.Chem_324_126889
PubMedSearch : Liu_2020_Food.Chem_324_126889
PubMedID: 32353659

Title : Directed Evolution of Pseudomonas fluorescens Lipase Variants With Improved Thermostability Using Error-Prone PCR - Guan_2020_Front.Bioeng.Biotechnol_8_1034
Author(s) : Guan L , Gao Y , Li J , Wang K , Zhang Z , Yan S , Ji N , Zhou Y , Lu S
Ref : Front Bioeng Biotechnol , 8 :1034 , 2020
Abstract : Lipases catalyze the hydrolysis of fats and oils, and have been widely used in various industrial fields. However, bacterial lipases have a lower thermostability in industrial processes, which was a limiting factor in their industrial application. In this study, we obtained an improve variant of Pseudomonas fluorescens lipase (PFL) with enhanced thermostability using classical error-prone PCR. Wild-type PFL showed an optimal temperature and pH of 50degC and pH 7.5, respectively. Due to the low thermostability of PFL, a library containing over 3000 individual mutants as constructed using error-prone PCR. Screening for thermotolerance yielded the mutants L218P and P184C/M243C with T (m) values of 62.5 and 66.0degC, which was 2.5 and 6degC higher than that of the WT, respectively. The combination of the two mutants (P184C/M243C/L218P) resulted in an approximately additive effect with a T (m) value of 68.0degC. Although the increase of T (m) was not substantial, the mutant also had dramatically increased methanol tolerance. Structural analysis revealed that the introduction of a disulfide bond between P184C and M243C and the substitution of Pro to reduce the flexibility of a loop increased the thermostability of PFL, which provides a theoretical foundation for improving the thermostability and methanol tolerance of lipase family I.1 to resist the harsh conditions of industrial processes.
ESTHER : Guan_2020_Front.Bioeng.Biotechnol_8_1034
PubMedSearch : Guan_2020_Front.Bioeng.Biotechnol_8_1034
PubMedID: 32984290
Gene_locus related to this paper: psefl-lipa

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

Title : Biochemical Mechanisms, Cross-resistance and Stability of Resistance to Metaflumizone in Plutella xylostella - Shen_2020_Insects_11_
Author(s) : Shen J , Li Z , Li D , Wang R , Zhang S , You H , Li J
Ref : Insects , 11 : , 2020
Abstract : The diamondback moth, Plutella xylostella (L.) is an important pest of cruciferous crops worldwide. It has developed resistance to many conventional and novel insecticide classes. Metaflumizone belongs to the new chemical class of semicarbazone insecticides. To delay the development of metaflumizone resistance in P. xylostella and to guide insecticide use in the field, the biochemical mechanisms, cross-resistance spectrum, and stability of resistance to metaflumizone were studied in a laboratory-selected resistant strain (metaflu-SEL). Synergism tests with the carboxylesterase inhibitor triphenyl phosphate (TPP), the glutathione S-transferase depletor diethyl maleate (DEM), and the P450 inhibitor piperonyl butoxide(PBO) had no obvious effect on metaflumizone in the metaflu-SEL strain and the susceptible strain (SS) of P. xylostella, with synergism ratios that ranged from 1.02 to 1.86. Biochemical studies revealed that the cytochrome P450-dependent monooxygenase increased only 1.13-fold in the metaflu-SEL strain compared with the UNSEL stain; meanwhile, carboxylesterase and glutathione S-transferase activity showed no difference. These results suggest that these detoxification enzymes may be not actively involved in metaflumizone resistance. Furthermore, the metaflu-SEL population showed a moderate level of cross-resistance to indoxacarb (11.63-fold), but only very low cross-resistance to spinosad (1.75-fold), spinetoram (3.52-fold), abamectin (2.81-fold), beta-cypermethrin (0.71-fold), diafenthiuron (0.79-fold), chlorantraniliprole (2.16-fold), BT (WG-001) (3.34-fold), chlorfenapyr (0.49-fold), and chlorfluazuron (0.97-fold). Moreover, metaflumizone resistance decreased from 1087.85- to 1.23-fold in the metaflu-SEL strain after 12 generations without exposure to metaflumizone. These results are useful for formulating insecticide resistance management strategies to control P. xylostella and to delay the development of metaflumizone resistance in the field.
ESTHER : Shen_2020_Insects_11_
PubMedSearch : Shen_2020_Insects_11_
PubMedID: 32429053

Title : Rolling circle amplification promoted magneto-controlled photoelectrochemical biosensor for organophosphorus pesticides based on dissolution of core-shell MnO(2) nanoflower@CdS mediated by butyrylcholinesterase - Tang_2020_Mikrochim.Acta_187_450
Author(s) : Tang J , Li J , Xiong P , Sun Y , Zeng Z , Tian X , Tang D
Ref : Mikrochim Acta , 187 :450 , 2020
Abstract : A photoelectrochemical (PEC) aptasensing platform is devised for sensitive detection of an organophosphorus pesticide based on dissolution of core-shell MnO(2) nanoflower@CdS (MnO(2) NF@CdS) by thiocholine (TCh). TCH is produced from the butyrylcholinesterase-acetylthiocholine system, accompanied by target-triggered rolling circle amplification (RCA). The core-shell MnO(2) NF@CdS with excellent PEC performance was synthesized and employed as a photo-sensing platform. The target was detected on a functionalized magnetic probe with the corresponding aptamer. Upon malathion introduction, the aptamer was detached from the magnetic beads, while capture DNA (cDNA, with primer fragment) remained on the beads. The primer fragment in cDNA can trigger the RCA reaction to form a long single-stranded DNA (ssDNA). Furthermore, a large number of butyrylcholinesterase (BChE) were assembled on the long ssDNA strands through the hybridization with the S(2)-Au-BChE probe. Thereafter, TCh generated from hydrolysis of ATCh by BChE can reduce MnO(2) NF (core) to Mn(2+) and release the CdS nanoparticles (shell) from the platform electrode, significantly enhancing the PEC signal. Under optimal conditions, the proposed aptasensor exhibited high sensitivity for malathion with a low detection limit of 0.68 pg mL(-1). Meanwhile, it also presents outstanding specificity, reproducibility, and stability. Importantly, the sensing platform provides a new concept for detection of pesticide. Graphical abstract Herein, this work devised a photoelectrochemical (PEC) aptasensing platform for sensitive detection of organophosphorus pesticide based on dissolution of core-shell MnO(2) nanoflower@CdS (MnO(2) NF@CdS) by the as-produced thiocholine (TCh) from the butyrylcholinesterase-acetylthiocholine system, accompanying with the target-triggered rolling circle amplification (RCA).
ESTHER : Tang_2020_Mikrochim.Acta_187_450
PubMedSearch : Tang_2020_Mikrochim.Acta_187_450
PubMedID: 32676787

Title : Biological Impact and Enzyme Activities of Spodoptera litura (Lepidoptera: Noctuidae) in Response to Synergistic Action of Matrine and Beauveria brongniartii - Wu_2020_Front.Physiol_11_584405
Author(s) : Wu J , Li J , Zhang C , Yu X , Cuthbertson AGS , Ali S
Ref : Front Physiol , 11 :584405 , 2020
Abstract : Matrine, a naturally occurring heterocyclic compound, has been shown to enhance the pathogenicity of the entomopathogenic fungus Beauveria brongniartii against Spodoptera litura. In the current study, the biological impacts and synergism activities of these two agents on nutritional efficiency and antioxidant enzymes in S. litura were explored. Our results showed a high antifeedant activity of B. brongniartii and matrine on S. litura. The S. litura larvae were unable to pupate and emerge when treated with combinations of matrine and B. brongniartii. Following on, we measured the activities of five important antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), acetylcholinesterase (AChE), and glutathione-S-transferase (GST)] when treated with B. brongniartii SB010 (1 x 10(9) spores/ml), matrine (0.5 mg/ml), and B. brongniartii SB010 (1 x 10(9) spores/ml) + matrine (0.5 mg/ml). The results indicated the detoxification activity of the five enzymes in the fat body and hemolymph of S. litura when facing a combined B. brongniartii and matrine challenge. The activities of the enzymes were significantly lower than that of the control group 7 days post-treatment, indicating the inhibitory effect of the two xenobiotics. Matrine had better inhibition effects than B. brongniartii in a majority of the trials. The improved detoxification activity of the five enzymes may be the internal mechanism of synergism of matrine on B. brongniartii.
ESTHER : Wu_2020_Front.Physiol_11_584405
PubMedSearch : Wu_2020_Front.Physiol_11_584405
PubMedID: 33224038

Title : Silencing of soluble epoxide hydrolase 2 gene reduces H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells via activating PI3K\/Akt\/GSK3beta signaling pathway - Li_2020_Cytotech__
Author(s) : Li J , Luo J , Zhang Y , Tang C , Wang J , Chen C
Ref : Cytotechnology , : , 2020
Abstract : Oxidative stress plays a vital role in the occurrence and development of intestinal injury. Soluble epoxide hydrolase 2 gene (EPHX2) is a class of hydrolytic enzymes. We aim to explore the effects and molecular mechanism of siEPHX2 on H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells. IEC-6 cells were transfected with EPHX2-siRNA and control si RNA plasmids by lipofectamine 2000 transfection reagent. The transfected samples were treated with H2O2 (50, 100, 200, 300, 400, and 500 micromol/L) for 12, 24, and 48 h, respectively. Cell viability was determined by cell counting kit-8 (CCK-8). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed by respective detection kits. Mitochondrial membrane potential (MMP), cell apoptosis and reactive oxygen species (ROS) and the levels of factors were determined by flow cytometer, quantitative real-time PCR (qRT-PCR) and western blot assays, respectively. We found that the IC50 of H2O2 was 200 micromol/L at 24 h, and the transfection of siEHPX2 in H2O2-induced IEC-6 cells significantly promoted the cell viability, SOD activity and MMP rate, and reduced the rates of ROS and apoptosis as well as LDH and MDA contents. siEHPX2 up-regulated the B-cell lymphoma-2 (Bcl-2) level and down-regulated the levels of fibroblast-associated (Fas), Fas ligand (Fasl), Bcl-2 associated X protein (Bax), and Caspase-3. Moreover, the phosphorylation levels of phosphoinositide 3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase3beta (GSK3beta) were up-regulated. We proved that siEPHX2 had a protective effect on H2O2-induced oxidative damage in IEC-6 cells through activating PI3K/Akt/GSK3beta signaling pathway.
ESTHER : Li_2020_Cytotech__
PubMedSearch : Li_2020_Cytotech__
PubMedID: 31907700

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

Title : Enzymatic Synthesis of beta-Sitosterol Laurate by Candida rugosa Lipase AY30 in the Water\/AOT\/Isooctane Reverse Micelle - Chen_2020_Appl.Biochem.Biotechnol__
Author(s) : Chen S , Li J , Fu Z , Wei G , Li H , Zhang B , Zheng L , Deng Z
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Phytosterols are regarded as compounds able to reduce total and low-density lipoprotein cholesterol in the blood, and their esterified derivatives could help to improve the effectiveness of this function. In the present study, the water/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/isooctane reverse micelle (RM) system was set up as a reaction medium for Candida rugosa lipase AY30 (CRL AY30) to synthesize beta-sitosterol laurate (beta-SLE). The product was identified by TLC, FT-IR, and HPLC-APCI-QqQ-MS/MS and quantified by HPLC. Through stepwise optimization, it was found that CRL AY30 had the highest activity in the water/AOT/isooctane RM system where 50 mM PBS with a pH of 7.5 was adopted as water core to carry CRL AY30, and the proportion of [CRL AY30] (mg/mL), [water] (mM), and [AOT] (mM) was set in 3:375:25, respectively, in isooctane. After screened with single-factor experiments, the esterification reaction conditions in the CRL AY30-water/AOT/isooctane RM system were further optimized by the response surface method as follows: the mole ratio of beta-sitosterol to lauric acid of 1:3.5 (25 mM beta-sitosterol), the enzyme load of 18% (w/w total reactants), the reaction temperature of 47 degrees C, and the reaction time of 48 h. As a result, the maximum esterification rate was up to 88.12 +/- 0.79%.
ESTHER : Chen_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Chen_2020_Appl.Biochem.Biotechnol__
PubMedID: 32388606

Title : Trace water activity could improve the formation of 1,3-oleic-2-medium chain-rich triacylglycerols by promoting acyl migration in the lipase RM IM catalyzed interesterification - Peng_2020_Food.Chem_313_126130
Author(s) : Peng B , Chen F , Liu X , Hu JN , Zheng LF , Li J , Deng ZY
Ref : Food Chem , 313 :126130 , 2020
Abstract : New structured lipids with 1,3-oleic-2-medium chain (OMO) triacylglycerols were synthesized by promoting acyl migration in Lipozyme RM IM catalyzed interesterification between coconut oil (CO) and high oleic rapeseed oil (HORO). Results from an orthogonal design L(25)(5(5)) showed that the maximal yield of OMO-structured triacylglycerols was 45.65% under the following conditions: the molar ratio of CO to HORO, 50:50; enzyme dosage, 12 wt%; reaction temperature, 60 degreeC; reaction time, 2 h; water activity, 0.07. Low water activity showed a high rate of acyl migration (10.86% vs 5.07% no water system), which promoted OMO synthesis due to medium-chain fatty acid migration to the sn-2 position. In a low water content (5%) system of the molecular dynamics simulation, water molecules stabilized the whole structure of RM IM through hydrogen bonding, which helped fix lipase-catalyzed active sites, making substrates more easily inserted into active sites, resulting in increased enzyme activity.
ESTHER : Peng_2020_Food.Chem_313_126130
PubMedSearch : Peng_2020_Food.Chem_313_126130
PubMedID: 31935664

Title : Discovery of Aryl Formyl Piperidine Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase Inhibitors - Zhi_2020_J.Med.Chem__
Author(s) : Zhi Z , Zhang W , Yao J , Shang Y , Hao Q , Liu Z , Ren Y , Li J , Zhang G , Wang J
Ref : Journal of Medicinal Chemistry , : , 2020
Abstract : Most of the current MAGL inhibitors function by an irreversible mechanism of action, causing a series of side effects. Herein, starting from irreversible inhibitors, 25 compounds were synthesized and evaluated in vitro for MAGL inhibition, among which, compound 36 showed the most potent inhibitory activity (IC50 = 15 nM).Crucially, docking studies demonstrated that the m-chlorine-substituted aniline fragment occupied a hydrophobic sub-pocket enclosed by side chains of Val191, Tyr194, Val270, and Lys273, which creatively identify a new key anchoring point for the development of new MAGL inhibitors. Furthermore, in vivo evaluation innovatively revealed that this reversible inhibitor 36 significantly displayed the depressive-like behaviors induced by reserpine. To the best of our knowledge, this is the first time that reversible inhibitors of MAGL were developed to support MAGL as a potential therapeutic target for depression.
ESTHER : Zhi_2020_J.Med.Chem__
PubMedSearch : Zhi_2020_J.Med.Chem__
PubMedID: 32429662

Title : Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle - Huang_2020_Front.Mol.Neurosci_13_154
Author(s) : Huang K , Li J , Ito M , Takeda JI , Ohkawara B , Ogi T , Masuda A , Ohno K
Ref : Front Mol Neurosci , 13 :154 , 2020
Abstract : The neuromuscular junction (NMJ) is a prototypic chemical synapse between the spinal motor neuron and the motor endplate. Gene expression profiles of the motor endplate are not fully elucidated. Collagen Q (ColQ) is a collagenic tail subunit of asymmetric forms of acetylcholinesterase and is driven by two distinct promoters. pColQ1 is active throughout the slow-twitch muscle, whereas pColQ1a is active at the motor endplate of fast-twitch muscle. We made a transgenic mouse line that expresses nuclear localization signal (NLS)-attached Cre recombinase under the control of pColQ1a (pColQ1a-Cre mouse). RiboTag mouse expresses an HA-tagged ribosomal subunit, RPL22, in cells expressing Cre recombinase. We generated pColQ1a-Cre:RiboTag mouse, and confirmed that HA-tagged RPL22 was enriched at the NMJ of tibialis anterior (TA) muscle. Next, we confirmed that Chrne and Musk that are specifically expressed at the NMJ were indeed enriched in HA-immunoprecipitated (IP) RNA, whereas Sox10 and S100b, markers for Schwann cells, and Icam1, a marker for vascular endothelial cells, and Pax3, a marker for muscle satellite cells, were scarcely detected. Gene set enrichment analysis (GSEA) of RNA-seq data showed that "phosphatidylinositol signaling system" and "extracellular matrix receptor interaction" were enriched at the motor endplate. Subsequent analysis revealed that genes encoding diacylglycerol kinases, phosphatidylinositol kinases, phospholipases, integrins, and laminins were enriched at the motor endplate. We first characterized the gene expression profile under translation at the motor endplate of TA muscle using the RiboTag technique. We expect that our gene expression profiling will help elucidate molecular mechanisms of the development, maintenance, and pathology of the NMJ.
ESTHER : Huang_2020_Front.Mol.Neurosci_13_154
PubMedSearch : Huang_2020_Front.Mol.Neurosci_13_154
PubMedID: 33117128

Title : Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease - Li_2020_Acta.Pharm.Sin.B_10_646
Author(s) : Li X , Lu J , Xu Y , Wang J , Qiu X , Fan L , Li B , Liu W , Mao F , Zhu J , Shen X , Li J
Ref : Acta Pharm Sin B , 10 :646 , 2020
Abstract : Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (Abeta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD.
ESTHER : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedSearch : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedID: 32322468

Title : Cognitive-enhancing effects of fibrauretine on Abeta1-42-induced Alzheimer's disease by compatibilization with ginsenosides - Zhang_2020_Neuropeptides__102020
Author(s) : Zhang M , Chen W , Zong Y , Shi K , Li J , Zeng F , He Z , Du R
Ref : Neuropeptides , :102020 , 2020
Abstract : Fibrauretine is the main active ingredient in rattan stems of Fibraurea recisa Pierre. The aim of this study was to evaluate the cognitive-enhancing effects and underlying molecular mechanisms of fibrauretine compatibilized with ginsenosides on Alzheimer's disease (AD) induced in mice with amyloid beta-protein (Abeta1-42). The results showed that the spatial learning and memory abilities of AD mice were significantly enhanced after combined treatment with fibrauretine and ginsenosides using the Morris water maze test. The levels of acetylcholinesterase (AChE) and phosphorylated Tau protein (p-Tau) in brain tissue and the levels of nitric oxide (NO), malondialdehyde (MDA), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were significantly increased in Abeta1-42-induced AD mice, and these effects were reversed after combined treatment with fibrauretine and ginsenosides. By contrast, a significant increase in the levels of catalase (CAT), superoxide dismutase (SOD), choline acetyltransferase (ChAT) and glutathione peroxidase (GSH-Px) was observed in the combined treatment group. The results of haematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) analysis, immunohistochemistry (IHC) and Western blot analysis showed that the apoptosis rate, Bax, nuclear factor kappa-B p65 (NF-kappaBp65), cleaved caspase-3 and cleaved caspase-9 expression levels were obviously decreased and that the Bcl-2 expression levels were significantly increased in the hippocampi of mice treated with fibrauretine and ginsenosides. The results of this study show that the ameliorative effect of fibrauretine against AD can be significantly enhanced by compatibilization with ginsenosides. The underlying molecular mechanisms of fibrauretine may be related to antioxidation and anti-apoptosis.
ESTHER : Zhang_2020_Neuropeptides__102020
PubMedSearch : Zhang_2020_Neuropeptides__102020
PubMedID: 31982159

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

Title : Seladelicatulasine A-G, C(27) steroidal glycosides with cholinesterase inhibitory activities from Selaginella delicatula - Yao_2020_Phytochemistry_180_112514
Author(s) : Yao CP , Li J , Liu JF , Zou ZX , Kang FH , Li XM , Li D , Xu KP , Xu PS , Tan GS
Ref : Phytochemistry , 180 :112514 , 2020
Abstract : Seven undescribed C(27) steroidal glycosides, Seladelicatulasine A-G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC(50) values of 0.31, 0.09, and 0.04 muM, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC(50) values of 0.37 and 0.65 muM, respectively.
ESTHER : Yao_2020_Phytochemistry_180_112514
PubMedSearch : Yao_2020_Phytochemistry_180_112514
PubMedID: 32950771

Title : Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors - Yu_2020_Food.Funct_11_6643
Author(s) : Yu Z , Ji H , Shen J , Kan R , Zhao W , Li J , Ding L , Liu J
Ref : Food Funct , 11 :6643 , 2020
Abstract : Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE 1) play vital roles in the development and progression of Alzheimer's disease (AD). The objective of the present study was to identify fish roe-derived anti-AD peptides with activities against AChE, BChE, and BACE 1. Fish roe proteins were cleaved in silico by gastrointestinal proteases, and the released peptides were collected. Subsequently, the toxicity, solubility, and biological properties of these novel di- and tri-peptides were predicted and validated. Finally, potential anti-AD peptides were docked to targets, i.e., AChE, BChE, and BACE 1. A novel anti-AD tripeptide WIR with potent inhibition of AChE and BACE 1 was identified, with IC(50) values of 43.32 +/- 1.22 microM and 2.27 +/- 0.35 mM, respectively. In addition, the inhibition rate of WIR (at a concentration of 1.06 +/- 0.87 microM) against BChE was 33.5%, and the peptide WIR was able to simultaneously interact with AChE, BChE, and BACE 1. Residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key roles in the interaction with peptide WIR. In summary, peptide WIR exhibits the potential to be an effective treatment for AD.
ESTHER : Yu_2020_Food.Funct_11_6643
PubMedSearch : Yu_2020_Food.Funct_11_6643
PubMedID: 32656560

Title : Therapeutic efficacy and immunoregulatory effect of Qiangji Jianli Capsule for patients with myasthenia gravis: Study protocol for a series of randomized, controlled N-of-1 trials - Weng_2020_Medicine.(Baltimore)_99_e23679
Author(s) : Weng S , Fan Z , Qiu G , Liu F , Huang L , Li J , Jiang X , Song Z , Gao Y , Zhong Z , He L , Kang L , Wu Y , Chen B , Jiang Q
Ref : Medicine (Baltimore) , 99 :e23679 , 2020
Abstract : INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease in which antibodies directly target components of the neuromuscular junction, causing neuromuscular conduction damage that leads to muscle weakness. The current pharmaceutical treatment for MG is still not ideal to address the problems of disease progression, high recurrence rate, and drug side effects. Clinical observations suggest that traditional Chinese medicine (TCM) can strengthen immunity and improve symptoms of MG patients, delay the progression of the disease, reduce or even prevent the need for immunosuppressive therapy when used in combination with acetylcholinesterase inhibitors or low-dose prednisone, as well as improve the quality of life of patients. The Qiangji Jianli Capsule (QJC) is a combination of medicinal herbs which is used in traditional Chinese medicine. Since MG is a rare disorder, randomized controlled trials comparing large cohorts are difficult to conduct. Therefore, we proposed to aggregate data from a small series of N-of-1 trials to assess the effect of the Chinese medical prescription QJC, which strengthens the spleen and nourishes Qi, as an add-on treatment for MG with spleen and stomach Qi deficiency syndrome. METHODS AND ANALYSIS: Single-center, randomized, double-blind, multiple crossover N-of-1 studies will compare QJC versus placebo in 5 adult MG patients with spleen and stomach Qi deficiency syndrome. Patients will undergo 3 cycles of two 4-week intervention periods. According to the treatment schedule, patients will continue to be treated with pyridine bromide tablets, prednisone acetate, tablets and/or tacrolimus capsules throughout the entire trial. Each period consisting of 4-week oral add-on treatment with QJC will be compared with 4-week add-on treatment with a placebo. The primary endpoints are quantitative myasthenia gravis (QMG) test; measurement of the amount of Treg cells and cytokines such as interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-17A (IL-17A), and transforming growth factor-beta (TGF-beta); and corticosteroid or immunosuppressive agent dosage. Secondary outcome measures: Clinical: Evaluation of the effect of TCM syndromes; MG-activities of daily living (MG-ADL) scales; adverse events. ETHICS AND DISSEMINATION: This study was approved by The First Affiliated Hospital of Guangzhou University of Chinese Medicine (GZUCM), No. ZYYECK[2019]038. The results will be published in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorization and reimbursement purposes. Trial registration: Chinese Clinical Trial Register, ID: ChiCTR2000033516. Registered on 3 June 2020,
ESTHER : Weng_2020_Medicine.(Baltimore)_99_e23679
PubMedSearch : Weng_2020_Medicine.(Baltimore)_99_e23679
PubMedID: 33371107

Title : The Trp183 is essential in lactonohydrolase ZHD detoxifying zearalenone and zearalenols - Zhou_2020_Biochem.Biophys.Res.Commun_522_986
Author(s) : Zhou H , Li L , Zhan B , Wang S , Li J , Hu XJ
Ref : Biochemical & Biophysical Research Communications , 522 :986 , 2020
Abstract : Lactonohydrolase ZHD can detoxify oestrogenic mycotoxin zearalenone and zearalenols through hydrolysis and decarboxylation. The detail mechanism, especially the role of Trp183, which interacts with substrate through p-pi interaction and one hydrogen bond, is still unknown. The Trp183 mutants abolished activity to ZEN, alpha-ZOL and beta-ZOL, except that W183F mutant retained about 40% activity against alpha-ZOL. In two W183F-reactant complex structures the reactants still bind at the active position and it suggested that this p-pi interaction takes responsible for the reactants recognization and allocation. Further, the ZHD-productant complex structures showed that the resorcinol ring of hydrolysed alpha-ZOL and hydrolysed beta-ZOL move a distance of one ring as compare to the resorcinol ring of reactant alpha-ZOL and beta-ZOL. The same movement also found in comparison of hydrolysed ZEN and ZEN. In the structure of W183F complex with hydrolysed alpha-ZOL the resorcinol ring of hydrolysed alpha-ZOL doesn't move as compare to the resorcinol ring of reactant alpha-ZOL. It suggested the Trp183 coordinated hydrogen bond takes responsible for the movement of the hydrolysed product. These functional and structural results suggested that Trp183 is essential for ZHD detoxifying zearalenone and zearalenols.
ESTHER : Zhou_2020_Biochem.Biophys.Res.Commun_522_986
PubMedSearch : Zhou_2020_Biochem.Biophys.Res.Commun_522_986
PubMedID: 31810602
Gene_locus related to this paper: biooc-ZHD101

Title : Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease - Wu_2020_Chem.Biol.Interact_334_109350
Author(s) : Wu M , Zhu X , Zhang Y , Wang M , Liu T , Han J , Li J , Li Z
Ref : Chemico-Biological Interactions , 334 :109350 , 2020
Abstract : A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC(50) = 0.28 +/- 0.05 M) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Abeta self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu(2+) and Zn(2+). In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.
ESTHER : Wu_2020_Chem.Biol.Interact_334_109350
PubMedSearch : Wu_2020_Chem.Biol.Interact_334_109350
PubMedID: 33307048

Title : Significant improvement in catalytic activity and enantioselectivity of a Phaseolus vulgaris epoxide hydrolase, PvEH3, towards ortho-cresyl glycidyl ether based on the semi-rational design - Zhang_2020_Sci.Rep_10_1680
Author(s) : Zhang C , Liu Y , Li C , Xu Y , Su Y , Li J , Zhao J , Wu M
Ref : Sci Rep , 10 :1680 , 2020
Abstract : The investigation of substrate spectrum towards five racemic (rac-) aryl glycidyl ethers (1a-5a) indicated that E. coli/pveh3, an E. coli BL21(DE3) transformant harboring a PvEH3-encoding gene pveh3, showed the highest EH activity and enantiomeric ratio (E) towards rac-3a. For efficiently catalyzing the kinetic resolution of rac-3a, the activity and E value of PvEH3 were further improved by site-directed mutagenesis of selected residues. Based on the semi-rational design of an NC-loop in PvEH3, four single-site variants of pveh3 were amplified by PCR, and intracellularly expressed in E. coli BL21(DE3), respectively. E. coli/pveh3(E134K) and /pveh3(T137P) had the enhanced EH activities of 15.3 +/- 0.4 and 16.1 +/- 0.5 U/g wet cell as well as E values of 21.7 +/- 1.0 and 21.2 +/- 1.1 towards rac-3a. Subsequently, E. coli/pveh3(E134K/T137P) harboring a double-site variant gene was also constructed, having the highest EH activity of 22.4 +/- 0.6 U/g wet cell and E value of 24.1 +/- 1.2. The specific activity of the purified PvEH3(E134K/T137P) (14.5 +/- 0.5 U/mg protein) towards rac-3a and its catalytic efficiency (k(cat)/K(m) of 5.67 mM(-1) s(-1)) for (S)-3a were 1.7- and 3.54-fold those (8.4 +/- 0.3 U/mg and 1.60 mM(-1) s(-1)) of PvEH3. The gram-scale kinetic resolution of rac-3a using whole wet cells of E. coli/pveh3(E134K/T137P) was performed at 20 degC for 7.0 h, producing (R)-3a with 99.4% ee(s) and 38.5 +/- 1.2% yield. Additionally, the mechanism of PvEH3(E134K/T137P) with remarkably improved E value was analyzed by molecular docking simulation.
ESTHER : Zhang_2020_Sci.Rep_10_1680
PubMedSearch : Zhang_2020_Sci.Rep_10_1680
PubMedID: 32015448
Gene_locus related to this paper: phavu-PvEH3

Title : Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF-kappaB activation - Li_2020_Exp.Eye.Res__108003
Author(s) : Li J , Chen Y , Zhang X , Ye S , Yi J , Chen Q , Liu Q
Ref : Experimental Eye Research , :108003 , 2020
Abstract : Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and retinitis. However, the underlying mechanism of retinal inflammation remains largely unknown. Recent studies demonstrated that acetylcholinesterase (ACHE) is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-alpha (TNF-alpha) in heterozygous ACHE knockout mice (ACHE(+/-)) and wild type mice (ACHE(+/+)). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b(+) inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE (+/-) and ACHE(+/+) mice. ARPE-19cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b(+) inflammatory cells infiltration as well as vascular hyperpermeability in ACHE(+/+) mice injected with TNF-alpha. However, TNF-alpha-injected ACHE (+/-) mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b(+) cells. Moreover, TNF-alpha-induced retinal vascular leakage was significantly reduced in ACHE (+/-) mice. Similarly, TNF-alpha-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-alpha treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-kappaB in cultured-ARPE-19cells. Genetic and pharmaceutical suppression of ACHE markedly attenuated TNF-alpha-induced ICAM-1 expression. Meanwhile, inhibition of ACHE reduced TNF-alpha-induced phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta in ARPE-19cells. The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-kappaB signaling activation.
ESTHER : Li_2020_Exp.Eye.Res__108003
PubMedSearch : Li_2020_Exp.Eye.Res__108003
PubMedID: 32184102

Title : Propoxur resistance associated with insensitivity of acetylcholinesterase (AChE) in the housefly, Musca domestica (Diptera: Muscidae) - You_2020_Sci.Rep_10_8400
Author(s) : You C , Shan C , Xin J , Li J , Ma Z , Zhang Y , Zeng X , Gao X
Ref : Sci Rep , 10 :8400 , 2020
Abstract : Two unique housefly strains, PSS and N-PRS (near-isogenic line with the PSS), were used to clarify the mechanisms associated with propoxur resistance in the housefly, Musca domestica. The propoxur-selected resistant (N-PRS) strain exhibited >1035-fold resistance to propoxur and 1.70-, 12.06-, 4.28-, 57.76-, and 57.54-fold cross-resistance to beta-cypermethrin, deltamethrin, bifenthrin, phoxim, and azamethiphos, respectively, compared to the susceptible (PSS) strain. We purified acetylcholinesterase (AChE) from the N-PRS and PSS strains using a procainamide affinity column and characterized the AChE. The sensitivity of AChE to propoxur based on the bimolecular rate constant (Ki) was approximately 100-fold higher in the PSS strain compared to the N-PRS strain. The cDNA encoding Mdace from both the N-PRS strain and the PSS strain were cloned and sequenced using RT-PCR. The cDNA was 2073 nucleotides long and encoded a protein of 691 amino acids. A total of four single nucleotide polymorphisms (SNPs), I162M, V260L, G342A, and F407Y, were present in the region of the active site of AChE from the N-PRS strain. The transcription level and DNA copy number of Mdace were significantly higher in the resistant strain than in the susceptible strain. These results indicated that mutations combined with the up-regulation of Mdace might be essential in the housefly resistance to propoxur.
ESTHER : You_2020_Sci.Rep_10_8400
PubMedSearch : You_2020_Sci.Rep_10_8400
PubMedID: 32439946

Title : FRACPRED-2D-PRM: A fraction prediction algorithm-assisted two-dimensional liquid chromatography-based parallel reaction monitoring-mass spectrometry approach for measuring low-abundance proteins in human plasma - Shi_2020_Proteomics__e2000175
Author(s) : Shi J , Xiao J , Li J , Wang X , Her L , Sorensen MJ , Zhu HJ
Ref : Proteomics , :e2000175 , 2020
Abstract : Multidimensional fractionation-based enrichment methods improve the sensitivity of proteomic analysis for low-abundance proteins. However, a major limitation of conventional multidimensional proteomics is the extensive labor and instrument time required for analyzing many fractions obtained from the first dimension separation. Here, we present a fraction prediction algorithm-assisted two-dimensional LC-based parallel reaction monitoring-mass spectrometry (FRACPRED-2D-PRM) approach for measuring low-abundance proteins in human plasma. Plasma digests were separated by the first dimension high-pH RP-LC with data-dependent acquisition (DDA). We then used the FRACPRED algorithm to predict the retention time of undetectable target peptides according to those of other abundant plasma peptides during the first dimension separation. Fractions predicted to contain target peptides were analyzed by the second dimension low-pH nano RP-LC PRM. We demonstrated the accuracy and robustness of fraction prediction with the FRACPRED algorithm by measuring two low-abundance proteins, aldolase B and carboxylesterase 1, in human plasma. The FRACPRED-2D-PRM proteomics approach demonstrated markedly improved efficiency and sensitivity over conventional 2D-LC proteomics assays. We expect that this approach will be widely used in the study of low-abundance proteins in plasma and other complex biological samples. This article is protected by copyright. All rights reserved.
ESTHER : Shi_2020_Proteomics__e2000175
PubMedSearch : Shi_2020_Proteomics__e2000175
PubMedID: 33085175

Title : Karrikin Signaling Acts Parallel to and Additively with Strigolactone Signaling to Regulate Rice Mesocotyl Elongation in Darkness - Zheng_2020_Plant.Cell_32_2780
Author(s) : Zheng J , Hong K , Zeng L , Wang L , Kang S , Qu M , Dai J , Zou L , Zhu L , Tang Z , Meng X , Wang B , Hu J , Zeng D , Zhao Y , Cui P , Wang Q , Qian Q , Wang Y , Li J , Xiong G
Ref : Plant Cell , 32 :2780 , 2020
Abstract : Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCF(D3) ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3 OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR24(5DS) and GR24 (ent-5DS) specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark.
ESTHER : Zheng_2020_Plant.Cell_32_2780
PubMedSearch : Zheng_2020_Plant.Cell_32_2780
PubMedID: 32665307

Title : Carboxylesterase genes in nitenpyram-resistant brown planthoppers, Nilaparvata lugens - Mao_2020_Insect.Sci__
Author(s) : Mao K , Ren Z , Li W , Cai T , Qin X , Wan H , Jin BR , He S , Li J
Ref : Insect Sci , : , 2020
Abstract : Carboxylesterases (CarEs) represent one of the major detoxification enzyme families involved in insecticide resistance. However, the function of specific CarE genes in insecticide resistance is still unclear in the insect Nilaparvata lugens (Stal), a notorious rice crop pest in Asia. In this study, a total of 29 putative CarE genes in N. lugens were identified, and they were divided into seven clades; further, the beta-esterase clade was significantly expanded. Tissue-specific expression analysis found that seventeen CarE genes were abundantly distributed in the midgut and fat body, while twelve CarE genes were highly expressed in the head. The expression of most CarE genes was significantly induced in response to the challenge of nitenpyram, triflumezopyrim, chlorpyrifos, isoprocarb and etofenprox. Among these, the expression levels of NlCarE2, NlCarE4, NlCarE9, NlCarE17 and NlCarE24 were increased by each insecticide. RT-qPCR and RNAi assays revealed the NlCarE1 gene to be a candidate gene mainly involved in nitenpyram resistance, while simultaneously silencing NlCarE1 and NlCarE19 produced a stronger effect than silencing either one individually, suggesting a cooperative relationship in resistance formation. These findings lay the foundation for further clarification of insecticide resistance mediated by CarE in N. lugens. This article is protected by copyright. All rights reserved.
ESTHER : Mao_2020_Insect.Sci__
PubMedSearch : Mao_2020_Insect.Sci__
PubMedID: 32495409

Title : Deletion of bem46 retards spore germination and may be related to the polar growth of Aspergillus fumigatus - Ma_2020_Med.Mycol_58_690
Author(s) : Ma Y , Ji Y , Yang J , Li W , Li J , Cen W , Wang Y , Feng W
Ref : Med Mycol , 58 :690 , 2020
Abstract : Bud emergence 46 (BEM46), a member of the alpha/beta hydrolase superfamily, has been reported to be essential for polarized growth in Neurospora crassa. However, the role of BEM46 in aspergillus fumigatus (A. fumigatus) remains unclear. In this study, we constructed an A. fumigatus strain expressing BEM46 fused with enhanced green fluorescent protein, and a Deltabem46 mutant, to explore the localization and the role of growth of BEM46 in A. fumigatus, respectively. Confocal laser scanning microscopy revealed that BEM46 was dominantly expressed in the sites where hyphae germinated from conidia in A. fumigatus. When compared with the control strain, the Deltabem46 mutant exhibited insignificant morphological changes but delayed germination. No significant changes were found regarding the radial growth of both strains in response to various antifungal agents. These results suggest that BEM46 plays an essential role in timely germination in A. fumigatus. From the observation of fluorescence localization, we infer that that BEM46 might be involved in polarized growth in A. fumigatus.
ESTHER : Ma_2020_Med.Mycol_58_690
PubMedSearch : Ma_2020_Med.Mycol_58_690
PubMedID: 31711175
Gene_locus related to this paper: aspfu-q4wgd5

Title : Pediococcus pentosaceus B49 from human colostrum ameliorates constipation in mice - Huang_2020_Food.Funct_11_5607
Author(s) : Huang J , Li S , Wang Q , Guan X , Qian L , Li J , Zheng Y , Lin B
Ref : Food Funct , 11 :5607 , 2020
Abstract : Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 x 109 CFU or 5 x 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.
ESTHER : Huang_2020_Food.Funct_11_5607
PubMedSearch : Huang_2020_Food.Funct_11_5607
PubMedID: 32525185

Title : Preventive Effects of Different Fermentation Times of Shuidouchi on Diphenoxylate-Induced Constipation in Mice - Chen_2019_Foods_8_
Author(s) : Chen L , Zhang J , Suo H , Wang W , Wang H , Zhang Y , Hu Q , Zhao X , Li J
Ref : Foods , 8 : , 2019
Abstract : This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product. By improving its processing technology, it can incur better biological activity and become a health food. The Shuidouchi-treated mice were evaluated using constipation-related kits, quantitative polymerase chain reaction (qPCR), and Western blot assays. After the mice were fed 72-h-fermented Shuidouchi (72-SDC) for 9 d, the defecation time to excrete the first black stool was lower than that of the control and 24-SDC and 48-SDC groups, but was much higher than that of the normal group. The gastrointestinal (GI) transit of the small intestine of the 72-SDC group was higher than that of the control and the 24-SDC and 48-SDC groups, but lower that of the normal group. Meanwhile, 72-SDC could significantly increase the levels of ghrelin, endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE) in the serum of constipated mice compared to the levels in mice in the control group. Moreover, 72-SDC could raise c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GNDF), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression levels, and reduce transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels in small-intestinal tissue compared to the levels in the control group. Meanwhile, 72-SDC also raised ghrelin mRNA expression in gastric tissue and transient receptor potential ankyrin 1 (TRPA1) mRNA expression in colon tissue compared to the control group mice; these effects were stronger than those of 24-SDC and 48-SDC. Shuidouchi has good preventative effects on constipation and performs best when fermented for at least 72 h.
ESTHER : Chen_2019_Foods_8_
PubMedSearch : Chen_2019_Foods_8_
PubMedID: 30832248

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

Title : A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review - Li_2019_Gene_704_113
Author(s) : Li T , Feng Y , Liu Y , He C , Liu J , Chen H , Deng Y , Li M , Li W , Song J , Niu Z , Sang S , Wen J , Men M , Chen X , Li J , Liu X , Ling J
Ref : Gene , 704 :113 , 2019
Abstract : Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.
ESTHER : Li_2019_Gene_704_113
PubMedSearch : Li_2019_Gene_704_113
PubMedID: 30974196
Gene_locus related to this paper: human-ABHD12

Title : Effect of Salvia miltiorrhiza on acetylcholinesterase: Enzyme kinetics and interaction mechanism merging with molecular docking analysis - Tang_2019_Int.J.Biol.Macromol_135_303
Author(s) : Tang H , Song P , Li J , Zhao D
Ref : Int J Biol Macromol , 135 :303 , 2019
Abstract : Acetylcholinesterase (AchE) serves as an important target for Alzheimer's disease. Salvia miltiorrhiza has been used to treat cardiovascular disease for hundreds of years. However, the interaction between S. miltiorrhiza and AchE is still inadequate. Herein, an integrated method including molecular docking and experimental studies was employed to investigate the interaction. Consequently, some components were screened as potent AchE inhibitors by in silico and in vitro. Among them, miltirone (MT) and salvianolic acid A (SAA) reversibly inhibited AchE in a mixed-competitive manner. Fluorescence data revealed that SAA and salvianolic acid C (SAC) strongly quenched the intrinsic fluorescence of AchE through a static quenching mechanism, and the binding was spontaneous and dominated by hydrophobic interaction inferred by the thermodynamic parameters. The synchronous and ANS-binding fluorescence spectra suggested that SAA and SAC could bind to the enzyme and induce its conformation changes of secondary structures, which was further confirmed by Fourier transform infrared spectra. Meanwhile, molecular docking presented the probable binding modes of inhibitors to AchE and highlighted the key role of hydrophobic interaction and hydrogen bonds for the stability of docking complex. These findings put more insights into understanding the interaction of S. miltiorrhiza chemicals and AchE, as well as Alzheimer's disease.
ESTHER : Tang_2019_Int.J.Biol.Macromol_135_303
PubMedSearch : Tang_2019_Int.J.Biol.Macromol_135_303
PubMedID: 31128195

Title : Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B - Liu_2019_Clin.Microbiol.Infect_25_514 e1
Author(s) : Liu D , Li J , Lu W , Wang Y , Zhou X , Huang D , Li X , Ding R , Zhang Z
Ref : Clin Microbiol Infect , 25 :514 e1 , 2019
Abstract : OBJECTIVES: To evaluate the performance of a new mathematical model gamma-glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus gamma-glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B. METHODS: A complete cohort of 2343 patients was divided into early and late cohort depending on the time of liver biopsy. With reference to the Scheuer standard, liver pathologic stage 2 or higher and stage 4 or higher were defined as significant fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of investigated models. RESULTS: In the early cohort, the areas under ROC curves (AUROCs) of GCPR in predicting significant fibrosis of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients (0.782 and 0.775) were both significantly greater than those of GPR (0.748 and 0.747) (Z = 8.198 and Z = 6.023, both p <0.0001); the AUROCs of GCPR in predicting cirrhosis of HBeAg-positive and HBeAg-negative patients (0.842 and 0.861) were both significantly greater than those of GPR (0.802 and 0.823) (Z = 6.686 and Z = 6.116, both p <0.0001). In early, late and complete cohorts, using a single cutoff of GCPR > 0.080, the specificities of GCPR in predicting significant fibrosis of HBeAg-positive patients were 83.3%, 88.2% and 85.0% and of HBeAg-negative patients were 87.6%, 87.4% and 87.6%, respectively; and the sensitivities of GCPR in predicting cirrhosis of HBeAg-positive patients were 81.9%, 88.7% and 84.2% and of HBeAg-negative patients were 83.1%, 82.1% and 82.7%, respectively. CONCLUSIONS: GCPR has higher performance than GPR in predicting significant fibrosis and cirrhosis of chronic hepatitis B.
ESTHER : Liu_2019_Clin.Microbiol.Infect_25_514 e1
PubMedSearch : Liu_2019_Clin.Microbiol.Infect_25_514 e1
PubMedID: 29906588

Title : Strigolactone promotes cytokinin degradation through transcriptional activation of CYTOKININ OXIDASE\/DEHYDROGENASE 9 in rice - Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
Author(s) : Duan J , Yu H , Yuan K , Liao Z , Meng X , Jing Y , Liu G , Chu J , Li J
Ref : Proc Natl Acad Sci U S A , 116 :14319 , 2019
Abstract : Strigolactones (SLs), a group of terpenoid lactones derived from carotenoids, are plant hormones that control numerous aspects of plant development. Although the framework of SL signaling that the repressor DWARF 53 (D53) could be SL-dependently degraded via the SL receptor D14 and F-box protein D3 has been established, the downstream response genes to SLs remain to be elucidated. Here we show that the cytokinin (CK) content is dramatically increased in shoot bases of the rice SL signaling mutant d53 By examining transcript levels of all the CK metabolism-related genes after treatment with SL analog GR24, we identified CYTOKININ OXIDASE/DEHYDROGENASE 9 (OsCKX9) as a primary response gene significantly up-regulated within 1 h of treatment in the wild type but not in d53 We also found that OsCKX9 functions as a cytosolic and nuclear dual-localized CK catabolic enzyme, and that the overexpression of OsCKX9 suppresses the browning of d53 calli. Both the CRISPR/Cas9-generated OsCKX9 mutants and OsCKX9-overexpressing transgenic plants showed significant increases in tiller number and decreases in plant height and panicle size, suggesting that the homeostasis of OsCKX9 plays a critical role in regulating rice shoot architecture. Moreover, we identified the CK-inducible rice type-A response regulator OsRR5 as the secondary SL-responsive gene, whose expression is significantly repressed after 4 h of GR24 treatment in the wild type but not in osckx9 These findings reveal a comprehensive plant hormone cross-talk in which SL can induce the expression of OsCKX9 to down-regulate CK content, which in turn triggers the response of downstream genes.
ESTHER : Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
PubMedSearch : Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
PubMedID: 31235564

Title : ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield - Ou_2019_Nat.Commun_10_1078
Author(s) : Ou J , Peng Y , Yang W , Zhang Y , Hao J , Li F , Chen Y , Zhao Y , Xie X , Wu S , Zha L , Luo X , Xie G , Wang L , Sun W , Zhou Q , Li J , Liang H
Ref : Nat Commun , 10 :1078 , 2019
Abstract : The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.
ESTHER : Ou_2019_Nat.Commun_10_1078
PubMedSearch : Ou_2019_Nat.Commun_10_1078
PubMedID: 30842415
Gene_locus related to this paper: human-ABHD5

Title : The influence of temperature on the toxicity of insecticides to Nilaparvata lugens (Stal) - Mao_2019_Pestic.Biochem.Physiol_156_80
Author(s) : Mao K , Jin R , Li W , Ren Z , Qin X , He S , Li J , Wan H
Ref : Pestic Biochem Physiol , 156 :80 , 2019
Abstract : The toxicity of insecticides is associated with a variety of factors including temperature, and global warming is bound to lead to the outbreak of pests; therefore, it is important to study the influence of temperature on insecticide toxicity and pest control. In this study, the influence of temperature on the toxicity of insecticides to Nilaparvata lugens (BPH) was determined. The results showed that the sensitivity of BPH to cycloxaprid (LC50=42.5-0.388mg/L), nitenpyram (LC50=3.49-0.187mg/L), triflumezopyrim (LC50=0.354-0.0533mg/L) and chlorpyrifos (LC50=36.3-7.41mg/L) increased significantly when the temperature changed from 18 degrees C to 36 degrees C. BPH sensitivity to etofenprox (LC50=9.04-54.2mg/L) was also affected by temperature. Additionally, the feeding amount and the activities of three detoxification enzymes [cytochrome P450 (P450), glutathione S-transferase (GST) and carboxylesterase (CarE)] of BPH at different temperatures were also measured. The feeding amounts were positively correlated with temperature increases while the activities of P450 and GST were significantly inhibited. The correlation analysis showed that changes in P450 activity (but not GST activity) were closely related to the sensitivity of BPH to cycloxaprid, nitenpyram, chlorpyrifos, and etofenprox according to the variation in temperatures. This study provides a theoretical basis for the rational use of chemical pesticides under the global warming trend and provides a reference for the integrated management of BPH in the field.
ESTHER : Mao_2019_Pestic.Biochem.Physiol_156_80
PubMedSearch : Mao_2019_Pestic.Biochem.Physiol_156_80
PubMedID: 31027584

Title : STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p\/STAT3 axis and PI3K\/AKT signalling pathway - Wen_2019_Cell.Prolif_52_e12569
Author(s) : Wen J , Wang H , Dong T , Gan P , Fang H , Wu S , Li J , Zhang Y , Du R , Zhu Q
Ref : Cell Prolif , 52 :e12569 , 2019
Abstract : OBJECTIVES: Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC. MATERIALS AND METHODS: qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration. RESULTS: High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p. CONCLUSIONS: STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.
ESTHER : Wen_2019_Cell.Prolif_52_e12569
PubMedSearch : Wen_2019_Cell.Prolif_52_e12569
PubMedID: 30657221
Gene_locus related to this paper: human-ABHD11

Title : Alkaloids with acetylcholinesterase inhibitory activity from Corydalis racemosa (Thunb.) Pers - Yao_2019_Nat.Prod.Res__1
Author(s) : Yao HN , Peng ZT , Zhang YF , Liu DF , Huang BF , Tu PF , Zhao YF , Huo HX , Li J
Ref : Nat Prod Res , :1 , 2019
Abstract : Two new isoquinoline alkaloids (1 and 2) along with fourteen known alkaloids (3-16) were isolated from Corydalis racemosa (Thunb.) Pers. Their structures were elucidated by analyzing spectroscopic and spectrometric data (NMR, UV, IR, and MS) and comparing their spectroscopic, spectrometric and physicochemical data with the values archived in the literature. The absolute configurations of new compounds were determined via X-ray crystallographic assay and electronic circular dichroism calculations. Acetylcholinesterase (AChE) inhibitory activity of all compounds was evaluated. Compounds 5, 6, 9, 11, and 12 exhibited inhibitory activity against AChE with IC50 values ranged from 10.2 to 63.4 muM.
ESTHER : Yao_2019_Nat.Prod.Res__1
PubMedSearch : Yao_2019_Nat.Prod.Res__1
PubMedID: 31813298

Title : New biphenanthrenes with butyrylcholinesterase inhibitory activitiy from Cremastra appendiculata - Liu_2019_Nat.Prod.Res__1
Author(s) : Liu L , Yin QM , Gao Q , Li J , Jiang Y , Tu PF
Ref : Nat Prod Res , :1 , 2019
Abstract : Encouraged by the in vitro potent inhibitory activity on butyrylcholinesterase (BChE) of 95% ethanol extract of Cremastra appendiculata (D. Don) Makino tubers, a further phytochemical investigation on C. appendiculata tubers was conducted, which led to the isolation of a pair of new biphenanthrene atropisomers, namely cremaphenanthrene F-G (1-2). Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical method. It is the first time that biphenanthrene atropisomers have been isolated from the plant kingdom. Compound 1 showed potent BChE inhibitory effect with IC50 value of 14.62 +/- 2.15 muM. Compound 2 exhibited weak BChE inhibitory effect with IC50 value of 79.56 +/- 0.78 muM. Meanwhile, 1 and 2 were found to be inactive for acetylcholinesterase (AChE) inhibition. These findings suggested that compound 1 was a promising selective BChE inhibitor for AD prevention and treatment.
ESTHER : Liu_2019_Nat.Prod.Res__1
PubMedSearch : Liu_2019_Nat.Prod.Res__1
PubMedID: 31117825

Title : Leek-derived codoped carbon dots as efficient fluorescent probes for dichlorvos sensitive detection and cell multicolor imaging - Hu_2019_Anal.Bioanal.Chem_411_7879
Author(s) : Hu Y , Li J , Li X
Ref : Anal Bioanal Chem , 411 :7879 , 2019
Abstract : A biomass nitrogen and sulfur codoped carbon dots (NS-Cdots) was prepared by a simple and clean hydrothermal method using leek, and was employed as efficient fluorescent probes for sensitive detection of organophosphorus pesticides (OPs). The leek-derived NS-Cdots emitted blue fluorescence, but was quenched by H2O2. Due to acetylcholinesterase/choline oxidase-based cascade enzymatic reaction that produces H2O2 and the inhibition effect of OPs on acetylcholinesterase activity, a NS-Cdots-based fluorescence "off-on" method to detect OPs-dichlorvos (DDVP) was developed. More sensitivity and wider linear detection range were achieved from 1.0 x 10(-9) to 1.0 x 10(-3) M (limit of detection = 5.0 x 10(-10) M). This developed method was applied to the detection of DDVP in Chinese cabbage successfully. The average recoveries were in the range of 96.0~104.0% with a relative standard deviation of less than 3.3%. In addition, the NS-Cdots fluorescent probes were also employed successfully in multicolor imaging of living cells, manifesting that the NS-Cdots fluorescent probes have great application potential in agricultural and biomedical fields. Graphical Abstract.
ESTHER : Hu_2019_Anal.Bioanal.Chem_411_7879
PubMedSearch : Hu_2019_Anal.Bioanal.Chem_411_7879
PubMedID: 31691847

Title : Anti-cholinesterase activities of constituents isolated from Lycopodiastrum casuarinoides - Liu_2019_Fitoterapia__104366
Author(s) : Liu Y , Li J , Li D , Li XM , Zhou G , Xu KP , Kang FH , Zou ZX , Xu PS , Tan GS
Ref : Fitoterapia , :104366 , 2019
Abstract : Phytochemical investigation of the ethyl acetate extract of Lycopodiastrum casuarinoides (Spring) Holub (Lycopodiaceae) led to the isolation of nine compounds, including two new serratene triterpenoids, serrat-14-en-3alpha,21alpha-diol (1), 26-nor-8-oxo-21-one-alpha-onocerin (6), one new abietane diterpenoid, lycocasuarinone A (7), one new sesquiterpene acid, 7, 9-diene-1,4-epoxy-2-hydroxy-10-carboxylic acid (8) and one new chromone derivative, 5,7-dihydroxy-2-methyl esterchromone (9), together with four known serratene triterpenoids (2-5). Abietane diterpenoid (7) and sesquiterpene acid (8) from Lycopodiastrum casuarinoides are reported for the first time. Their structures and stereochemistry were unambiguously elucidated by spectroscopic analysis and comparison with known ones. All the compounds were tested for acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. Bioactivity assays revealed that compound 6 exhibited the most potent AChE inhibitory effect.
ESTHER : Liu_2019_Fitoterapia__104366
PubMedSearch : Liu_2019_Fitoterapia__104366
PubMedID: 31629868

Title : HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra\/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents - Alali_2019_Chemistry_25_11892
Author(s) : Alali KT , Liu J , Chen R , Liu Q , Zhang H , Li J , Hou J , Li R , Wang J
Ref : Chemistry , 25 :11892 , 2019
Abstract : Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials.
ESTHER : Alali_2019_Chemistry_25_11892
PubMedSearch : Alali_2019_Chemistry_25_11892
PubMedID: 31309626

Title : Treatment Effects of Jinlingzi Powder and Its Extractive Components on Gastric Ulcer Induced by Acetic Acid in Rats - Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
Author(s) : Zhao X , Li J , Meng Y , Cao M , Wang J
Ref : Evid Based Complement Alternat Med , 2019 :7365841 , 2019
Abstract : Jinlingzi powder comprises Melia toosendan Sieb. et Zucc. and Corydalis yanhusuo (Y.H. Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu and is usually applied in clinic as traditional Chinese medicine for pain. The present study aims to investigate the therapeutic actions of Jinlingzi powder and its extracted components and theirs treatment mechanism on the acetic acid induced-gastric ulcer in rats. The gastric ulcer model was induced by the administration of acetic acid in rats (84 male). Jinlingzi powder water decoction, its polysaccharide, and nonalkaloid and alkaloid components were used to investigate the therapeutic actions on the acetic acid induced-gastric ulcer by measuring the related pharmacy and pharmacodynamic factors, including ulcer index, ulcer area, ulcer healing rate, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), neurotensin (NT), platelet activating factor (PAF), thromboxane B2 (TXB2), and vascular endothelial growth factor (VEGF) in rat serum, acetylcholinesterase (AChE) in brain tissue, prostaglandin E2 (PGE2), and basic fibroblast growth factor (bFGF) in gastric tissue. Among the various groups, Jinlingzi powder and the nonalkaloid components caused significant changes in IL-8, TNF-alpha, NT, PAF TXB2, and VEGF values in the serum. The AChE content in the rats' brain tissue was also reduced after using Jinlingzi powder and the nonalkaloid components. Additionally, Jinlingzi powder and the nonalkaloid components considerably affect the amount of PGE2 and bFGF in a rat's stomach tissue. Therefore, Jinlingzi powder and the nonalkaloid components can effectively inhibit neutral neutrophil activation, prevent capillaries thrombosis, and protect gastric mucosa. Thus, the nonalkaloid components of the Jinlingzi powder play a key role in the treatment of gastric ulcer.
ESTHER : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedSearch : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedID: 30719066

Title : Functional analysis of four upregulated carboxylesterase genes associated with fenpropathrin resistance in Tetranychus cinnabarinus (Boisduval) - Wei_2019_Pest.Manag.Sci_75_252
Author(s) : Wei P , Li J , Liu X , Nan C , Shi L , Zhang Y , Li C , He L
Ref : Pest Manag Sci , 75 :252 , 2019
Abstract : BACKGROUND: Carboxylesterases (CarEs) are important in pesticide resistance. Four overexpressed CarE genes with inducible character were screened out in fenpropathrin-resistant Tetranychus cinnabarinus, but their functional roles remained to be further analyzed by RNAi and protein expression. RESULTS: Feeding a single double-stranded (ds)RNA of each of four genes led to gene-specific downregulation of mRNA, decreased esterase activity and diminished resistance in T. cinnabarinus. More interestingly, feeding four dsRNAs simultaneously led to a more significant decrease in enzymatic activity and fold resistance than feeding a single dsRNA individually, suggesting that these CarE genes were involved in fenpropathrin-resistance and had cooperative roles. The gene CarE6 was regarded as the primary and representative candidate to be functionally expressed, because silencing of CarE6 led to the most significant decrease in resistance level. The activity of CarE6 protein was competitively inhibited by fenpropathrin. It could effectively decompose 41.7 +/- 0.09% of fenpropathrin within 3 h, proving that CarE6 protein was capable of metabolizing fenpropathrin effectively in T. cinnabarinus. CONCLUSION: The results confirm that four CarE genes are cooperatively involved in fenpropathrin resistance and the metabolic enzymes encoded by these overexpressed genes do indeed metabolize acaricide in resistant T. cinnabarinus in the evolution of acaricide resistance. (c) 2018 Society of Chemical Industry.
ESTHER : Wei_2019_Pest.Manag.Sci_75_252
PubMedSearch : Wei_2019_Pest.Manag.Sci_75_252
PubMedID: 29877064
Gene_locus related to this paper: tetur-t1k786

Title : Different construction strategies affected on the physiology of Pichia pastoris strains highly expressed lipase by transcriptional analysis of key genes - Huang_2019_Bioengineered_10_150
Author(s) : Huang J , Wang Q , Bu W , Chen L , Yang Z , Zheng W , Li Y , Li J
Ref : Bioengineered , 10 :150 , 2019
Abstract : We demonstrated previously that expression of Rhizomucor miehei lipase (RML) in Pichia pastoris could be significantly increased by addition of gene propeptide, optimized signal peptide codons and manipulation of gene dosage. In this study, effects of various strategies on the protein synthesis and secretion pathways were analyzed. Using nine strains previously constructed, we evaluated cell culture properties, enzymatic activities, and analyzed transcriptional levels of nine genes involved in protein synthesis and secretion pathways by qPCR. We observed that (i) Addition of propeptide decreased lipase folding stress by down-regulated four UPR-related genes. (ii) Signal peptide codons optimization had no effect on host with no change in the nine detected genes. (iii) Folding stress and limited transport capacity produced when rml gene dosage exceed 2. Different limiting factors on lipase expression in strains with different construction strategies were identified. This study provides a theoretical basis for further improving RML by transforming host.
ESTHER : Huang_2019_Bioengineered_10_150
PubMedSearch : Huang_2019_Bioengineered_10_150
PubMedID: 31079540

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 : Effects of Lecanicillium lecanii strain JMC-01 on the physiology, biochemistry, and mortality of Bemisia tabaci Q-biotype nymphs - Xie_2019_PeerJ_7_e7690
Author(s) : Xie T , Jiang L , Li J , Hong B , Wang X , Jia Y
Ref : PeerJ , 7 :e7690 , 2019
Abstract : Background: Lecanicillium lecanii is an entomopathogenic fungi, which was isolated from insects suffering from disease. Now, it is an effective bio-control resource that can control agricultural pests such as whitefly and aphids. There are many studies on the control of various agricultural pests by L. lecanii, but no report on its control of Bemisia tabaci biotype-Q exists. In this work, we studied the susceptibility of B. tabaci Q-biotype (from Ningxia, China) to L. lecanii JMC-01 in terms of nymph mortality and the changes in detoxifying protective enzymes activities. Methods: B. tabaci nymphs were exposed to L. lecanii JMC-01 conidia by immersion with the host culture. Mortality was assessed daily for all nymph stages. The detoxifying and protective enzyme activity changes, weight changes, and fat, and water contents of the nymphs were determined spectrophotometrically. Results: All instars of B. tabaci died after being infested with 1 x 10(8) conidia/mL. The 2nd-instar nymphs were the most susceptible, followed by the 3rd-instar nymphs. The corrected cumulative mortality of the 2nd- and 3rd-instar nymphs was 82.22% and 75.55%, respectively. The levels of detoxifying and protective enzymes initially increased and then decreased. The highest activities of carboxylesterase, acetylcholinesterase, peroxidase, and catalase occurred on the 3rd day, reaching 10.5, 0.32, 20, and 6.3 U/mg prot, respectively. These levels were 2.2-, 4.3-, 2.4-, and 1.4-fold the control levels, respectively. The highest activities of glutathione-S transferase and superoxide dismutase on the 2nd day were, respectively, 64 and 43.5 U/mg prot. These levels were, respectively, 2.7 and 1.1-fold that of the control level. The water and fat content in the infected B. tabaci nymphs decreased and differed significantly from the control levels. The weight increased continuously in the first 24 h, decreasing thereafter. At 72 h, the infestation level was about 0.78-fold that of the control level. Conclusions: The studied L. lecanii JMC-01 strain is pathogenic to the B. tabaci Q-biotype. This strain interferes with the normal functioning of detoxifying and protective enzymes, and is also involved in the disruption of normal physiological metabolism in B. tabaci.
ESTHER : Xie_2019_PeerJ_7_e7690
PubMedSearch : Xie_2019_PeerJ_7_e7690
PubMedID: 31576242

Title : One-step orientated immobilization of nanobodies and its application for immunoglobulin purification - Fu_2019_J.Chromatogr.A_1603_15
Author(s) : Fu J , Li J , Wang W , Wu H , Zhou P , Li Y , He Q , Tu Z
Ref : Journal of Chromatography A , 1603 :15 , 2019
Abstract : Affinity chromatography technologies play an important role in the purification of antibodies. To prepare affinity materials, prior isolation and purification of affinity ligands are required before coupling onto solid supports, which is quite expensive and laborious in large-scale applications. In this study, a one-step approach which circumvents the ligand purification procedures was developed to fabricate affinity gel for purifying immunoglobulin G (IgG). A self-labeling tag, haloalkane dehalogenase, was fused to the C-terminal of an anti-Fc variable domain of the heavy chain of the heavy-chain antibody (AFV) which was isolated in previous work. The AFV binds to various sources of IgG and is highly thermal stable. The fusion protein, namely HAFV, was expressed in Escherichia coli as a soluble protein. The binding affinity of HAFV to the Fc region of IgG was characterized and compared with the untagged anti-Fc nanobody. Next, the HAFV was immobilized directly from the crude cell lysate of isopropylthio-beta-D-galactoside (IPTG) induced E. coli. The effects of NaCl concentrations and pH on the capacity of the HAFV resin were investigated. In addition, the one-step coupled HAFV resin was compared with the AFV resin and commercial resins (Protein A and Protein G) by evaluating the static capacity and stability. Though the Protein A (8.34+/-0.37mg/ml) and Protein G (9.19+/-0.28mg/ml) showed higher static capacity, the static capacity of HAFV resin (8.21+/-0.30mg/ml) was better than that of the untagged AFV gel (6.48+/-0.56mg/ml). The recovery results calculated for the reusability and stability show that there is no significant difference between the results obtained for the HAFV gel with those of the untagged AFV gel and commercial Protein A and G. After stored at 37 for 7 days and recycled 10 times, the static capacity of HAFV gel remains above 78%. Our strategy is site-specific, cost-effective, reproducible, and has the potential to dramatically cut down the costs of affinity materials for IgG purification.
ESTHER : Fu_2019_J.Chromatogr.A_1603_15
PubMedSearch : Fu_2019_J.Chromatogr.A_1603_15
PubMedID: 31213362
Gene_locus related to this paper: xanau-halo1

Title : Characterization of the prognostic values of the NDRG family in gastric cancer - Yu_2019_Therap.Adv.Gastroenterol_12_1756284819858507
Author(s) : Yu C , Hao X , Zhang S , Hu W , Li J , Sun J , Zheng M
Ref : Therap Adv Gastroenterol , 12 :1756284819858507 , 2019
Abstract : Background: The N-myc downstream-regulated gene (NDRG) family, NDRG1-4, has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the NDRG family in GC. Methods: The prognostic values of the NDRG family were evaluated by Kaplan-Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results: High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2 (-) GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16-2.33, p = 0.0046]. In HER2 (+) GC, NDRG4 showed a poor prognosis (HR = 1.4, 95% CI: 1.06-1.85, p = 0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2-2.59, p = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4(+) T-cells showed the highest correlation with NDRG4 (correlation = 0.341, p = 2.14e(-11)). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation = 0.438, p = 00e(+)00). Conclusions: This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.
ESTHER : Yu_2019_Therap.Adv.Gastroenterol_12_1756284819858507
PubMedSearch : Yu_2019_Therap.Adv.Gastroenterol_12_1756284819858507
PubMedID: 31384305

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

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

Title : Serum Triglyceride Lipase Concentrations are Independent Risk Factors for Coronary Artery Disease and In-Stent Restenosis - Yu_2019_J.Atheroscler.Thromb_26_762
Author(s) : Yu X , Lu J , Li J , Guan W , Deng S , Deng Q , Ye H , Han W , Yu Y , Zhang R
Ref : J Atheroscler Thromb , 26 :762 , 2019
Abstract : AIM: Endothelial lipase (EL), hepatic lipase (HL), and lipoprotein lipase (LPL) are all triglyceride lipases and are associated with coronary artery disease (CAD). However, whether they can be simultaneous independent risk factors for CAD is unknown. In the present study, we investigated whether the three lipases can be independent risk factors simultaneously for CAD and whether combining these lipases could provide greater predictive power than high-density lipoprotein cholesterol (HDL-c) for the development of CAD. METHODS: Eighty-six patients with CAD and 65 healthy controls were enrolled in the study. Additionally, 38 patients who underwent one-year follow-up angiography after percutaneous coronary intervention with stent implantation were collected to investigate in-stent restenosis. Serum EL, HL, and LPL concentrations were measured and compared with other coronary risk factors. RESULTS: Serum EL and HL concentrations were both significantly increased in patients with CAD or in-stent restenosis, whereas serum LPL concentration was reduced significantly in patients with CAD. Multivariate logistic regression analysis indicated that the three lipases were simultaneous independent risk factors for CAD. However, only serum EL concentration was considered an independent risk factor for in-stent restenosis. Importantly, the receiver operating characteristic curve showed that the combined measurement of the three lipases displayed better predictive power than HDL-c or any one of the three lipases for CAD. CONCLUSIONS: Serum EL concentration was an independent risk factor for both CAD and in-stent restenosis. Moreover, the combined assessment of serum EL, HL, and LPL concentrations as multiple risk factors provided potent predictive power for CAD.
ESTHER : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedSearch : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedID: 30651409

Title : A multifunctional bis-(-)-nor-meptazinol-oxalamide hybrid with metal-chelating property ameliorates Cu(II)-induced spatial learning and memory deficits via preventing neuroinflammation and oxido-nitrosative stress in mice - Tan_2019_J.Trace.Elem.Med.Biol_52_199
Author(s) : Tan X , Zhou Y , Gong P , Guan H , Wu B , Hou L , Feng X , Zheng W , Li J
Ref : J Trace Elem Med Biol , 52 :199 , 2019
Abstract : Excess copper exposure is a risk factor of neurodegeneration related to Alzheimer's disease (AD). Evidence indicates that, besides promoting amyloid beta aggregation, activation of neuroinflammation and oxido-nitrosative stress (two key pathophysiological processes of AD) may also play important roles in Cu(II)-induced neuronal injury. Therefore, the copper-chelating strategy has gained attention in search for new anti-AD drugs. We previously reported a novel multifunctional compound N(1),N(2)-bis(3-(S)-meptazinol-propyl) oxalamide (ZLA), a bis-(-)-nor-meptazinol-oxalamide hybrid with properties of dual binding site acetylcholinesterase (AChE) inhibition and Cu(II)/Zn(II) chelation. The present study was aimed to explore its effect on cognitive deficits caused by intrahippocampal injection of Cu(II) in mice. Results showed that ZLA (2, 5 mg/kg; i.p.) treatment significantly ameliorated the Cu(II)-induced impairment of hippocampus-dependent learning and memory, whereas rivastigmine, an AChE inhibitor showing a similar potency of enzyme inhibition to ZLA, had no obvious effect. Immunohistochemical and Western blot analyses revealed that ZLA attenuated the decrease in hippocampal expression of microtubule-associated protein 2 (MAP2, a dendritic marker) in Cu(II)-challenged mice. Further analysis showed that ZLA suppressed the Cu(II)-evoked microglial activation. Moreover, it inhibited the Cu(II)-evoked production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1beta and expression of inducible nitric oxide synthase in the hippocampus. The Cu(II)-induced oxidative and nitrosative stress in the hippocampus was also attenuated after ZLA treatment. Collectively, these results suggest that ZLA ameliorates the Cu(II)-caused cognitive deficits. Inhibition of neuroinflammation and oxido-nitrosative stress, and thus ameliorating neuronal injury, may be the potential mechanism for the anti-amnesic effect of ZLA.
ESTHER : Tan_2019_J.Trace.Elem.Med.Biol_52_199
PubMedSearch : Tan_2019_J.Trace.Elem.Med.Biol_52_199
PubMedID: 30732883

Title : Liver function and energy metabolism in hepatocellular carcinoma developed in patients with hepatitis B-related cirrhosis - Ren_2019_Medicine.(Baltimore)_98_e15528
Author(s) : Ren M , Li J , Xue R , Wang Z , Coll SL , Meng Q
Ref : Medicine (Baltimore) , 98 :e15528 , 2019
Abstract : Energy metabolism in patients with Hepatocellular carcinoma (HCC) accompanying by hepatitis B cirrhosis is unknown.To compare the differences in liver functions and energy metabolism between patients with hepatitis B-related cirrhosis and patients with HCC.This was a retrospective study of patients with hepatitis B-related cirrhosis (LC group, n = 75) and patients with HCC accompanying by hepatitis B cirrhosis (HCC group, n = 80) treated in Beijing You'an Hospital between January 2013 and June 2017. The resting energy expenditure (REE), respiratory quotient (RQ), carbohydrate oxidation rate (CHO%), fat oxidation rate (FAT%), and protein oxidation rate (PRO%) were measured using a metabolic cart. Liver function, renal function, blood coagulation, etc. were collected.Compared to the LC group, patients with HCC had normal metabolism, but RQ (0.83 +/- 0.07 vs 0.85 +/- 0.08, P = .073) and CHO% (35.5% vs 49%, P = .013) were lower and FAT% was higher (41% vs 33%, P = .030). Compared with patients with LC group, albumin (ALB), gamma-glutamyltranspeptadase (GGT), alkaline phosphatase (AKP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and prothrombin time activity (PTA) were elevated in the HCC group, while total bilirubin (TB), total bile acid (TBA), and international normalized ratio (INR) were reduced (P < .05). Cholinesterase (CHE) was positively correlated with RQ, CHO, and CHO% (P < .05), while negatively correlated with FAT and FAT% (P < .05). AKP was negatively correlated with RQ, CHO, and CHO% (P < .05), while positively correlated with FAT and FAT% (P < .05). TBA was negatively correlated with RQ and CHO (P < .05), while positively correlated with FAT (P < .05).HCC leads to increased liver synthetic function and improve the liver functions of patients with LC, at least to some extent, but the nutritional metabolism was poor.
ESTHER : Ren_2019_Medicine.(Baltimore)_98_e15528
PubMedSearch : Ren_2019_Medicine.(Baltimore)_98_e15528
PubMedID: 31083199

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Biodegradability and biodegradation pathway of di-(2-ethylhexyl) phthalate by Burkholderia pyrrocinia B1213 - Li_2019_Chemosphere_225_443
Author(s) : Li J , Zhang J , Yadav MP , Li X
Ref : Chemosphere , 225 :443 , 2019
Abstract : This study was conducted to investigate the biodegradation of di-(2-ethylhexyl) phthalate (DEHP) by Burkholderia pyrrocinia B1213. The results showed that DEHP at concentration of 500 mg/L in a mineral salt medium containing 1.0% yeast extract can be almost completely degraded (98.05%) by strain B1213. The optimal condition for DEHP degradation was pH 7.0, temperature 30 degreesC. Moreover, B1213 shows better degradation effect on long-chain PAEs, such as DEHP, which provides a great potential for its use in bioremediation of soils contaminated with PAEs. The kinetic studies showed that DEHP depletion curves fit well to the modified Gompertz model. The mono(2-ethylhexyl) phthalate (MEHP), mono-dibutyl phthalate (MBP), phthalic acid (PA) and 4-oxo-hexanoic acid were identified as the metabolites of DEHP by HPLC-ESI-QTOFMS. The detection of MBP and 4-oxo-hexanoic acid as intermediates prompted us to propose a novel and more complete DEHP biodegradation pathway compared to the classic pathway: DEHP is first degraded to MEHP by esterases, which is then converted to MBP through beta-oxidation. Then MBP is degraded to PA by esterases, which is then converted to protocatechuate (PCA) under aerobic conditions rapidly. PCA is ultimately cleaved to generate CO(2) and H(2)O via 4-oxo-hexanoic acid.
ESTHER : Li_2019_Chemosphere_225_443
PubMedSearch : Li_2019_Chemosphere_225_443
PubMedID: 30897469

Title : Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV - Jiang_2019_Viruses_11_
Author(s) : Jiang Y , Li J , Teng Y , Sun H , Tian G , He L , Li P , Chen Y , Guo Y , Zhao G , Zhou Y , Sun S
Ref : Viruses , 11 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
ESTHER : Jiang_2019_Viruses_11_
PubMedSearch : Jiang_2019_Viruses_11_
PubMedID: 30634407

Title : Integrated Approaches to Reveal Genes Crucial for Tannin Degradation in Aureobasidium melanogenum T9 - Zhang_2019_Biomolecules_9_439
Author(s) : Zhang LL , Li J , Wang YL , Liu S , Wang ZP , Yu XJ
Ref : Biomolecules , 9 :439 , 2019
Abstract : Tannins biodegradation by a microorganism is one of the most efficient ways to produce bioproducts of high value. However, the mechanism of tannins biodegradation by yeast has been little explored. In this study, Aureobasidium melanogenum T9 isolated from red wine starter showed the ability for tannins degradation and had its highest biomass when the initial tannic acid concentration was 20 g/L. Furthermore, the genes involved in the tannin degradation process were analyzed. Genes tan A, tan B and tan C encoding three different tannases respectively were identified in the A. melanogenum T9. Among these genes, tan A and tan B can be induced by tannin acid simultaneously at both gene transcription and protein expression levels. Our assay result showed that the deletion of tanA and tanB resulted in tannase activity decline with 51.3 +/- 4.1 and 64.1 +/- 1.9 U/mL, respectively, which is much lower than that of A. melanogenum T9 with 91.3 +/- 5.8 U/mL. In addition, another gene coding gallic acid decarboxylase (gad) was knocked out to better clarify its function. Mutant deltagad completely lost gallic acid decarboxylase activity and no pyrogallic acid was seen during the entire cultivation process, confirming that there was a sole gene encoding decarboxylase in the A. melanogenum T9. These results demonstrated that tanA, tanB and gad were crucial for tannin degradation and provided new insights for the mechanism of tannins biodegradation by yeast. This finding showed that A. melanogenum has potential in the production of tannase and metabolites, such as gall acid and pyrogallol.
ESTHER : Zhang_2019_Biomolecules_9_439
PubMedSearch : Zhang_2019_Biomolecules_9_439
PubMedID: 31480670
Gene_locus related to this paper: 9pezi-a0a5c2gyu2 , 9pezi-a0a5c2gyv0 , 9pezi-a0a5c2h0r5

Title : Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease - Huang_2019_Chem.Biol.Drug.Des_93_110
Author(s) : Huang W , Wang Y , Li J , Zhang Y , Ma X , Zhu P
Ref : Chemical Biology Drug Des , 93 :110 , 2019
Abstract : Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218 nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid beta-protein 1-42 (Abeta1-42 ). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).
ESTHER : Huang_2019_Chem.Biol.Drug.Des_93_110
PubMedSearch : Huang_2019_Chem.Biol.Drug.Des_93_110
PubMedID: 29543387

Title : Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site - Chaton_2019_Sci.Rep_9_20267
Author(s) : Chaton CT , Rodriguez ES , Reed RW , Li J , Kenner CW , Korotkov KV
Ref : Sci Rep , 9 :20267 , 2019
Abstract : Mycobacterium tuberculosis is the cause of the world's most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.
ESTHER : Chaton_2019_Sci.Rep_9_20267
PubMedSearch : Chaton_2019_Sci.Rep_9_20267
PubMedID: 31889085
Gene_locus related to this paper: myctu-metx , myca9-b1mg17 , mychd-k5b926

Title : Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents - Xu_2019_ACS.Chem.Neurosci_10_482
Author(s) : Xu Y , Zhang J , Wang H , Mao F , Bao K , Liu W , Zhu J , Li X , Zhang H , Li J
Ref : ACS Chem Neurosci , 10 :482 , 2019
Abstract : Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC50 = 0.032 +/- 0.007 muM) and MAO-B (IC50 = 2.117 +/- 0.061 muM), along with the improved blood-brain barrier (BBB) permeability, antioxidant ability, and good copper chelating property in vitro. Animal studies showed that compound 1c.HCl could inhibit the cerebral AChE/MAO-B activities and alleviate scopolamine-induced cognitive impairment in mice. Combined with good oral bioavailability ( F = 45.55%), these findings demonstrated that compound 1c may be a potent brain permeable multifunctional candidate for the treatment of AD.
ESTHER : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedSearch : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedID: 30110536

Title : [Isolation and identification of endophytic fungi from Huperzia serrata and their metabolites' inhibitory activities against acetylcholinesterase and anti-inflammatory activities] - Qi_2019_Zhongguo.Zhong.Yao.Za.Zhi_44_3213
Author(s) : Qi BW , Mo T , Zhang X , Yan YR , Xu XP , Yang HY , Wang XH , Li J , Shi SP , Liu X
Ref : Zhongguo Zhong Yao Za Zhi , 44 :3213 , 2019
Abstract : A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg.L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg.L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.
ESTHER : Qi_2019_Zhongguo.Zhong.Yao.Za.Zhi_44_3213
PubMedSearch : Qi_2019_Zhongguo.Zhong.Yao.Za.Zhi_44_3213
PubMedID: 31602874

Title : A Conserved Tyrosine Residue in Slitrk3 Carboxyl-Terminus Is Critical for GABAergic Synapse Development - Li_2019_Front.Mol.Neurosci_12_213
Author(s) : Li J , Han W , Wu K , Li YD , Liu Q , Lu W
Ref : Front Mol Neurosci , 12 :213 , 2019
Abstract : Single-passing transmembrane protein, Slitrk3 (Slit and Trk-like family member 3, ST3), is a synaptic cell adhesion molecule highly expressed at inhibitory synapses. Recent studies have shown that ST3, through its extracellular domain, selectively regulates inhibitory synapse development via the trans-synaptic interaction with presynaptic cell adhesion molecule, receptor protein tyrosine phosphatase delta (PTPdelta) and the cis-interaction with postsynaptic cell adhesion molecule, Neuroligin 2 (NL2). However, little is known about the physiological function of ST3 intracellular, carboxyl (C)-terminal region. Here we report that in heterologous cells, ST3 C-terminus is not required for ST3 homo-dimerization and trafficking to the cell surface. In contrast, in hippocampal neurons, ST3 C-terminus, more specifically, the conserved tyrosine Y969 (in mice), is critical for GABAergic synapse development. Indeed, overexpression of ST3 Y969A mutant markedly reduced the gephyrin puncta density and GABAergic transmission in hippocampal neurons. In addition, single-cell genetic deletion of ST3 strongly impaired GABAergic transmission. Importantly, wild-type (WT) ST3, but not the ST3 Y969A mutant, could fully rescue GABAergic transmission deficits in neurons lacking endogenous ST3, confirming a critical role of Y969 in the regulation of inhibitory synapses. Taken together, our data identify a single critical residue in ST3 C-terminus that is important for GABAergic synapse development and function.
ESTHER : Li_2019_Front.Mol.Neurosci_12_213
PubMedSearch : Li_2019_Front.Mol.Neurosci_12_213
PubMedID: 31551708

Title : Efficient heterologous expression of an alkaline lipase and its application in hydrolytic production of free astaxanthin - Huang_2018_Biotechnol.Biofuels_11_181
Author(s) : Huang J , Yang Z , Zhu R , Qian X , Wang Y , Li Y , Li J
Ref : Biotechnol Biofuels , 11 :181 , 2018
Abstract : Background: Astaxanthin, a naturally occurring carotenoid pigment molecule, displays strong antioxidant, anti-cancer, and immunity-enhancing properties, and is often utilized in food, biomedical, cosmetic, and other industries. Free astaxanthin has better solubility than astaxanthin esters (Ast-E), and is a useful auxiliary ingredient in health foods and medicines. Our goal was to establish an improved enzymatic method for preparation of free astaxanthin from natural sources (e.g., the microalga Haematococcus pluvialis), to expand the potential applications of free astaxanthin. Results: The alkaline lipase gene proalip and its propeptide were cloned and successfully fusion-expressed in Pichia pastoris X-33. The recombinant lipase was termed Lipase-YH. Through optimization of culture conditions (medium formulation, pH, added methanol concentration), cell growth (OD600) and secreted enzyme activity respectively reached to 280 and 2050 U/mL in a 50-L autofermentor. Activity of Lipase-YH enzyme powder was about 40,000 U/g. Hydrolysis of Ast-E (extracted from H. pluvialis) by Lipase-YH occurred in aqueous phase, and reaction conditions were optimized based on emulsification method and enzyme/substrate ratio. The highest enzymatic reaction rate was observed for substrate concentration 200 mug/mL, with maximal free astaxanthin yield (80%) at 1 h, and maximal Ast-E hydrolysis rate 96%, as confirmed by TLC, HPLC, and mass spectroscopy. Conclusion: A novel, efficient enzymatic process was developed for production of free astaxanthin through hydrolysis of Ast-E. Lipase activity was enhanced, and production cost was greatly reduced. The unique structure of free astaxanthin allows linkage to various functional compounds, which will facilitate development of novel pharmaceutical and food products in future studies.
ESTHER : Huang_2018_Biotechnol.Biofuels_11_181
PubMedSearch : Huang_2018_Biotechnol.Biofuels_11_181
PubMedID: 29983744
Gene_locus related to this paper: penex-Q9HFW6

Title : Crystal structure of acetylcholinesterase catalytic subunits of the malaria vector Anopheles gambiae - Han_2018_Insect.Sci_25_721
Author(s) : Han Q , Wong DM , Robinson H , Ding H , Lam PC , Totrov MM , Carlier PR , Li J
Ref : Insect Sci , 25 :721 , 2018
Abstract : Acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses in the central nervous system (Toutant, 1989). Inhibition of the enzyme in insects could lead to the death of insects rapidly; thus AChE has been a molecular target for developing insecticides. This article is protected by copyright. All rights reserved.
ESTHER : Han_2018_Insect.Sci_25_721
PubMedSearch : Han_2018_Insect.Sci_25_721
PubMedID: 28247978
Gene_locus related to this paper: anoga-ACHE1

Title : Select beta- and gamma-branched 1-alkylpyrazol-4-yl methylcarbamates exhibit high selectivity for inhibition of Anopheles gambiae versus human acetylcholinesterase - Carlier_2018_Pestic.Biochem.Physiol_151_32
Author(s) : Carlier PR , Chen QH , Verma A , Wong DM , Mutunga JM , Muller J , Islam R , Shimozono AM , Tong F , Li J , Totrov M , Bloomquist JR
Ref : Pestic Biochem Physiol , 151 :32 , 2018
Abstract : The widespread emergence of pyrethroid-resistant Anopheles gambiae has intensified the need to find new contact mosquitocides for indoor residual spraying and insecticide treated nets. With the goal of developing new species-selective and resistance-breaking acetylcholinesterase (AChE)-inhibiting mosquitocides, in this report we revisit the effects of carbamate substitution on aryl carbamates, and variation of the 1-alkyl group on pyrazol-4-yl methylcarbamates. Compared to aryl methylcarbamates, aryl dimethylcarbamates were found to have lower selectivity for An. gambiae AChE (AgAChE) over human AChE (hAChE), but improved tarsal contact toxicity to G3 strain An. gambiae. Molecular modeling studies suggest the lower species-selectivity of the aryl dimethylcarbamates can be attributed to a less flexible acyl pocket in AgAChE relative to hAChE. The improved tarsal contact toxicity of the aryl dimethylcarbamates relative to the corresponding methylcarbamates is attributed to a range of complementary phenomena. With respect to the pyrazol-4-yl methylcarbamates, the previously observed low An. gambiae-selectivity of compounds bearing alpha-branched 1-alkyl groups was improved by employing beta- and gamma-branched 1-alkyl groups. Compounds 22a (cyclopentylmethyl), 21a (cyclobutylmethyl), and 26a (3-methylbutyl) offer 250-fold, 120-fold, and 96-fold selectivity, respectively, for inhibition of AgAChE vs. hAChE. Molecular modeling studies suggests the high species-selectivity of these compounds can be attributed to the greater mobility of the W84 side chain in the choline-binding site of AgAChE, compared to that of W86 in hAChE. Compound 26a has reasonable contact toxicity to G3 strain An. gambiae (LC50 = 269 mug/mL) and low cross-resistance to Akron strain (LC50 = 948 mug/mL), which bears the G119S resistance mutation.
ESTHER : Carlier_2018_Pestic.Biochem.Physiol_151_32
PubMedSearch : Carlier_2018_Pestic.Biochem.Physiol_151_32
PubMedID: 30524149

Title : Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain - Li_2018_Neurosci_384_203
Author(s) : Li J , Rao D , Gibbs RB
Ref : Neuroscience , 384 :203 , 2018
Abstract : Cholinergic projections have been shown to interact with estrogens in ways that influence synaptic plasticity and cognitive performance. The mechanisms are not well understood. The goal of this study was to investigate whether cholinergic projections influence brain estrogen production by affecting aromatase (ARO), or influence estrogen signaling by affecting estrogen receptor expression. In the first experiment, ovariectomized rats received intraseptal injection of the selective immunotoxin 192IgG-saporin to destroy cholinergic inputs to the hippocampus. In the second experiment ovariectomized rats received daily intraperitoneal injections of the cholinesterase inhibitors donepezil or galantamine for 1week. ARO activity and relative levels of ARO, ERalpha, ERss, and GPR30 mRNAs were quantified in the hippocampus, frontal cortex, amygdala and preoptic area. Results show that the cholinergic lesions effectively removed cholinergic inputs to the hippocampus, but had no significant effect on ARO or on relative levels of ER mRNAs. Likewise, injections of the cholinesterase inhibitors had no effect on ARO or ER expression in most regions of the brain. This suggests that effects of cholinergic inputs on synaptic plasticity and neuronal function are not mediated by effects on local estrogen production or ER expression. One exception was the amygdala where treating with galantamine was associated with a significant increase in ARO activity. The amygdala is a key structure involved in registering fear and anxiety. Hence this finding may be clinically relevant to elderly patients who are treated for memory impairment and who also struggle with fear and anxiety disorders.
ESTHER : Li_2018_Neurosci_384_203
PubMedSearch : Li_2018_Neurosci_384_203
PubMedID: 29852246

Title : Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders - Hussain_2018_Int.J.Biol.Sci_14_341
Author(s) : Hussain G , Rasul A , Anwar H , Aziz N , Razzaq A , Wei W , Ali M , Li J , Li X
Ref : Int J Biol Sci , 14 :341 , 2018
Abstract : Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines. In conventional medicational therapies, several plants have been reported to bestow remedial effects. Phytochemicals from medicinal plants can provide a better and safer alternative to synthetic molecules. Many phytochemicals have been identified that cure the human body from a number of diseases. The present article reviews the potential efficacy of plant-derived alkaloids, which possess potential therapeutic effects against several NDDs including Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD), Epilepsy, Schizophrenia, and stroke. Alkaloids include isoquinoline, indole, pyrroloindole, oxindole, piperidine, pyridine, aporphine, vinca, beta-carboline, methylxanthene, lycopodium, and erythrine byproducts. Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of alpha-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist.
ESTHER : Hussain_2018_Int.J.Biol.Sci_14_341
PubMedSearch : Hussain_2018_Int.J.Biol.Sci_14_341
PubMedID: 29559851

Title : Guided Evolution of Recombinant Bombyx mori Acetylcholinesterase II by Homology Modeling to Change Pesticide Sensitivity -
Author(s) : Cai J , Wang B , Li J , Chen Z , Rao M , Muyldermans S , Hua X , Xie X , Wang H , Yang J , Xu Z , Shen Y , Sun Y
Ref : Int J Mol Sci , 19 : , 2018
PubMedID: 30373269

Title : Identification of carboxylesterase genes associated with pyrethroid resistance in the malaria vector Anopheles sinensis (Diptera: Culicidae) - Wu_2018_Pest.Manag.Sci_74_159
Author(s) : Wu XM , Xu BY , Si FL , Li J , Yan ZT , Yan ZW , He X , Chen B
Ref : Pest Manag Sci , 74 :159 , 2018
Abstract : BACKGROUND: Carboxylesterases (CCEs) are one of three large detoxification enzyme families. Some CCEs are active on synthetic insecticides with ester structures. Anopheles sinensis is an important malaria vector in eastern Asia. This study identified and characterized the CCE genes in the A. sinensis genome and determined CCE genes associated with pyrethroid resistance using RNA sequencing (RNA-seq) and quantitative reverse transcription - polymerase chain reaction (qRT-PCR), in A. sinensis from Anhui, Chongqing, and Yunnan in China. RESULTS: Fifty-seven putative CCEs were identified and placed into three classes, 12 subfamilies and 14 clades through phylogenetic and homology analyses. Exon sizes ranged from 31 to 4317 bp, with 49 CCEs having two to five exons and eight having six to 11 exons. A total of 183 introns were recognized with sizes ranging from 31 to 4317 bp. The 57 CCEs were located on 14 scaffolds, with 70% located on four scaffolds. The alpha-esterase subfamily was significantly expanded compared with that of Anopheles gambiae. In a pyrethroid-resistant strain, RNA-seq detected five upregulated CCE genes and qRT-PCR detected 12 upregulated CCE genes. The alpha-esterase 10 (AsAe10) and acetylcholinesterase 1 (AsAce1) genes were the main CCE genes associated with pyrethroid resistance. CONCLUSION: This information will be useful for further study of the CCE gene family and pyrethroid resistance mechanisms mediated by CCEs. (c) 2017 Society of Chemical Industry.
ESTHER : Wu_2018_Pest.Manag.Sci_74_159
PubMedSearch : Wu_2018_Pest.Manag.Sci_74_159
PubMedID: 28731595

Title : Surrogating and redirection of pyrazolo[1,5-a]pyrimidin-7(4H)-one core, a novel class of potent and selective DPP-4 inhibitors - Deng_2018_Bioorg.Med.Chem_26_903
Author(s) : Deng X , Shen J , Zhu H , Xiao J , Sun R , Xie F , Lam C , Wang J , Qiao Y , Tavallaie MS , Hu Y , Du Y , Li J , Fu L , Jiang F
Ref : Bioorganic & Medicinal Chemistry , 26 :903 , 2018
Abstract : The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC(50): 80 nM), while maintaining other key cellular parameters such as high selectivity, low cytotoxicity and good cell viability. Subsequent optimization of b2 based on docking analysis and structure-based drug design knowledge resulted in d1. Compound d1 has nearly 2-fold increase of inhibitory activity (IC(50): 49 nM) and over 1000-fold selectivity against DPP-8 and DPP-9. Further in vivo IPGTT assays showed that compound b2 effectively reduce glucose excursion by 34% at the dose of 10 mg/kg in diabetic mice. Herein we report the optimization and design of a potent and highly selective series of pyrazolo[1,5-a]pyrimidin-7(4H)-one DPP-4 inhibitors.
ESTHER : Deng_2018_Bioorg.Med.Chem_26_903
PubMedSearch : Deng_2018_Bioorg.Med.Chem_26_903
PubMedID: 29373269

Title : Multiple mutations and overexpression of the MdaE7 carboxylesterase gene associated with male-linked malathion resistance in housefly, Musca domestica (Diptera: Muscidae) - Zhang_2018_Sci.Rep_8_224
Author(s) : Zhang Y , Li J , Ma Z , Shan C , Gao X
Ref : Sci Rep , 8 :224 , 2018
Abstract : Two unique housefly strains, MSS and N-MRS, were selected and used to clarify mechanisms of sex-associated malathion resistance in the housefly, Musca domestica. Compared with the lab-susceptible CSS strain, susceptible females and resistant males were observed in the malathion-susceptible MSS strain, while the malathion-resistant near-isogenic line, N-MRS, achieved similar resistance level between genders. Significant synergistic effect of the esterase-inhibitor DEF on resistant houseflies pointed to the important involvement of esterase in this specific malathion resistance. Examination of the carboxylesterase gene MdalphaE7 in malathion resistant housefly populations found seven, non-synonymous SNP mutations (Ser(250)-Thr, Trp(251)-Ser, Met(303)-Ile, Leu(354)-Phe, Ser(357)-Leu, Trp(378)-Arg and Ser(383)-Thr), not found in susceptible houseflies, revealing a strong correlation between these mutations and the development of malathion resistance. Further genetic analysis conducted with bioassays by topical application and nucleotide polymorphism detection provided a first line of molecular evidence for a linkage between a male-determining factor and MdalphaE7 gene in the MSS and N-MRS males. This linkage results in a much higher level of malathion resistance for males than females in the MSS strain. Lastly, quantitative real-time PCR showed that MdalphaE7 was over expressed in the resistant strain due to the increased transcription level of mRNA rather than gene duplication.
ESTHER : Zhang_2018_Sci.Rep_8_224
PubMedSearch : Zhang_2018_Sci.Rep_8_224
PubMedID: 29317643
Gene_locus related to this paper: musdo-EST23aes07

Title : Association between the PON1 Q192R polymorphism and coronary heart disease in Chinese: A meta-analysis - Zhang_2018_Medicine.(Baltimore)_97_e11151
Author(s) : Zhang Z , Ou J , Cai P , Niu B , Li J
Ref : Medicine (Baltimore) , 97 :e11151 , 2018
Abstract : BACKGROUND: The relation has not been reported consistently between the PON1 Q192R polymorphism and coronary heart disease (CHD). To clarify the discrepancy, we performed the present meta-analysis to evaluate the association between the PON1 gene Q192R polymorphism and CHD risk in Chinese population. METHODS: We conducted a comprehensive search of the PubMed, EMBASE, and China National Knowledge Infrastructure databases for all available case-control studies. Two reviewers independently selected studies. Data were analyzed by STATA software package v 12.0. RESULTS: Thirteen studies investigating the association between the PON1 Q192R polymorphism and risk of CHD were selected in this meta-analysis with 4353 cases and 4882 controls. The association between the PON1 Q192R polymorphism and CHD is statistically significant under the recessive genetic model (R/R vs Q/R + Q/Q, odds ratio [OR] = 1.111, 95% confidence interval [CI] = 1.017-1.214). We observed no statistical association between PON1 Q192R polymorphism and risk of CHD under allele model (R vs Q, OR = 1.087, 95% CI = 0.976-1.209), homozygous model (RR vs QQ, OR = 1.192, 95% CI = 0.949-1.496), and dominant genetic model (Q/R + R/R vs Q/Q, OR = 1.127, 95% CI = 0.938-1.354). CONCLUSION: This meta-analysis suggests that the PON1 Q192R polymorphism has a weak association with CHD risk in Chinese.
ESTHER : Zhang_2018_Medicine.(Baltimore)_97_e11151
PubMedSearch : Zhang_2018_Medicine.(Baltimore)_97_e11151
PubMedID: 29952962

Title : Rice DWARF14 acts as an unconventional hormone receptor for strigolactone - Yao_2018_J.Exp.Bot_69_2355
Author(s) : Yao R , Wang L , Li Y , Chen L , Li S , Du X , Wang B , Yan J , Li J , Xie D
Ref : J Exp Bot , 69 :2355 , 2018
Abstract : Strigolactones (SLs) act as an important class of phytohormones to regulate plant shoot branching, and also serve as rhizosphere signals to mediate interactions of host plants with soil microbes and parasitic weeds. SL receptors in dicots, such as DWARF14 in Arabidopsis (AtD14), RMS3 in pea, and ShHTL7 in Striga, serve as unconventional receptors that hydrolyze SLs into a D-ring-derived intermediate CLIM and irreversibly bind CLIM to trigger SL signal transduction. Here, we show that D14 from the monocot rice can complement Arabidopsis d14 mutant and interact with the SL signaling components in Arabidopsis. Our results further reveal that rice D14, similar to SL receptors in dicots, also serves as an unconventional hormone receptor that generates and irreversibly binds the active form of SLs. These findings uncover the conserved functions of D14 proteins in monocots and dicots.
ESTHER : Yao_2018_J.Exp.Bot_69_2355
PubMedSearch : Yao_2018_J.Exp.Bot_69_2355
PubMedID: 29365172

Title : Design, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer's Disease - Mao_2018_ACS.Chem.Neurosci_9_328
Author(s) : Mao F , Wang H , Ni W , Zheng X , Wang M , Bao K , Ling D , Li X , Xu Y , Zhang H , Li J
Ref : ACS Chem Neurosci , 9 :328 , 2018
Abstract : Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer's disease (AD). Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, 1w.Cit (citrate of 1w) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the molecular docking simulations of 1w with hAChE and hPDE5A confirmed that our design strategy was rational. In summary, our research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small molecule probe to validate the novel AD therapeutic approach in vivo.
ESTHER : Mao_2018_ACS.Chem.Neurosci_9_328
PubMedSearch : Mao_2018_ACS.Chem.Neurosci_9_328
PubMedID: 29068218

Title : Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) - Ni_2018_ACS.Chem.Neurosci_9_1625
Author(s) : Ni W , Wang H , Li X , Zheng X , Wang M , Zhang J , Gong Q , Ling D , Mao F , Zhang H , Li J