Zhang L

References (346)

Title : Facile and selective recognition of sulfonylurea pesticides based on the multienzyme-like activities enhancement of nanozymes combining sensor array - Tian_2024_J.Hazard.Mater_469_133847
Author(s) : Tian T , Song D , Zhang L , Huang H , Li Y
Ref : J Hazard Mater , 469 :133847 , 2024
Abstract : Traditional identification methods based on cholinesterase inhibition are limited to recognizing organic phosphorus and carbamate esters, and their response to sulfonylurea pesticides is weak. Residual sulfonylurea pesticides can pose a threat to human health. So, it is very important to develop an effective, rapid and portable method for sulfonylurea pesticides detection. Herein, we first found that sulfonylurea pesticides have activity-enhancing effects on copper-based nanozymes, and then combined them with the array technology to construct a six-channel sensing array method for selectively identifying sulfonylurea pesticides and detecting total concentration of sulfonylurea pesticides (the limit of detection was 0.03 microg/mL). This method has good selectivity towards sulfonylurea pesticides. In addition, a smartphone-based colorimetric paper sensor analysis method was developed to achieve the on-site detection of the total concentration of sulfonylurea pesticides. And this array can also be used for individual differentiation (1-100 microg/mL). Our work not only investigates the specific responses of copper-based nanozymes to sulfonylurea pesticides, but also develops a simple method that contributes to directly detect sulfonylurea pesticides at the source of pollution, providing insights for further research on sulfonylurea pesticides detection and filling the gap in pesticide residue studies.
ESTHER : Tian_2024_J.Hazard.Mater_469_133847
PubMedSearch : Tian_2024_J.Hazard.Mater_469_133847
PubMedID: 38422731

Title : Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets - Pan_2024_Foods_13_
Author(s) : Pan Y , Li Z , Zhao X , Du Y , Zhang L , Lu Y , Yang L , Cao Y , Qiu J , Qian Y
Ref : Foods , 13 : , 2024
Abstract : Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.
ESTHER : Pan_2024_Foods_13_
PubMedSearch : Pan_2024_Foods_13_
PubMedID: 38397589

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 : Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier - Zhang_2024_Dig.Dis.Sci__
Author(s) : Zhang JH , Lin AP , Zhang L , Ruan DD , Gao MZ , Chen Q , Yu HP , Liao LS , Lin XF , Fang ZT , Lin F , Lu SY , Luo JW , Zheng XL , Chen MS
Ref : Digestive Diseases & Sciences , : , 2024
Abstract : BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.
ESTHER : Zhang_2024_Dig.Dis.Sci__
PubMedSearch : Zhang_2024_Dig.Dis.Sci__
PubMedID: 38564148
Gene_locus related to this paper: human-LIPA

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

Title : Transcriptomic Association Analysis of the Metabolic Mechanism of Sulfamethoxazole in Channel Catfish (Ictalurus punctatus) - Du_2024_Animals.(Basel)_14_
Author(s) : Du X , Sun R , Zhang L , Liu Y , Ai X
Ref : Animals (Basel) , 14 : , 2024
Abstract : Sulfamethoxazole is a widely used antimicrobial drug used to treat bacterial diseases in aquaculture. To understand the gene expression in channel catfish liver after treatment with sulfamethoxazole, in this study, the treatment group received sulfamethoxazole (100 mg/kg bw), which was administered orally once, and samples were taken at 5 h, 12 h, and 6 d after the administration of sulfamethoxazole, while the control group was orally administered sterile water. To further identify potentially significant genes, a transcriptome analysis using RNA-seq was carried out. More than 50 million high-quality reads were found. After filtering and quality analysis, these reads were identified as 54,169,682, 51,313,865, 51,608,845, and 49,333,491. After counting 23,707 of these transcripts for gene expression, it was discovered that 14,732 of them had genes with differential expression. Moreover, we found that the annotation with the most GO variation was "cellular process" (1616 genes), "metabolic process" (1268 genes), "binding" (1889 genes), and "catalytic activity" (1129 genes). KEGG pathways showed that the "metabolic pathway" was the pathway that was significantly enriched in both experimental groups when comparing the experimental groups: 5 h and 12 h (128 genes); 5 h and 6 d (332 genes); and 12 h and 6 d (348 genes). Also, UDP- glucuronosyltransferase (ugt), which is associated with glucuronidation, and UDP-glucuronosyltransferase 2C1-like (ugt2a1) showed significant upregulation. Carboxylesterase 5A-like (ces3), which promotes fatty acyl and cholesteryl ester metabolism, and the glutathione transferase family were upregulated in the expression of sulfamethoxazole metabolism in the liver, which significantly affected the metabolic effects of the drug. Meanwhile, dypd, uck2b, and rrm2, which are related to nucleotide synthesis and metabolism, were upregulated. Our study extends the knowledge of gene expression in drug metabolism in channel catfish and further provides insight into the molecular mechanism of sulfamethoxazole metabolism.
ESTHER : Du_2024_Animals.(Basel)_14_
PubMedSearch : Du_2024_Animals.(Basel)_14_
PubMedID: 38612297

Title : Multifunctional Ni-NPC Single-Atom Nanozyme for Removal and Smartphone-Assisted Visualization Monitoring of Carbamate Pesticides - Xu_2024_Inorg.Chem__
Author(s) : Xu X , Ma M , Gao J , Sun T , Guo Y , Feng D , Zhang L
Ref : Inorg Chem , : , 2024
Abstract : A multifunctional single-atom nanozyme, denoted as 3D Ni,N-codoped porous carbon (Ni-NPC), was devised that exhibits remarkable adsorption capabilities and a repertoire of enzyme mimetic functions (oxidase- and peroxidase-like). These attributes stem from the distinctive mesoporous thin-shell structure and well-dispersed Ni sites. The efficient adsorption capacity of Ni-NPC was assessed with respect to three carbamate pesticides (CMPs): metolcarb, carbaryl, and isoprocarb. Moreover, a colorimetric detection method for CMP was established based on its robust peroxidase-like catalytic activity and sequential catalytic interactions with acetylcholinesterase. Furthermore, a portable colorimetric sensor based on a hydrogel sphere integrated with a smartphone platform was devised. This sensor enables rapid, on-site, and quantitative assessment of CMP, boasting an extraordinarily low detection limit of 1.5 ng mL(-1). Notably, this sensor was successfully applied to the analysis of CMP levels in lake water and vegetable samples (pakchoi and rape), propelling the progress of real-time detection technologies in food and environment monitoring.
ESTHER : Xu_2024_Inorg.Chem__
PubMedSearch : Xu_2024_Inorg.Chem__
PubMedID: 38163760

Title : Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters - Guo_2024_Theranostics_14_2036
Author(s) : Guo J , Miao G , Zhang W , Shi H , Lai P , Xu Y , Zhang L , Chen G , Han Y , Zhao Y , Liu G , Wang Y , Huang W , Xian X
Ref : Theranostics , 14 :2036 , 2024
Abstract : Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5(-/-)) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5(-/-) hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5(-/-) hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5(-/-) hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5(-/-) hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.
ESTHER : Guo_2024_Theranostics_14_2036
PubMedSearch : Guo_2024_Theranostics_14_2036
PubMedID: 38505614

Title : Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer - Zhou_2024_J.Transl.Med_22_55
Author(s) : Zhou L , Du K , Dai Y , Zeng Y , Luo Y , Ren M , Pan W , Liu Y , Zhang L , Zhu R , Feng D , Tian F , Gu C
Ref : J Transl Med , 22 :55 , 2024
Abstract : Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.
ESTHER : Zhou_2024_J.Transl.Med_22_55
PubMedSearch : Zhou_2024_J.Transl.Med_22_55
PubMedID: 38218866

Title : Molecular Insights into the Enhanced Activity and\/or Thermostability of PET Hydrolase by D186 Mutations - Qu_2024_Molecules_29_
Author(s) : Qu Z , Zhang L , Sun Y
Ref : Molecules , 29 : , 2024
Abstract : PETase exhibits a high degradation activity for polyethylene terephthalate (PET) plastic under moderate temperatures. However, the effect of non-active site residues in the second shell of PETase on the catalytic performance remains unclear. Herein, we proposed a crystal structure- and sequence-based strategy to identify the key non-active site residue. D186 in the second shell of PETase was found to be capable of modulating the enzyme activity and stability. The most active PETase(D186N) improved both the activity and thermostability with an increase in T(m) by 8.89 degreesC. The PET degradation product concentrations were 1.86 and 3.69 times higher than those obtained with PETase(WT) at 30 and 40 degreesC, respectively. The most stable PETase(D186V) showed an increase in T(m) of 12.91 degreesC over PETase(WT). Molecular dynamics (MD) simulations revealed that the D186 mutations could elevate the substrate binding free energy and change substrate binding mode, and/or rigidify the flexible Loop 10, and lock Loop 10 and Helix 6 by hydrogen bonding, leading to the enhanced activity and/or thermostability of PETase variants. This work unraveled the contribution of the key second-shell residue in PETase in influencing the enzyme activity and stability, which would benefit in the rational design of efficient and thermostable PETase.
ESTHER : Qu_2024_Molecules_29_
PubMedSearch : Qu_2024_Molecules_29_
PubMedID: 38542974

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

Title : Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors - Wang_2024_J.Org.Chem__
Author(s) : Wang K , Wang R , Yan Z , Li Y , Shi Y , Ge JY , Bai Y , Chen Z , Zhang L
Ref : J Org Chem , : , 2024
Abstract : Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.
ESTHER : Wang_2024_J.Org.Chem__
PubMedSearch : Wang_2024_J.Org.Chem__
PubMedID: 38720168

Title : Glutamate, Humic Acids and Their Combination Modulate the Phenolic Profile, Antioxidant Traits, and Enzyme-Inhibition Properties in Lettuce - De Gregorio_2023_Plants.(Basel)_12_
Author(s) : De Gregorio MA , Zengin G , Alp-Turgut FN , Elbasan F , Ozfidan-Konakci C , Arikan B , Yildiztugay E , Zhang L , Lucini L
Ref : Plants (Basel) , 12 : , 2023
Abstract : Lettuce (Lactuca sativa L., Asteraceae) is a popular vegetable leafy crop playing a relevant role in human nutrition. Nowadays, novel strategies are required to sustainably support plant growth and elicit the biosynthesis of bioactive molecules with functional roles in crops including lettuce. In this work, the polyphenolic profile of lettuce treated with glutamic acid (GA), humic acid (HA), and their combination (GA + HA) was investigated using an untargeted metabolomics phenolic profiling approach based on high-resolution mass spectrometry. Both aerial and root organ parts were considered, and a broad and diverse phenolic profile could be highlighted. The phenolic profile included flavonoids (anthocyanins, flavones, flavanols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low molecular weight phenolics (tyrosol equivalents), lignans and stilbenes. Overall, GA and HA treatments significantly modulated the biosynthesis of flavanols, lignans, low molecular weight phenolics, phenolic acids, and stilbene. Thereafter, antioxidant capacity was evaluated in vitro with 2,2-diphenyln-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays. In addition, this study examined the inhibitory properties of enzymes, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, alpha-amylase, and alpha-glucosidase. Compared to individual treatments, the combination of GA + HA showed stronger antioxidant abilities in free radical scavenging and reducing power assays in root samples. Moreover, this combination positively influenced the inhibitory effects of root samples on AChE and BChE and the tyrosinase inhibitory effect of leaf samples. Concerning Pearson's correlations, antioxidant and enzyme inhibition activities were related to phenolic compounds, and lignans in particular correlated with radical scavenging activities. Overall, the tested elicitors could offer promising insights for enhancing the functional properties of lettuce in agricultural treatments.
ESTHER : De Gregorio_2023_Plants.(Basel)_12_
PubMedSearch : De Gregorio_2023_Plants.(Basel)_12_
PubMedID: 37176879

Title : Computation-Based Design of Salt Bridges in PETase for Enhanced Thermostability and Performance for PET Degradation - Qu_2023_Chembiochem_24_e202300373
Author(s) : Qu Z , Chen K , Zhang L , Sun Y
Ref : Chembiochem , 24 :e202300373 , 2023
Abstract : Polyethylene terephthalate (PET) is one of the most widely used plastics, and the accumulation of PET poses a great threat to the environment. IsPETase can degrade PET rapidly at moderate temperatures, but its application is greatly limited by the low stability. Herein, molecular dynamics (MD) simulations combined with a sequence alignment strategy were adopted to introduce salt bridges into the flexible region of IsPETase to improve its thermal stability. In the designed variants, the T(m) values of IsPETase(I168R/S188D) and IsPETase(I168R/S188E) were 7.4 and 8.7 degreesC higher than that of the wild type, respectively. The release of products degraded by IsPETase(I168R/S188E) was 4.3times that of the wild type. Tertiary structure characterization demonstrated that the structure of the variants IsPETase(I168R/S188D) and IsPETase(I168R/S188E) became more compact. Extensive MD simulations verified that a stable salt bridge was formed between the residue R168 and D186 in IsPETase(I168R/S188D) , while in IsPETase(I168R/S188E) an R168-D186-E188 salt bridge network was observed. These results confirmed that the proposed computation-based salt bridge design strategy could efficiently generate variants with enhanced thermal stability for the long-term degradation of PET, which would be helpful for the design of enzymes with improved stability.
ESTHER : Qu_2023_Chembiochem_24_e202300373
PubMedSearch : Qu_2023_Chembiochem_24_e202300373
PubMedID: 37639367
Gene_locus related to this paper: idesa-peth

Title : Rational Design of Disulfide Bridges in BbPETase(CD) for Enhancing the Enzymatic Performance in PET Degradation - Huang_2023_Molecules_28_3528
Author(s) : Huang D , Zhang L , Sun Y
Ref : Molecules , 28 :3528 , 2023
Abstract : Polyethylene terephthalate (PET) is one of the most prevalent transparent thermoplastics. It is commonly utilized due to its low cost and high durability. With the massive accumulation of waste PET, however, serious environmental pollution has become a global problem. Compared to traditional chemical degradation, biodegradation of PET catalyzed by PET hydrolase (PETase) is more environmentally friendly and energy-efficient. BbPETase(CD) from the Burkholderiales bacterium is a PETase that shows favorable properties for application in the biodegradation of PET. To enhance the enzymatic performance of this enzyme, this work focuses on the rational design of disulfide bridges in BbPETase(CD). We utilized two computational algorithms to predict the probable disulfide-bridge mutations in BbPETase(CD), and five variants were acquired from the computations. Among these, the N364C/D418C variant with one additional disulfide bond showed higher expression than the wild-type enzyme (WT) and the best enzymatic performance. The melting temperature (T(m)) of the N364C/D418C variant presented an increase of 14.8 degreesC over that of WT (56.5 degreesC), indicating that the additional disulfide bond significantly raised the thermodynamic stability of the enzyme. Kinetic experiments at different temperatures also demonstrated the thermal stability increase of the variant. The variant also showed significantly increased activity over WT when using bis(hydroxyethyl) terephthalate (BHET) as the substrate. More remarkably, the N364C/D418C variant exhibited approximately an 11-fold increase over the WT enzyme in the long-term (14 days) degradation of PET films. The results prove that the rationally designed disulfide bond significantly improved the enzymatic performance of the enzyme for PET degradation.
ESTHER : Huang_2023_Molecules_28_3528
PubMedSearch : Huang_2023_Molecules_28_3528
PubMedID: 37110762
Gene_locus related to this paper: 9burk-a0a1f4jxw8

Title : N-terminal lid swapping contributes to the substrate specificity and activity of thermophilic lipase TrLipE - Fang_2023_Front.Microbiol_14_1193955
Author(s) : Fang Y , Liu F , Shi Y , Yang T , Xin Y , Gu Z , Shi G , Zhang L
Ref : Front Microbiol , 14 :1193955 , 2023
Abstract : TrLipE is a thermophilic lipase that has potential commercial applications because of its catalytic ability under extreme conditions. Consistent with most lipases, the lid of TrLipE is located over the catalytic pocket, controls the substrate channel to the active center, and regulates the substrate specificity, activity, and stability of the enzyme through conformational changes. TrLipE from Thermomicrobium roseum has potential industrial applications, which is hindered by its weak enzymatic activity. Here, 18 chimeras (TrL1-TrL18) were reconstructed by N-terminal lid swapping between TrLipE and structurally similar enzymes. The results showed that the chimeras had a similar pH range and optimum pH as wild TrLipE but a narrower temperature range of 40-80 degreesC, and TrL17 and the other chimeras showed lower optimum temperatures of 70 degreesC and 60 degreesC, respectively. In addition, the half-lives of the chimeras were lower than those of TrLipE under optimum temperature conditions. Molecular dynamics simulations indicated that chimeras had high RMSD, RMSF, and B-factor values. When p-nitrophenol esters with different chains were used as substrates, compared with TrLipE, most of the chimeras had a low K(m) and high k(cat) value. The chimeras TrL2, TrL3, TrL17, and TrL18 could specifically catalyze the substrate 4-nitrophenyl benzoate, with TrL17 showing the highest k(cat)/K(m) value of 363.88 +/- 15.83 L min(-1) mmol(-1). Mutants were then designed by investigating the binding free energies of TrL17 and 4-nitrophenyl benzoate. The results indicated that single, double, and triple substitution variants (M89W and I206N; E33W/I206M and M89W/I206M; and M89W/I206M/L21I and M89W/I206N/L21I, respectively) presented approximately 2- to 3-fold faster catalysis of 4-nitrophenyl benzoate than the wild TrL17. Our observations will facilitate the development of the properties and industrial applications of TrLipE.
ESTHER : Fang_2023_Front.Microbiol_14_1193955
PubMedSearch : Fang_2023_Front.Microbiol_14_1193955
PubMedID: 37434709
Gene_locus related to this paper: therp-b9l0x7

Title : Antennal transcriptomic analysis of carboxylesterases and glutathione S-transferases associated with odorant degradation in the tea gray geometrid, Ectropis grisescens (Lepidoptera, Geometridae) - Zhang_2023_Front.Physiol_14_1183610
Author(s) : Zhang F , Chen Y , Zhao X , Guo S , Hong F , Zhi Y , Zhang L , Zhou Z , Zhang Y , Zhou X , Li X
Ref : Front Physiol , 14 :1183610 , 2023
Abstract : Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown. Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively. Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae. Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens.
ESTHER : Zhang_2023_Front.Physiol_14_1183610
PubMedSearch : Zhang_2023_Front.Physiol_14_1183610
PubMedID: 37082242

Title : MAGL inhibition relieves synovial inflammation and pain via regulating NOX4-Nrf2 redox balance in osteoarthritis - Li_2023_Free.Radic.Biol.Med_208_13
Author(s) : Li X , Tao H , Zhou J , Zhang L , Shi Y , Zhang C , Sun W , Chu M , Chen K , Gu C , Yang X , Geng D , Hao Y
Ref : Free Radic Biol Med , 208 :13 , 2023
Abstract : Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage injury, hyperplasia of bone and inflammatory lesions of synovium. Monoacylglycerol lipase (MAGL), a member of the alpha/beta hydrolase superfamily, is involved in regulation of injury protection and immune-inflammation response. Autoinflammatory response of the synovium and the release of inflammatory mediators play critical roles in occurrence of early-stage OA. Fibroblast-like synoviocytes (FLSs) are resident mesenchymal cells of the synovial tissue. Considering that MAGL inhibition regulates the inflammatory signaling cascade, it is crucial to ascertain the biological effects and specific mechanisms of MAGL in alleviating inflammatory infiltration of OA FLSs. The aim of this study was to investigate the effect of MAGL on biological function in OA FLSs. Results from in vitro experiments showed that MAGL blockade not only effectively inhibited proliferation, invasion and migration of FLSs, but also downregulated expression of inflammatory-associated proteins. Sequencing results indicated that MAGL inhibition significantly suppressed NOX4-mediated oxidative stress, thus promoting Nrf2 nuclear accumulation and inhibiting generation of intracellular reactive oxygen species (ROS). Attenuation of NOX4 further alleviated redox dysplasia and ultimately improved tumor-like phenotypes, such as abnormal proliferation, migration and migration of FLSs. In vivo results corroborated this finding, with MAGL inhibition found to modulate pain and disease progression in an OA rat model. Collectively, these results indicate that MAGL administration is an ideal therapy treating OA.
ESTHER : Li_2023_Free.Radic.Biol.Med_208_13
PubMedSearch : Li_2023_Free.Radic.Biol.Med_208_13
PubMedID: 37516370
Gene_locus related to this paper: human-MGLL

Title : Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea - Yang_2023_Bioorg.Chem_138_106625
Author(s) : Yang Z , Cao Z , Wang W , Chen Y , Huang W , Jiao S , Chen S , Chen L , Liu Y , Mao J , Zhang L , Li Z
Ref : Bioorg Chem , 138 :106625 , 2023
Abstract : Human carboxylesterase 2 (hCES2A), one of the most important serine hydrolases distributed in the small intestine and colon, plays a crucial role in the hydrolysis of various prodrugs and esters. Accumulating evidence has demonstrated that the inhibition of hCES2A effectively alleviate the side effects induced by some hCES2A-substrate drugs, including delayed diarrhea caused by the anticancer drug irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC(50) = 5.02 +/- 0.67 microM) and high selectivity on hCES2A. Molecular docking and molecular dynamics simulations indicated that LK-44 can formed stable hydrogen bonds with amino acids surrounding the active cavity of hCES2A. The results of inhibition kinetics studies unveiled that LK-44 inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a K(i) value of 5.28 microM. Notably, LK-44 exhibited low toxicity towards HepG2 cells according to the MTT assay. Importantly, in vivo studies showed that LK-44 significantly reduced the side effects of irinotecan-induced diarrhea. These findings suggested that LK-44 is a potent inhibitor of hCES2A with high selectivity against hCES1A, which has potential as a lead compound for the development of more effective hCES2A inhibitors to mitigate irinotecan-induced delayed diarrhea.
ESTHER : Yang_2023_Bioorg.Chem_138_106625
PubMedSearch : Yang_2023_Bioorg.Chem_138_106625
PubMedID: 37300962
Gene_locus related to this paper: human-CES2

Title : Habitual feeding patterns impact polystyrene microplastic abundance and potential toxicity in edible benthic mollusks - Wang_2023_Sci.Total.Environ_866_161341
Author(s) : Wang S , Zheng L , Shen M , Zhang L , Wu Y , Li G , Guo C , Hu C , Zhang M , Sui Y , Dong X , Lv L
Ref : Sci Total Environ , 866 :161341 , 2023
Abstract : That increasing microplastics (MPs, <5 mm) eventually end up in the sediment which may become a growing menace to diverse benthic lives is worthy of attention. In this experiment, three edible mollusks including one deposit-feeding gastropod (Bullacta exarate) and two filter-feeding bivalves (Cyclina sinensis and Mactra veneriformis) were exposed to polystyrene microplastic (PS-MP) for 7 days and depurated for 3 days. PS-MP numbers in the digestive system and non-digestive system, digestive enzymes, oxidative stress indexes, and a neurotoxicity index of three mollusks were determined at day 0, 3, 7, 8 and 10. After seven-day exposure, the PS-MP were found in all three mollusks' digestive and non-digestive systems. And PS-MP in M. veneriformis (9.57 +/- 2.19 items/individual) was significantly higher than those in C. sinensis (3.00 +/- 2.16 items/individual) and B. exarate (0.83 +/- 1.07 items/individual) at day 7. Three-day depuration could remove most of the PS-MP in the mollusks, and higher PS-MP clearance rates were found in filter-feeding C. sinensis (77.78 %) and M. veneriformis (82.59 %) compared to surface deposit-feeding B. exarate (50.00 %). The digestive enzymes of B. exarate significantly reacted to PS-MP exposure, while oxidative responses were found in C. sinensis. After three-day depuration, the changes of digestive enzymes and the oxidative states were fixed, but neurotoxicity induced by PS-MP was not recoverable. Besides, it is noteworthy that changes of digestive enzymes and acetylcholinesterase are related to feeding patterns.
ESTHER : Wang_2023_Sci.Total.Environ_866_161341
PubMedSearch : Wang_2023_Sci.Total.Environ_866_161341
PubMedID: 36603620

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

Title : Remodeling the polymer-binding cavity to improve the efficacy of PBAT-degrading enzyme - Yang_2023_J.Hazard.Mater_464_132965
Author(s) : Yang Y , Cheng S , Zheng Y , Xue T , Huang JW , Zhang L , Guo RT , Chen CC
Ref : J Hazard Mater , 464 :132965 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT) is among the most widely applied synthetic polyesters that are utilized in the packaging and agricultural industries, but the accumulation of PBAT wastes has posed a great burden to ecosystems. Using renewable enzymes to decompose PBAT is an eco-friendly solution to tackle this problem. Recently, we demonstrated that cutinase is the most effective PBAT-degrading enzyme and that an engineered cutinase termed TfCut-DM could completely decompose PBAT film to terephthalate (TPA). Here, we report crystal structures of a variant of leaf compost cutinase in complex with soluble fragments of PBAT, including BTa and TaBTa. In the TaBTa complex, one TPA moiety was located at a polymer-binding site distal to the catalytic center that has never been experimentally validated. Intriguingly, the composition of the distal TPA-binding site shows higher diversity relative to the one proximal to the catalytic center in various cutinases. We thus modified the distal TPA-binding site of TfCut-DM and obtained variants that exhibit higher activity. Notably, the time needed to completely degrade the PBAT film to TPA was shortened to within 24 h by TfCut-DM Q132Y (5813 mol per mol protein). Taken together, the structural information regarding the substrate-binding behavior of PBAT-degrading enzymes could be useful guidance for direct enzyme engineering.
ESTHER : Yang_2023_J.Hazard.Mater_464_132965
PubMedSearch : Yang_2023_J.Hazard.Mater_464_132965
PubMedID: 37979420
Gene_locus related to this paper: 9bact-g9by57

Title : The exogenous application of naringenin and rosmarinic acid modulates functional traits in Lepidium sativum - Salehi_2023_J.Sci.Food.Agric__
Author(s) : Salehi H , Zhang L , Nur Alp-Turgut F , Arikan B , Elbasan F , Ozfidan-Konakci C , Balci M , Zengin G , Yildiztugay E , Lucini L
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Phenolic modulators have attracted attention for their potential in shaping functional traits in plants. This work investigated the impact of naringenin (Nar) and rosmarinic acid (RA) on the functional properties of Lepidium sativum leaves and roots. RESULTS: Untargeted metabolomics identified a diverse phenolic profile, including flavonoids, phenolic acids, low molecular weight phenolics, lignans, and stilbenes. Cluster, AMOPLS, and OPLS-DA multivariate analyses confirmed tissue-specific modulation of bioactive compounds. The tissue was the hierarchically most influential factor, explaining 27% of observed variability, while the treatment and their interaction were statistically insignificant. Thereafter, various in vitro assays were employed to assess antioxidant capacity, including DPPH, ABTS, CUPRAC, FRAP, metal chelating, and PMD assays. Extracts were also tested for inhibitory effects on cholinesterase, amylase, glucosidase, and tyrosinase enzymes. RA application positively impacted antioxidant and enzyme inhibitory activities, holding valuable implications in shaping the health-promoting properties of L. sativum. CONCLUSION: The untargeted metabolomics analysis showed a significant tissue-dependent modulation of bioactive compounds, determining no synergistic effect between applying phenolic compounds in combination. Specifically, the sole application of rosmarinic acid increased anthocyanins and hydroxyphenyl propanoic acid content on leaves, which was strictly related to enhancing the biological activities. This article is protected by copyright. All rights reserved.
ESTHER : Salehi_2023_J.Sci.Food.Agric__
PubMedSearch : Salehi_2023_J.Sci.Food.Agric__
PubMedID: 37994181

Title : Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH(2)(Fe) - Zhao_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Zhao D , Liu J , Zhou Y , Zhang L , Zhong Y , Yang Y , Zhao B , Yang M , Wang Y
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH(2)(Fe) nanoparticles with a size of -100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH(2)(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
ESTHER : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 36867458

Title : Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine - Jin_2023_Biomed.Pharmacother_165_115215
Author(s) : Jin S , Zhang L , Wang L
Ref : Biomed Pharmacother , 165 :115215 , 2023
Abstract : Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-beta-rutinoside/6-hydroxykaempferol 3,6-di-O-beta-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Abeta, tau, and alpha-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
ESTHER : Jin_2023_Biomed.Pharmacother_165_115215
PubMedSearch : Jin_2023_Biomed.Pharmacother_165_115215
PubMedID: 37494786

Title : Organophosphate Level Evaluation for the Poisoning Treatment by Enzyme Activation Regeneration Strategy with Oxime-Functionalized ZIF-8 Nanoparticles - Shen_2023_Anal.Chem__
Author(s) : Shen A , Hao X , Li M , Zhao Y , Li Z , Hou L , Duan R , Zhang P , Zhang L , Yang Y
Ref : Analytical Chemistry , : , 2023
Abstract : In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 microg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R(2) = 0.9889), and the LOD was 0.073 microg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.
ESTHER : Shen_2023_Anal.Chem__
PubMedSearch : Shen_2023_Anal.Chem__
PubMedID: 37358141

Title : Discovery of novel carboxylesterase 2 inhibitors for the treatment of delayed diarrhea and ulcerative colitis - Cao_2023_Biochem.Pharmacol__115742
Author(s) : Cao Z , Liu Y , Chen S , Wang W , Yang Z , Chen Y , Jiao S , Huang W , Chen L , Sun L , Li Z , Zhang L
Ref : Biochemical Pharmacology , :115742 , 2023
Abstract : Human carboxylesterase 2 (hCES2) is an enzyme that metabolizes irinotecan to SN-38, a toxic metabolite considered a significant source of side effects (lethal delayed diarrhea). The hCES2 inhibitors could block the hydrolysis of irinotecan in the intestine and thus reduce the exposure of intestinal SN-38, which may alleviate irinotecan-associated diarrhea. However, existing hCES2 inhibitors (except loperamide) are not used in clinical applications due to lack of validity or acceptable safety. Therefore, developing more effective and safer drugs for treating delayed diarrhea is urgently needed. This study identified a lead compound 1 with a novel scaffold by high-throughput screening in our in-house library. After a comprehensive structure-activity relationship study, the optimal compound 24 was discovered as an efficient and highly selective hCES2 inhibitor (hCES2: IC(50) = 6.72 microM; hCES1: IC(50) > 100 microM). Further enzyme kinetics study indicated that compound 24 is a reversible inhibitor of hCES2 with competitive inhibition mode (Ki = 6.28 microM). The cell experiments showed that compound 24 could reduce the level of hCES2 in living cells (IC(50) = 6.54 microM). The modeling study suggested that compound 24 fitted very well with the binding pocket of hCES2 by forming multiple interactions. Notably, compound 24 can effectively treat irinotecan-induced delayed diarrhea and DSS-induced ulcerative colitis, and its safety has also been verified in subtoxic studies. Based on the overall pharmacological and preliminary safety profiles, compound 24 is worthy of further evaluation as a novel agent for irinotecan-induced delayed diarrhea.
ESTHER : Cao_2023_Biochem.Pharmacol__115742
PubMedSearch : Cao_2023_Biochem.Pharmacol__115742
PubMedID: 37567318

Title : beta-Carbolines norharman and harman change neurobehavior causing neurological damage in Caenorhabditis elegans - Zhang_2023_Food.Funct_14_10031
Author(s) : Zhang L , Liu J , Xu B , Wu D , Wu Y , Li G
Ref : Food Funct , 14 :10031 , 2023
Abstract : beta-Carbolines norharman and harman, belonging to the class of heterocyclic aromatic amines (HAAs), are typical hazardous substances produced during the thermal processing of food. Compared to other HAAs, there have been limited reports on the toxicity of beta-carbolines. Nevertheless, the current studies are concerned with the neurotoxic effects of norharman and harman at high doses. It is still unknown whether the relatively low dose of beta-carbolines in foods induces neurotoxicity and the mechanism of the toxicity. In this study, C. elegans was exposed to a series of gradients of norharman and harman (0, 0.05, 5, and 10 mg L(-1)). The survival rate and indicators of ethology (locomotor behaviors, foraging behavior, and chemotaxis ability) were assessed. The antioxidant system and the contents of neurotransmitters, as well as the activity of acetylcholinesterase (AChE), were evaluated. Additionally, the RNA-seq screening of differentially expressed genes (DEGs) revealed the potential molecular mechanisms of norharman- and harman-induced toxic effects. Our results indicated that the risk of long-term exposure to norharman and harman at low doses (food-related doses) should be emphasized. Moreover, beta-carbolines might induce neurotoxicity by causing oxidative damage, regulating the content of neurotransmitters, and interfering with cytochrome P450 metabolism. This study would provide a toxicological basis for the neurotoxicity of beta-carbolines and lay the foundation for the risk assessment of endogenous pollutants in food.
ESTHER : Zhang_2023_Food.Funct_14_10031
PubMedSearch : Zhang_2023_Food.Funct_14_10031
PubMedID: 37927231

Title : Review of the therapeutic potential of Forsythiae Fructus on the central nervous system: Active ingredients and mechanisms of action - Zhang_2023_J.Ethnopharmacol__117275
Author(s) : Zhang L , Lang F , Feng J , Wang J
Ref : J Ethnopharmacol , :117275 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has gained significant attention in recent years owing to its multi-component, multi-target, and multi-pathway advantages in treating various diseases. Forsythiae Fructus, derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is one such traditional Chinese medicine with numerous in vivo and ex vivo therapeutic effects, including anti-inflammatory, antibacterial, and antiviral properties. Forsythiae Fructus contains more than 200 chemical constituents, with forsythiaside, forsythiaside A, forsythiaside B, isoforsythiaside, forsythin, and phillyrin being the most active ingredients. Forsythiae Fructus exerts neuroprotective effects by modulating various pathways, including oxidative stress, anti-inflammation, NF-kappaB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARgamma signaling pathway. AIM OF THE STUDY: This review aims to highlight the potential therapeutic effects of Forsythiae Fructus on the central nervous system and summarize the current knowledge on the active ingredients of Forsythia Fructus and their effects on different pathways involved in neuroprotection. MATERIALS AND METHODS: In this review, we conducted a comprehensive search of databases (PubMed, Google Scholar, Web of Science, China Knowledge Resource Integrated, local dissertations and books) up until June 2023 using key terms such as forsythia suspensa, Forsythiae Fructus, forsythiaside, isoforsythiaside, forsythin, phillyrin, Alzheimer's disease, Parkinson's disease, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, aging, and herpes simplex virus encephalitis. RESULTS: Our findings indicate that Forsythiae Fructus and its active ingredients own therapeutic effects on the central nervous system by modulating various pathways, including oxidative stress, anti-inflammation, NF-kappaB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, the gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARgamma signaling pathway. CONCLUSION: Forsythiae Fructus and its active ingredients have demonstrated promising neuroprotective properties. Future in vivo and clinical studies of Forsythiae Fructus and its active ingredients should be conducted to establish precise dosage and standard guidelines for a more effective application in the treatment of neurological disorders.
ESTHER : Zhang_2023_J.Ethnopharmacol__117275
PubMedSearch : Zhang_2023_J.Ethnopharmacol__117275
PubMedID: 37797873

Title : Genetic analysis and management of a familial hypercholesterolemia pedigree with polygenic variants: Case report - Han_2023_Medicine.(Baltimore)_102_e34534
Author(s) : Han Y , Zhang L , Tao H , Wu J , Zhai J
Ref : Medicine (Baltimore) , 102 :e34534 , 2023
Abstract : RATIONALE: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder typically caused by low density lipoprotein receptor (LDLR) gene mutation. Herein, we reported a FH pedigree with polygenic variants: LDLR, apolipoprotein B (APOB), and epoxide hydrolase 2 (EPHX2). PATIENT CONCERNS: A 10-year-old boy mainly presented multiple skin xanthomas and hypercholesterolemia. His family visited our hospital and was performed with pedigree whole exome sequencing (WES) at 20 + 3 weeks gestation of the mother's second pregnancy. DIAGNOSES: Based on the clinical features and genetic analysis, the pedigree was diagnosed with familial hypercholesterolemia. INTERVENTIONS: After genetic counseling, the couple opted to continue the pregnancy. Treatment advice and follow-up were offered to them. OUTCOMES: A novel compound heterozygous LDLR mutation: c.1009G>T and c.68-2A>G, derived from his parents respectively was revealed through pedigree WES, meanwhile, a maternal APOB gene variant: c.1670A>G and a paternal EPHX2 gene variant: c.548 dup of the proband were found together. Furthermore, the same compound heterozygous LDLR mutation as his was confirmed in his sister without APOB and EPHX2 variants in her fetal stage. LESSONS: WES combined with clinical features is essential for the diagnosis of FH, however, prenatal genetic testing results might bring more challenges to prenatal genetic counseling. Furthermore, it is more important to provide the guidance and early intervention for such families in the long run.
ESTHER : Han_2023_Medicine.(Baltimore)_102_e34534
PubMedSearch : Han_2023_Medicine.(Baltimore)_102_e34534
PubMedID: 37565868

Title : Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations - Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
Author(s) : Guo L , Zhu X , Zhang L , Xu Y
Ref : Ther Adv Drug Safety , 14 :20420986231220222 , 2023
Abstract : BACKGROUND: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments. OBJECTIVES: This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment. DESIGN: After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges. METHODS: Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models. RESULTS: Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child-Pugh-A, Child-Pugh-B, and Child-Pugh-C hepatic impairment, respectively. CONCLUSION: The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.
ESTHER : Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
PubMedSearch : Guo_2023_Ther.Adv.Drug.Saf_14_20420986231220222
PubMedID: 38157240

Title : Oxymatrine-mediated prevention of amyloid beta-peptide-induced apoptosis on Alzheimer's model PC12 cells: in vitro cell culture studies and in vivo cognitive assessment in rats - Zhu_2023_Inflammopharmacology__
Author(s) : Zhu Y , Wang Z , Gao C , Zhang L , Sui R
Ref : Inflammopharmacology , : , 2023
Abstract : Alzheimer's disease (AD) is a major neurological disease affecting elderly individuals worldwide. Existing drugs only reduce the symptoms of the disease without addressing the underlying causes. Commonly, Abeta25-35 peptide aggregation is the main reason for AD development. Recently, the discovery of multiple protein-targeting molecules has provided a new strategy for treating AD. This study demonstrates the neuroprotective potential of oxymatrine against multiple mechanisms, such as acetylcholinesterase, mitochondrial damage, and beta-amyloid-induced cell toxicity. The in vitro cell culture studies showed that oxymatrine possesses significant potential to inhibit acetylcholine esterase and promotes antioxidant, antiapoptotic effects while preventing Abeta25-35 peptide aggregation in PC12 cells. Furthermore, oxymatrine protects PC12 cells against Abeta25-35-induced cytotoxicity and down-regulates the reactive oxygen species generation. The in vivo acute toxicological studies confirm the safety of oxymatrine without causing organ damage or death in animals. Overall, this study provided evidence that oxymatrine is an efficient neuroprotective agent, with a potential to be a multifunctional drug for Alzheimer's disease treatment. These findings present a reliable and synergistic approach for treating AD.
ESTHER : Zhu_2023_Inflammopharmacology__
PubMedSearch : Zhu_2023_Inflammopharmacology__
PubMedID: 37515653

Title : Cisplatin increases carboxylesterases through increasing PXR mediated by the decrease of DEC1 - Xu_2023_J.Biomed.Res__431
Author(s) : Xu M , Zhang L , Lin L , Qiang Z , Liu W , Yang J
Ref : J Biomed Res , :431 , 2023
Abstract : cis-Diamminedichloroplatinum (CDDP) is widely used for the treatment of various solid cancers. Here we reported that CDDP increased the expression and enzymatic activities of carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2), along with the upregulation of pregnane X receptor (PXR) and the downregulation of differentiated embryonic chondrocyte-expressed gene 1 (DEC1) in human hepatoma cells, primary mouse hepatocytes, mouse liver and intestine. The overexpression or knockdown of PXR alone upregulated or downregulated the CES1 and CES2 expression, respectively. The increases in CES1 and CES2 expression levels induced by CDDP abolished or enhanced by PXR knockdown or overexpression, implying that CDDP induces carboxylesterases through the activation of PXR. Likewise, the overexpression or knockdown of DEC1 alone significantly decreased or increased PXR and its targets. Moreover, the increases of PXR and its targets induced by CDDP were abolished or alleviated by the overexpression or knockdown of DEC1. The overexpression or knockdown of DEC1 affected the response of PXR to CDDP, but not vice versa, suggesting that CDDP increases carboxylesterases by upregulating PXR mediated by the decrease of DEC1. In addition, CDDP did not increase DEC1 mRNA degradation but suppressed DEC1 promoter reporter activity, indicating that it suppresses DEC1 transcriptionally. The combined use of CDDP and irinotecan had a synergistic effect on two cell lines, especially when CDDP was used first.
ESTHER : Xu_2023_J.Biomed.Res__431
PubMedSearch : Xu_2023_J.Biomed.Res__431
PubMedID: 37990879

Title : Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection - Wan_2022_Mikrochim.Acta_189_300
Author(s) : Wan Y , Wang H , Zhang L , Chen Y , Li S , Zhou J , Zhang Q , Xia L
Ref : Mikrochim Acta , 189 :300 , 2022
Abstract : A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples.
ESTHER : Wan_2022_Mikrochim.Acta_189_300
PubMedSearch : Wan_2022_Mikrochim.Acta_189_300
PubMedID: 35904635

Title : The Functional Characterization of Carboxylesterases Involved in the Degradation of Volatile Esters Produced in Strawberry Fruits - Zhang_2022_Int.J.Mol.Sci_24_383
Author(s) : Zhang L , Zhou K , Wang M , Li R , Dai X , Liu Y , Jiang X , Xia T , Gao L
Ref : Int J Mol Sci , 24 :383 , 2022
Abstract : Volatile ester compounds are important contributors to the flavor of strawberry, which affect consumer preference. Here, the GC-MS results showed that volatile esters are the basic aroma components of strawberry, banana, apple, pear, and peach, and the volatile esters were significantly accumulated with the maturation of strawberry fruits. The main purpose of this study is to discuss the relationship between carboxylesterases (CXEs) and the accumulation of volatile ester components in strawberries. FaCXE2 and FaCXE3 were found to have the activity of hydrolyzing hexyl acetate, Z-3-hexenyl acetate, and E-2-hexenyl acetate to the corresponding alcohols. The enzyme kinetics results showed that FaCXE3 had the higher affinity for hexyl acetate, E-2-hexenyl acetate, and Z-3-hexenyl acetate compared with FaCXE2. The volatile esters were mainly accumulated at the maturity stages in strawberry fruits, less at the early stages, and the least during the following maturation stages. The expression of FaCXE2 gradually increased with fruit ripening and the expression level of FaCXE3 showed a decreasing trend, which suggested the complexity of the true function of CXEs. The transient expression of FaCXE2 and FaCXE3 genes in strawberry fruits resulted in a significantly decreased content of volatile esters, such as Z-3-hexenyl acetate, methyl hexanoate, methyl butyrate, and other volatile esters. Taken together, FaCXE2 and FaCXE3 are indeed involved in the regulation of the synthesis and degradation of strawberry volatile esters.
ESTHER : Zhang_2022_Int.J.Mol.Sci_24_383
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_24_383
PubMedID: 36613824
Gene_locus related to this paper: frave-FanCXE17 , frave-FanCXE19 , frave-FanCXE3 , frave-FanCXE2 , fraan-FaTA

Title : Flavin-enabled reductive and oxidative epoxide ring opening reactions - De_Nat.Commun_13_4896
Author(s) : De BC , Zhang W , Yang C , Mandi A , Huang C , Zhang L , Liu W , Ruszczycky MW , Zhu Y , Ma M , Bashiri G , Kurtan T , Liu Hw , Zhang C
Ref : Nat Commun , 13 :4896 , 2022
Abstract : Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis.
ESTHER : De_Nat.Commun_13_4896
PubMedSearch : De_Nat.Commun_13_4896
PubMedID: 35986005

Title : Screening and identification of anti-acetylcholinesterase ingredients from Tianzhi granule based on ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry and in silico analysis - Zhao_2022_J.Ethnopharmacol__115641
Author(s) : Zhao N , Liu D , Wang Y , Zhang X , Zhang L
Ref : J Ethnopharmacol , :115641 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Tianzhi granule (TZG) is a traditional Chinese formula that is widely used for the treatment of vascular dementia (VaD). AIM OF THE STUDY: To discover the herbs in TZG possessing acetylcholinesterase (AChE) inhibitory activity and to screen the anti-acetylcholinesterase ingredients from active herbs. MATERIALS AND METHODS: In vitro AChE inhibitory activity assay of eleven herbal extracts was conducted. An ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry method was established to screen and identify the anti-acetylcholinesterase ingredients from active extracts. In addition, in vitro AChE inhibitory activity assay and molecular docking were adopted for further investigation. Moreover, ultra-performance liquid chromatography-mass spectrometry was performed for the content determination of active compounds in TZG. RESULTS: Three herbs in TZG showed significant AChE inhibitory activity. A total of thirteen active ingredients were screened out and identified, and all of these compounds were present in TZG. Five available commercial standards presented moderate AChE inhibitory activity, and all of which have a relatively high content in TZG. CONCLUSION: A number of herbs and compounds with acetylcholinesterase inhibitory activity were found in TZG, which provided a scientific basis for the material basis and quality control research of TZG.
ESTHER : Zhao_2022_J.Ethnopharmacol__115641
PubMedSearch : Zhao_2022_J.Ethnopharmacol__115641
PubMedID: 35973628

Title : New insights into the function of plant tannase with promiscuous acyltransferase activity - Chen_2022_Plant.J__
Author(s) : Chen Y , Jiang C , Yin S , Zhuang J , Zhao Y , Zhang L , Jiang X , Liu Y , Gao L , Xia T
Ref : Plant J , : , 2022
Abstract : Plant tannases (TAs) or tannin acyl hydrolases, a class of recently reported carboxylesterase (CXE) in tannin-rich plants, are involved in the degalloylation of two important secondary metabolites: flavan-3-ol gallates and hydrolyzable tannins (HTs). In this paper, we have made a new progress on the function of Camellia sinensis (Cs) TA-it is a hydrolase with promiscuous acyltransferase activity in vitro and in vivo experiments and promotes the synthesis of simple galloyl glucoses and flavan-3-ols gallates in plants. We gained the new understanding to the functions of CsTA through enzyme analysis, protein mass spectrometry identification, metabolic analysis of plants by genetic modification. Firstly, CsTA was proved that it is not only a hydrolase but also an acyltransferase. In the two-step covalent catalytic reaction, when CsTA hydrolyzes the galloylated compounds epigallocatechin-3-gallate (EGCG) or 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) into their degalloylated forms, a long-lived Ser159-linked galloyl-enzyme covalent intermediate is also formed. Under nucleophilic attack, the galloyl group on the intermediate is transferred to the nucleophilic acyl acceptors (including water, methanol, flavan-3-ols and simple galloyl glucoses). Then, metabolic analysis suggested that transiently overexpression of TAs in young strawberry fruits, young leaves of tea plants and young leaves of Chinese bayberry actually increased the total content of simple galloyl glucoses and flavan-3-ol gallates. Overall, these findings provide new insights into the promiscuous acyltransferase activity of plant tannase.
ESTHER : Chen_2022_Plant.J__
PubMedSearch : Chen_2022_Plant.J__
PubMedID: 36534122
Gene_locus related to this paper: camsi-CsTA

Title : Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins - Liu_2022_J.Transl.Med_20_418
Author(s) : Liu X , Hua F , Yang D , Lin Y , Zhang L , Ying J , Sheng H , Wang X
Ref : J Transl Med , 20 :418 , 2022
Abstract : Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.
ESTHER : Liu_2022_J.Transl.Med_20_418
PubMedSearch : Liu_2022_J.Transl.Med_20_418
PubMedID: 36088343

Title : Surface Modification of Magnetic ZIF-90 Nanoparticles Improves the Microenvironment of Immobilized Lipase and Its Application in Esterification - Suo_2022_Langmuir__
Author(s) : Suo H , Geng X , Sun Y , Zhang L , Yang J , Yang F , Yan H , Hu Y , Xu L
Ref : Langmuir , : , 2022
Abstract : Interactions of enzymes with supports significantly affect the activity and stability of immobilized enzymes. Herein, amino-functionalized ionic liquid (IL)-grafted magnetic zeolitic imidazolate framework-90 (MZIF-90) was prepared and used to immobilize porcine pancreatic lipase (PPL). The nanocomposites were fully characterized; meanwhile, the interactions between ILs and ZIF-90 were calculated based on density functional theory. The prepared biocatalyst (PPL-ILs/MZIF-90) had a lipase loading of 178.3 mg/g and hydrolysis activity up to 287.5 U/g. When the biocatalyst was used to synthesize isoamyl acetate, the reaction media, molar ratio of alcohol/acid, temperature, and reaction time were optimized. Under the optimized reaction conditions (in hexane, alcohol/acid = 3:1, under 45 degreesC, reacted for 9 h), the ester yield reached 85.5%. The results of the stability test showed that PPL-ILs/MZIF-90 retained 88.7% of the initial activity after storing for 35 days and 92.5% of the initial activity after reusing for seven cycles for synthesizing isoamyl acetate. Moreover, the secondary structure analysis showed that the synthesized supports protected the active conformation of immobilized lipase, which lead to the enhanced catalytic performance. Additionally, the biocatalyst can be easily separated with a magnet, which facilitated the reusability. This study provides insights regarding the application of metal organic framework composites in the field of enzyme catalysis.
ESTHER : Suo_2022_Langmuir__
PubMedSearch : Suo_2022_Langmuir__
PubMedID: 36448653

Title : Identification of Host Molecules Involved in the Proliferation of Nucleopolyhedrovirus in Bombyx mori - Xu_2022_J.Agric.Food.Chem__
Author(s) : Xu J , Xie X , Ma Q , Zhang L , Li Y , Chen Y , Li K , Xiao Y , Tettamanti G , Xu H , Tian L
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : The Bombyx mori nucleopolyhedrovirus (BmNPV), a foodborne infectious virus, is the pathogen causing nuclear polyhedrosis and high lethality in the silkworm. In this study, we characterized the molecules involved in BmNPV-silkworm interaction by RNA sequencing of the fat body isolated from the virus-susceptible strain P50. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that the upregulated differentially expressed genes (DEGs) were mainly involved in translation, signal transduction, folding, sorting, and degradation, as well as transport and catabolism, while the downregulated DEGs were predominantly enriched in the metabolism of carbohydrates, amino acids, and lipids at 72 h post BmNPV infection. Knockout of the upregulated somatomedin-B and thrombospondin type-1 domain-containing protein, probable allantoicase, trifunctional purine biosynthetic protein adenosine-3, and Psl and pyoverdine operon regulator inhibited the proliferation of BmNPV, while knockout of the downregulated clip domain serine protease 3 and carboxylesterase clade H, member 1 promoted it. The molecules herein identified provide a foundation for developing strategies and designing drugs against BmNPV.
ESTHER : Xu_2022_J.Agric.Food.Chem__
PubMedSearch : Xu_2022_J.Agric.Food.Chem__
PubMedID: 36321811

Title : Transcriptomic Identification and Expression Profile Analysis of Odorant-Degrading Enzymes from the Asian Corn Borer Moth, Ostrinia furnacalis - Zhang_2022_Insects_13_
Author(s) : Zhang L , Shen Y , Jiang X , Liu S
Ref : Insects , 13 : , 2022
Abstract : The Asian corn borer moth Ostrinia furnacalis is an important lepidopteran pest of maize in Asia. Odorant-degrading enzymes (ODEs), including carboxylesterases (CCEs), glutathione S-transferases (GSTs), cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and aldehyde oxidases (AOXs), are responsible for rapid inactivation of odorant signals in the insect antennae. In this study, we performed a transcriptome assembly for the antennae of O. furnacalis to identify putative ODE genes. Transcriptome sequencing revealed 35,056 unigenes, and 21,012 (59.94%) of these were annotated by searching against the reference sequences in the NCBI non-redundant (NR) protein database. For functional classification, these unigenes were subjected to Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. We identified 79 genes encoding putative ODEs: 19 CCEs, 17 GSTs, 24 CYPs, 13 UGTs, and 6 AOXs. BLASTX best hit results indicated that these genes shared quite high amino acid identities with their respective orthologs from other lepidopteran species. Reverse transcription-quantitative PCR showed that OfurCCE2, OfurCCE5, and OfurCCE18 were enriched in male antennae, while OfurCCE7 and OfurCCE10 were enriched in female antennae. OfurCCE14 and OfurCCE15 were expressed at near-equal amounts in the antennae of both sexes. Our findings establish a solid foundation for future studies aimed at understanding the olfactory functions of these genes in O. furnacalis.
ESTHER : Zhang_2022_Insects_13_
PubMedSearch : Zhang_2022_Insects_13_
PubMedID: 36354851

Title : Ancestral sequence reconstruction and spatial structure analysis guided alteration of longer-chain substrate catalysis for Thermomicrobium roseum lipase - Ma_2022_Enzyme.Microb.Technol_156_109989
Author(s) : Ma D , Xin Y , Guo Z , Shi Y , Zhang L , Li Y , Gu Z , Ding Z , Shi G
Ref : Enzyme Microb Technol , 156 :109989 , 2022
Abstract : Thermomicrobium roseum DSM 5159 lipase (TrLip) is an enzyme with marked thermostability and excellent solvent resistance. However, TrLip reveals relatively high catalytic efficiency on short-chain substrates but poor activity against mid-long or long-chain fatty acids, which would limit its industrial application. In this study, ancestral sequence reconstruction (ASR), a common engineering tool for the evolutionary history of protein families, was employed to identify the natural evolutionary trends within 5 A around the catalytic center. Two mutation libraries were constructed, one for the catalytic center and the other for the pocket flexibility. A total of 69 mutants were expressed and purified in the Escherichia coli expression system to determine the kinetic parameters, and W219G could significantly enhance the catalytic efficiency against substrates with 12-, 16- and 18-carbon side chains. In addition, the double mutant W219G/F265M could further catalyze the breakdown of the above three substrates up to 6.34-, 4.21- and 4.86-folds compared to the wild-type TrLip, while the initial pH and thermostability were maintained. Through bioinformatics analysis, the significantly enhanced catalytic efficiency against longer-side chain substrates should be associated with the reduction of steric hindrance. With the outstanding stability and the promoted activity, TrLip should be of great potential in chemical and food industry.
ESTHER : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedSearch : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedID: 35134708
Gene_locus related to this paper: therp-b9l0x7

Title : Multiple acetylcholinesterases in Pardosa pseudoannulata brain worked collaboratively to provide protection from organophosphorus insecticides - Lin_2022_Ecotoxicol.Environ.Saf_248_114301
Author(s) : Lin X , Zhang Y , Yang B , Zhang L , Chen Y , Liu Z
Ref : Ecotoxicology & Environmental Safety , 248 :114301 , 2022
Abstract : Acetylcholinesterase (AChE) is an essential neurotransmitter hydrolase in nervous systems of animals and its number varies among species. So far, five AChEs have been identified in the natural enemy Pardosa pseudoannulata. Here we found that Ppace1, Ppace2 and Ppace5 were highly expressed in the spider brain, among which the mRNA level of Ppace5, but not Ppace1 and Ppace2, could be up-regulated by organophosphorus insecticides at their sublethal concentrations. In spider brain, the treatment by organophosphorus insecticides at the sublethal concentrations could increase total AChE activity, although high concentrations inhibited the activity. The activity that increased from the sublethal concentration pretreatment could compensate for the activity inhibition due to subsequent application of organophosphorus insecticides at lethal concentrations, and consequently reduce the mortality of spiders. PpAChE1 and PpAChE2 were highly sensitive to organophosphorus insecticides, and their activities would be strongly inhibited by the insecticides. In contrast, PpAChE5 displayed relative insensitivity towards organophosphorus insecticides, but with the highest catalytic efficiency for ACh. That meant the up-regulation of Ppace5 under insecticide exposure was important for maintaining AChE activity in spider brain, when PpAChE1 and PpAChE2 were inhibited by organophosphorus insecticides. The study demonstrated that multiple AChEs in the spider brain worked collaboratively, with part members for maintaining AChE activity and other members responding to organophosphorus inhibition, to provide protection from organophosphorus insecticides. In fields, high concentration insecticides are often applied when ineffective controls of insect pests occur due to relative-low concentration of insecticides in last round application. This application pattern of organophosphorus insecticides provides more chances for P. pseudoannulata to survive and controlling insect pests as a natural enemy.
ESTHER : Lin_2022_Ecotoxicol.Environ.Saf_248_114301
PubMedSearch : Lin_2022_Ecotoxicol.Environ.Saf_248_114301
PubMedID: 36410143
Gene_locus related to this paper: 9arac-KU501290 , 9arac-KU501289 , 9arac-KU501288 , 9arac-KU501287 , 9arac-v5qqc6 , 9arac-v5qqr1

Title : Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative - Zeng_2022_Front.Immunol_13_1113070
Author(s) : Zeng Z , Liu R , Cao W , Yang L , Lin Y , Bi X , Jiang T , Deng W , Wang S , Lu H , Sun F , Shen G , Chang M , Lu Y , Wu S , Hao H , Xu M , Chen X , Hu L , Zhang L , Wan G , Xie Y , Li M
Ref : Front Immunol , 13 :1113070 , 2022
Abstract : AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.
ESTHER : Zeng_2022_Front.Immunol_13_1113070
PubMedSearch : Zeng_2022_Front.Immunol_13_1113070
PubMedID: 36685494

Title : Biodegradation of Free Gossypol by Helicoverpa armigera Carboxylesterase Expressed in Pichia pastoris - Zhang_2022_Toxins.(Basel)_14_816
Author(s) : Zhang L , Yang X , Huang R , Nie C , Niu J , Chen C , Zhang W
Ref : Toxins (Basel) , 14 :816 , 2022
Abstract : Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial degradation of gossypol produces metabolites that reduce feed quality. We adopted an enzymatic method to degrade free gossypol safely and effectively. We cloned the gene cce001a encoding carboxylesterase (CarE) into pPICZalphaA and transformed it into Pichia pastoris GS115. The target protein was successfully obtained, and CarE CCE001a could effectively degrade free gossypol with a degradation rate of 89%. When esterase was added, the exposed toxic groups of gossypol reacted with different amino acids and amines to form bound gossypol, generating substances with (M + H) m/z ratios of 560.15, 600.25, and 713.46. The molecular formula was C(27)H(28)O(13), C(34)H(36)N(2)O(6), and C(47)H(59)N(3)O(3). The observed instability of the hydroxyl groups caused the substitution and shedding of the group, forming a substance with m/z of 488.26 and molecular formula C(31)H(36)O(5). These properties render the CarE CCE001a a valid candidate for the detoxification of cotton meal. Furthermore, the findings help elucidate the degradation process of gossypol in vitro.
ESTHER : Zhang_2022_Toxins.(Basel)_14_816
PubMedSearch : Zhang_2022_Toxins.(Basel)_14_816
PubMedID: 36548713

Title : Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals - Yang_2022_ACS.Omega_7_30720
Author(s) : Yang Y , Liu J , Liu L , Zhou Y , Zhang L , Zhong Y , Zhao D , Wang Y
Ref : ACS Omega , 7 :30720 , 2022
Abstract : A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.
ESTHER : Yang_2022_ACS.Omega_7_30720
PubMedSearch : Yang_2022_ACS.Omega_7_30720
PubMedID: 36092617

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 : Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes - Yu_2022_PLoS.Pathog_18_e1010552
Author(s) : Yu X , Tong L , Zhang L , Yang Y , Xiao X , Zhu Y , Wang P , Cheng G
Ref : PLoS Pathog , 18 :e1010552 , 2022
Abstract : Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.
ESTHER : Yu_2022_PLoS.Pathog_18_e1010552
PubMedSearch : Yu_2022_PLoS.Pathog_18_e1010552
PubMedID: 35679229

Title : Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe - Yang_2022_Anal.Chem__
Author(s) : Yang Y , Zhang L , Wang J , Cao Y , Li S , Qin W , Liu Y
Ref : Analytical Chemistry , : , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.
ESTHER : Yang_2022_Anal.Chem__
PubMedSearch : Yang_2022_Anal.Chem__
PubMedID: 36121878

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 : Improved Aitongxiao prescription (I-ATXP) induces apoptosis, cell cycle arrest and blocks exosomes release in hepatocellular carcinoma (HCC) cells - Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
Author(s) : Huang MB , Gao Z , Xia M , Zhao X , Fan X , Lin S , Zhang L , Huang L , Wei A , Zhou H , Wu JY , Roth WW , Bond VC , Leng J
Ref : Int Journal de Physiologie Pathophysiol Pharmacol , 14 :90 , 2022
Abstract : BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy globally, after lung cancer, accounting for 85-90% of primary liver cancer. Hepatitis B virus (HBV) infection is considered the leading risk factor for HCC development in China. HCC is a highly malignant cancer whose metastasis is primarily influenced by the tumor microenvironment. The role of exosomes in cancer development has become the focus of much research due to the many newly described contents of exosomes, which may contribute to tumorigenesis. However, the possible role exosomes play in the interactions between HCC cells and their surrounding hepatic milieu is mainly unknown. We discovered an Improved Aitongxiao Prescription (I-ATXP): an 80% alcohol extract from a mix of 15 specific plant and animal compounds, which had been shown to have an anticancer effect through inducing apoptosis and cell cycle arrest and blocking exosomes release in HCC cells. However, the anticancer mechanism of I-ATXP on human liver carcinoma is still unclear. OBJECTIVE: Due to its inhibitory effects on chemical carcinogenesis and inflammation, I-ATXP has been proposed as an effective agent for preventing or treating human liver carcinoma. In this study, we aimed to explore the effect of I-ATXP on proliferation, apoptosis, and cell cycles of different HCC cell lines. We investigated the impact of I-ATXP on exosomes' secretion derived from these HCC cells. METHODS: The inhibitory effect of I-ATXP on proliferation and cytotoxicity of HepG2, SMMC7721, HKCL-C3 HCC cell lines, and MIHA immortalized hepatocyte cell line was assessed by CCK-8 assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry using Annexin V-FITC/PI staining. The expression of Alix and CD63 of exosome marker proteins was detected by western blotting. The exosome protein concentration was measured by a fluorescent plate reader. The exosome-specific enzyme activity was measured by acetylcholinesterase (AchE) assay, and exosome morphological characteristics were identified by transmission electron microscopy (TEM). RESULTS: I-ATXP inhibited the growth of HCC cells in a dose and time-dependent manner. Flow cytometry analysis showed that I-ATXP induced G0/G1 phase arrest and cell apoptosis. The I-ATX reduced HepG2, SMMC7721, and HKCI-C HCC cell lines exosomes release and low-dose I-ATXP significantly enhanced the growth inhibition induced by 5-Fu. Western blot analysis shows that after HCC cell lines were treated with various concentrations of I-ATXP (0.125-1 mg/ml) for 24 h, exosomes derived from three different HCC cells expressed exosome-specific proteins Alix and CD63. Compared with the untreated group, with the increment of the concentration of I-ATXP, the expression of exosome-specific proteins Alix and CD63 were reduced. These results suggest that I-ATXP can inhibit the release of exosomes with Alix and CD63 protein from HCC cells. CONCLUSIONS: I-ATXP is a traditional Chinese medicine that acts as an effective agent for preventing or treating human liver carcinoma. (i) I-ATXP can effectively inhibit cell proliferation of different HCC cells in a time and dose-dependent manner. Compared with 5-Fu, I-ATXP exhibited more selective proliferation inhibition in HCC cells, displaying traditional Chinese medicine advantages on tumor therapy and providing the experimental basis for I-ATXP clinical application. (ii) I-ATXP can induce apoptosis and cell cycle arrest in HCC cells. The CCK-8 assay results indicated that I-ATXP could inhibit HCC cell proliferation mediated by apoptosis and cell cycle arrest. (iii) I-ATXP can inhibit both the exosome releases and expression of CD63, and Alix derived from HCC cells, but the exosomes derived from liver cancer cells affect liver cancer cells' biological properties such as proliferation, invasion, and migration. These suggest that I-ATXP may affect HCC cells via regulation of exosomes of HCC cells, further indicating the potential clinical values of I-ATXP for the prevention or treatment of human liver carcinoma.
ESTHER : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedSearch : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedID: 35619665

Title : Substrate-Binding Mode of a Thermophilic PET Hydrolase and Engineering the Enzyme to Enhance the Hydrolytic Efficacy - Zeng_2022_ACS.Catal_12_3033
Author(s) : Zeng W , Li X , Yang Y , Min J , Huang JW , Liu W , Niu D , Yang X , Han X , Zhang L , Dai L , Chen CC , Guo RT
Ref : ACS Catal , 12 :3033 , 2022
Abstract : Polyethylene terephthalate (PET) is among the most extensively produced plastics, but huge amounts of PET wastes that have accumulated in the environment have become a serious threat to the ecosystem. Applying PET hydrolytic enzymes to depolymerize PET is an attractive measure to manage PET pollution, and searching for more effective enzymes is a prerequisite to achieve this goal. A thermostable cutinase that originates from the leaf-branch compost termed ICCG is the most effective PET hydrolase reported so far. Here, we illustrated the crystal structure of ICCG in complex with the PET analogue, mono(2-hydroxyethyl)terephthalic acid, to reveal the enzyme-substrate interaction network. Furthermore, we applied structure-based engineering to modify ICCG and screened for variants that exhibit higher efficacy than the parental enzyme. As a result, several variants with the measured melting temperature approaching 99 C and elevated PET hydrolytic activity were obtained. Finally, crystallographic analyses were performed to reveal the structural stabilization effects mediated by the introduced mutations. These results are of importance in the context of understanding the mechanism of action of the thermostable PET hydrolytic enzyme and shall be beneficial to the development of PET biodegradation platforms.
ESTHER : Zeng_2022_ACS.Catal_12_3033
PubMedSearch : Zeng_2022_ACS.Catal_12_3033
PubMedID:
Gene_locus related to this paper: 9bact-g9by57

Title : A Portable Fluorescent Hydrogel-Based Device for On-Site Quantitation of Organophosphorus Pesticides as Low as the Sub-ppb Level - Wang_2022_Front.Chem_10_855281
Author(s) : Wang T , Zhang L , Xin H
Ref : Front Chem , 10 :855281 , 2022
Abstract : Portable devices possess powerful application prospects in on-site sensing without the limitation of bulky instruments. Given the relevance of pesticides to food safety, we herein fabricated a robust gold nanocluster (AuNC)-based hydrogel test kit for precisely quantified chlorpyrifos by using a three-dimensional (3D) printed subsidiary device. In this work, the fluorescence of AuNC-based hydrogel could be efficiently quenched by cobalt oxyhydroxide nanoflakes (CoOOH NFs) through the Forster resonance energy transfer effect. Chlorpyrifos as an acetylcholinesterase inhibitor controls the enzymatic hydrolysis reaction and further regulates the production of thiocholine that could decompose CoOOH nanoflakes into Co(2+), resulting in the fluorescence response of AuNC-based hydrogel. By using a homemade subsidiary device and smartphone, the fluorescence color was transformed into digital information, achieving the on-site quantitative detection of chlorpyrifos with the limit of detection of 0.59 ng ml(-1). Owing to specific AuNC signatures and hydrogel encapsulation, the proposed fluorescence hydrogel test kit displayed high sensitivity, good selectivity, and anti-interference capability in a real sample analysis, providing great potential in on-site applications.
ESTHER : Wang_2022_Front.Chem_10_855281
PubMedSearch : Wang_2022_Front.Chem_10_855281
PubMedID: 35572106

Title : Polar substitutions on the surface of a lipase substantially improve tolerance in organic solvents - Davari_2022_ChemSusChem__
Author(s) : Davari MD , Cui H , Vedder M , Zhang L , Jaeger KE , Schwaneberg U
Ref : ChemSusChem , : , 2022
Abstract : Biocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSs often reduce enzymatic activity which limits the use enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating the molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape in “BSLA-SSM library. By systematically analyzing 39 structural-, solvation-, and interaction energy-based observables, we discovered hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variants in OS. Moreover, the fingerprints of 1644 polar-related variants in three OSs demonstrated substituting aromatic to polar residue(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering enable to be a powerful and general strategy for generating OS-tolerant lipases and other enzymes, thereby adapting the catalyst to the desired reaction and process with OSs.
ESTHER : Davari_2022_ChemSusChem__
PubMedSearch : Davari_2022_ChemSusChem__
PubMedID: 35007408
Gene_locus related to this paper: bacsu-lip

Title : GR24-mediated enhancement of salt tolerance and roles of H(2)O(2) and Ca(2+) in regulating this enhancement in cucumber - Zhang_2022_J.Plant.Physiol_270_153640
Author(s) : Zhang XH , Ma C , Zhang L , Su M , Wang J , Zheng S , Zhang TG
Ref : J Plant Physiol , 270 :153640 , 2022
Abstract : This study investigated the regulation of the exogenous strigolactone (SL) analog GR24 in enhancing the salt tolerance and the effects of calcium ion (Ca(2+)) and hydrogen peroxide (H(2)O(2)) on GR24's regulation effects in cucumber. The seedlings were sprayed with (1) distilled water (CK), (2) NaCl, (3) GR24, then NaCl, (4) GR24, then H(2)O(2) scavenger, then NaCl, and (5) GR24, then Ca(2+) blocker, then NaCl. The second true leaf was selected for biochemical assays. Under the salt stress, the exogenous GR24 maintained the ion balance, increased the activity of antioxidant enzymes, reduced the membrane lipid peroxidation, and increased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), accompanied by a decrease in relative conductivity, an increase in the proline content, and elevated gene expression levels of antioxidant enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, calcium-dependent protein kinases (CDPKs), salt overly sensitive SOS1, CBL-interacting protein kinase 2 (CIPK2), and calcineurin B-like protein 3 (CBL3). Such protective effects triggered by GR24 were attenuated or almost abolished by ethylene glycol tetraacetic acid (EGTA), lanthanum chloride (LaCl3, Ca(2+) channel blocker), diphenyleneiodonium (DPI, NADPH oxidase inhibitor), and dimethylthiourea (DMTU, hydroxyl radical scavenger). Our data suggest that exogenous GR24 is highly effective in alleviating salt-induced damages via modulating antioxidant capabilities and improving ionic homeostasis and osmotic balance and that H(2)O(2) and Ca(2+) are required for GR24-mediated enhancement of salt tolerance.
ESTHER : Zhang_2022_J.Plant.Physiol_270_153640
PubMedSearch : Zhang_2022_J.Plant.Physiol_270_153640
PubMedID: 35168135

Title : Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury - Zeng_2022_Front.Pharmacol_13_962480
Author(s) : Zeng Z , Yi W , Dong JP , Chen QQ , Sun FF , Lu HH , Lin YJ , Bi XY , Yang L , Lu Y , Zhang L , Li MH , Xie Y
Ref : Front Pharmacol , 13 :962480 , 2022
Abstract : Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 +/- 2010.40 U/L vs. 6248.52 +/- 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury.
ESTHER : Zeng_2022_Front.Pharmacol_13_962480
PubMedSearch : Zeng_2022_Front.Pharmacol_13_962480
PubMedID: 35991883

Title : Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis - Lang_2022_BMC.Pediatr_22_295
Author(s) : Lang B , Han L , Zeng L , Zhang Q , Chen S , Huang L , Jia Z , Yu Q , Zhang L
Ref : BMC Pediatr , 22 :295 , 2022
Abstract : BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.
ESTHER : Lang_2022_BMC.Pediatr_22_295
PubMedSearch : Lang_2022_BMC.Pediatr_22_295
PubMedID: 35590273

Title : A novel indene-chalcone-based fluorescence probe with lysosome-targeting for detection of endogenous carboxylesterases and bioimaging - Zhang_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_278_121329
Author(s) : Zhang L , Yan JL , Wang Y , Zhao XL , Wu WN , Fan YC , Xu ZH , Yan LL
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 278 :121329 , 2022
Abstract : An indene-chalcone-based fluorescence probe 1 was synthesized and characterized. Under physiological conditions (containing 5% DMSO), probe 1 showed satisfactory stability with a low background signal and recognized carboxylesterases (CEs) based on the catalytic hydrolysis of ester groups, releasing a significant green fluorescence. Probe 1 presents several features including a short response time (within 20 min), low detection limit (1.3 x 10(-4) U/mL) and large stokes shift (over 155 nm). Notably, commercial lysosomal dye co-staining experiments illustrated the lysosomal localization function of 1, with the probe also being used for cell and zebrafish imaging of endogenous CEs.
ESTHER : Zhang_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_278_121329
PubMedSearch : Zhang_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_278_121329
PubMedID: 35576837

Title : An esterase-activatable curcumin prodrug for tumor-targeting therapy - Liu_2022_Chem.Commun.(Camb)__
Author(s) : Liu L , Zhang L , Tao M , Wang M , Dong L , Hai Z
Ref : Chem Commun (Camb) , : , 2022
Abstract : A tumor-targeting therapy strategy is urgently needed to increase the accumulation of drugs in tumors and reduce the side effects in normal tissues. Herein, we developed an esterase-activatable curcumin prodrug Cur-RGD for tumor-targeting therapy. Armed with the tumor-targeting RGD peptide and in situ esterase-triggered drug release, this prodrug Cur-RGD can efficiently improve the therapeutic effect of curcumin in tumors.
ESTHER : Liu_2022_Chem.Commun.(Camb)__
PubMedSearch : Liu_2022_Chem.Commun.(Camb)__
PubMedID: 36373630

Title : Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer - Wang_2022_BMC.Cancer_22_635
Author(s) : Wang Y , Fang T , Yin X , Zhang L , Zhang X , Zhang D , Zhang Y , Wang X , Wang H , Xue Y
Ref : BMC Cancer , 22 :635 , 2022
Abstract : BACKGROUND: The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. METHODS: We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. RESULTS: Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. CONCLUSION: AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.
ESTHER : Wang_2022_BMC.Cancer_22_635
PubMedSearch : Wang_2022_BMC.Cancer_22_635
PubMedID: 35681154
Gene_locus related to this paper: human-AADAC

Title : Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) - Zhang_2022_Pest.Manag.Sci__
Author(s) : Zhang L , Wang L , Chen J , Zhang J , He Y , Lu Y , Cai J , Chen X , Wen X , Xu Z , Wang C
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2022_Pest.Manag.Sci__
PubMedSearch : Zhang_2022_Pest.Manag.Sci__
PubMedID: 35192738

Title : Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative - Liu_2022_Molecules_27_9062
Author(s) : Liu W , Zhao D , He Z , Hu Y , Zhu Y , Zhang L , Jin L , Guan L , Wang S
Ref : Molecules , 27 :9062 , 2022
Abstract : Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.
ESTHER : Liu_2022_Molecules_27_9062
PubMedSearch : Liu_2022_Molecules_27_9062
PubMedID: 36558194

Title : Molecular and Biochemical Analyses of a Novel Trifunctional Endoxylanase\/Endoglucanase\/Feruloyl Esterase from the Human Colonic Bacterium Bacteroides intestinalis DSM 17393 - Zhang_2022_J.Agric.Food.Chem__
Author(s) : Zhang R , Lin D , Zhang L , Zhan R , Wang S , Wang K
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : A novel enzyme Bi76 comprising GH10, E_set_Esterase_N, and CE1 modules was identified, with the highest homology (62.9%) with a bifunctional endoxylanase/feruloyl esterase among characterized enzymes. Interestingly, Bi76 hydrolyzed glucan substrates besides xylans and feruloylated substrates, suggesting that it is the first characterized trifunctional endoxylanase/endoglucanase/feruloyl esterase. Analyses of truncation variants revealed that GH10 and E_set_Esterase_N + CE1 modules encoded endoxylanase/endoglucanase and feruloyl esterase activities, respectively. Synergism analyses indicated that endoxylanase, alpha-l-arabinofuranosidase, and feruloyl esterase acted cooperatively in releasing ferulic acid (FA) and xylooligosaccharides from feruloylated arabinoxylan. The interdomain synergism of Bi76 overmatched the intermolecular synergism of TM1 and TM2. Importantly, Bi76 exhibited good capacity in producing FA, releasing 5.20, 4.38, 2.12, 1.35, 0.46, and 0.19 mg/g from corn bran, corn cob, wheat bran, corn stover, rice husk, and rice bran, respectively. This study expands the trifunctional endoxylanase/endoglucanase/feruloyl esterase repertoire and demonstrates the great potential of Bi76 in agricultural residue utilization.
ESTHER : Zhang_2022_J.Agric.Food.Chem__
PubMedSearch : Zhang_2022_J.Agric.Food.Chem__
PubMedID: 35316064
Gene_locus related to this paper: 9bace-b3c594

Title : Untargeted Phenolic Profiling and Functional Insights of the Aerial Parts and Bulbs of Drimia maritima (L.) Stearn - Zhang_2022_Plants.(Basel)_11_
Author(s) : Zhang L , Zengin G , Mahomoodally MF , Yildiztugay E , Jugreet S , Simal-Gandara J , Rouphael Y , Pannico A , Lucini L
Ref : Plants (Basel) , 11 : , 2022
Abstract : Drimia maritima (L.) Stearn (squill), belonging to the Asparagaceae family, is acknowledged as a medicinally valuable species from the Drimia genera. In this study, water, methanol, and ethyl acetate extracts of D. maritima aerial parts and bulbs were investigated for their polyphenols profile and evaluated for their antioxidant and enzyme inhibition properties. Phenolics were profiled through an untargeted metabolomics approach using an ultra-high pressure liquid chromatograph coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). This analysis revealed an enrichment of low molecular weight phenolics and flavonoids in the aerial parts of D. maritima, while lignans mainly characterized bulb extracts. Antioxidant capacity was investigated by different assays, including phosphomolybdenum assays, radical scavenging (DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), as well as reducing ability (CUPRAC: cupric reducing antioxidant capacity; FRAP: ferric reducing antioxidant power), and metal chelating. In radical scavenging and reducing power assays, the water extract of aerial parts exhibited the strongest ability (DPPH: 36.99 mg trolox equivalent (TE)/g; ABTS: 85.96 mg TE/g; CUPRAC: 87.37 mg TE/g; FRAP: 55.43 mg TE/g). In general, the ethyl acetate extracts from aerial parts and bulbs provided the weakest antioxidant capacity. Concerning enzyme inhibitory activities, the water extracts of the bulb were poorly active, while the ethyl acetate extracts from both plant portions displayed the best alpha-amylase inhibitory abilities. The best acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) abilities were recorded by ethyl acetate extract of aerial parts (2.36 mg galantamine equivalent (GALAE)/g) and bulbs (5.10 mg GALAE/g), respectively. Overall, these results support the medicinal aptitude of D. maritima and its possible use as a natural source of antioxidants and enzyme inhibitors with functional potential.
ESTHER : Zhang_2022_Plants.(Basel)_11_
PubMedSearch : Zhang_2022_Plants.(Basel)_11_
PubMedID: 35270070

Title : UHPLC-QTOF-MS based metabolomics and biological activities of different parts of Eriobotrya japonica - Zhang_2021_Food.Res.Int_143_110242
Author(s) : Zhang L , Saber FR , Rocchetti G , Zengin G , Hashem MM , Lucini L
Ref : Food Res Int , 143 :110242 , 2021
Abstract : Eriobotrya japonica, commonly known as loquat, has been used traditionally for the treatment of different diseases. Herein, untargeted profiling based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to depict the phytochemical profile of loquat roots, leaves, stems, seeds, and fruits. This allowed the tentative annotation of 349 compounds, representing different phytochemical classes that included flavonoids, phenolic acids, lignans, stilbenes, and terpenoids. Among others, low molecular weight phenolics (tyrosol derivatives) and terpenoids were the most abundant phytochemicals. After that, in vitro antioxidant and enzyme inhibition assays were applied to investigate the biological activity of the different organs of Eriobotrya japonica. Roots of E. japonica exhibited the highest antioxidant capacity, showing 181.88, 275.48, 325.18, 169.74 mg Trolox equivalent (TE)/g in DPPH, ABTS, CUPRAC, and FRAP assays, respectively. Furthermore, the root extract of E. japonica strongly inhibited butyryl cholinesterase (3.64 mg galantamine equivalent (GALAE)/g), whereas leaves, stems, seeds, and fruits showed comparable inhibition of both acetyl and butyryl cholinesterases. All the investigated organs of E. japonica exhibited in vitro tyrosinase inhibition (57.27-71.61 mg Kojic Acid Equivalent (KAE)/g). Our findings suggest a potential food and pharmaceutical exploitation of different organs of E. japonica (mainly roots) in terms of enrichment with health-promoting phenolics and triterpenes.
ESTHER : Zhang_2021_Food.Res.Int_143_110242
PubMedSearch : Zhang_2021_Food.Res.Int_143_110242
PubMedID: 33992354

Title : Functional Characterization and Crystal Structure of the Bifunctional Thioesterase Catalyzing Epimerization and Cyclization in Skyllamycin Biosynthesis - Yu_2021_ACS.Catalysis_11_11733
Author(s) : Yu J , Juan S , Chi C , Liu T , Geng T , Cai Z , Dong W , Shi C , Ma X , Zhang Z , Xing B , Jin H , Zhang L , Dong S , Yang D , Ma M
Ref : ACS Catal , 11 :11733 , 2021
Abstract : The d-amino acid residues are hallmark building blocks of nonribosomal peptides. Here, we report the bifunctional thioesterase domain (TE domain) Skyxy-TE that catalyzes both epimerization and cyclization in skyllamycin biosynthesis. Skyxy-TE specifically catalyzes the epimerization of the C-terminal l-amino acid residue of the linear substrate, then catalyzes regioselective intramolecular cyclization. The crystal structure of Skyxy-TE was solved at 2.25 and site-directed mutagenesis was performed, revealing key residues involved in the epimerization and cyclization. This study expands the understanding of the versatile TE domains and facilitates chemoenzymatic synthesis or combinatorial biosynthesis in the future.
ESTHER : Yu_2021_ACS.Catalysis_11_11733
PubMedSearch : Yu_2021_ACS.Catalysis_11_11733
PubMedID:
Gene_locus related to this paper: strsq-a0a1j0r317

Title : The functional potential of nine Allium species related to their untargeted phytochemical characterization, antioxidant capacity and enzyme inhibitory ability - Rocchetti_2021_Food.Chem_368_130782
Author(s) : Rocchetti G , Zhang L , Bocchi S , Giuberti G , Ak G , Elbasan F , Yildiztugay E , Ceylan R , Picot-Allain MCN , Mahomoodally MF , Lucini L , Zengin G
Ref : Food Chem , 368 :130782 , 2021
Abstract : In this study, the aerial parts and bulbs of nine Allium species were investigated for their functional phytochemical profile, in vitro antioxidant activities, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-amylase, alpha-glucosidase, and tyrosinase inhibitory properties. Phenolics, alkaloids, glucosinolates and other sulfur-containing compounds were distinctively profiled in the different species. Maceration in methanol allowed recovering the highest cumulative phenolic content in A. scabrifolium (42.31 mg/g), followed by A. goekyigiti (33.15 mg/g) and A. atroviolaceum (28.35 mg/g). The aerial parts of all Allium species showed high in vitro antioxidant activity whereas methanolic extract of A. cappadocicum bulb showed the highest inhibition against AChE (2.44 mg galantamine equivalent/g) and the water extracts of A. isauricum aerial part were the best BChE inhibitors (4.31 mg galantamine equivalent/g). Bulbs were the richer source of oligosaccharides, and in vitro digestion determined an increase of oligosaccharides bioaccessibility. A promising nutraceutical potential could be highlighted in our understudied Allium species.
ESTHER : Rocchetti_2021_Food.Chem_368_130782
PubMedSearch : Rocchetti_2021_Food.Chem_368_130782
PubMedID: 34392121

Title : Less unfavorable salt-bridges on the enzyme surface results in more organic cosolvent resistance - Cui_2021_Angew.Chem.Int.Ed.Engl__
Author(s) : Cui H , Eltoukhy L , Zhang L , Markel U , Jaeger KE , Davari MD , Schwaneberg U
Ref : Angew Chem Int Ed Engl , : , 2021
Abstract : Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co-)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6-fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137-fold, and half-life up to 3.3-fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50-100 degreesC. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs- and/or thermal-resistant lipases and other alpha/beta-hydrolases.
ESTHER : Cui_2021_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Cui_2021_Angew.Chem.Int.Ed.Engl__
PubMedID: 33687787
Gene_locus related to this paper: bacsu-LIPB

Title : Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 GAG knock-in mice - Yokoi_2021_IBRO.Neurosci.Rep_11_1
Author(s) : Yokoi F , Dang MT , Zhang L , Dexter KM , Efimenko I , Krishnaswamy S , Villanueva M , Misztal CI , Gerard M , Lynch P , Li Y
Ref : IBRO Neurosci Rep , 11 :1 , 2021
Abstract : DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous deltaGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.
ESTHER : Yokoi_2021_IBRO.Neurosci.Rep_11_1
PubMedSearch : Yokoi_2021_IBRO.Neurosci.Rep_11_1
PubMedID: 34189496

Title : Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota - Zhang_2021_Environ.Pollut_277_116767
Author(s) : Zhang J , Meng H , Kong X , Cheng X , Ma T , He H , Du W , Yang S , Li S , Zhang L
Ref : Environ Pollut , 277 :116767 , 2021
Abstract : Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 microm and 9-Nitroanthracene (9-NAnt, 5 and 500 microg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works.
ESTHER : Zhang_2021_Environ.Pollut_277_116767
PubMedSearch : Zhang_2021_Environ.Pollut_277_116767
PubMedID: 33640823

Title : Case Report\/Case Series: Rare case of anti-LGI1 limbic encephalitis with rapidly progressive dementia, psychiatric symptoms, and frequently seizures: A case report - Wu_2021_Medicine.(Baltimore)_100_e26654
Author(s) : Wu H , Mei F , Liu L , Zhang L , Hao H , Zhang S
Ref : Medicine (Baltimore) , 100 :e26654 , 2021
Abstract : RATIONALE: Anti leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis (LE) is rare autoimmune encephalitis, characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, mental disorders, and refractory hyponatremia. As a type of treatable rapidly progressive dementia with a good prognosis, early, and accurate diagnosis is essential. We present a case of anti-LGI1 LE who was initially misdiagnosed with Alzheimer disease because his clinical manifestations were similar to Alzheimer disease. PATIENT CONCERNS: A male patient presenting with rapidly progressive dementia, faciobrachial dystonic seizures, psychiatric disturbance, and refractory hyponatremia was admitted. The scores of Mini-Mental State Examination, Montreal Cognitive Assessment, and Neuropsychiatric Inventory were 19/30, 16/30, and 91/144, respectively. Brain magnetic resonance images indicated moderate atrophy of the hippocampus and abnormally hyperintensities in the left medial temporal and hippocampus. DIAGNOSIS: The patient was diagnosed with anti-LGI1 LE based on the presence of LGI-1 antibodies in the cerebrospinal fluid and serum and clinical manifestations. INTERVENTIONS: Patient was treated with glucocorticoid against LGI1, antiepileptic drug, cholinesterase inhibitors, and other adjuvant therapy. OUTCOMES: The patient showed marked improvement on immunotherapy. Clinical symptoms were disappeared and the LGI-1 antibodies in cerebrospinal fluid and serum were both negative at the time of discharge. CONCLUSIONS: Recognition of the specific symptoms and LGI-1 antibody test will be helpful for the early diagnosis, prompt immunotherapy, and good prognosis. This case raises the awareness that rapidly progressive dementia with frequent seizures could be caused by immunoreactions.
ESTHER : Wu_2021_Medicine.(Baltimore)_100_e26654
PubMedSearch : Wu_2021_Medicine.(Baltimore)_100_e26654
PubMedID: 34398024

Title : Long-Wavelength Ratiometric Fluorescent Probe for the Early Diagnosis of Diabetes - Wang_2021_Anal.Chem_93_11461
Author(s) : Wang J , Zhang L , Qu Y , Yang Y , Cao T , Cao Y , Iqbal A , Qin W , Liu Y
Ref : Analytical Chemistry , 93 :11461 , 2021
Abstract : Diabetes is a metabolic disease caused by high blood sugar. Patients are often suffering from high blood pressure and arteriosclerosis, which may even evolve into liver disease, kidney disease, and other diabetic complications. Dipeptide peptidase IV (DPP-IV) plays an important role in regulating blood sugar levels and is one of the targets for the diagnosis and treatment of diabetes. Here, a long-wavelength ratiometric fluorescent probe DCDHFNH(2)-dpp4 for detecting DPP-IV was designed and synthesized. DCDHFNH(2)-dpp4 was used to detect DPP-IV in healthy, tumor-bearing, and diabetic mice, and only diabetic mice showed strong fluorescence signals. In organ imaging, it is found that DPP-IV is relatively enriched in the liver of diabetic mice. In addition, probe DCDHFNH(2)-dpp4 also exhibited a significant ratiometric fluorescence signal in the serum of diabetic mice. Therefore, the fluorescent probe DCDHFNH(2)-dpp4 has shown outstanding potential in the early diagnosis of diabetes, and DCDHFNH(2)-dpp4 is hopeful to be applied to actual clinical medicine.
ESTHER : Wang_2021_Anal.Chem_93_11461
PubMedSearch : Wang_2021_Anal.Chem_93_11461
PubMedID: 34369744

Title : Clinical Evaluation and Test of a Modified Lp-PLA2 Kit in Diagnosing Atherosclerosis - Yuan_2021_Clin.Lab_67_
Author(s) : Yuan L , Hou L , Zhang L , Qin Z , Yu C
Ref : Clin Lab , 67 : , 2021
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been identified as an inflammatory marker tightly correlated with the onset of atherosclerosis. Although several methodologies have been developed to detect Lp-PLA2, including enzyme-linked immunosorbent assay, Lp-PLA2 detection is still time- and resource-consuming with poor antiinterference ability and low sensitivity. Thus, it is urgent to explore new methodology for Lp-PLA2 detection. METHODS: In the current study, we evaluated the clinical performance of a modified Lp-PLA2 quantitative assay kit based on magnetic particle chemiluminescence, and analyzed the levels of Lp-PLA2 in atherosclerosis patients using this kit. RESULTS: Our results showed that the magnetic particle chemiluminescence method could effectively dissociate Lp-PLA2 from lipoprotein and finish the test within 20 minutes with high accuracy and good repeatability, as demonstrated by the results of linear measurement range, precision, and recovery rate. Furthermore, our preliminary data revealed that serum Lp-PLA2 levels were correlated to the presence and degree of atherosclerotic plaques. CONCLUSIONS: Lp-PLA2 could be helpful in diagnosing atherosclerosis.
ESTHER : Yuan_2021_Clin.Lab_67_
PubMedSearch : Yuan_2021_Clin.Lab_67_
PubMedID: 34383412

Title : Putative carboxylesterase gene identification and their expression patterns in Hyphantria cunea (Drury) - Ye_2021_PeerJ_9_e10919
Author(s) : Ye J , Mang D , Kang K , Chen C , Zhang X , Tang Y , E RP , Song L , Zhang QH , Zhang L
Ref : PeerJ , 9 :e10919 , 2021
Abstract : The olfactory system of insects is important for behavioral activities as it recognizes internal and external volatile stimuli in the environment. Insect odorant degrading enzymes (ODEs), including antennal-specific carboxylesterases (CXEs), are known to degrade redundant odorant molecules or to hydrolyze important olfactory sex pheromone components and plant volatiles. Compared to many well-studied Type-I sex pheromone-producing lepidopteran species, the molecular mechanisms of the olfactory system of Type-II sex pheromone-producing Hyphantria cunea (Drury) remain poorly understood. In the current study, we first identified a total of ten CXE genes based on our previous H. unea antennal transcriptomic data. We constructed a phylogenetic tree to evaluate the relationship of HcunCXEs with other insects' CXEs, and used quantitative PCR to investigate the gene expression of H. cunea CXEs (HcunCXEs). Our results indicate that HcunCXEs are highly expressed in antennae, legs and wings, suggesting a potential function in degrading sex pheromone components, host plant volatiles, and other xenobiotics. This study not only provides a theoretical basis for subsequent olfactory mechanism studies on H. cunea, but also offers some new insights into functions and evolutionary characteristics of CXEs in lepidopteran insects. From a practical point of view, these HcunCXEs might represent meaningful targets for developing behavioral interference control strategies against H. cunea.
ESTHER : Ye_2021_PeerJ_9_e10919
PubMedSearch : Ye_2021_PeerJ_9_e10919
PubMedID: 33717687
Gene_locus related to this paper: cname-a0a1u9x1s5 , cname-a0a1u9x1s9 , cname-a0a1u9x1t4 , cname-a0a1u9x1t5 , cname-a0a1u9x1t2 , cname-a0a1u9x1t3 , cname-a0a1u9x1t0 , cname-a0a1u9x1s7 , cname-a0a1u9x1t1 , cname-a0a1u9x1s8 , cname-a0a1u9x1t9 , cname-a0a1u9x1t7 , cname-a0a1u9x1t8 , cname-a0a1u9x1u2 , cname-a0a1u9x1u1

Title : Design, synthesis, and cholinesterase inhibition assay of liquiritigenin derivatives as anti-Alzheimer's activity - Guan_2021_Bioorg.Med.Chem.Lett__128306
Author(s) : Guan L , Peng D , Zhang L , Jia J , Jiang H
Ref : Bioorganic & Medicinal Chemistry Lett , :128306 , 2021
Abstract : The marine environment is a rich resource for discovering functional materials, and seaweed is recognized for its potential use in biology and medicine. Liquiritigenin has been isolated and identified from Sargassum pallidum. To find new anti-Alzheimer's activity, we designed and synthesized thirty-two 7-prenyloxy-2,3-dihydroflavanone derivatives (3a-3p) and 5-hydroxy-7-prenyloxy-2,3-dihydro- flavanone derivatives (4a-4p) as cholinesterases inhibitors based on liquiritigenin as the lead compound. Inhibition screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) indicated that all synthesized compounds possessed potent AChE inhibitory activity and moderated to weak BuChE inhibitory activity in vitro. Kinetic studies demonstrated that compound 4o inhibited AChE via a dual binding site ability. In addition, all compounds displayed the radical scavenging effects. Finally, the molecular docking simulation of 4o in AChE active site displayed good agreement with the obtained the pharmacological results.
ESTHER : Guan_2021_Bioorg.Med.Chem.Lett__128306
PubMedSearch : Guan_2021_Bioorg.Med.Chem.Lett__128306
PubMedID: 34371131

Title : Exposure of Helicoverpa armigera Larvae to Plant Volatile Organic Compounds Induces Cytochrome P450 Monooxygenases and Enhances Larval Tolerance to the Insecticide Methomyl - Wu_2021_Insects_12_
Author(s) : Wu C , Ding C , Chen S , Wu X , Zhang L , Song Y , Li W , Zeng R
Ref : Insects , 12 : , 2021
Abstract : Plants release an array of volatile chemicals into the air to communicate with other organisms in the environment. Insect attack triggers emission of herbivore-induced plant volatiles (HIPVs). How insect herbivores use these odors to plan their detoxification systems is vital for insect adaptation to environmental xenobiotics. Here we show that the larvae of Helicoverpa armigera (Hubner), a broadly polyphagous lepidopteran herbivore, have the capacity to use plant volatiles as cues to upregulate multiple detoxification systems, including cytochrome P450 monooxygenases (P450s), for detoxification of insecticides. Olfactory exposure of the fifth instars to two terpene volatiles limonene and nerolidol, and two green-leaf volatiles 2-heptanone and cis-3-hexenyl acetate significantly reduced larval susceptibility to the insecticide methomyl. However, larval pretreatment with piperonyl butoxide (PBO), a known P450 inhibitor, neutralized the effects of volatile exposure. Furthermore, larval exposure to the four plant volatiles enhanced activities of P450 enzymes in midguts and fatbodies, and upregulated expression of CYP6B2, CYP6B6 and CYP6B7, P450s involved in detoxification of the insecticide. Larval exposure to 2-heptanone and limonene volatiles also enhanced activities of glutathione-s-transferase and carboxylesterase. Our findings suggest that olfactory exposure to HIPVs enhances larval insecticide tolerance via induction of detoxification P450s.
ESTHER : Wu_2021_Insects_12_
PubMedSearch : Wu_2021_Insects_12_
PubMedID: 33808968

Title : General features to enhance enzymatic activity of poly(ethylene terephthalate) hydrolysis - Chen_2021_Nat.Catal_4_425
Author(s) : Chen CC , Han X , Li X , Jiang P , Niu D , Ma L , Liu W , Li S , Qu Y , Hu H , Min J , Yang Y , Zhang L , Zeng W , Huang JW , Dai L , Guo RT , Chen, CC
Ref : Nature Catalysis , 4 :425 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic and a major contributor to plastic pollution. IsPETase, from the PET-assimilating bacterium Ideonella sakaiensis, is a unique PET-hydrolytic enzyme that shares high sequence identity to canonical cutinases, but shows substrate preference towards PET and exhibits higher PET-hydrolytic activity at ambient temperature. Structural analyses suggest that IsPETase harbours a substrate-binding residue, W185, with a wobbling conformation and a highly flexible W185-locating beta6-beta7 loop. Here, we show that these features result from the presence of S214 and I218 in IsPETase, whose equivalents are strictly His and Phe, respectively, in all other homologous enzymes. We found that mutating His/Phe residues to Ser/Ile could enhance the PET-hydrolytic activity of several IsPETase-like enzymes. In conclusion, the Ser/Ile mutations should provide an important strategy to improve the activity of potential PET-hydrolytic enzymes with properties that may be useful for various applications.
ESTHER : Chen_2021_Nat.Catal_4_425
PubMedSearch : Chen_2021_Nat.Catal_4_425
PubMedID:
Gene_locus related to this paper: 9burk-a0a1f4jxw8 , idesa-peth

Title : A ratiometric fluorescence strategy based on inner filter effect for Cu(2+)-mediated detection of acetylcholinesterase - Li_2021_Mikrochim.Acta_188_385
Author(s) : Li Y , Liang H , Lin B , Yu Y , Wang Y , Zhang L , Cao Y , Guo M
Ref : Mikrochim Acta , 188 :385 , 2021
Abstract : A novel ratiometric fluorescence strategy for detection of acetylcholestinerase (AChE) is proposed based on carbon nitride quantum dots (g-CNQD) and the complex (PA) formed between phenylboronic acid (PBA) and alizarin red S (ARS). PA showed fluorescence at 598 nm and quenched the fluorescence of g-CNQD at 438 nm. Through UV-visible absorption, fluorescence, and fluorescence lifetime measurements, the quenching effect was demonstrated as inner filter effect (IFE). When Cu(2+) was added, the coordination of ARS and Cu(2+) decreased the fluorescence of PA at 598 nm and recovered that of g-CNQD at 438 nm. In the presence of AChE it catalyzed the hydrolysis of acetylthiocholine (ATCh) to produce thiocholine (TCh) which competed with ARS for binding to Cu(2+); thus, the fluorescence at 598 nm increased and that at 438 nm decreased again. Under the mediation of Cu(2+), the fluorescence ratio F(598)/F(438) of PA-CNQD probe had good linear relationship with AChE concentration in the range 0.5-15 mU/mL with a detection limit of 0.36 mU/mL. The method was successfully applied to the determination of AChE in human serum and the screening of inhibitors.
ESTHER : Li_2021_Mikrochim.Acta_188_385
PubMedSearch : Li_2021_Mikrochim.Acta_188_385
PubMedID: 34664146

Title : Late-Stage Modification of Medicine: Pd-Catalyzed Direct Synthesis and Biological Evaluation of N-Aryltacrine Derivatives - Wan_2021_ACS.Omega_6_9960
Author(s) : Wan LX , Zhen YQ , He ZX , Zhang Y , Zhang L , Li X , Gao F , Zhou XL
Ref : ACS Omega , 6 :9960 , 2021
Abstract : A new series of N-aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)-tacrine (3g) and N-(4-methoxypyridin-2-yl)-tacrine (3o) showed the most potent activity against AChE (IC(50) values of 1.77 and 1.48 microM, respectively). The anti-AChE activity of 3g and 3o was 3.5 times more than that of tacrine (IC(50) value of 5.16 microM). Compound 3o also displayed anti-BuChE activity with an IC(50) value of 19.00 microM. Cell-based assays against HepG2 and SH-SY5Y cell lines revealed that 3o had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H(2)O(2)-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound 3o a new promising multifunctional candidate for the treatment of Alzheimer's disease.
ESTHER : Wan_2021_ACS.Omega_6_9960
PubMedSearch : Wan_2021_ACS.Omega_6_9960
PubMedID: 33869976

Title : A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 \% Ho(3+)@NaYF(4) upconversion nano-probe - Zhao_2021_Talanta_235_122784
Author(s) : Zhao X , Zhang L , Yan X , Lu Y , Pan J , Zhang M , Wang C , Suo H , Jia X , Liu X , Lu G
Ref : Talanta , 235 :122784 , 2021
Abstract : Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.
ESTHER : Zhao_2021_Talanta_235_122784
PubMedSearch : Zhao_2021_Talanta_235_122784
PubMedID: 34517642

Title : Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (alpha-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities - Wang_2021_Foods_10_
Author(s) : Wang Z , Tu Z , Xie X , Cui H , Kong KW , Zhang L
Ref : Foods , 10 : , 2021
Abstract : This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 microg GAE/mg DE) and flavonoid content (455.22 microg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful alpha-glucosidase inhibitory ability with the IC(50) value of 190.03 microg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC(50) values of 37.92 and 13.43 microg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.
ESTHER : Wang_2021_Foods_10_
PubMedSearch : Wang_2021_Foods_10_
PubMedID: 33546380

Title : Identification of Detoxification Esterase StrH Initiating Strobilurin Fungicides Degradation in Hyphomicrobium sp. DY-1 - Jiang_2021_Appl.Environ.Microbiol__
Author(s) : Jiang W , Gao Q , Zhang L , Liu Y , Zhang M , Ke Z , Zhou Y , Hong Q
Ref : Applied Environmental Microbiology , : , 2021
Abstract : Strobilurin fungicides are widely used in agricultural production due to their broad-spectrum and fungal mitochondrial inhibitory activities. However, their massive application has detained the growth of eukaryotic algae and increased the collateral damage in freshwater systems, notably the harmful cyanobacterial blooms (HCBs). In this study, a strobilurin fungicide-degrading strain Hyphomicrobium sp. DY-1 was isolated and characterized successfully. Moreover, a novel esterase gene strH responsible for the de-esterification of strobilurin fungicides was cloned, and the enzymatic properties of StrH were studied. For trifloxystrobin, StrH displayed the maximum activity at 50 degreesC and pH 7.0. The catalytic efficiency (k (cat)/K (m)) of StrH for different strobilurin fungicides were 196.32+/-2.30 microM(-1).s(-1) (trifloxystrobin), 4.64+/-0.05 microM(-1).s(-1) (picoxystrobin), 2.94+/-0.02 microM(-1).s(-1) (pyraclostrobin), and (2.41+/-0.19)x10(-2) microM(-1).s(-1) (azoxystrobin). StrH catalyzed the de-esterification of a variety of strobilurin fungicides generating the corresponding parent acid to achieve the detoxification of strobilurin fungicides and relieve strobilurin fungicides growth inhibition on Chlorella This research will provide insight into the microbial remediation of strobilurin fungicides-contaminated environments.IMPORTANCEStrobilurin fungicides have been widely acknowledged as an essential group of pesticides worldwide. So far, their residues and toxic effects on aquatic organisms have been reported in different parts of the world. Microbial degradation could eliminate xenobiotics from the environment. Therefore, the degradation of strobilurin fungicides by microorganisms has also been reported. However, little is known about the involvement of enzyme or gene in strobilurin fungicides degradation. In this study, a novel esterase gene strH responsible for the detoxification of strobilurin fungicides was cloned in the newly isolated strain Hyphomicrobium sp. DY-1. This degradation process detoxifies the strobilurin fungicides and relieves their growth inhibition on Chlorella.
ESTHER : Jiang_2021_Appl.Environ.Microbiol__
PubMedSearch : Jiang_2021_Appl.Environ.Microbiol__
PubMedID: 33741617
Gene_locus related to this paper: hypsm-strH

Title : The UHPLC-QTOF-MS Phenolic Profiling and Activity of Cydonia oblonga Mill. Reveals a Promising Nutraceutical Potential - Zhang_2021_Foods_10_
Author(s) : Zhang L , Rocchetti G , Zengin G , Ak G , Saber FR , Montesano D , Lucini L
Ref : Foods , 10 : , 2021
Abstract : Cydonia oblonga Mill., normally known as the quince fruit, has been widely used in agro-food industries mainly to produce jams and jellies. However, other parts of the plants are still underutilized and not completely assessed for their nutraceutical profile. Therefore, in this work, the polyphenolic profile of C. oblonga was investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. Several compounds were identified in the different parts of the plants, including flavonoids (i.e., anthocyanins, flavones, flavan-3-ols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low-molecular-weight phenolics (tyrosol equivalents), lignans, and stilbenes. Overall, C. oblonga leaves showed the highest in vitro antioxidant potential, as revealed by 2,2-difenil-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays, being 189.5, 285.6, 158.9, and 348.8 mg Trolox Equivalent/g, respectively. The enzymes acetyl- and butyryl-cholinesterases were both inhibited by the different plant parts of C. oblonga, with stems showing the higher inhibitory potential. Interestingly, the fruit extracts were the only parts inhibiting the alpha-glucosidase, with a value of 1.36 mmol acarbose equivalents (ACAE)/g. On the other hand, strong tyrosinase inhibition was found for stems and leaves, being 72.11 and 68.32 mg Kojic acid Equivalent/g, respectively. Finally, a high number of significant (0.05 < p < 0.01) correlations were outlined between phenolics (mainly anthocyanins, flava-3-ols, and tyrosol equivalents) and the different biological assays. Taken together, our findings suggest a potential exploitation of C. oblonga leaves and stems for the food, pharmaceutical, and cosmetic industries.
ESTHER : Zhang_2021_Foods_10_
PubMedSearch : Zhang_2021_Foods_10_
PubMedID: 34071443

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 : Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets - Zhang_2021_Talanta_228_122268
Author(s) : Zhang L , Zhang Q , Liu Q , Wu X , Dong Y , Wang GL
Ref : Talanta , 228 :122268 , 2021
Abstract : Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity.
ESTHER : Zhang_2021_Talanta_228_122268
PubMedSearch : Zhang_2021_Talanta_228_122268
PubMedID: 33773716

Title : Metabolomic profiling and biological properties of six Limonium species: novel perspectives for nutraceutical purposes - Senizza_2021_Food.Funct_12_3443
Author(s) : Senizza B , Zhang L , Rocchetti G , Zengin G , Ak G , Yildiztugay E , Elbasan F , Jugreet S , Mahomoodally MF , Lucini L
Ref : Food Funct , 12 :3443 , 2021
Abstract : The genus Limonium includes important halophyte plants containing a variety of bioactive compounds of therapeutic interest. In the present work, the untargeted phytochemical profiles of both aerial part and root extracts from six Limonium species namely, L. bellidifolium, L. globuliferum, L. gmelinii, L. lilacinum, L. sinuatum and L. iconicum from Turkey were determined. Furthermore, several biological activities (in vitro antioxidant and enzyme inhibitory effects) were investigated. Overall, significant amounts of total phenolics (43.64-238.18 mg g-1) and flavonoids (1.61-129.69 mg g-1) were recorded. Particularly, the root extracts of L. gmelinii, L. iconicum and L. globuliferum showed the highest total phenolic content (204.13-238.18 mg g-1), whilst the highest total flavonoid content was recorded in the root extracts of L. gmelinii (129.69 mg g-1). Overall, the tested extracts demonstrated potent radical scavenging activities in both DPPH (2,2- diphenyl-1-picrylhydrazyl) and ABTS (3-ethylbenzothiazoline-6-sulphonic acid) (90.10-507.94 mg g-1 and 163.39-1175.34 mg g-1, respectively). However, the highest scavenging potential (p < 0.05) was displayed by the root extracts of L. iconicum. Conversely, the metal chelating ability assay revealed that L. lilacinum root extract showed the highest activity (21.03 mg g-1). Interestingly, all the extracts were found to be active inhibitors of cholinesterases (AChE (acetylcholinesterase): 4.20-5.11 mg GALAE (galantamine equivalent) per g; BChE (butyrylcholinesterase): 3.89-10.75 mg GALAE per g), amylase (0.52-1.09 mmol ACAE (acarbose equivalent) per g) and tyrosinase (119.41-155.67 mg KAE (kojic acid equivalent) per g), unlike for glucosidase (2.31-2.41 mmol ACAE per g). Taken together, these findings demonstrated a diverse chemical profiles and biological of the extracts, to be potentially considered as phytotherapeutic or functional ingredients due to their antioxidant properties and inhibition of key enzymes involved in several diseases.
ESTHER : Senizza_2021_Food.Funct_12_3443
PubMedSearch : Senizza_2021_Food.Funct_12_3443
PubMedID: 33900332

Title : Influence of seasonal migration on evolution of insecticide resistance in Plutella xylostella - Wang_2021_Insect.Sci__
Author(s) : Wang M , Zhu B , Zhang L , Xiao Y , Liang P , Wu K
Ref : Insect Sci , : , 2021
Abstract : The diamondback moth, Plutella xylostella (L.), is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control. The migration regularity, migratory behavior, and relationship between flight and reproduction of P. xylostella have been widely reported. However, the effect of migration on insecticide resistance in this pest is still unclear. In this study, the effect of migration on P. xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017-2019. The bioassay results showed that the early season populations of P. xylostella from South China possessed much higher resistance to insecticides because of intensive insecticide application; alternatively, the late season populations migrated from Northeast China, where the insecticides were only used occasionally, showed much lower insecticide resistance. The genome re-sequencing results revealed that, among the eight mutations involved in insecticide resistance, the frequencies of two acetylcholinesterase mutations (A298S and G324A) responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations. The results indicated that P. xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance. These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P. xylostella, and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Insect.Sci__
PubMedSearch : Wang_2021_Insect.Sci__
PubMedID: 34873833

Title : Overexpression of serum lncRNA-ABHD11-AS1 as poor prognosis of patients with papillary thyroid carcinoma - Hou_2021_Exp.Mol.Pathol_121_104658
Author(s) : Hou S , Zhuang YY , Lin QY , Chen Z , Zhao HG , Zhang L , Lin CH
Ref : Exp Mol Pathol , 121 :104658 , 2021
Abstract : This paper was aimed at exploring the correlation of long non-coding RNA (lncRNA)-ABHD11 Antisense RNA1 (ABHD11-AS1) with the poor prognosis of patients with papillary thyroid carcinoma (PTC) and at investigating its effects on the survival of PTC cells. Serum was respectively collected from 64 PTC patients who were admitted to our hospital (PTC group) and from 50 healthy controls who underwent physical examinations (HC group) both from April 2011 to April 2015. The expression levels of ABHD11-AS1 in the serum were detected, and the values of it for diagnosis and prognosis (5-year follow-ups) were analyzed. The knockdown and overexpression models of ABHD11-AS1 in were constructed to explore the effects of the models on their proliferation, cycles and apoptosis. According to the data, the expression levels of serum ABHD11-AS1 in the PTC patients were remarkably higher than those in the healthy controls, and the area under the curve (AUC) for distinguishing the patients from the controls was 0.920. In the analysis of prognosis, the levels in patients with a poor prognosis were remarkably higher than those in patients with a good prognosis. According to the curves of overall survival rates (OSRs), the high levels of ABHD11-AS1 were remarkably correlated with the poor prognosis (a lower 5-year OSR). COX analysis showed that TNM staging, lymph node metastasis and ABHD11-AS1 were the independent prognostic factors of PTC patients. In the cell experiments, knocking down ABHD11-AS1 remarkably inhibited PTC cells from proliferation, arrested them in G0/G1 phase, and induced their apoptosis, negatively affecting their survival indices. Overexpressing this RNA had positive effects on the survival indices. Taken together, high levels of serum ABHD11-AS1 are related to the poor prognosis of PTC patients, and knocking down its expression can inhibit the survival of PTC cells.
ESTHER : Hou_2021_Exp.Mol.Pathol_121_104658
PubMedSearch : Hou_2021_Exp.Mol.Pathol_121_104658
PubMedID: 34102210

Title : Untargeted Phytochemical Profile, Antioxidant Capacity and Enzyme Inhibitory Activity of Cultivated and Wild Lupin Seeds from Tunisia - Ben Hassine_2021_Molecules_26_
Author(s) : Ben Hassine A , Rocchetti G , Zhang L , Senizza B , Zengin G , Mahomoodally MF , Ben-Attia M , Rouphael Y , Lucini L , El-Bok S
Ref : Molecules , 26 : , 2021
Abstract : Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar (Lupinus albus) and two wild accessions (Lupinus cossentinii and Lupinus luteus), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus. The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii. The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus. The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics.
ESTHER : Ben Hassine_2021_Molecules_26_
PubMedSearch : Ben Hassine_2021_Molecules_26_
PubMedID: 34200152

Title : Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents - Zhao_2021_Inorg.Chem__
Author(s) : Zhao D , Liu J , Zhang L , Zhou Y , Zhong Y , Yang Y , Huang C , Wang Y
Ref : Inorg Chem , : , 2021
Abstract : Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), -potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.
ESTHER : Zhao_2021_Inorg.Chem__
PubMedSearch : Zhao_2021_Inorg.Chem__
PubMedID: 34969248

Title : Genome-wide analysis of the serine carboxypeptidase-like protein family in Triticum aestivum reveals TaSCPL184-6D is involved in abiotic stress response - Xu_2021_BMC.Genomics_22_350
Author(s) : Xu X , Zhang L , Zhao W , Fu L , Han Y , Wang K , Yan L , Li Y , Zhang XH , Min DH
Ref : BMC Genomics , 22 :350 , 2021
Abstract : BACKGROUND: The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. RESULTS: In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. CONCLUSIONS: We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat.
ESTHER : Xu_2021_BMC.Genomics_22_350
PubMedSearch : Xu_2021_BMC.Genomics_22_350
PubMedID: 33992092

Title : Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the alpha\/beta-fold epoxide hydrolase Alp1U - Zhang_2020_J.Biol.Chem_295_16987
Author(s) : Zhang L , De BC , Zhang W , Mandi A , Fang Z , Yang C , Zhu Y , Kurtan T , Zhang C
Ref : Journal of Biological Chemistry , 295 :16987 , 2020
Abstract : Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an alpha/beta-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (1), and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A W186/W187/Y247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in alpha/beta-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, while the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U, and provided a new approach for engineering regioselective epoxide hydrolases.
ESTHER : Zhang_2020_J.Biol.Chem_295_16987
PubMedSearch : Zhang_2020_J.Biol.Chem_295_16987
PubMedID: 33004437
Gene_locus related to this paper: stram-q1rqu8

Title : Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria - Zhan_2020_Bioorg.Chem_102_104136
Author(s) : Zhan G , Miao R , Zhang F , Chang G , Zhang L , Zhang X , Zhang H , Guo Z
Ref : Bioorg Chem , 102 :104136 , 2020
Abstract : Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C(22) yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 muM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC(50) value of 16.39 +/- 1.41 muM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.
ESTHER : Zhan_2020_Bioorg.Chem_102_104136
PubMedSearch : Zhan_2020_Bioorg.Chem_102_104136
PubMedID: 32738570

Title : Enhancing bio-catalytic activity and stability of lipase nanogel by functional ionic liquids modification - Zou_2020_Colloids.Surf.B.Biointerfaces_195_111275
Author(s) : Zou B , Yan Y , Xia J , Zhang L , Adesanya IO
Ref : Colloids Surf B Biointerfaces , 195 :111275 , 2020
Abstract : A novel integrated lipase nanogel based on functional ionic liquid modification and polymerization immobilization with improved stability was designed. Characterization before and after modification and polymerization was conducted using infrared spectroscopy, Circular dichroism spectroscopy, fluorescence spectroscopy, and scanning electron microscopy. It was shown that the modification of the ionic liquid influenced the catalytic behavior of lipase significantly due to the changed structure and surface properties of lipase. The enzymatic properties, including acid-base stability, thermal stability, organic solvents stability, and storage stability of CRL nanogel, were investigated in the p-nitrophenyl palmitate hydrolysis reaction (CRL, Lipase from Candida Rugosa). The results indicated that CRL nanogel has a better pH, heat, and organic solvent tolerance after immobilization. After seven weeks of storage, the natural CRL gradually lost its enzymatic activity, and only 17.5+/-1.7 % of the catalytic activity remained, the residual activity of CRL nanogel was 97.3+/-1.8 %. It was indicated that the novel CRL nanogel was an excellent biocatalyst.
ESTHER : Zou_2020_Colloids.Surf.B.Biointerfaces_195_111275
PubMedSearch : Zou_2020_Colloids.Surf.B.Biointerfaces_195_111275
PubMedID: 32739774

Title : Pharmacological effects of harmine and its derivatives: a review - Zhang_2020_Arch.Pharm.Res_43_1259
Author(s) : Zhang L , Li D , Yu S
Ref : Arch Pharm Res , 43 :1259 , 2020
Abstract : Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure-activity relationship of harmine derivatives has been summarized.
ESTHER : Zhang_2020_Arch.Pharm.Res_43_1259
PubMedSearch : Zhang_2020_Arch.Pharm.Res_43_1259
PubMedID: 33206346

Title : Tuning Butyrylcholinesterase Inactivation and Reactivation by Polymer-Based Protein Engineering - Zhang_2020_Adv.Sci.(Weinh)_7_1901904
Author(s) : Zhang L , Baker SL , Murata H , Harris N , Ji W , Amitai G , Matyjaszewski K , Russell AJ
Ref : Adv Sci (Weinh) , 7 :1901904 , 2020
Abstract : Organophosphate nerve agents rapidly inhibit cholinesterases thereby destroying the ability to sustain life. Strong nucleophiles, such as oximes, have been used as therapeutic reactivators of cholinesterase-organophosphate complexes, but suffer from short half-lives and limited efficacy across the broad spectrum of organophosphate nerve agents. Cholinesterases have been used as long-lived therapeutic bioscavengers for unreacted organophosphates with limited success because they react with organophosphate nerve agents with one-to-one stoichiometries. The chemical power of nucleophilic reactivators is coupled to long-lived bioscavengers by designing and synthesizing cholinesterase-polymer-oxime conjugates using atom transfer radical polymerization and azide-alkyne "click" chemistry. Detailed kinetic studies show that butyrylcholinesterase-polymer-oxime activity is dependent on the electrostatic properties of the polymers and the amount of oxime within the conjugate. The covalent coupling of oxime-containing polymers to the surface of butyrylcholinesterase slows the rate of inactivation of paraoxon, a model nerve agent. Furthermore, when the enzyme is covalently inhibited by paraoxon, the covalently attached oxime induced inter- and intramolecular reactivation. Intramolecular reactivation will open the door to the generation of a new class of nerve agent scavengers that couple the speed and selectivity of biology to the ruggedness and simplicity of synthetic chemicals.
ESTHER : Zhang_2020_Adv.Sci.(Weinh)_7_1901904
PubMedSearch : Zhang_2020_Adv.Sci.(Weinh)_7_1901904
PubMedID: 31921563

Title : Total flavonoids of Selaginella pulvinata alleviates cognitive impairment in mice - Zhang_2020_Biomed.Rep_13_8
Author(s) : Zhang L , Zhang Y , Hou Y , Li H , Li C , Xin J , Zhou N , Li Q , Song Y , Zhang Z
Ref : Biomed Rep , 13 :8 , 2020
Abstract : Cognitive impairment (CI) refers to dysfunctional cognition, which encompasses a spectrum of disorders, ranging from mild cognitive impairment to dementia. Any factor that results in cortical damage may cause CI. Total flavonoids of Selaginella pulvinata (TFSP), have shown promising antioxidant and protective effects in animal models. In the present study, mice were intraperitoneally treated with scopolamine, sodium nitrite or 45% ethanol to induce memory impairment, and the effects were assessed using a step-down test. After performing the behavioural test, hippocampal sections were collected for anatomical analysis, and the brain and serum levels of memory-related molecules were evaluated. The results showed that TFSP improved memory in a mouse model of CI significantly. Serum data were consistent with the behavioural results: TFSP increased blood acetylcholine levels through modulation of the acetylcholinesterase and choline acetyltransferase levels. It also ameliorated oxidative stress in neurons, increasing superoxide dismutase, glutathione peroxidase and inhibiting nitric oxide synthase levels in the brain. These results suggest that TFSP may exhibit potential as a clinical treatment for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and senile dementia.
ESTHER : Zhang_2020_Biomed.Rep_13_8
PubMedSearch : Zhang_2020_Biomed.Rep_13_8
PubMedID: 32607237

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 : In vitro gastrointestinal digestibility of phytosterol oleogels: influence of self-assembled microstructures on emulsification efficiency and lipase activity - Dong_2020_Food.Funct_11_9503
Author(s) : Dong L , Lv M , Gao X , Zhang L , Rogers M , Cao Y , Lan Y
Ref : Food Funct , 11 :9503 , 2020
Abstract : The objective of this study was to investigate the influence of self-assembled microstructure on lipid digestibility in phytosterol (gamma-oryzanol and beta-sitosterol) oleogels. Different molar ratios of gamma-oryzanol and beta-sitosterol yielded a variety of crystal morphologies; the resulting gels were tested for their lipid emulsification efficiency, release rate of free fatty acids (FFAs) during lipolysis, and their effect on lipase behavior. Results indicated that oleogels were harder to emulsify when compared to oil samples. The emulsification efficiencly was affected by both the gel strength and crystal morphology of the self-assembled structures within phytosterol oleogels. In oil emulsions, intestinal digestion resulted in more extensive lipid droplet coalescence with increased particle size when compared to oleogel emulsions. The FFA release rate suggested that the extent of lipid digestion was correlated to the emulsification efficiency. The interfacial binding of lipase indicated that the amount of lipase adsorption was positively correlated to the interface area created during the emulsification process. Finally, isothermal titration calorimetry results indicated that self-assembled structures within these oleogels physically obstructed the interaction between lipase and lipid. Ultimately, this led to lower reaction rate during gastrointestinal digestion. Collectively, these results may have important implications in designing oleogel systems with controlled lipid digestibility as well as controlling the bioavailability of delivered lipid-soluble bioactive compounds.
ESTHER : Dong_2020_Food.Funct_11_9503
PubMedSearch : Dong_2020_Food.Funct_11_9503
PubMedID: 32955534

Title : Metal-Organic Frameworks Conjugated Lipase with Enhanced Bio-catalytic Activity and Stability - Zou_2020_Appl.Biochem.Biotechnol__
Author(s) : Zou B , Zhang L , Xia J , Wang P , Yan Y , Wang X , Adesanya IO
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Covalent immobilization of lipase onto a solid carrier is an effective way to enhance stability. Immobilization inhibits the activity of lipase due to decreased flexibility of enzyme structure via the covalent bond. In this study, monomer of the metal-organic frameworks (MOFs) material ZIF-8 (2-methyl imidazole-4-carboxylic acid) was innovatively used as a chemical modifier of Candida nrugosa lipase (CRL). The circular dichroism spectra results show that the CRL molecule was altered by chemical modification and thus its catalytic activity was 1.3 times higher than that of the free CRL. The modified CRL molecule was further immobilized in the "skeleton" of ZIF-8 through the monomer while in situ forming the cell skeleton of the MOFs, which prevent the active center from being destroyed. The results show that conjugation of chemical modification and immobilized enzymes ensure that there was no obvious reduction in the activity of CRL after immobilization and the stability of CRL was improved. Especially, the organic solvent stability of the modified immobilization CRL in isopropanol was significantly improved and retained more than 148% of its activity.
ESTHER : Zou_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Zou_2020_Appl.Biochem.Biotechnol__
PubMedID: 32323142

Title : The Strength of the Nutrient Solution Modulates the Functional Profile of Hydroponically Grown Lettuce in a Genotype-Dependent Manner - Senizza_2020_Foods_9_
Author(s) : Senizza B , Zhang L , Miras-Moreno B , Righetti L , Zengin G , Ak G , Bruni R , Lucini L , Sifola MI , El-Nakhel C , Corrado G , Rouphael Y
Ref : Foods , 9 : , 2020
Abstract : Considering that functional components of plant foods are mainly secondary-metabolism products, we investigated the shaping of health-promoting compounds in hydroponically grown butterhead lettuce (Lactuca sativa L. var. capitata) as a function of the strength of the nutrient solution utilized. To this aim, untargeted metabolomics profiling, in vitro antioxidant capacity (total phenolics, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays), and the inhibition of selected enzyme activities were investigated in two butterhead lettuce cultivars with different pigmentation, i.e., green and red Salanova. Full-strength nutrition, together with half- and quarter-strength solutions of macronutrients, was tested. Our results indicate that by reducing the nutrients strength, we could elicit a distinctive shaping of the phenolic profile of lettuce. It is noteworthy that only specific classes of phenolics (namely, lignans and phenolic acids, followed by flavones and anthocyanins) were modulated by the induction of nutritional eustress (fold-change values in the range between -5 and +11). This indicates that specific responses, rather than a generalized induction of phenolic compounds, could be observed. Nonetheless, a genotype-dependent response could be observed, with the red cultivar being much more responsive to nutritional deprivation than the green Salanova lettuce. Indeed, analysis of variance (ANOVA) confirmed a genotype x nutrition interaction in red Salanova (p < 0.001). As a consequence of the changes in phenolic composition, also the antioxidant capacity (p < 0.001) and amylase inhibition (p < 0.001) properties were affected by the growing conditions. However, the effect on cholinesterase and tyrosinase inhibition was poorly affected by the nutritional strength. Provided that yields are not compromised, the application of a controlled nutritional eustress in hydroponically cultivated lettuce may represent a valuable strategy to produce food with tailored functional features in a sustainable manner.
ESTHER : Senizza_2020_Foods_9_
PubMedSearch : Senizza_2020_Foods_9_
PubMedID: 32825768

Title : A ratiometric fluorescence probe based on graphene quantum dots and o-phenylenediamine for highly sensitive detection of acetylcholinesterase activity - Ye_2020_Mikrochim.Acta_187_511
Author(s) : Ye M , Lin B , Yu Y , Li H , Wang Y , Zhang L , Cao Y , Guo M
Ref : Mikrochim Acta , 187 :511 , 2020
Abstract : By using graphene quantum dots (GQDs) and o-phenylenediamine (OPD), a ratiometric fluorescence probe was designed for the highly sensitive and selective detection of AChE. GQDs with strong fluorescence were synthesized by the one-step hydrothermal method. The optimal emission wavelength of GQDs was 450 nm at the excitation wavelength of 375 nm. MnO(2) nanosheets with a wide absorption band of 300-600 nm were prepared at room temperature. Because of the extensive overlap between the absorption spectrum of MnO(2) nanosheets and the excitation and emission spectra of GQDs, the fluorescence of GQDs at 450 nm was efficiently quenched by the inner-filter effect. Meanwhile, due to the peroxidase-like activity of MnO(2) nanosheets, OPD was catalytically oxidized to 2,3-diaminophenazine (oxOPD), a yellow fluorescent substance with a new emission peak at 572 nm. When AChE was present, the substrate acetylthiocholine (ATCh) was hydrolyzed to thiocholine (TCh) that is capable of decomposing MnO(2) nanosheets. Therefore, the quench of GQDs and the oxidation of OPD by MnO(2) nanosheets were suppressed, resulting in the fluorescence recovery of GQDs at 450 nm, while the fluorescence decrease of oxOPD at 572 nm. Utilizing the fluorescence intensity ratio F(450)/F(572) as the signal readout, the ratiometric fluorescence method was established to detect AChE activity. The ratio F(450)/F(572) against the AChE concentration demonstrated two linear relationships in the range 0.1-2.0 and 2.0-4.5 mU mL(-1) with a detection limit of 0.09 mU mL(-1). The method was applied to the detection of positive human serum samples and the analysis of the inhibitor neostigmine. Due to the advantages of high sensitivity, favorable selectivity, and strong anti-interference, the method possesses an application prospect in clinical diagnosis of AChE and the screening of inhibitors. Graphical abstract Schematic presentation of a ratiometric fluorescence method for the detection of acetylcholinesterase (AChE). The fluorescence of graphene quantum dots (GQDs) is quenched and o-phenylenediamine (OPD) is oxidized to generate fluorescent product 2,3-diaminophenazine (oxOPD) by MnO(2) nanosheets. When AChE is present, acetylthiocholine iodide (ATCh) is hydrolyzed to thiocholine (TCh) with reducibility for decomposing MnO(2) nanosheets. Due to the decomposition of MnO(2) nanosheets, the quenching of GQDs and oxidation of OPD are suppressed. The fluorescence of GQDs at 450 nm is enhanced, while the fluorescence of oxOPD at 572 nm is reduced. The fluorescence intensity ratio F(450)/F(572) is used to establish the ratiometric fluorescence method for AChE activity.
ESTHER : Ye_2020_Mikrochim.Acta_187_511
PubMedSearch : Ye_2020_Mikrochim.Acta_187_511
PubMedID: 32833082

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

Title : Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea - Wang_2020_Environ.Pollut_267_115397
Author(s) : Wang X , Hu M , Gu H , Zhang L , Shang Y , Wang T , Zeng J , Ma L , Huang W , Wang Y
Ref : Environ Pollut , 267 :115397 , 2020
Abstract : In recent years, antibiotics have been widely detected in coastal waters of China, which raising concerns for coastal biodiversity and aquaculture. This study evaluated the effects of short-term exposure of norfloxacin (NOR) on oxidative stress and intestinal health of the large yellow croaker Pseudosciaena crocea. Juvenile fish were exposed to four concentrations of NOR (0.1, 10, 100 and 1000 g/L) for 14 days. The results showed that NOR inhibited growth and threatened the survival of juveniles. According to the changes of intestinal microbiota, we found that NOR led to a significant decrease in intestinal microbiota diversity, with the decreased relative abundance of Proteobacteria, but the increased Tenericutes. From the perspective of microbial function, NOR inhibited metabolism, cellular defence mechanism and information transduction process. In terms of biochemical indicators, NOR caused an increase in malondialdehyde (MDA) level and inhibited superoxide dismutase (SOD) and acetyl cholinesterase (AChE) activities. Catalase (CAT) activity was activated at low concentration but significantly inhibited at high concentration of NOR. Moreover, there was a high correlation between change in biochemical indicators and change in the microbial community. Overall, environmentally relevant concentrations (0.1 g/L) and high concentrations (10, 100 and 1000 g/L) of NOR have negative effects on the defence function and intestinal health of large yellow croaker juveniles.
ESTHER : Wang_2020_Environ.Pollut_267_115397
PubMedSearch : Wang_2020_Environ.Pollut_267_115397
PubMedID: 33254654

Title : Molluscicidal activity of fatty acids in the kernel of Chimonanthus praecox cv. Luteus against the golden apple snail Pomacea canaliculata - Zhang_2020_Pestic.Biochem.Physiol_167_104620
Author(s) : Zhang L , Zou Z
Ref : Pestic Biochem Physiol , 167 :104620 , 2020
Abstract : The fatty acid composition of the kernel of Chimonanthus praecox cv. Luteus (FKC) was analyzed by gas chromatography-mass spectrometry (GC-MS), its ability to kill Pomacea canaliculata was detected, and the degree of damage and physiological and biochemical effects of an FKC soaking treatment on the hepatopancreas tissue of P. canaliculata were evaluated. In total, 16 fatty acids were detected in FKC, among which 13 were qualitatively identified; octadecadienoic acid (56.76%) and palmitic acid (17.03%) had the highest contents. After 48 h of treatment with FKC, the hepatopancreas of P. canaliculata had a large area of necrosis. The contents of soluble sugar, soluble protein, and albumin (Alb) in the hepatopancreas of P. canaliculata decreased with increasing FKC concentration. The content of malondialdehyde (MDA) and the activities of cereal third transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AKP), and acetylcholinesterase (AChE) increased with increasing FKC concentration. The results showed that FKC has an obvious negative effect on the hepatopancreas cell structure and physiological function of P. canaliculata, i.e., has strong molluscicidal activity.
ESTHER : Zhang_2020_Pestic.Biochem.Physiol_167_104620
PubMedSearch : Zhang_2020_Pestic.Biochem.Physiol_167_104620
PubMedID: 32527423

Title : Amino acid, fatty acid, and carbohydrate metabolomic profiles with ginsenoside-induced insecticidal efficacy against Ostrinia furnacalis (Guenee) - Liu_2020_J.Ginseng.Res_44_544
Author(s) : Liu S , Wang X , Zhang R , Song M , Zhang N , Li W , Wang Y , Xu Y , Zhang L
Ref : J Ginseng Res , 44 :544 , 2020
Abstract : Background: Previous studies have shown the insecticidal efficacy of ginsenosides. In the present study, we aimed to investigate the metabolic mechanism related to the inhibitory effect of panaxadiol saponins (PDSs) against the Asian corn borer Ostrinia furnacalis (Guenee). Methods: Third instar larvae of O. furnacalis were fed normal diets with different concentrations of PDSs for 4 days. The consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food were recorded. A targeted gas chromatography-mass spectrometry assay was performed to detect the profiles of amino acids, fatty acids, and carbohydrates in larvae of O. furnacalis. In addition, the activity of detoxification-related enzymes was determined. Results and Conclusions: PDSs decreased the consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food in the 3rd instar larvae of O. furnacalis in a dose-dependent manner. PDSs decreased 15 free amino acids, 16 free fatty acids, and 5 carbohydrates and increased the levels of palmitoleic acid, palmitic acid, and 9-octadecenoic acid in the 3rd instar larvae. The activity of detoxification-related enzymes, such as acetylcholinesterase, glutathione S-transferase, cytochrome P450, carboxylesterase, trehalase, acid phosphatase, and alkaline phosphatase, was reduced in a dose-dependent manner in the 3rd instar larvae exposed to PDSs. These data confirmed the inhibitory effect of PDSs against growth, food utilization, and detoxification in the 3rd instar larvae of O. furnacalis and the potential for using PDSs as an efficient tool for insect pest management for O. furnacalis larvae.
ESTHER : Liu_2020_J.Ginseng.Res_44_544
PubMedSearch : Liu_2020_J.Ginseng.Res_44_544
PubMedID: 32617034

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

Title : Molecular Basis for the Biosynthesis of an Unusual Chain-Fused Polyketide Gregatin A - Wang_2020_J.Am.Chem.Soc_142_8464
Author(s) : Wang WG , Wang H , Du LQ , Li M , Chen L , Yu J , Cheng GG , Zhan MT , Hu QF , Zhang L , Yao M , Matsuda Y
Ref : Journal of the American Chemical Society , 142 :8464 , 2020
Abstract : Gregatin A (1) is a fungal polyketide featuring an alkylated furanone core, but the biosynthetic mechanism to furnish the intri-guing molecular skeleton has yet to be elucidated. Herein, we have identified the biosynthetic gene cluster of gregatin A (1) in Penicillium sp. sh18, and investigated the mechanism that produces the intriguing structure of 1 by in vivo and in vitro recon-stitution of its biosynthesis. Our study established the biosynthetic route leading to 1, and illuminated that 1 is generated by the fusion of two different polyketide chains, which are, amazingly, synthesized by a single PKS GrgA with the aid of a trans-acting enoylreductase GrgB. Chain fusion, as well as chain hydrolysis, is catalyzed by an alpha/beta hydrolase GrgF, hybridizing the C11 and C4 carbon chains by Claisen condensation. Finally, structural analysis and mutational experiments using GrgF provided insight into how the enzyme facilitates the unusual chain-fusing reaction. In unraveling a new biosynthetic strategy involving a bifunc-tional PKS and a polyketide fusing enzyme, our study expands our knowledge concerning fungal polyketide biosynthesis.
ESTHER : Wang_2020_J.Am.Chem.Soc_142_8464
PubMedSearch : Wang_2020_J.Am.Chem.Soc_142_8464
PubMedID: 32275405
Gene_locus related to this paper: pensq-GrgF

Title : Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice - Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
Author(s) : Wu R , Zhong S , Ni M , Zhu X , Chen Y , Chen X , Zhang L , Chen J
Ref : Evid Based Complement Alternat Med , 2020 :8617143 , 2020
Abstract : BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products.
ESTHER : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedSearch : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedID: 33014116

Title : Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes - Mckernan_2020_Biorxiv__
Author(s) : McKernan KJ , Helbert Y , Kane LT , Ebling H , Zhang L , Liu B , Eaton Z , McLaughlin S , Kingan S , Baybayan P , Concepcion G , Jordan M , Riva A , Barbazuk W , Harkins T
Ref : Biorxiv , : , 2020
Abstract : Cannabis is a diverse and polymorphic species. To better understand cannabinoid synthesis inheritance and its impact on pathogen resistance, we shotgun sequenced and assembled a Cannabis trio (sibling pair and their offspring) utilizing long read single molecule sequencing. This resulted in the most contiguous Cannabis sativa assemblies to date. These reference assemblies were further annotated with full-length male and female mRNA sequencing (Iso-Seq) to help inform isoform complexity, gene model predictions and identification of the Y chromosome. To further annotate the genetic diversity in the species, 40 male, female, and monoecious cannabis and hemp varietals were evaluated for copy number variation (CNV) and RNA expression. This identified multiple CNVs governing cannabinoid expression and 82 genes associated with resistance to Golovinomyces chicoracearum, the causal agent of powdery mildew in cannabis. Results indicated that breeding for plants with low tetrahydrocannabinolic acid (THCA) concentrations may result in deletion of pathogen resistance genes. Low THCA cultivars also have a polymorphism every 51 bases while dispensary grade high THCA cannabis exhibited a variant every 73 bases. A refined genetic map of the variation in cannabis can guide more stable and directed breeding efforts for desired chemotypes and pathogen-resistant cultivars.
ESTHER : Mckernan_2020_Biorxiv__
PubMedSearch : Mckernan_2020_Biorxiv__
PubMedID:
Gene_locus related to this paper: cansa-a0a7j6fzj4

Title : Catalytic Detoxification of Organophosphorus Nerve Agents by Butyrylcholinesterase-Polymer-Oxime Bioscavengers - Zhang_2020_Biomacromolecules_21_3867
Author(s) : Zhang L , Murata H , Amitai G , Smith PN , Matyjaszewski K , Russell AJ
Ref : Biomacromolecules , 21 :3867 , 2020
Abstract : Organophosphorus nerve agents (OPNAs), used in chemical warfare, irreversibly inhibit essential cholinesterases (ChEs) in the cholinergic neurotransmission system. Several potent nucleophilic oximes have been approved for the treatment of acute poisoning by OPNAs, but they are rapidly cleared from blood circulation. Butyrylcholinesterase (BChE) stoichiometrically binds nerve agents, but because the molecular weight of a nerve agent is about 500-fold less than the enzyme, the bioscavenger has had limited utility. We synthesized BChE-polymer-oxime conjugates using atom transfer radical polymerization (ATRP) and azide-alkyne "click" chemistry. The activity of the BChE-polymer-oxime conjugates was dependent on the degree of oxime loading within the copolymer side chains. The covalent modification of oxime-containing copolymers prolonged the activity of BChE in the presence of the VX- and cyclosarin-fluorogenic analogues EMP-MeCyC and CMP-MeCyC, respectively. After complete inactivation by VX and cyclosarin fluorogenic analogues, the conjugates demonstrated efficient self-reactivation of up to 80% within 3-6 h. Repeated inhibition and high-level self-reactivation assays revealed that the BChE-polymer-oxime conjugates were excellent reactivators of OPNA-inhibited BChE. Recurring self-reactivation of BChE-polymer-oxime conjugates following repeated BChE inhibition by fluorogenic OPNAs (Flu-OPNAs) opens the door to developing the next generation of nerve agent "catalytic" bioscavengers.
ESTHER : Zhang_2020_Biomacromolecules_21_3867
PubMedSearch : Zhang_2020_Biomacromolecules_21_3867
PubMedID: 32786529

Title : Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1 - Yu_2020_Ecotoxicol.Environ.Saf_194_110378
Author(s) : Yu H , Wang L , Lin Y , Liu W , Tuyiringire D , Jiao Y , Zhang L , Meng Q , Zhang Y
Ref : Ecotoxicology & Environmental Safety , 194 :110378 , 2020
Abstract : The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics.
ESTHER : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedSearch : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedID: 32146194

Title : Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro -
Author(s) : Wang M , Cao R , Zhang L , Yang X , Liu J , Xu M , Shi Z , Hu Z , Zhong W , Xiao G
Ref : Cell Res , 30 :269 , 2020
PubMedID: 32020029

Title : Embryonic development and oxidative stress effects in the larvae and adult fish livers of zebrafish (Danio rerio) exposed to the strobilurin fungicides, kresoxim-methyl and pyraclostrobin - Mao_2020_Sci.Total.Environ_729_139031
Author(s) : Mao L , Jia W , Zhang L , Zhang Y , Zhu L , Sial MU , Jiang H
Ref : Sci Total Environ , 729 :139031 , 2020
Abstract : Two important strobilurin fungicides, kresoxim-methyl and pyraclostrobin, are widely used globally. Their effects on embryonic development and oxidative stress effects in the larvae and adult fish livers of zebrafish (Danio rerio) were assessed in our study. The hatching, mortality, and teratogenic rates were determined when the eggs of fish were exposed to kresoxim-methyl and pyraclostrobin for 24-144 h postfertilization (hpf). For further study, the effects of kresoxim-methyl and pyraclostrobin on antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)], detoxification enzymes [carboxylesterase (CarE) and glutathione S-transferase (GST)] and the malondialdehyde (MDA) content of larval zebrafish (96 h) and male or female adult zebrafish livers (up to 28 d) were evaluated for potential toxicity mechanisms. The study of embryonic development revealed that both kresoxim-methyl and pyraclostrobin caused developmental toxicity (hatching inhibition, mortality, and teratogenic rates) increase with significant concentration- and time-dependent responses, and the 144-h median lethal values (LC50) of kresoxim-methyl and pyraclostrobin were 195.0 and 81.3 mug L(-1), respectively. In the larval zebrafish study, both kresoxim-methyl and pyraclostrobin at the highest concentrations (100 mug L(-1) and 15 mug L(-1), respectively) significantly increased the CAT, POD and CarE activities and MDA content compared with those of the control group (P < 0.05). We further found that oxidative stress effects in adult zebrafish livers caused by long-term kresoxim-methyl and pyraclostrobin exposure differed with time and sex. Regarding the residues in natural waters, the potential adverse effects of kresoxim-methyl and pyraclostrobin would be relatively low for adult zebrafish but must not be overlooked for zebrafish embryos/larvae (hatching impairment). Our results from the detoxification enzyme study also initially indicated that adult zebrafish had a greater detoxification ability than larvae and that males had a greater detoxification ability than females.
ESTHER : Mao_2020_Sci.Total.Environ_729_139031
PubMedSearch : Mao_2020_Sci.Total.Environ_729_139031
PubMedID: 32387777

Title : Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor gamma pathway - Sun_2020_Sci.Total.Environ_711_134810
Author(s) : Sun W , Duan X , Chen H , Zhang L , Sun H
Ref : Sci Total Environ , 711 :134810 , 2020
Abstract : Recent studies have shown that exposure to some organophosphates, such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), can affect adipogenesis in preadipocytes. 2-Ethylhexyl diphenyl phosphate (EHDPP), an organophosphate, is frequently detected in various environmental media. However, there is less information about the toxicity effects and the mechanism by which EHDPP affects preadipocytes. In the present study, we investigated whether EHDPP could induce differentiation in 3T3-L1 preadipocytes through the peroxisome proliferator-activated receptor gamma (PPARgamma) signaling pathway. The fluorescence competitive binding assay and the dual-luciferase reporter gene assay were used to assess the binding affinity and activation of PPARgamma, and the results showed that EHDPP can bind to the ligand binding domain of PPARgamma (PPARgamma-LBD) and activate PPARgamma in vitro. Exposure to EHDPP for 10 days extensively induced adipogenesis in 3T3-L1 preadipocytes as assessed by lipid accumulation and gene expression of adipogenic markers of fatty acid binding protein 4 (FABP4), lipoprotein lipase (Lpl), adiponectin (Adip), and fatty acid synthase (Fasn). Furthermore, the preadipocytes differentiation was blocked by the PPARgamma-specific antagonist GW9662, indicating that the PPARgamma signaling pathway plays an important part in 3T3-L1 cell differentiation induced by EHDPP. Taken together, EHDPP can bind to PPARgamma-LBD, activate PPARgamma receptor, and induce cell differentiation via the PPARgamma signaling pathway in 3T3-L1 preadipocytes.
ESTHER : Sun_2020_Sci.Total.Environ_711_134810
PubMedSearch : Sun_2020_Sci.Total.Environ_711_134810
PubMedID: 31812418

Title : The influence of in vitro gastrointestinal digestion on the Perilla frutescens leaf extract: Changes in the active compounds and bioactivities - Wang_2020_J.Food.Biochem__e13530
Author(s) : Wang ZX , Lin QQ , Tu ZC , Zhang L
Ref : J Food Biochem , :e13530 , 2020
Abstract : In this study, the influence of in vitro gastrointestinal digestion on the Perilla frutescens leaf extract (PFLE) were measured. Results revealed that total phenolic content (TPC) and total flavonoid content (TFC) were significantly decreased after simulated digestion (ca. 53% of phenolics and 40% of flavonoids). The IC(50) value of DPPH. scavenging activity and ABTS(+) scavenging ability increased by 23% and 56%, respectively, while ferric reducing antioxidant power reduced by 53%. For the inhibition ability on alpha-glucosidase, acetylcholinesterase, and MCF-7 cell proliferation, their IC(50) values increased by 360%, 197%, and 25%, respectively. Three phenolic acids and one flavonoid in PFLE were quantified by high-performance liquid chromatography. Overall, although significant losses of the active components and biological activities occurred during in vitro gastrointestinal digestion, it still showed the potential as an oral agent for treatment and prevention of oxidative stress, cancer, diabetes, and Alzheimer's disease. PRACTICAL APPLICATIONS: As an important annual herbaceous plant with rich biochemical compounds and many biological functions, Perilla frutescens leave is widely used in the food and traditional Chinese medicine. However, the dynamic changes of its active compounds and activities during the digestion process are unclear. In this study, the digestion results in significant loss of the active ingredients and biological activities of P. frutescens leaf extract (PFLE), particularly in the gastric digestion. In addition, PFLE remains to show certain antioxidant activity, alpha-glucosidase inhibitory ability, acetylcholinesterase inhibitory ability, and MCF-7 cell proliferation inhibitory ability after digestion. Therefore, this research might facilitate further research and development of P. frutescens.
ESTHER : Wang_2020_J.Food.Biochem__e13530
PubMedSearch : Wang_2020_J.Food.Biochem__e13530
PubMedID: 33084119

Title : Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line - Sun_2020_Proteomics.Clin.Appl_14_e1900080
Author(s) : Sun R , Dong C , Li R , Chu H , Liu J , Hao D , Zhang L , Zhao B , Wang L , Zhang Y
Ref : Proteomics Clin Appl , 14 :e1900080 , 2020
Abstract : PURPOSE: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with HCC. EXPERIMENTAL DESIGN: In this study, proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent are performed. Then the expression level and function of differentially expressed plasma membrane proteins are verified. RESULTS: In total, 25 plasma membrane proteins are shown differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 are upregulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 is closely related to the chemoresistance of Bel/5Fu to 5-Fu. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with HCC.
ESTHER : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedSearch : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedID: 32067389
Gene_locus related to this paper: human-EPHX1

Title : Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Tian_2019_Bioorg.Chem__103477
Author(s) : Tian C , Qiang X , Song Q , Cao Z , Ye C , He Y , Deng Y , Zhang L
Ref : Bioorg Chem , :103477 , 2019
Abstract : The complex pathogenesis of Alzheimer's disease (AD) calls for multitarget approach for disease management. Herein, a series of novel flurbiprofen-chalcone hybrid Mannich base derivatives were designed and synthesized. The biological screening results indicated that most of the derivatives exhibited potent multi-target effects involved in AD. In particular, compound 6c bearing a pyrrolidine group showed the highest activities against self- and Cu(2+)-induced Abeta1-42 aggregation (70.65% and 54.89% at 25.0 microM, respectively), highly selective inhibition towards AChE and MAO-B (IC50 = 7.15 muM and 0.43 muM respectively), good antioxidant ability and metal-chelating property. Moreover, 6c displayed excellent anti-neuroinflammatory activity and appropriate BBB permeability in vitro. These outstanding results qualified compound 6c as a promising multifunctional agent for further development of disease-modifying treatment of AD.
ESTHER : Tian_2019_Bioorg.Chem__103477
PubMedSearch : Tian_2019_Bioorg.Chem__103477
PubMedID: 31818478

Title : Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis - Shang_2019_Cancer.Res_79_5513
Author(s) : Shang S , Ji X , Zhang L , Chen J , Li C , Shi R , Xiang W , Kang X , Zhang D , Yang F , Dai R , Chen P , Chen S , Chen Y , Li Y , Miao H
Ref : Cancer Research , 79 :5513 , 2019
Abstract : Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.
ESTHER : Shang_2019_Cancer.Res_79_5513
PubMedSearch : Shang_2019_Cancer.Res_79_5513
PubMedID: 31439546
Gene_locus related to this paper: human-ABHD5

Title : Chemical composition and biological activities of an essential oil from the aerial parts of Artemisia Gmelinii weber ex Stechm - Xu_2019_Nat.Prod.Res__1
Author(s) : Xu Q , Zhang L , Yu S , Xia G , Zhu J , Zang H
Ref : Nat Prod Res , :1 , 2019
Abstract : The aerial parts of Artemisia gmelinii Weber ex Stechm were collected from the northeast of China. The essential oil was obtained by hydrodistillation and analysed by GC-MS. A set of 66 compounds were identified representing 99.1% of the oil composition. The major compounds in the oil were cyclobutaneethanol, endo-borneol, germacrene D, eucalyptol, selin-6-en-4alpha-ol, bisabolone oxide A, caryophyllene and terpinen-4-ol. Moreover, the essential oil was evaluated for its antioxidant, antidiabetic, and anticholinesterase activities in vitro. Additionally, the antioxidant potential of the oil was evaluated using DPPH and ABTS assays. The oil showed good antidiabetic activity with an IC50 of 63.2 microg/mL, which was similar to that of the positive control acarbose, and weak anticholinesterase activities. These findings demonstrated that the essential oil of Artemisia gmelinii may be a good natural antidiabetic.
ESTHER : Xu_2019_Nat.Prod.Res__1
PubMedSearch : Xu_2019_Nat.Prod.Res__1
PubMedID: 31177847

Title : Identification and Development of an Irreversible Monoacylglycerol Lipase (MAGL) Positron Emission Tomography (PET) Radioligand with High Specificity - Zhang_2019_J.Med.Chem_62_8532
Author(s) : Zhang L , Butler CR , Maresca KP , Takano A , Nag S , Jia Z , Arakawa R , Piro JR , Samad T , Smith DL , Nason DM , O'Neil S , McAllister L , Schildknegt K , Trapa P , McCarthy TJ , Villalobos A , Halldin C
Ref : Journal of Medicinal Chemistry , 62 :8532 , 2019
Abstract : Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging. Herein, we report the identification of the potent and selective irreversible MAGL inhibitor 7 (PF-06809247) as a suitable radioligand lead, which upon radiolabeling was found to exhibit a high level of MAGL specificity; this enabled cross-species measurement of MAGL brain expression (Bmax), assessment of in vivo binding in the rat, and nonhuman primate PET imaging.
ESTHER : Zhang_2019_J.Med.Chem_62_8532
PubMedSearch : Zhang_2019_J.Med.Chem_62_8532
PubMedID: 31483137

Title : Bio-\/Nanoimmobilization Platform Based on Bioinspired Fibrin-Bone@Polydopamine-Shell Adhesive Composites for Biosensing - Zhang_2019_ACS.Appl.Mater.Interfaces_11_47311
Author(s) : Zhang L , Liu Z , Zha S , Liu G , Zhu W , Xie Q , Li Y , Ying Y , Fu Y
Ref : ACS Appl Mater Interfaces , 11 :47311 , 2019
Abstract : Inspired by blood coagulation and mussel adhesion, we report novel adhesive fibrin-bone@polydopamine (PDA)-shell composite matrix as highly efficient immobilization platform for biomacromolecules and nanomaterials. Fibrin, as a bioglue, and PDA, as a chemical adhesive, are integrated in a one-pot simultaneous polymerization consisting of biopolymerization of fibrinogen and chemical polymerization of dopamine. Fibrin fibers act as adhesive bones to construct scaffold, while PDA coat on the scaffold to form adhesive shell, generating 3D porous composite matrix with unique bone@shell structure. Two types of enzymes (glucose oxidase and acetylcholinesterase) and Au nanoparticles were adopted as respective model biomolecules and nanomaterials to investigate the immobilization capability of the matrix. The bionanocomposites showed high efficiency in capturing nanoparticles and enzymes, as well as significant mass-transfer and biocatalysis efficiencies. Therefore, the bionanocomposites exhibited significant potential in biosensing of glucose and paraoxon with limits of detection down to 5.2 muM and 4 ppt, respectively. The biological-chemical-combined polymerization strategy and composite platform with high immobilization capacity and mass-transfer efficiency open up a novel way for the preparation of high-performance bionanocomposites for various applications, in particular, biosensing.
ESTHER : Zhang_2019_ACS.Appl.Mater.Interfaces_11_47311
PubMedSearch : Zhang_2019_ACS.Appl.Mater.Interfaces_11_47311
PubMedID: 31742992

Title : Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein - Zhou_2019_Nat.Commun_10_3068
Author(s) : Zhou H , Chen Y , Zhang S , Niu P , Qin K , Jia W , Huang B , Lan J , Zhang L , Tan W , Wang X
Ref : Nat Commun , 10 :3068 , 2019
Abstract : Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.
ESTHER : Zhou_2019_Nat.Commun_10_3068
PubMedSearch : Zhou_2019_Nat.Commun_10_3068
PubMedID: 31296843

Title : Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium - Zhang_2019_Chemosphere_226_817
Author(s) : Zhang L , Chen L , Meng Z , Zhang W , Xu X , Wang Z , Qin Y , Deng Y , Liu R , Zhou Z , Diao J
Ref : Chemosphere , 226 :817 , 2019
Abstract : Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance.
ESTHER : Zhang_2019_Chemosphere_226_817
PubMedSearch : Zhang_2019_Chemosphere_226_817
PubMedID: 30965253

Title : Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2 - Yu_2019_Int.J.Mol.Sci_20_
Author(s) : Yu M , Zhang L , Liu Y , Liu D , Guo Z
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets alpha/beta-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.
ESTHER : Yu_2019_Int.J.Mol.Sci_20_
PubMedSearch : Yu_2019_Int.J.Mol.Sci_20_
PubMedID: 31035455
Gene_locus related to this paper: human-ABHD2

Title : The adverse effect of TCIPP and TCEP on neurodevelopment of zebrafish embryos\/larvae - Li_2019_Chemosphere_220_811
Author(s) : Li R , Wang H , Mi C , Feng C , Zhang L , Yang L , Zhou B
Ref : Chemosphere , 220 :811 , 2019
Abstract : Tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl)phosphate (TCEP) are two widely used chlorinated organophosphate flame retardants (ClOPFRs), and have been frequently detected in various environmental media. Concern is now growing whether TCIPP and TCEP can cause neurotoxicity since they have similar chemical structure with organophosphorus pesticide. Therefore, in this study, zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TCIPP or TCEP (0, 100, 500 or 2500mug/L) or a model neurotoxicant, chlorpyrifos (CPF, 100mug/L) to investigate the adverse effects and possible mechanisms of TCIPP and TCEP on neurodevelopment. Our results showed that CPF exposure resulted in developmental toxicity including decreased hatching, survival rates and increased malformation rates (e.g., spinal curvature) as well as behavior changes such as decreased locomotive activity in dark stimulation. In contrast, TCIPP and TCEP showed no significant effects on developmental parameters, but caused similar effects on locomotive activity at high concentration, indicating that although not as potent as CPF, TCIPP and TCEP may still cause adverse effects on neurodevelopment. Furthermore, our results suggest that TCIPP and TCEP showed no effects on acetylcholine content or AChE activity, which were considered as the main targets of CPF. However, TCIPP and TCEP exposure can significantly down-regulate the expression of selected genes and proteins related to neurodevelopment (e.g., mbp, syn2a, and alpha1-tubulin) similar as CPF did. Besides that, TCIPP and TCEP can also affect the transcription of shha and gap43, which were not affected by CPF, pointing out a complex mechanism underlying TCIPP and TCEP's neurodevelopmental toxicity. Overall, our results demonstrated that TCEP and TCIPP may have adverse effect on the neurodevelopment of zebrafish embryos/larvae, but the underlying mechanism is not via the inhibition of acetyl cholinesterase activity.
ESTHER : Li_2019_Chemosphere_220_811
PubMedSearch : Li_2019_Chemosphere_220_811
PubMedID: 30612050

Title : Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments - Zhou_2019_Bioorg.Chem_93_103322
Author(s) : Zhou Y , Sun W , Peng J , Yan H , Zhang L , Liu X , Zuo Z
Ref : Bioorg Chem , 93 :103322 , 2019
Abstract : Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
ESTHER : Zhou_2019_Bioorg.Chem_93_103322
PubMedSearch : Zhou_2019_Bioorg.Chem_93_103322
PubMedID: 31585263

Title : Tempol Attenuates Neuropathic Pain by Inhibiting Nitric Oxide Production - Jia_2019_Anal.Cell.Pathol.(Amst)_2019_8253850
Author(s) : Jia D , Wang H , Han B , Zhang L , Guo J
Ref : Anal Cell Pathol (Amst) , 2019 :8253850 , 2019
Abstract : Background: Neuropathic pain not only affects individual life quality but also increases economic burden for the society. Treatment to alleviate neuropathic pain is required. Methodology: Fifty rats were randomly assigned into sham, spinal nerve ligation, and three treatment groups with different doses of Tempol (100, 200, and 300 mg/kg, respectively), with 10 rats in each group. A neuropathic pain model was created with spinal nerve L5 and L6 ligation. Mechanical allodynia and thermal hyperalgesia were tested preoperatively (day 0) and postoperatively (days 1, 3, 5, and 7). Spinal cord levels of nitric oxide, as well as activities of nitric oxide synthase and acetylcholinesterase, were tested in postoperative day 7. Results: Compared with rats in the spinal nerve ligation group, rats in Tempol treatment groups had decreased responses to mechanical pain and cold plate stimulations. A high dose of Tempol produced more attenuating effects. The level of nitric oxide and activity of nitric oxide synthase were also decreased with Tempol treatments, whereas no significant changes were observed in the activity of acetylcholinesterase. Conclusions: Tempol attenuated an experimental rat model with neuropathic pain by inhibiting nitric oxide production.
ESTHER : Jia_2019_Anal.Cell.Pathol.(Amst)_2019_8253850
PubMedSearch : Jia_2019_Anal.Cell.Pathol.(Amst)_2019_8253850
PubMedID: 31223559

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

Title : Ester-Producing Mechanism of Ethanol O-acyltransferase EHT1 Gene in Pichia pastoris from Shanxi Aged Vinegar - Chen_2019_Biomed.Res.Int_2019_4862647
Author(s) : Chen J , Nan R , Wang R , Zhang L , Shi J
Ref : Biomed Res Int , 2019 :4862647 , 2019
Abstract : The ethanol O-acyltransferase EHT1 is an important element of key signaling pathways and is widely expressed in yeast strains. In this study, we investigated the expression of EHT1 in the overexpression lines or knockout system of Pichia pastoris using qRT-PCR and western blotting. The amount of total protein was determined using the Bradford method; the esterase activity was determined using p-nitrophenyl acetate as a substrate, and the production of volatile fatty acids in wild-type, knockout, and over-expression systems was detected using SPME GC-MS. The esterase activity of EHT1-knockout P. pastoris was significantly lower than that in wild type (P<0.01), and the activities of esterase in three EHT1-overexpressing strains-OE-1, OE-2, and OE-3-were significantly higher than those in wild type (P<0.01). In the EHT1-knockout strain products, the contents of nine volatile fatty acids were significantly lower than those in wild type (P<0.01), and the relative percentages of three fatty acids, methyl nonanoate, methyl decanoate, and ethyl caprate, were significantly lower than those in the other six species in the wild-type and knockout groups (P<0.05). The nine volatile fatty acids in the fermentation products of the overexpressed EHT1 gene were significantly higher than those in the wild-type group (P<0.01). The relative percentages of the three fatty acid esters, methyl nonanoate, methyl caprate, and ethyl caprate, were significantly higher than those in the other six species (P<0.05). EHT1 plays an important regulatory role in esterase activity and the production of medium-chain volatile fatty acids.
ESTHER : Chen_2019_Biomed.Res.Int_2019_4862647
PubMedSearch : Chen_2019_Biomed.Res.Int_2019_4862647
PubMedID: 30719444
Gene_locus related to this paper: kompc-f2qms6

Title : Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection - Jia_2019_Emerg.Microbes.Infect_8_760
Author(s) : Jia W , Channappanavar R , Zhang C , Li M , Zhou H , Zhang S , Zhou P , Xu J , Shan S , Shi X , Wang X , Zhao J , Zhou D , Perlman S , Zhang L
Ref : Emerg Microbes Infect , 8 :760 , 2019
Abstract : The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naive hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
ESTHER : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedSearch : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedID: 31130102

Title : Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis - Sun_2019_Ann.Gen.Psychiatry_18_6
Author(s) : Sun H , Yang Y , Zhang L , Wu H , Zhang H , Li H
Ref : Ann Gen Psychiatry , 18 :6 , 2019
Abstract : Background: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD.
ESTHER : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedSearch : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedID: 31139237
Gene_locus related to this paper: human-NLGN4X

Title : Cell-Membrane-Cloaked Oil Nanosponges Enable Dual-Modal Detoxification - Chen_2019_ACS.Nano_13_7209
Author(s) : Chen Y , Zhang Y , Zhuang J , Lee JH , Wang L , Fang RH , Gao W , Zhang L
Ref : ACS Nano , 13 :7209 , 2019
Abstract : The lack of pharmaceutical antidotes for deadly toxicants has motivated tremendous research interests in seeking synthetic nanoscavengers to absorb and neutralize harmful biological or chemical agents. Herein, we report a cell-membrane-cloaked oil nanosponge formulation capable of dual-modal detoxification. The biomimetic oil nanosponge consists of an olive oil nanodroplet wrapped by a red blood cell membrane. In such a construct, the oil core can nonspecifically soak up toxicants through physical partition and the cell membrane shell can specifically absorb and neutralize toxicants through biological binding. The dual-modal detoxification capability of the oil nanosponges was validated using three distinct organophosphates (OPs), including paraoxon, diisopropyl fluorophosphate, and dichlorvos. By inhibiting acetylcholinesterase, OPs cause the accumulation of acetylcholine, which leads to neuromuscular disorders and even death. In mouse models of OP poisoning, the oil nanosponges reduced clinical signs of OP intoxication, lowered OP concentration in tissues, and greatly enhanced mouse survival in both the therapeutic regimen and the prophylactic regimen. Overall, oil nanosponges combine the merits of both cell membrane and oil nanodroplets for safe and effective detoxification, which also serve as a prototype of multimodal detoxification platforms.
ESTHER : Chen_2019_ACS.Nano_13_7209
PubMedSearch : Chen_2019_ACS.Nano_13_7209
PubMedID: 31117372

Title : Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis - Yu_2019_Am.J.Emerg.Med_37_1611
Author(s) : Yu S , Zhang L , Gao Y , Walline J , Lu X , Ma Y , Zhu H , Yu X , Li Y
Ref : Am J Emerg Med , 37 :1611 , 2019
Abstract : OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR=2.54, 95% CI (1.33, 4.86), p=0.005] and lower the mortality rate [OR=0.31, 95% CI (0.13, 0.74), p=0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD=-1.52, 95% CI (-2.64, 0.40), p=0.008; AST, SMD=-1.66, 95% CI (-3.15, 0.16), p=0.03; TBIL, SMD=-1.26, 95% CI (-2.32, 0.20), p=0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD=2.15, 95% CI (1.60, 2.71), p<0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR=0.19, 95% CI (0.05, 0.71), p=0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended.
ESTHER : Yu_2019_Am.J.Emerg.Med_37_1611
PubMedSearch : Yu_2019_Am.J.Emerg.Med_37_1611
PubMedID: 30527914

Title : Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative - Zhu_2019_Eur.J.Med.Chem_168_330
Author(s) : Zhu Z , Yang T , Zhang L , Liu L , Yin E , Zhang C , Guo Z , Xu C , Wang X
Ref : Eur Journal of Medicinal Chemistry , 168 :330 , 2019
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid beta-peptide (Abeta) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Abeta aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Abeta-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Abeta toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Abeta toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs.
ESTHER : Zhu_2019_Eur.J.Med.Chem_168_330
PubMedSearch : Zhu_2019_Eur.J.Med.Chem_168_330
PubMedID: 30826509

Title : Food up-take and reproduction performance of Daphnia magna under the exposure of Bisphenols - Liu_2018_Ecotoxicol.Environ.Saf_170_47
Author(s) : Liu Y , Yan Z , Zhang L , Deng Z , Yuan J , Zhang S , Chen J , Guo R
Ref : Ecotoxicology & Environmental Safety , 170 :47 , 2018
Abstract : Because the application of Bisphenol A (BPA) was restricted, many substitutes, such as Bisphenol F (BPF) and Bisphenol S (BPS), were developed as BPA substitutes. Therefore, environmental impacts of BPA and its substitutes on aquatic organisms should be concerned, especially their combined toxicity. In this study, the impacts of BPA, BPF, BPS and their mixture on the feeding behavior, reproduction and physiological function of daphnids were synthetically evaluated, involving the duration and mode of exposure. In short-term exposure tests, feeding rates of D. magna decreased after exposure to BPA, BPF, BPS and their mixture, while the inhibition reversed into stimulation in the recovery period. It may benefit from overcompensation of D. magna. In long-term exposure tests, the inhibition effect on the reproduction and growth of the exposed D. magna was difficult to recover, and only some experimental groups have a certain recovery. In conclusion, environmental risk of BPA, BPF, BPS and their mixture on the behavior of D. magna increased with prolonged exposure time. Moreover, relative activities of trypsin, amylase (AMS), acetylcholinesterase (AChE), carbonic anhydrase (CA), glutathione peroxidase (GPx) and super oxidase dimutase (SOD) of the exposed daphnids decreased in most treatment groups, indicating the disorder of digestive, nervous and antioxidative system of D. magna. Interestingly, inhibition of enzymes activities decreased with the increase of the exposure time, which implied the tolerance may be occurred.
ESTHER : Liu_2018_Ecotoxicol.Environ.Saf_170_47
PubMedSearch : Liu_2018_Ecotoxicol.Environ.Saf_170_47
PubMedID: 30522006

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins - Wang_2018_Genetica_146_179
Author(s) : Wang D , Zhang L , Hu J , Gao D , Liu X , Sha Y
Ref : Genetica , 146 :179 , 2018
Abstract : Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of alpha/beta hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.
ESTHER : Wang_2018_Genetica_146_179
PubMedSearch : Wang_2018_Genetica_146_179
PubMedID: 29468429

Title : Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B - Wu_2018_Liver.Int_38_1930
Author(s) : Wu D , Rao Q , Chen W , Ji F , Xie Z , Huang K , Chen E , Zhao Y , Ouyang X , Zhang S , Jiang Z , Zhang L , Xu L , Gao H , Li L
Ref : Liver Int , 38 :1930 , 2018
Abstract : BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.
ESTHER : Wu_2018_Liver.Int_38_1930
PubMedSearch : Wu_2018_Liver.Int_38_1930
PubMedID: 29654711

Title : Genomic Analysis of Microbulbifer sp. Strain A4B-17 and the Characterization of Its Metabolic Pathways for 4-Hydroxybenzoic Acid Synthesis - Tian_2018_Front.Microbiol_9_3115
Author(s) : Tian J , Zhu L , Wang W , Zhang L , Li Z , Zhao Q , Xing K , Feng Z , Peng X
Ref : Front Microbiol , 9 :3115 , 2018
Abstract : The marine bacterium Microbulbifer sp. A4B-17 produces secondary metabolites such as 4-hydroxybenzoic acid (4HBA) and esters of 4HBA (parabens). 4HBA is a useful material in the synthesis of the liquid crystal. Parabens are man-made compounds that have been extensively used since the 1920s in the cosmetic, pharmaceutical, and food industries for their effective antimicrobial activity. In this study, we completed the sequencing and annotation of the A4B-17 strain genome and found all genes for glucose utilization and 4HBA biosynthesis. Strain A4B-17 uses the Embden-Meyerhof-Parnas (EMP), hexose monophosphate (HMP), and Entner-Doudoroff (ED) pathways to utilize glucose. Other sugars such as fructose, sucrose, xylose, arabinose, galactose, mannitol, and glycerol supported cell growth and 4HBA synthesis. Reverse transcriptional analysis confirmed that the key genes involved in the glucose metabolism were functional. Paraben concentrations were proportionally increased by adding alcohols to the culture medium, indicating that strain A4B-17 synthesizes the 4HBA and the alcohols separately and an esterification reaction between them is responsible for the paraben synthesis. A gene that codes for a carboxylesterase was proposed to catalyze this reaction. The temperature and NaCl concentration for optimal growth were determined to be 35 degrees C and 22.8 g/L.
ESTHER : Tian_2018_Front.Microbiol_9_3115
PubMedSearch : Tian_2018_Front.Microbiol_9_3115
PubMedID: 30619190

Title : Crius: A novel fragment-based algorithm of de novo substrate prediction for enzymes - Yao_2018_Protein.Sci_27_1526
Author(s) : Yao Z , Jiang S , Zhang L , Gao B , He X , Zhang JZH , Wei D
Ref : Protein Science , 27 :1526 , 2018
Abstract : The study of enzyme substrate specificity is vital for developing potential applications of enzymes. However, the routine experimental procedures require lot of resources in the discovery of novel substrates. This article reports an in silico structure-based algorithm called Crius, which predicts substrates for enzyme. The results of this fragment-based algorithm show good agreements between the simulated and experimental substrate specificities, using a lipase from Candida antarctica (CALB), a nitrilase from Cyanobacterium syechocystis sp. PCC6803 (Nit6803), and an aldo-keto reductase from Gluconobacter oxydans (Gox0644). This opens new prospects of developing computer algorithms that can effectively predict substrates for an enzyme.
ESTHER : Yao_2018_Protein.Sci_27_1526
PubMedSearch : Yao_2018_Protein.Sci_27_1526
PubMedID: 29722450

Title : Benzo(a)pyrene inhibits the accumulation and toxicity of cadmium in subcellular fractions of Eisenia fetida - Zhang_2018_Chemosphere_219_740
Author(s) : Zhang L , Zhou L , Han L , Zhao C , Norton JM , Li H , Hu F , Xu L
Ref : Chemosphere , 219 :740 , 2018
Abstract : Cadmium (Cd) and benzo [a]pyrene (BaP) often co-occur in the environment, and the critical body residue of organisms is used as an indicator of the toxic effects of contaminants. However, little is known about their distributions and toxicities when pollution of Cd and BaP are combined. Semi-static solution culture experiment was used to study the impacts of BaP on the subcellular distribution of the toxic metal Cd in the earthworm Eisenia fetida. We explored the mechanisms by which this organism responds to combined exposure to these pollutants by measuring the protein content of each of three subcellular fractions, as well as acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities. The subcellular partitioning of Cd was heterogeneous and Cd mainly accumulated in the cytosolic fraction (Fraction C), which was previously reported to be involved in metal immobilization. In Fraction C, Cd accumulation was correlated with the external concentration to which the earthworm had been exposed; however, in the presence of BaP, Cd accumulation was inhibited and plateaued at high external Cd concentrations. A principal component analysis revealed that this decreased Cd accumulation might be caused by increases in GST activity, which likely increased the excretion of Cd. BaP was also found to stimulate protein biosynthesis and upregulate AChE and GST activities in the debris fraction (Fraction E), indicating other potential detoxification mechanisms in this fraction. Granule fraction (Fraction D) had a lower protein content, AChE and GST activities than the other subcellular fractions, supporting previous findings that Fraction D is largely inert.
ESTHER : Zhang_2018_Chemosphere_219_740
PubMedSearch : Zhang_2018_Chemosphere_219_740
PubMedID: 30557731

Title : Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein - Zhang_2018_Cell.Rep_24_441
Author(s) : Zhang S , Zhou P , Wang P , Li Y , Jiang L , Jia W , Wang H , Fan A , Wang D , Shi X , Fang X , Hammel M , Wang S , Wang X , Zhang L
Ref : Cell Rep , 24 :441 , 2018
Abstract : The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the beta5-beta6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.
ESTHER : Zhang_2018_Cell.Rep_24_441
PubMedSearch : Zhang_2018_Cell.Rep_24_441
PubMedID: 29996104

Title : Dual-Channel Enzymatic Inhibition Measurement (DEIM) Coupling Isotope Substrate via Matrix-Assisted Laser Desorption\/Ionization Time of Flight Mass Spectrometry - Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
Author(s) : Tao M , Zhang L , Guo Y
Ref : J Am Soc Mass Spectrom , 29 :2427 , 2018
Abstract : A novel dual-channel enzymatic inhibition measurement (DEIM) method was developed to improve the repeatability with light/heavy isotope substrates, producing reliable relative standard deviations (< 3%) by employing acetylcholinesterase (AChE) as the model enzyme. The matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was adapted for enzyme-inhibited method due to its good salt-tolerance and high throughput; meanwhile, dual-channel enzymatic reactions were performed to improve the repeatability of each well. The acetylcholinesterase inhibition measurement was conducted by mixing the quenched enzyme reaction solution of blank group (with heavy isotope as substrate) and experimental group (with light isotope as substrate), of which the inhibition rate might be affected by isotope effects. Hence, inverse study and Km measurement were implemented to validate the method. The inverse study shows similar inhibition rate (68.9 and 70.3%) and the Km of isotope substrates are analogous (0.139 and 0.135 mM), which demonstrated that the novel method is feasible to AChE inhibition measurement. Finally, the method was applied to herb extracts, half of which exhibit inhibition to AChE. The precise dual-channel enzymatic inhibition measurement (DEIM) method could be regarded as a promising approach to potential enzyme inhibitor screening. Graphical Abstract .
ESTHER : Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
PubMedSearch : Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
PubMedID: 30159674

Title : Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations - Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
Author(s) : Zhang L , Li D , Cao F , Xiao W , Zhao L , Ding G , Wang ZZ
Ref : Comb Chem High Throughput Screen , 21 :41 , 2018
Abstract : AIM AND OBJECTIVE: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. MATERIAL AND METHOD: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. RESULTS: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e. Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. CONCLUSION: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD.
ESTHER : Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
PubMedSearch : Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
PubMedID: 29173156

Title : Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis - Xu_2018_J.Ind.Microbiol.Biotechnol_45_345
Author(s) : Xu Y , Tan G , Ke M , Li J , Tang Y , Meng S , Niu J , Wang Y , Liu R , Wu H , Bai L , Zhang L , Zhang B
Ref : J Ind Microbiol Biotechnol , 45 :345 , 2018
Abstract : Streptomyces lincolnensis is generally utilized for the production of lincomycin A (Lin-A), a clinically useful antibiotic to treat Gram-positive bacterial infections. Three methylation steps, catalyzed by three different S-adenosylmethionine (SAM)-dependent methyltransferases, are required in the biosynthesis of Lin-A, and thus highlight the significance of methyl group supply in lincomycin production. In this study, we demonstrate that externally supplemented SAM cannot be taken in by cells and therefore does not enhance Lin-A production. Furthermore, bioinformatics and in vitro enzymatic assays revealed there exist two SAM synthetase homologs, MetK1 (SLCG_1651) and MetK2 (SLCG_3830) in S. lincolnensis that could convert L-methionine into SAM in the presence of ATP. Even though we attempted to inactivate metK1 and metK2, only metK2 was deleted in S. lincolnensis LCGL, named as DeltametK2. Following a reduction of the intracellular SAM concentration, DeltametK2 mutant exhibited a significant decrease of Lin-A in comparison to its parental strain. Individual overexpression of metK1 or metK2 in S. lincolnensis LCGL either elevated the amount of intracellular SAM, concomitant with 15% and 22% increase in Lin-A production, respectively. qRT-PCR assays showed that overexpression of either metK1 or metK2 increased the transcription of lincomycin biosynthetic genes lmbA and lmbR, and regulatory gene lmbU, indicating SAM may also function as a transcriptional activator. When metK1 and metK2 were co-expressed, Lin-A production was increased by 27% in LCGL, while by 17% in a high-yield strain LA219X.
ESTHER : Xu_2018_J.Ind.Microbiol.Biotechnol_45_345
PubMedSearch : Xu_2018_J.Ind.Microbiol.Biotechnol_45_345
PubMedID: 29574602
Gene_locus related to this paper: strln-a0a1b1ma73 , strln-a0a1b1m575

Title : Comparative transcriptomic profiling of peripheral efferent and afferent nerve fibres at different developmental stages in mice - Wang_2018_Sci.Rep_8_11990
Author(s) : Wang H , Zhou Y , Cong M , Zhang L , Gu X , Tang X
Ref : Sci Rep , 8 :11990 , 2018
Abstract : Peripheral nerve injury impairs motor and sensory function in humans, and its functional recovery largely depends on the axonal outgrowth required for the accurate reinnervation of appropriate targets. To better understand how motor and sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray analysis was conducted to examine differential gene expression patterns in peripheral efferent and afferent fibres at different developmental stages in mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analyses revealed common and distinct features of enrichment for differentially expressed genes during motor and sensory nerve fibre development. Ingenuity Pathway Analysis (IPA) further indicated that the key differentially expressed genes were associated with trans-synaptic neurexin-neuroligin signalling components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of this study was to generate a framework of gene networks regulated during motor and sensory neuron differentiation/maturation. These data may provide new clues regarding the underlying cellular and molecular mechanisms that determine the intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our findings may thus facilitate further development of a potential intervention to manipulate the therapeutic efficiency of peripheral nerve repair in the clinic.
ESTHER : Wang_2018_Sci.Rep_8_11990
PubMedSearch : Wang_2018_Sci.Rep_8_11990
PubMedID: 30097601

Title : Effects of two strobilurins (azoxystrobin and picoxystrobin) on embryonic development and enzyme activities in juveniles and adult fish livers of zebrafish (Danio rerio) - Jia_2018_Chemosphere_207_573
Author(s) : Jia W , Mao L , Zhang L , Zhang Y , Jiang H
Ref : Chemosphere , 207 :573 , 2018
Abstract : Azoxystrobin and picoxystrobin are two primary strobilurin fungicides used worldwide. This study was conducted to test their effects on embryonic development and the activity of several enzyme in the zebrafish (Danio rerio). After fish eggs were separately exposed to azoxystrobin and picoxystrobin from 24 to 144h post fertilization (hpf), the mortality, hatching, and teratogenetic rates were measured. Additionally, effects of azoxystrobin and picoxystrobin on activities of three important antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)] and two primary detoxification enzymes [carboxylesterase (CarE) and glutathione S-transferase (GST)] and malondialdehyde (MDA) content in zebrafish larvae (96h) and livers of adult zebrafish of both sexes were also assessed for potential toxicity mechanisms. Based on the embryonic development test results, the mortality, hatching, and teratogenetic rates of eggs treated with azoxystrobin and picoxystrobin all showed significant dose- and time-dependent effects, and the 144-h LC50 values of azoxystrobin and picoxystrobin were 1174.9 and 213.8mugL(-1), respectively. In the larval zebrafish (96h) test, activities of CAT, POD, CarE, and GST and MDA content in azoxystrobin and picoxystrobin-treated zebrafish larvae increased significantly with concentrations of the pesticides compared with those in the control. We further revealed that azoxystrobin and picoxystrobin exposure both caused significant oxidative stress in adult fish livers and the changes differed between the sexes. Our results indicated that picoxystrobin led to higher embryonic development toxicity and oxidative stress than azoxystrobin in zebrafish and the male zebrafish liver had stronger ability to detoxify than that of the females.
ESTHER : Jia_2018_Chemosphere_207_573
PubMedSearch : Jia_2018_Chemosphere_207_573
PubMedID: 29843034

Title : Sublethal or not? Responses of multiple biomarkers in Daphnia magna to single and joint effects of BDE-47 and BDE-209 - Xiong_2018_Ecotoxicol.Environ.Saf_164_164
Author(s) : Xiong Q , Shi Y , Lu Y , Pan K , Dakhil MA , Zhang L , Xiao Y
Ref : Ecotoxicology & Environmental Safety , 164 :164 , 2018
Abstract : Polybrominated diphenyl ethers (PBDEs) are extremely incessant anthropogenic contaminants found in the environment, with dreadful risk to aquatic ecosystems. However, there is a limited amount of data concerning their impacts on freshwater organisms. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are significant components of total PBDEs in water. The sublethal effects of BDE-47, BDE-209 and their binary mixtures on the aquatic organism Daphnia magna were investigated in acute and chronic exposure experiments. Immobilization and heartbeat were studied in daphnids after 48h of exposure. Mortality rate, breed number, Cholinesterase (ChE), Glutathione S-transferases (GST) and Catalase (CAT) activities were evaluated after 21 days of exposure. The results showed that at 100 and 200mug/L concentration of BDE-47, immobilization rate of daphnids were inhibited by 44.0+/-16.7% and 88.0+/-10.9%, respectively. The binary mixture of BDE-47 and BDE-209 had uncongenial effects on immobilization of D. magna under acute toxicity test. BDE-209 significantly increased the heartbeat rate of daphnids, which increased even further when combined with BDE-47. After 21 days of exposure, daphnids exposed to single BDE-47 were physiologically altered. The combination of BDE-47 with BDE-209 significantly decreased the mortality rate of daphnids. Irrespective of the concentration, higher numbers of offsprings were produced in the mixtures compared to BDE-47 treatment alone. ChE activities significantly (p<0.05) decreased at concentrations of 2 and 4mug/L in single BDE-47 treatment, while GST activity significantly (p<0.05) decreased at 0.5mug/L. CAT activities significantly increased with BDE-47 treatments in all the tested concentrations (p<0.05). The mixtures significantly affect ChE (p<0.05), GST (p<0.05) and CAT activities (p<0.05). The results illustrated that the toxicity of the mixture of PBDE congeners exposed to aquatic organisms may have antagonistic effects. The 21 days chronic test in this study suggests that acute toxicity tests, i.e. 48-h tests, using Daphnia may lead to underestimation of risks associated with PBDEs, especially, BDE-209. Hence, there is a necessity to re-examine PBDE congeners' environmental risk in aquatic organisms.
ESTHER : Xiong_2018_Ecotoxicol.Environ.Saf_164_164
PubMedSearch : Xiong_2018_Ecotoxicol.Environ.Saf_164_164
PubMedID: 30107326

Title : Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding - Lau_2018_J.Infect.Dis_218_197
Author(s) : Lau SKP , Zhang L , Luk HKH , Xiong L , Peng X , Li KSM , He X , Zhao PS , Fan RYY , Wong ACP , Ahmed SS , Cai JP , Chan JFW , Sun Y , Jin D , Chen H , Lau TCK , Kok RKH , Li W , Yuen KY , Woo PCY
Ref : J Infect Dis , 218 :197 , 2018
Abstract : Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.
ESTHER : Lau_2018_J.Infect.Dis_218_197
PubMedSearch : Lau_2018_J.Infect.Dis_218_197
PubMedID: 29346682

Title : Insights into the effect and interaction mechanism of bisphenol S on lipids hydrolysis in sludge through multi-spectra, thermodynamics, and molecule docking analysis - Yang_2018_Environ.Sci.Pollut.Res.Int_25_7834
Author(s) : Yang H , Zhang L , Hou G , Liu C
Ref : Environ Sci Pollut Res Int , 25 :7834 , 2018
Abstract : As an alternative to bisphenol A, bisphenol S (BPS) is widely used in industrial production and daily life, which is then discharged into sewage treatment plants and accumulates in sludge. In this research, impact and interaction mechanism of BPS on lipids hydrolysis in sludge is studied from the respect of soluble organic matter and volatile organic fatty acids (VFAs). Multi-spectra, thermodynamics, molecule docking, and enzyme activity assay are applied to elucidate the effect mechanism of BPS on lipids hydrolysis. Results show that lipids hydrolysis is restrained due to the denaturation of lipase with BPS exposure. The interaction mechanism is involved in hydrophobic bond and hydrogen bond interaction in the activity region of lipase. This interaction not only results in an unfolding skeleton structure of lipase and a less hydrophobic microenvironment of tyrosine and tryptophan residues but also leads to fluorophore static quenching with the formation of lipase-BPS complex. The experimental results and the combined research methods not only contribute to the development of novel technique for sludge treatment containing micropollutant but also profit to clarify the interaction mechanism between other micropollutant and enzymes.
ESTHER : Yang_2018_Environ.Sci.Pollut.Res.Int_25_7834
PubMedSearch : Yang_2018_Environ.Sci.Pollut.Res.Int_25_7834
PubMedID: 29297162

Title : Study of the interactions of forsythiaside and rutin with acetylcholinesterase (AChE) - Yan_2018_Int.J.Biol.Macromol_119_1344
Author(s) : Yan X , Chen T , Zhang L , Du H
Ref : Int J Biol Macromol , 119 :1344 , 2018
Abstract : Acetylcholinesterase (AChE) inhibitors have been considered as candidates for the treatment of Alzheimer's disease (AD) and have been utilized in clinical trials. In the present study, the interactions of forsythiaside and rutin with AChE have been investigated, after discovering the inhibitory AChE activity of the two compounds. Forsythiaside and rutin both can bind to AChE to form forsythiaside-AChE and rutin-AChE complex, and thus quench the intrinsic fluorescence of AChE. The quenching mechanism, the binding sites, the binding forces, the binding constants and the energy transfer involved were studied in details. Forsythiaside and rutin show some properties in common, including the stoichiometric binding ratio of 1:1 with AChE and the full quenching of AChE fluorescence. At the same time, the two compounds distinctly present some different characters, for example, the binding constant of rutin is less than that of forsythiaside, and the interaction force and the affinity between forsythiaside and AChE are much bigger than that of rutin. Spectroscopy data and docking analysis powerfully support the findings that forsythiaside inhibit AChE activity more strongly than rutin. The current study will provide the better understanding on the nature of the possible interactions between forsythiaside and rutin with AChE.
ESTHER : Yan_2018_Int.J.Biol.Macromol_119_1344
PubMedSearch : Yan_2018_Int.J.Biol.Macromol_119_1344
PubMedID: 30048725

Title : A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae - Li_2018_Aquat.Toxicol_199_46
Author(s) : Li R , Zhang L , Shi Q , Guo Y , Zhang W , Zhou B
Ref : Aquat Toxicol , 199 :46 , 2018
Abstract : Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500mug/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100mug/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500mug/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and alpha1-tubulin) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500mug/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1nM) and inhibitor (chloroquine, CQ, 1muM) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and small a, Cyrillic1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500mug/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae.
ESTHER : Li_2018_Aquat.Toxicol_199_46
PubMedSearch : Li_2018_Aquat.Toxicol_199_46
PubMedID: 29605586

Title : Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi - Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
Author(s) : Zhang X , Wang TT , Xu QL , Xiong Y , Zhang L , Han H , Xu K , Guo WJ , Xu Q , Tan RX , Ge HM
Ref : Angew Chem Int Ed Engl , 57 :8184 , 2018
Abstract : Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.
ESTHER : Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
PubMedSearch : Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
PubMedID: 29797385
Gene_locus related to this paper: necsz-ntng , artsz-atng

Title : The Expression Pattern of PLIN2 in Differentiated Adipocytes from Qinchuan Cattle Analysis of Its Protein Structure and Interaction with CGI-58 - Li_2018_Int.J.Mol.Sci_19_
Author(s) : Li P , Wang Y , Zhang L , Ning Y , Zan L
Ref : Int J Mol Sci , 19 : , 2018
Abstract : PLIN2 (Perilipin-2) is a protein that can anchor on the membrane of lipid droplets (LDs), playing a vital role in the early formation of LDs and in the regulation of LD metabolism in many types of cells. However, little research has been conducted in cattle adipocytes. In the present study, we found that the expression of PLIN2 mRNA peaks at Day 2 during cattle adipocyte differentiation (p < 0.01), but PLIN2 protein levels maintain high abundance until Day 4 and then decrease sharply. We first built an interaction model using PyMOL. The results of a pull-down assay indicated that bovine PLIN2 and CGI-58 (ABHD5, α/β hydrolase domain-containing protein 5) had an interaction relationship. Furthermore, Bimolecular Fluorescence Complementation-Flow Cytometry (BiFC-FC) was used to explore the function of the PLIN2-CGI-58 interaction. Interestingly, we found that different combined models had different levels of fluorescence intensity; specifically, PLIN2-VN173+CGI-58-VC155 expressed in bovine adipocytes exhibited the highest level of fluorescence intensity. Our findings elucidate the PLIN2 expression pattern in cattle adipocytes, the protein structure and the function of protein(-)protein interactions (PPI) as well as highlight the characteristics of bovine PLIN2 during the early formation and accumulation of lipid droplets.
ESTHER : Li_2018_Int.J.Mol.Sci_19_
PubMedSearch : Li_2018_Int.J.Mol.Sci_19_
PubMedID: 29723991

Title : Fatal poisoning by terbufos following occupational exposure - Liang_2017_Clin.Toxicol.(Phila)__1
Author(s) : Liang Y , Tong F , Zhang L , Li W , Huang W , Zhou Y
Ref : Clinical Toxicology (Phila) , :1 , 2017
Abstract : CONTEXT: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. CASE: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 x 10-2 mug/ml in the heart blood and 0.17 mug/g in the liver. DISCUSSIONS: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors.
CONCLUSIONS: TBF is a highly toxic OP. Inadequate regulatory control, improper environmental application, and ineffective PPE resulted in a fatal human exposure.
ESTHER : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedSearch : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedID: 28681657

Title : The Relation Between Lipase Thermostability and Dynamics of Hydrogen Bond and Hydrogen Bond Network Based on Long Time Molecular Dynamics Simulation - Zhang_2017_Protein.Pept.Lett_24_643
Author(s) : Zhang L , Ding Y
Ref : Protein Pept Lett , 24 :643 , 2017
Abstract : BACKGROUND: Compared with the wild type of lipase (WTL), mutant lipase 6B has twelve mutations (A15S, F17S, A20E, N89Y, G111D, L114P, A132D, M134E, M137P, I157M, S163P, N166Y). The melting temperature of 6B (78.2 degrees C) is much higher than that of WTL (56 degrees C). Hydrogen bond (HB) play an important role in stabilizing the protein. It is important to analyze how mutations affect hydrogen bond and hydrogen bond network and explain how hydrogen bond and hydrogen bond network affect lipase thermostability by the change of the intensity of HB and HB networks with temperature changing. OBJECTIVE: Study the dynamics of HB and HB networks to find that how HBs and HB networks change over time and over temperature in WTL and 6B. METHOD: Long time MD simulations of WTL and 6B are carried out to analyze how mutations affect hydrogen bond and hydrogen bond network. All proteins were simulated at 300K, 325K, 350K, 375K, 400K for 300ns respectively. The definition of HB is that the distance between acceptor and donor is smaller than a cutoff 3.0 A and the angle between Donor-H and H-Acceptor is larger than 120o. If two or more HBs connect together, they formed HB network. In the network, residues that formed HB represent nodes, the HB interactions between residues represent edges. The persistence value of HB is computed by . RESULTS: The persistence values of HBs formed by mutations A15S, A20E, G111D, M137P, N166Y are significantly different from that of WTL. HB Glu20-Ser24, Asp111-Asp144, Leu160-Tyr166 and Lys170-Tyr166 are important to stabilize 6B. In addition, the HB networks dynamics show that there are three HB networks are more stable in mutants than that in WTL. The first HB network makes beta3, beta5, loop and 310-helix closely connect with each other at mutants. The second HB network increases the rigidity of the loop, alphaC, beta3 and beta5. The third HB network enhances the interaction between loops, alphaB and alphaC. CONCLUSION: The higher HB persistence value generally means that the HB is more stable. These mutations directly improve the stability of these HBs referring to their persistence values, which show that mutations strengthen the ability of HBs to withstand high temperature and then stabilize the secondary structure. It is thus clear that the mutations change the stability of HBs and the HB networks, which are responsible for increasing protein thermostability.
ESTHER : Zhang_2017_Protein.Pept.Lett_24_643
PubMedSearch : Zhang_2017_Protein.Pept.Lett_24_643
PubMedID: 28464764

Title : Protective effects of Forsythoside A on amyloid beta-induced apoptosis in PC12 cells by downregulating acetylcholinesterase - Yan_2017_Eur.J.Pharmacol_810_141
Author(s) : Yan X , Chen T , Zhang L , Du H
Ref : European Journal of Pharmacology , 810 :141 , 2017
Abstract : Increasing the acetylcholine level and fighting the neuroinflammation has always been taken as a treatment strategy for Alzheimer's disease (AD). Forsythoside A is a major component in Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese) that has been traditionally used as Chinese herbal medicine to treat the inflammation in China. This study examined the inhibitory acetylcholinesterase activities of Forsythoside A at chemical and biological level. Forsythoside A inhibited acetylcholinesterase in a mixed type of inhibition, with Ki of 47.68muM. Docking analysis strongly supported these findings. In PC12 cells Forsythoside A increased cell viability and suppressed acetylcholinesterase increased by Abeta25-35, thus alleviated the corresponding apoptosis. Taken together, these results suggest that Forsythoside A has the protective effects on Abeta25-35-induced apoptosis in PC12 cells by downregulating acetylcholinesterase, making it a potential functional food ingredient or drug candidate for the treatment of AD.
ESTHER : Yan_2017_Eur.J.Pharmacol_810_141
PubMedSearch : Yan_2017_Eur.J.Pharmacol_810_141
PubMedID: 28687196

Title : Matsutakone and Matsutoic Acid, Two (Nor)steroids with Unusual Skeletons from the Edible Mushroom Tricholoma matsutake - Zhao_2017_J.Org.Chem_82_7974
Author(s) : Zhao ZZ , Chen HP , Wu B , Zhang L , Li ZH , Feng T , Liu JK
Ref : J Org Chem , 82 :7974 , 2017
Abstract : Matsutakone (1), a novel sterol with an unprecedented polycyclic ring system, together with a new norsteroid matsutoic acid (2) were isolated from the fruiting bodies of Tricholoma matsutake. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and computational methods. Bioassay results showed that compounds 1 and 2 exhibited inhibitory activities against acetylcholinesterase (IC50 20.9 muM for 1).
ESTHER : Zhao_2017_J.Org.Chem_82_7974
PubMedSearch : Zhao_2017_J.Org.Chem_82_7974
PubMedID: 28691489

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : The sea cucumber genome provides insights into morphological evolution and visceral regeneration - Zhang_2017_PLoS.Biol_15_e2003790
Author(s) : Zhang X , Sun L , Yuan J , Sun Y , Gao Y , Zhang L , Li S , Dai H , Hamel JF , Liu C , Yu Y , Liu S , Lin W , Guo K , Jin S , Xu P , Storey KB , Huan P , Zhang T , Zhou Y , Zhang J , Lin C , Li X , Xing L , Huo D , Sun M , Wang L , Mercier A , Li F , Yang H , Xiang J
Ref : PLoS Biol , 15 :e2003790 , 2017
Abstract : Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.
ESTHER : Zhang_2017_PLoS.Biol_15_e2003790
PubMedSearch : Zhang_2017_PLoS.Biol_15_e2003790
PubMedID: 29023486
Gene_locus related to this paper: stija-a0a2g8k9s2 , stija-a0a2g8ka54 , stija-a0a2g8jd52 , stija-a0a2g8l0w8

Title : Control of secondary cell wall patterning involves xylan deacetylation by a GDSL esterase - Zhang_2017_Nat.Plants_3_17017
Author(s) : Zhang B , Zhang L , Li F , Zhang D , Liu X , Wang H , Xu Z , Chu C , Zhou Y
Ref : Nat Plants , 3 :17017 , 2017
Abstract : O-acetylation, a ubiquitous modification of cell wall polymers, has striking impacts on plant growth and biomass utilization and needs to be tightly controlled. However, the mechanisms that underpin the control of cell wall acetylation remain elusive. Here, we show a rice brittle leaf sheath1 (bs1) mutant, which contains a lesion in a Golgi-localized GDSL esterase that deacetylates the prominent hemicellulose xylan. Cell wall composition, detailed xylan structure characterization and enzyme kinetics and activity assays on acetylated sugars and xylooligosaccharides demonstrate that BS1 is an esterase that cleaves acetyl moieties from the xylan backbone at O-2 and O-3 positions of xylopyranosyl residues. BS1 thus plays an important role in the maintenance of proper acetylation level on the xylan backbone, which is crucial for secondary wall formation and patterning. Our findings outline a mechanism for how plants modulate wall acetylation and endow a plethora of uncharacterized GDSL esterases with surmisable activities.
ESTHER : Zhang_2017_Nat.Plants_3_17017
PubMedSearch : Zhang_2017_Nat.Plants_3_17017
PubMedID: 28260782

Title : Genome-wide identification of pathogenicity, conidiation and colony sectorization genes in Metarhizium robertsii - Zeng_2017_Environ.Microbiol_19_3896
Author(s) : Zeng G , Chen X , Zhang X , Zhang Q , Xu C , Mi W , Guo N , Zhao H , You Y , Dryburgh FJ , Bidochka MJ , St Leger RJ , Zhang L , Fang W
Ref : Environ Microbiol , 19 :3896 , 2017
Abstract : Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. About 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi were identified. By analysing a series of conidial pigmentation mutants, a new fungal pigmentation gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA regulates expression of these pigmentation genes. During conidiation Mr-BlrA up-regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK regulates fungal conidiation by controlling the conidiation regulatory pathway, and that all three pigmentation genes exercise feedback regulation of conidiation. This work provided the foundation for deeper understanding of the genetic processes behind M. robertsii adaptive phenotypes, and advances our insights into conidiation and pigmentation in this fungus.
ESTHER : Zeng_2017_Environ.Microbiol_19_3896
PubMedSearch : Zeng_2017_Environ.Microbiol_19_3896
PubMedID: 28447400
Gene_locus related to this paper: metaf-pks1

Title : Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation - Xu_2017_Brain.Behav_7_e00793
Author(s) : Xu X , Hu Z , Zhang L , Liu H , Cheng Y , Xia K , Zhang X
Ref : Brain Behav , 7 :e00793 , 2017
Abstract : INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing.
METHODS: In this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK293 cells expressing wild-type and mutant neuroligin.
RESULTS: We found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1-neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms. CONCLUSION: Our data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
ESTHER : Xu_2017_Brain.Behav_7_e00793
PubMedSearch : Xu_2017_Brain.Behav_7_e00793
PubMedID: 28948087
Gene_locus related to this paper: human-NLGN4X

Title : Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells - Fu_2017_Environ.Toxicol_32_1055
Author(s) : Fu G , Dai J , Zhang D , Zhu L , Tang X , Zhang L , Zhou T , Duan P , Quan C , Zhang Z , Song S , Shi Y
Ref : Environ Toxicol , 32 :1055 , 2017
Abstract : Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 muM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 muM) and glutathione peroxidase (GSH-Px) activity (50 and 100 muM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress.
ESTHER : Fu_2017_Environ.Toxicol_32_1055
PubMedSearch : Fu_2017_Environ.Toxicol_32_1055
PubMedID: 27416487

Title : Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita - Cui_2017_Exp.Parasitol_176_75
Author(s) : Cui R , Zhang L , Chen Y , Huang W , Fan C , Wu Q , Peng D , da Silva W , Sun X
Ref : Experimental Parasitology , 176 :75 , 2017
Abstract : The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant.
ESTHER : Cui_2017_Exp.Parasitol_176_75
PubMedSearch : Cui_2017_Exp.Parasitol_176_75
PubMedID: 28238686
Gene_locus related to this paper: melin-ACHE1 , melin-ACHE2 , melic-a0a0m5m7r8

Title : Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders - Bruns_2017_Neuropharmacol_128_351
Author(s) : Bruns RF , Mitchell SN , Wafford KA , Harper AJ , Shanks EA , Carter G , O'Neill MJ , Murray TK , Eastwood BJ , Schaus JM , Beck JP , Hao J , Witkin JM , Li X , Chernet E , Katner JS , Wang H , Ryder JW , Masquelin ME , Thompson LK , Love PL , Maren DL , Falcone JF , Menezes MM , Zhang L , Yang CR , Svensson KA
Ref : Neuropharmacology , 128 :351 , 2017
Abstract : DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease. DETQ markedly increased release of both acetylcholine and histamine in the prefrontal cortex, and increased levels of histamine metabolites in the striatum. In the hippocampus, the combination of DETQ and the cholinesterase inhibitor rivastigmine increased ACh to a greater degree than either agent alone. DETQ also increased phosphorylation of the AMPA receptor (GluR1) and the transcription factor CREB in the striatum, consistent with enhanced synaptic plasticity. In the Y-maze, DETQ increased arm entries but (unlike a D1 agonist) did not reduce spontaneous alternation between arms at high doses. DETQ enhanced wakefulness in EEG studies in hD1 mice and decreased immobility in the forced-swim test, a model for antidepressant-like activity. In rhesus monkeys, DETQ increased spontaneous eye-blink rate, a measure that is known to be depressed in Parkinson's disease. Together, these results provide support for potential utility of D1 potentiators in the treatment of several neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, cognitive impairment in schizophrenia, and major depressive disorder.
ESTHER : Bruns_2017_Neuropharmacol_128_351
PubMedSearch : Bruns_2017_Neuropharmacol_128_351
PubMedID: 29102759

Title : N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2 - Yang_2017_Oncotarget_8_47709
Author(s) : Yang X , Zhu F , Yu C , Lu J , Zhang L , Lv Y , Sun J , Zheng M
Ref : Oncotarget , 8 :47709 , 2017
Abstract : N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Calpha (PKCalpha), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.
ESTHER : Yang_2017_Oncotarget_8_47709
PubMedSearch : Yang_2017_Oncotarget_8_47709
PubMedID: 28537875
Gene_locus related to this paper: human-NDRG1

Title : Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time - Chen_2017_Molecules_22_E795
Author(s) : Chen T , Li Y , Zhang L
Ref : Molecules , 22 :E795 , 2017
Abstract : It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC50: 149 +/- 6.0 mumol/L; hesperidin, 52.4 mumol/L; kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time, IC50 notably reached 2.9 +/- 0.5 mumol/L), two polyphenols (chlorogenic acid, 3150 +/- 120 mumol/L; caffeic acid, 1394 +/- 52 mumol/L), two lignans (phillyrin, promoter; arctigenin, 2129 +/- 10.5 mumol/L), and two phenethyl alcohol (forsythiaside A, 2155 +/- 8.5 mumol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase.
ESTHER : Chen_2017_Molecules_22_E795
PubMedSearch : Chen_2017_Molecules_22_E795
PubMedID: 28498356

Title : Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor - Rosenberg_2017_Chem.Biol.Interact_274_50
Author(s) : Rosenberg YJ , Mao L , Jiang X , Lees J , Zhang L , Radic Z , Taylor P
Ref : Chemico-Biological Interactions , 274 :50 , 2017
Abstract : Organophosphate (OP) nerve agents and pesticides trigger a common mechanism of neurotoxicity resulting from critical targeting and inhibition of acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Therapeutic countermeasures have thus focused on either administering an oxime post-exposure, that can rapidly reactivate OP-inhibited AChE, or by preventing OP poisoning through administering pre-exposure treatments that scavenge OPs before they inhibit their physiological AChE targets. While several pyridinium aldoxime antidotes are currently approved, their utility is impaired due to their inability to cross the blood-brain barrier (BBB) efficiently. The present study utilized a macaque (Ma) model to demonstrate the efficacy of a novel zwitterionic and centrally acting oxime RS194B to reactivate sarin- and paraoxon-inhibited macaque AChE and butyrylcholinesterase (BChE) in vitro and to further assess the capacity of RS194B to effect a reversal of clinical symptoms following sarin inhalation in vivo. In vitro, oxime reactivation of MaAChE and MaBChE was shown to be comparable to their human orthologs, while the macaque studies indicated that IM administration of 62.5 mg/kg of RS194B and 0.28 mg/kg atropine after continuous exposure to 49.6 mug/kg sarin vapor, rapidly reactivated the inhibited AChE and BChE in blood and reversed both early and advanced clinical symptoms of sarin-induced toxicity following pulmonary exposure within 1 h. The rapid cessation of autonomic and central symptoms, including convulsions, observed in macaques bodes well for the use of RS194B as an intra- or post-exposure human treatment and validates the macaque model in generating efficacy and toxicology data required for approval under the FDA Animal rule.
ESTHER : Rosenberg_2017_Chem.Biol.Interact_274_50
PubMedSearch : Rosenberg_2017_Chem.Biol.Interact_274_50
PubMedID: 28693885

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

Title : Adhesions of extracellular surface-layer associated proteins in Lactobacillus M5-L and Q8-L - Zhang_2016_J.Dairy.Sci_99_1011
Author(s) : Zhang Y , Xiang X , Lu Q , Zhang L , Ma F , Wang L
Ref : J Dairy Sci , 99 :1011 , 2016
Abstract : Surface-layer associated proteins (SLAP) that envelop Lactobacillus paracasei ssp. paracasei M5-L and Lactobacillus casei Q8-L cell surfaces are involved in the adherence of these strain to the human intestinal cell line HT-29. To further elucidate some of the properties of these proteins, we assessed the yields and expressions of SLAP under different incubation conditions. An efficient and selective extraction of SLAP was obtained when cells of Lactobacillus were treated with 5 M LiCl at 37 degrees C in aerobic conditions. The SLAP of Lactobacillus M5-L and Q8-L in cell extracts were visualized by SDS-PAGE and identified by Western blotting with sulfo-N-hydroxysuccinimide-biotin-labeled HT-29 cells as adhesion proteins. Atomic force microscopy contact imaging revealed that Lactobacillus strains M5-L and Q8-L normally display a smooth, homogeneous surface, whereas the surfaces of M5-L and Q8-L treated with 5 M LiCl were rough and more heterogeneous. Analysis of adhesion forces revealed that the initial adhesion forces of 1.41 and 1.28 nN obtained for normal Lactobacillus M5-L and Q8-L strains, respectively, decreased to 0.70 and 0.48 nN, respectively, following 5 M LiCl treatment. Finally, the dominant 45-kDa protein bands of Lactobacillus Q8-L and Lactobacillus M5-L were identified as elongation factor Tu and surface antigen, respectively, by liquid chromatography-tandem mass spectrometry.
ESTHER : Zhang_2016_J.Dairy.Sci_99_1011
PubMedSearch : Zhang_2016_J.Dairy.Sci_99_1011
PubMedID: 26709174
Gene_locus related to this paper: lacpl-LP.0796

Title : Respiratory toxicity of cyanobacterial aphantoxins from Aphanizomenon flos-aquae DC-1 in the zebrafish gill - Zhang_2016_Aquat.Toxicol_176_106
Author(s) : Zhang L , Liu SY , Zhang J , Zhang JK , Hu CX , Liu YD
Ref : Aquat Toxicol , 176 :106 , 2016
Abstract : Aphantoxins from Aphanizomenon flos-aquae are frequently identified in eutrophic waterbodies worldwide. These toxins severely endanger environmental safety and human health due to the production of paralytic shellfish poisons (PSPs). Although the molecular mechanisms of aphantoxin neurotoxicity have been studied, many questions remain to be resolved such as in vivo alterations in branchial histology and neurotransmitter inactivation induced by these neurotoxins. Aphantoxins extracted from a naturally isolated strain of A. flos-aquae DC-1 were determined by high performance liquid chromatography. The basic components of the isolated aphantoxins identified were gonyautoxin 1 (GTX1), gonyautoxin 5 (GTX5), and neosaxitoxin (neoSTX), which comprised 34.04, 21.28, and 12.77% of the total, respectively. Zebrafish (Danio rerio) was administrated 5.3 or 7.61mg STX equivalents (eq)/kg (low and high doses, respectively) of the A. flos-aquae DC-1 aphantoxins by intraperitoneal injection. Histological alterations and changes in neurotransmitter inactivation in the gills of zebrafish were investigated for 24h following exposure. Aphantoxin exposure significantly increased the activities of gill alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and resulted in histological alterations in the gills during the first 12h of exposure, indicating the induction of functional and structural damage. Gill acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were inhibited significantly, suggesting an alteration of neurotransmitter inactivation in zebrafish gills. The observed alterations in gill structure and function followed a time- and dose-dependent pattern. The results demonstrate that aphantoxins or PSPs lead to structural damage and altered function in the gills of zebrafish, including changes in histological structure and increases in the activities of AST and ALT. The inhibition of the activities of AChE and MAO suggest that aphantoxins or PSPs could induce respiratory toxicity in the zebrafish gill. Furthermore, these parameters may be used as bioindicators for investigating aphantoxin exposure and cyanobacterial blooms in nature.
ESTHER : Zhang_2016_Aquat.Toxicol_176_106
PubMedSearch : Zhang_2016_Aquat.Toxicol_176_106
PubMedID: 27130970

Title : Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors - Si_2016_Bioorg.Med.Chem.Lett_26_2380
Author(s) : Si W , Zhang T , Zhang L , Mei X , Dong M , Zhang K , Ning J
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :2380 , 2016
Abstract : A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44nM and 13.58nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.
ESTHER : Si_2016_Bioorg.Med.Chem.Lett_26_2380
PubMedSearch : Si_2016_Bioorg.Med.Chem.Lett_26_2380
PubMedID: 27017111

Title : Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation - Zhang_2016_J.Pharmacol.Exp.Ther_359_374
Author(s) : Zhang J , Zhang L , Sun X , Yang Y , Kong L , Lu C , Lv G , Wang T , Wang H , Fu F
Ref : Journal of Pharmacology & Experimental Therapeutics , 359 :374 , 2016
Abstract : Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.
ESTHER : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedSearch : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedID: 27535978

Title : Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet - Zhang_2016_Int.J.Mol.Sci_17_
Author(s) : Zhang L , Cai Y , Wei S , Ling Y , Zhu L , Li D , Cai Z
Ref : Int J Mol Sci , 17 : , 2016
Abstract : Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency.
ESTHER : Zhang_2016_Int.J.Mol.Sci_17_
PubMedSearch : Zhang_2016_Int.J.Mol.Sci_17_
PubMedID: 27999286

Title : Development of a neuroprotective potential algorithm for medicinal plants - Liu_2016_Neurochem.Int_100_164
Author(s) : Liu W , Ma H , DaSilva NA , Rose KN , Johnson SL , Zhang L , Wan C , Dain JA , Seeram NP
Ref : Neurochem Int , 100 :164 , 2016
Abstract : Medicinal plants are promising candidates for Alzheimer's disease (AD) research but there is lack of systematic algorithms and procedures to guide their selection and evaluation. Herein, we developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Abeta) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation. The twenty-three herbal extracts were initially evaluated for: 1) total polyphenol content (Folin-Ciocalteu assay), 2) free radical scavenging capacity (DPPH assay), 3) ferric reducing antioxidant power (FRAP assay), 4) reactive carbonyl species scavenging capacity (methylglyoxal trapping assay), 5) anti-glycative effects (BSA-fructose, and BSA-methylglyoxal assays) and, 6) anti-Abeta fibrillation effects (thioflavin-T assay). Based on assigned index scores from the initial screening, twelve extracts with a cumulative NPA score >/=40 were selected for further evaluation for their: 1) inhibitory effects on AChE activity, 2) in vitro anti-inflammatory effects on murine BV-2 microglial cells (Griess assay measuring levels of lipopolysaccharide-induced nitric oxide species), and 3) in vivo neuroprotective effects on Caenorhabditis elegans post induction of Abeta1-42 induced neurotoxicity and paralysis. Among these, four extracts had a cumulative NPA score >/=60 including Phyllanthus emblica (amla; Indian gooseberry), Mucuna pruriens (velvet bean), Punica granatum (pomegranate) and Curcuma longa (turmeric; curcumin). These extracts also showed protective effects on H2O2 induced cytotoxicity in differentiated cholinergic human neuronal SH-SY5Y and murine BV-2 microglial cells and reduced tau protein levels in the SH-SY5Y neuronal cells. While published animal data support the neuroprotective effects of several of these Ayurvedic medicinal plant extracts, some remain unexplored for their anti-AD potential. Therefore, the NPA may be utilized, in part, as a strategy to help guide the selection of promising medicinal plant candidates for future AD-based research using animal models.
ESTHER : Liu_2016_Neurochem.Int_100_164
PubMedSearch : Liu_2016_Neurochem.Int_100_164
PubMedID: 27693453

Title : Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences - Liu_2016_Mol.Neurobiol_53_4972
Author(s) : Liu YW , Zhang L , Li Y , Cheng YQ , Zhu X , Zhang F , Yin XX
Ref : Molecular Neurobiology , 53 :4972 , 2016
Abstract : Acetylcholinesterase (AChE) is impaired in brain of diabetic animals, which may be one of the reasons for diabetes-associated cognitive decline. However, the mechanism is still unknown. The present study was designed to investigate whether the increased expression of AChE in central neurons under high glucose (HG) condition was due to activation of mammalian target of rapamycin (mTOR) signaling. It was found that more production of reactive oxygen species, and higher levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE were detected in HT-22 cells in HG group than normal glucose group after culture for 24 h, which were all attenuated by an antioxidant N-acetyl-L-cysteine. A PI3K inhibitor LY294002 significantly decreased the levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE protein expression in HG-cultured HT-22 cells, and an mTOR inhibitor rapamycin markedly reduced the levels of phospho-mTOR, phospho-p70S6K, and AChE expression. Furthermore, compared with normal rats, diabetic rats showed remarkable increases in levels of AChE activity and expression, malondialdehyde, phospho-mTOR, phospho-p70S6K, and a significant decrease in total superoxide dismutase activity in both hippocampus and cerebral cortex. However, much lower levels of phospho-mTOR, phospho-p70S6K, and AChE expression occurred in both brain regions of diabetic rats treated with rapamycin when compared with untreated ones. These results indicated that mTOR signaling was activated through the activation of PI3K/Akt pathway mediated by oxidative stress in HG-cultured HT-22 cells and diabetic rat brains, which contributed to the elevated protein expression of AChE in central neurons under the condition of HG.
ESTHER : Liu_2016_Mol.Neurobiol_53_4972
PubMedSearch : Liu_2016_Mol.Neurobiol_53_4972
PubMedID: 26374551

Title : Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B - Wang_2016_Appl.Microbiol.Biotechnol_100_5883
Author(s) : Wang P , He J , Sun Y , Reynolds M , Zhang L , Han S , Liang S , Sui H , Lin Y
Ref : Applied Microbiology & Biotechnology , 100 :5883 , 2016
Abstract : To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells.
ESTHER : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedSearch : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedID: 26969039

Title : Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation - Hagstrom_2017_Arch.Toxicol_91_2837
Author(s) : Hagstrom D , Hirokawa H , Zhang L , Radic Z , Taylor P , Collins ES
Ref : Archives of Toxicology , 91 :2837 , 2016
Abstract : The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D. japonica cholinesterase (DjChE) activity departs from conventional AChE and BChE classifications. Inhibition by classic protonable amine and quaternary reversible inhibitors (ethopropazine, donepezil, tacrine, edrophonium, BW284c51, propidium) shows that DjChE is far less sensitive to these inhibitors than human AChE, suggesting discrete differences in active center and peripheral site recognition and structures. Additionally, we find that different OPs (chlorpyrifos oxon, paraoxon, dichlorvos, diazinon oxon, malaoxon) and carbamylating agents (carbaryl, neostigmine, physostigmine, pyridostigmine) differentially inhibit DjChE activity in vitro. DjChE was most sensitive to diazinon oxon and neostigmine and least sensitive to malaoxon and carbaryl. Diazinon oxon-inhibited DjChE could be reactivated by the quaternary oxime, pralidoxime (2-PAM), and the zwitterionic oxime, RS194B, with RS194B being significantly more potent. Sodium fluoride (NaF) reactivates OP-DjChE faster than 2-PAM. As one of the most ancient true cholinesterases, DjChE provides insight into the evolution of a hybrid enzyme before the separation into distinct AChE and BChE enzymes found in higher vertebrates. The sensitivity of DjChE to OPs and capacity for reactivation validate the use of planarians for OP toxicology studies.
ESTHER : Hagstrom_2017_Arch.Toxicol_91_2837
PubMedSearch : Hagstrom_2017_Arch.Toxicol_91_2837
PubMedID: 27990564
Gene_locus related to this paper: dugja-CHE1 , dugja-CHE2

Title : Baicalein improves behavioral dysfunction induced by Alzheimer's disease in rats - Zhou_2016_Neuropsychiatr.Dis.Treat_12_3145
Author(s) : Zhou L , Tan S , Shan YL , Wang YG , Cai W , Huang XH , Liao XY , Li HY , Zhang L , Zhang BJ , Lu ZQ
Ref : Neuropsychiatr Dis Treat , 12 :3145 , 2016
Abstract : BACKGROUND: Alzheimer's disease (AD) is considered to be a neurodegenerative disorder that is characterized by increased oxidative stress. Medicinal plants, with their antioxidant properties, have been used to cure several human diseases. The aim of the current study was to explore the protective and therapeutic effect of baicalein on AD-induced rats. MATERIALS AND
METHODS: Swiss Wistar rats were used in the study. The rats were divided into five groups. Group I: normal control group treated with water; Group II: disease control treated with AlCl3 to induce the mimicking AD for 4 successive weeks (SW); Group III: normal control group treated with baicalein (5 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group IV: normal control group treated with baicalein (10 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group V: normal control group treated with rivastigmine (0.3 mg/kg) for 2 SW followed by combination of rivastigmine and AlCl3 for 4 SW. Moreover, the therapeutic groups are as follows: Group VI: AD disease control treated with AlCl3 for 4 SW and serving as the therapeutic positive group; Group VII: AD disease control + baicalein (5 mg/kg) for 12 SW; Group VIII: AD disease control + baicalein (10 mg/kg) for 12 SW; Group IX: AD disease control + rivastigmine (0.3 mg/kg) for 12 SW. Behavioral test, T-maze, and rotarod test were also performed before and after the treatment. At the end of the experimental study, all the rats were sacrificed and their brains were removed and divided into two portions. The first portion was homogenated for estimating the level of acetylcholinesterase (AchE) and acetylcholine (Ach). Another portion was used for histopathological evaluation.
RESULTS: The current investigation showed that baicalein significantly reduced the duration of revolving on the rotarod, cage activity, and T-maze activity in a dose-dependent manner compared with the AD control group rats. It also altered the AchE and Ach levels in the brain homogenates. The histopathology study also provides strength to the protective effect of baicalein. CONCLUSION: The current study showed that baicalein significantly (P<0.05) improved the biochemical and histopathological condition of AD in rats.
ESTHER : Zhou_2016_Neuropsychiatr.Dis.Treat_12_3145
PubMedSearch : Zhou_2016_Neuropsychiatr.Dis.Treat_12_3145
PubMedID: 28003750

Title : Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography - Zha_2016_J.Med.Chem_59_114
Author(s) : Zha X , Lamba D , Zhang L , Lou Y , Xu C , Kang D , Chen L , Xu Y , De Simone A , Samez S , Pesaresi A , Stojan J , Lopez MG , Egea J , Andrisano V , Bartolini M
Ref : Journal of Medicinal Chemistry , 59 :114 , 2016
Abstract : Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and beta-amyloid self-aggregation. Selected compounds displayed significant inhibition of human beta-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both beta-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 muM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.
ESTHER : Zha_2016_J.Med.Chem_59_114
PubMedSearch : Zha_2016_J.Med.Chem_59_114
PubMedID: 26632651
Gene_locus related to this paper: torca-ACHE

Title : Novel Natural Oximes and Oxime Esters with a Vibralactone Backbone from the Basidiomycete Boreostereum vibrans - Chen_2016_ChemistryOpen_5_142
Author(s) : Chen HP , Zhao ZZ , Li ZH , Dong ZJ , Wei K , Bai X , Zhang L , Wen CN , Feng T , Liu JK
Ref : ChemistryOpen , 5 :142 , 2016
Abstract : A variety of novel natural products with significant bioactivities are produced by the basidiomycete Boreostereum vibrans. In the present study, we describe 16 novel natural oximes and oxime esters with a vibralactone backbone, vibralactoximes, which were isolated from the scale-up fermentation broth of B. vibrans. Their structures were determined through extensive spectroscopic analyses. These compounds represent the first oxime esters from nature. The hypothetical biosynthetic pathway of these compounds was also proposed. Seven compounds exhibited significant pancreatic lipase inhibitory activity, while ten compounds exhibited cytotoxicities against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480), with IC50 values comparable with those of cisplatin.
ESTHER : Chen_2016_ChemistryOpen_5_142
PubMedSearch : Chen_2016_ChemistryOpen_5_142
PubMedID: 27308232

Title : Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora - Zhang_2016_Sci.Rep_6_23122
Author(s) : Zhang L , Zhou Z , Guo Q , Fokkens L , Miskei M , Pocsi I , Zhang W , Chen M , Wang L , Sun Y , Donzelli BG , Gibson DM , Nelson DR , Luo JG , Rep M , Liu H , Yang S , Wang J , Krasnoff SB , Xu Y , Molnar I , Lin M
Ref : Sci Rep , 6 :23122 , 2016
Abstract : Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle.
ESTHER : Zhang_2016_Sci.Rep_6_23122
PubMedSearch : Zhang_2016_Sci.Rep_6_23122
PubMedID: 26975455
Gene_locus related to this paper: 9hypo-a0a151ga75 , 9hypo-a0a151gbh5 , 9hypo-a0a151gd50 , 9hypo-a0a151ggb9 , 9hypo-a0a151gjd5 , 9hypo-a0a151gtv2 , 9hypo-a0a151gxh2 , 9hypo-a0a151gaw8 , 9hypo-a0a151gia2

Title : Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys - Warren_2016_Nature_531_381
Author(s) : Warren TK , Jordan R , Lo MK , Ray AS , Mackman RL , Soloveva V , Siegel D , Perron M , Bannister R , Hui HC , Larson N , Strickley R , Wells J , Stuthman KS , Van Tongeren SA , Garza NL , Donnelly G , Shurtleff AC , Retterer CJ , Gharaibeh D , Zamani R , Kenny T , Eaton BP , Grimes E , Welch LS , Gomba L , Wilhelmsen CL , Nichols DK , Nuss JE , Nagle ER , Kugelman JR , Palacios G , Doerffler E , Neville S , Carra E , Clarke MO , Zhang L , Lew W , Ross B , Wang Q , Chun K , Wolfe L , Babusis D , Park Y , Stray KM , Trancheva I , Feng JY , Barauskas O , Xu Y , Wong P , Braun MR , Flint M , McMullan LK , Chen SS , Fearns R , Swaminathan S , Mayers DL , Spiropoulou CF , Lee WA , Nichol ST , Cihlar T , Bavari S
Ref : Nature , 531 :381 , 2016
Abstract : The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.
ESTHER : Warren_2016_Nature_531_381
PubMedSearch : Warren_2016_Nature_531_381
PubMedID: 26934220

Title : Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis - Wang_2015_Hepatology_61_870
Author(s) : Wang C , Zhao Y , Gao X , Li L , Yuan Y , Liu F , Zhang L , Wu J , Hu P , Zhang X , Gu Y , Xu Y , Wang Z , Li Z , Zhang H , Ye J
Ref : Hepatology , 61 :870 , 2015
Abstract : Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity.
ESTHER : Wang_2015_Hepatology_61_870
PubMedSearch : Wang_2015_Hepatology_61_870
PubMedID: 25179419

Title : The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration - Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
Author(s) : Xiao L , Yang G , Zhang L , Yang X , Zhao S , Ji Z , Zhou Q , Hu M , Wang Y , Chen M , Xu Y , Jin H , Xiao X , Hu G , Bao F , Hu Y , Wan P , Li L , Deng X , Kuang T , Xiang C , Zhu JK , Oliver MJ , He Y
Ref : Proc Natl Acad Sci U S A , 112 :5833 , 2015
Abstract : "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes.
ESTHER : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedSearch : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedID: 25902549
Gene_locus related to this paper: 9lami-a0a2z7c6k4 , 9lami-a0a2z7bgj4

Title : The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis - Li_2015_Chemosphere_135_387
Author(s) : Li D , Huang Q , Lu M , Zhang L , Yang Z , Zong M , Tao L
Ref : Chemosphere , 135 :387 , 2015
Abstract : The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, gammaH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of gammaH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis.
ESTHER : Li_2015_Chemosphere_135_387
PubMedSearch : Li_2015_Chemosphere_135_387
PubMedID: 26002045

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

Title : Biphasic photoelectrochemical sensing strategy based on in situ formation of CdS quantum dots for highly sensitive detection of acetylcholinesterase activity and inhibition - Hou_2015_Biosens.Bioelectron_75_359
Author(s) : Hou T , Zhang L , Sun X , Li F
Ref : Biosensors & Bioelectronics , 75 :359 , 2015
Abstract : Herein, we reported a facile and highly sensitive biphasic photoelectrochemical (PEC) sensing strategy based on enzymatic product-mediated in situ formation of CdS quantum dots (QDs), and assayed the activity and inhibition of acetylcholinesterase (AChE) in its optimal state. Upon the hydrolysis of acetylthiocholine catalyzed by AChE, the product thiocholine stabilizes the in situ formation of CdS QDs in homogenous solution. Due to the electrostatic attraction, the resulting tertiary amino group-functionalized CdS QDs are attached to the surface of the negatively charged indium tin oxide (ITO) electrode, generating significant PEC response upon illumination in the presence of electron donors. By taking full advantage of the in situ formation of CdS QDs in homogenous solution, this strategy is capable of detecting AChE activity and inhibition in its optimal state. A directly measured detection limit of 0.01mU/mL for AChE activity is obtained, which is superior to those obtained by some fluorescence methods. The inhibition of AChE activity by aldicarb is successfully detected, and the corresponding IC50 is determined to be 13mug/L. In addition to high sensitivity and good selectivity, this strategy also exhibits additional advantages of simplicity, low cost and easy operation. To the best of our knowledge, the as-proposed strategy is the first example demonstrating the application of CdS QDs formed in situ for biphasic PEC detection of enzyme activity and inhibition. More significantly, it opens up a new horizon for the development of homogenous PEC sensing platforms, and has great potential in probing many other analytes.
ESTHER : Hou_2015_Biosens.Bioelectron_75_359
PubMedSearch : Hou_2015_Biosens.Bioelectron_75_359
PubMedID: 26339933

Title : Outbred genome sequencing and CRISPR\/Cas9 gene editing in butterflies - Li_2015_Nat.Commun_6_8212
Author(s) : Li X , Fan D , Zhang W , Liu G , Zhang L , Zhao L , Fang X , Chen L , Dong Y , Chen Y , Ding Y , Zhao R , Feng M , Zhu Y , Feng Y , Jiang X , Zhu D , Xiang H , Feng X , Li S , Wang J , Zhang G , Kronforst MR , Wang W
Ref : Nat Commun , 6 :8212 , 2015
Abstract : Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system.
ESTHER : Li_2015_Nat.Commun_6_8212
PubMedSearch : Li_2015_Nat.Commun_6_8212
PubMedID: 26354079
Gene_locus related to this paper: papxu-a0a194pj15 , papxu-a0a194q254 , papma-a0a194rdx2 , papxu-a0a194q858 , papxu-a0a194pyl3 , papxu-a0a194q337 , papma-a0a194r1p9 , papma-a0a194r6h1 , papxu-a0a194q1w8 , papma-a0a194ql80 , papma-a0a0n1ipl3 , papma-a0a194qm14

Title : Unraveling adaptation of Pontibacter korlensis to radiation and infertility in desert through complete genome and comparative transcriptomic analysis - Dai_2015_Sci.Rep_5_10929
Author(s) : Dai J , Dai W , Qiu C , Yang Z , Zhang Y , Zhou M , Zhang L , Fang C , Gao Q , Yang Q , Li X , Wang Z , Jia Z , Chen X
Ref : Sci Rep , 5 :10929 , 2015
Abstract : The desert is a harsh habitat for flora and microbial life due to its aridness and strong radiation. In this study, we constructed the first complete and deeply annotated genome of the genus Pontibacter (Pontibacter korlensis X14-1(T) = CCTCC AB 206081(T), X14-1). Reconstruction of the sugar metabolism process indicated that strain X14-1 can utilize diverse sugars, including cellulose, starch and sucrose; this result is consistent with previous experiments. Strain X14-1 is also able to resist desiccation and radiation in the desert through well-armed systems related to DNA repair, radical oxygen species (ROS) detoxification and the OstAB and TreYZ pathways for trehalose synthesis. A comparative transcriptomic analysis under gamma radiation revealed that strain X14-1 presents high-efficacy operating responses to radiation, including the robust expression of catalase and the manganese transport protein. Evaluation of 73 novel genes that are differentially expressed showed that some of these genes may contribute to the strain's adaptation to radiation and desiccation through ferric transport and preservation.
ESTHER : Dai_2015_Sci.Rep_5_10929
PubMedSearch : Dai_2015_Sci.Rep_5_10929
PubMedID: 26057562
Gene_locus related to this paper: 9bact-a0a0e3zf06 , 9bact-a0a0e3zhq7

Title : Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2 - Yang_2015_J.Surg.Res_194_273
Author(s) : Yang B , Ni YF , Wang WC , Du HY , Zhang H , Zhang L , Zhang WD , Jiang T
Ref : J Surg Res , 194 :273 , 2015
Abstract : BACKGROUND: Successful drug treatment for ischemia--reperfusion-induced lung injury remains a major clinical problem. Melatonin (MT) is a hormone that is principally synthesized in the pineal gland. It has been shown to exhibit a variety of functions including anti-inflammatory and antioxidant effects. Previous reports on N-myc downstream-regulated gene (NDRG)2 have suggested that it is involved in cellular differentiation, development, antiapoptosis, anti-inflammatory cytokine, and antioxidant. The objective of this study was to test whether MT, a novel NDRG2 activator, can protect against intestinal ischemia-reperfusion-induced lung injury (IIRI). MATERIALS AND
METHODS: IIRI was induced in rats by occlusion of the superior mesenteric artery for 60 min, and the occlusion was then released for reperfusion. Rats were randomly divided into six groups as follows: control group; MT group; IIRI group; IIRI+5 mg/kg MT group; IIRI+15 mg/kg MT group; and IIRI+25 mg/kg MT group. The effects of MT on intestinal ischemia-reperfusion-induced lung pathologic changes, inflammatory cytokines release, myeloperoxidase and superoxide dismutase activities, and malondialdehyde level were examined. In addition, the NDRG2 activation in lung tissues was detected by Western blot analysis.
RESULTS: MT pretreatment attenuated edema and the pathologic changes in the lung. MT also decreased the levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 in bronchoalveolar lavage fluid. In addition, MT markedly prevented IIRI-induced elevation of malondialdehyde and myeloperoxidase levels, as well as reduction of superoxide dismutase activity. Furthermore, the expression of NDRG2 was activated by MT pretreatment in lung tissues.
CONCLUSIONS: The present study demonstrates that MT exerted protection against IIRI-induced oxidative stress. The potential mechanism of this action may attribute partly to the activation of NDRG2 expression.
ESTHER : Yang_2015_J.Surg.Res_194_273
PubMedSearch : Yang_2015_J.Surg.Res_194_273
PubMedID: 25491174

Title : Alleviating effects of bushen-yizhi formula on ibotenic Acid-induced cholinergic impairments in rat - Hou_2015_Rejuvenation.Res_18_111
Author(s) : Hou XQ , Zhang L , Yang C , Rong CP , He WQ , Zhang CX , Li S , Su RY , Chang X , Qin JH , Chen YB , Xian SX , Wang Q
Ref : Rejuvenation Res , 18 :111 , 2015
Abstract : This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.
ESTHER : Hou_2015_Rejuvenation.Res_18_111
PubMedSearch : Hou_2015_Rejuvenation.Res_18_111
PubMedID: 25482164

Title : Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats - Shen_2015_Stroke_46_2607
Author(s) : Shen H , Chen Z , Wang Y , Gao A , Li H , Cui Y , Zhang L , Xu X , Wang Z , Chen G
Ref : Stroke , 46 :2607 , 2015
Abstract : BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.
METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1beta and neuroligin-1 and the interaction between neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1beta and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin-1 might be good targets for improving cognitive function after SAH.
ESTHER : Shen_2015_Stroke_46_2607
PubMedSearch : Shen_2015_Stroke_46_2607
PubMedID: 26219651

Title : Complete Genome Sequence of Paenibacillus polymyxa CF05, a Strain of Plant Growth-Promoting Rhizobacterium with Elicitation of Induced Systemic Resistance - Lei_2015_Genome.Announc_3_e00198
Author(s) : Lei M , Lu P , Jin L , Wang Y , Qin J , Xu X , Zhang L
Ref : Genome Announc , 3 : , 2015
Abstract : Paenibacillus polymyxa CF05 is a Gram-positive rod-shaped bacterium isolated from the interior of an ancient tree, Cryptomeria fortunei, in China. This bacterium displays potent biocontrol effects against certain soil-borne diseases and the elicitation of induced systemic resistance in tomatoes. Here, we report the complete genome sequence of P. polymyxa CF05.
ESTHER : Lei_2015_Genome.Announc_3_e00198
PubMedSearch : Lei_2015_Genome.Announc_3_e00198
PubMedID: 25883277
Gene_locus related to this paper: paepo-a0a0f6ex20 , paepo-a0a0f6em71 , paepo-a0a0f6ezz0

Title : Association of and with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls - Ji_2015_Exp.Ther.Med_9_1831
Author(s) : Ji H , Dai D , Wang Y , Jiang D , Zhou X , Lin P , Ji X , Li J , Zhang Y , Yin H , Chen R , Zhang L , Xu M , Duan S , Wang Q
Ref : Exp Ther Med , 9 :1831 , 2015
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.
ESTHER : Ji_2015_Exp.Ther.Med_9_1831
PubMedSearch : Ji_2015_Exp.Ther.Med_9_1831
PubMedID: 26136901

Title : Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases - Zhang_2015_Forensic.Sci.Med.Pathol_11_570
Author(s) : Zhang L , Ma J , Li S , Xue R , Jin M , Zhou Y
Ref : Forensic Science Med Pathol , 11 :570 , 2015
Abstract : Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 microg/ml in heart blood, 39 microg/ml in femoral vein blood, 141 microg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.
ESTHER : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedSearch : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedID: 26481789

Title : Preparation and characterization of a novel thermostable lipase from Thermomicrobium roseum - Fang_2021_Catal.Sci.Technol_11_7386
Author(s) : Fang Y , Zhou Y , Xin Y , Shi Y , Guo Z , Li Y , Gu Z , Ding Z , Shi G , Zhang L
Ref : Catal Sci Technol , 11 :7386 , 2015
Abstract : In this study, a hypothetical lipase gene from Thermomicrobium roseum DSM 5159 (GenBank: ACM04789.1) was recombinantly expressed and characterized. The TrLIP gene was inserted into two different plasmids (pTIG and pMA5 constructed by our laboratory) and further expressed in E. coli BL21 and B. subtilis W600 (TrLIPB/E), respectively. After purification, TrLipE/B showed a single band at approx. 38 kDa on 10% reducing SDS-PAGE gels. The successful expression of TrLipE/B was further confirmed by peptide map fingerprinting (PMF) analysis. For both expression systems, the target enzyme revealed marked stability over a wide temperature and pH range. In E. coli BL21, the optimal temperature and pH were 85 C and 8.5, while these were 90 C and 9 in B. subtilis W600. Additionally, the studied TrLipE/B was found to show remarkable tolerance in mixed systems constituted by water and organic solvents. Depending on the different expression systems, TrLipB has better enzymatic properties, in particular, thermostability and organic solvent tolerance. Based on the circular dichroism (CD) analysis, the corresponding helix, beta-sheet, beta-turn and random coil compositions were slightly different between TrLipE (34.8%, 11.2%, 23.4% and 30.6%) and TrLipB (35.9%, 11.1%, 23.3% and 29.7%). The thermostability of TrLipE/B was further verified with nano-DSC analysis. The melting temperature (Tm) and denaturation enthalpy (deltaH) of TrLipE were 97.51 C and 1637 KJ mol-1, 98.53 C and 1463 kJ mol-1 for TrLipB. The substrate specificity and enzymatic kinetics were analyzed as well. The studied TrLipE/B's capability to catalyze p-nitrophenol esters with different carbon chain lengths was verified. Enzymatic transesterification of immobilized TrLipB was confirmed, with a molar conversion rate of 23.32%. This research therefore provides a candidate that could be applied for biocleanser production and organic synthesis, especially under environments requiring high temperature.
ESTHER : Fang_2021_Catal.Sci.Technol_11_7386
PubMedSearch : Fang_2021_Catal.Sci.Technol_11_7386
PubMedID:

Title : Draft Genome Sequence of Ralstonia pickettii AU12-08, Isolated from an Intravascular Catheter in Australia - Zhang_2014_Genome.Announc_2_e00027
Author(s) : Zhang L , Morrison M , Rickard CM
Ref : Genome Announc , 2 : , 2014
Abstract : Ralstonia pickettii is a nonfermenting Gram-negative bacillus that creates a significant problem in clinical settings, as it is a widespread cause of nosocomial infections. Here, we report the draft genome sequence of R. pickettii AU12-08, isolated from an intravascular catheter tip.
ESTHER : Zhang_2014_Genome.Announc_2_e00027
PubMedSearch : Zhang_2014_Genome.Announc_2_e00027
PubMedID: 24503988
Gene_locus related to this paper: 9rals-s9rw78 , 9rals-s9tfx3 , 9rals-s9teu7

Title : Transcriptomic comparison of thiamethoxam-resistance adaptation in resistant and susceptible strains of Aphis gossypii Glover - Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
Author(s) : Pan Y , Peng T , Gao X , Zhang L , Yang C , Xi J , Xin X , Bi R , Shang Q
Ref : Comparative Biochemistry & Physiology Part D Genomics Proteomics , 13C :10 , 2014
Abstract : A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P<=0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) alpha subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam.
ESTHER : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedSearch : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedID: 25528611

Title : Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides and Their Acetylcholinesterase Inhibitory Activity - Zhang_2014_Molecules_19_9999
Author(s) : Zhang DB , Chen JJ , Song QY , Zhang L , Gao K
Ref : Molecules , 19 :9999 , 2014
Abstract : Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-beta-d-glucopyranoside (4), along with ten known analogues 5-14, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed.
ESTHER : Zhang_2014_Molecules_19_9999
PubMedSearch : Zhang_2014_Molecules_19_9999
PubMedID: 25014530

Title : Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress - Zhang_2014_PLoS.One_9_e97878
Author(s) : Zhang L , Zhang C , Wu P , Chen Y , Li M , Jiang H , Wu G
Ref : PLoS ONE , 9 :e97878 , 2014
Abstract : BACKGROUND: Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. METHODOLOGY/PRINCIPAL FINDINGS: We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. CONCLUSIONS/SIGNIFICANCE: The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.
ESTHER : Zhang_2014_PLoS.One_9_e97878
PubMedSearch : Zhang_2014_PLoS.One_9_e97878
PubMedID: 24837971
Gene_locus related to this paper: jatcu-a0a067k7w6 , jatcu-a0a067juw0 , jatcu-a0a067jz21 , jatcu-a0a067jeh8 , jatcu-a0a067jvs1 , jatcu-a0a067jvz5 , jatcu-a0a067jc69 , jatcu-a0a067jpe1 , jatcu-a0a067jf51 , jatcu-a0a067kvu1 , jatcu-a0a067kfw0 , jatc