Liu X

References (368)

Title : Microarray and Functional Pathway Analyses Revealed Significantly Elevated Gene Expressions Associated with Metabolic Resistance to Oxamyl (Vydate) in Lygus lineolaris - Zhu_2024_Toxics_12_
Author(s) : Zhu YC , Du Y , Liu X , Portilla M , Chen J , Wang Y
Ref : Toxics , 12 : , 2024
Abstract : The tarnished plant bug (TPB, Lygus lineolaris) remains a major pest for a variety of crops. Frequent sprays on row crops, especially cotton, prompted resistance development in field populations. To maintain chemical control as an effective tool against the pest, knowledge of global gene regulations is desirable for better understanding and managing the resistance. Novel microarray expressions of 6688 genes showed 685 significantly upregulated and 1382 significantly downregulated genes in oxamyl-selected TPBs (Vyd1515FF[R]) from a cotton field. Among the 685 upregulated genes (participated in 470 pathways), 176 genes code 30 different enzymes, and 7 of the 30 participate in 24 metabolic pathways. Six important detoxification pathways were controlled by 20 genes, coding 11 esterases, two P450s, two oxidases, and three pathway-associated enzymes (synthases, reductase, and dehydrogenase). Functional analyses showed substantially enhanced biological processes and molecular functions, with hydrolase activity as the most upregulated molecular function (controlled by 166 genes). Eleven esterases belong to the acting on ester bond subclass of the 166 hydrolases. Surprisingly, only one GST showed significant upregulation, but it was not involved in any detoxification pathway. Therefore, this research reports a set of 20 genes coding 6 enzyme classes to detoxify a carbamate insecticide oxamyl in Vyd1515FF. Together with three previous reports, we have obtained the best knowledge of resistance mechanisms to all four conventional insecticide classes in the economically important crop pest. This valuable finding will greatly facilitate the development of molecular tools to monitor and manage the resistance and to minimize risk to environment.
ESTHER : Zhu_2024_Toxics_12_
PubMedSearch : Zhu_2024_Toxics_12_
PubMedID: 38535921

Title : Complete decomposition of poly(ethylene terephthalate) by crude PET hydrolytic enzyme produced in Pichia pastoris - Chen_2024_Chem.Eng.J_481_148418
Author(s) : Chen CC , Li X , Min J , Zeng Z , Ning Z , He H , Long X , Niu D , Peng R , Liu X , Yang Y , Huang JW , Guo RT
Ref : Chemical Engineering Journal , 481 :148418 , 2024
Abstract : Using enzymes to decompose poly(ethylene terephthalate) (PET) is an attractive strategy to the sustainable utilization of PET, and an effective production platform of PET degrading enzyme is a prerequisite to achieve this goal. Here, we exploited the industrial yeast strain Pichia pastoris to produce a potent PET hydrolase termed FAST-PETase, whose performance was further elevated by removing two N-linked glycosylations through molecular engineering. The expression of the yielded variant, FAST-PETase-212/277, was elevated by antibiotics selection and chaperon co-expression to exceed 3 g/L in a 30-L fermenter. Notably, the crude fermentation product can be directly applied to decompose PET without purification. More than 95 % postconsumer PET can be achieved by 0.5 mgenzyme gPET-1 in 24 h in a 10-L reaction system in a reactor. These results demonstrate the economic viability of producing PET hydrolytic enzyme with modern fermentation facilities for large scale PET decomposition.
ESTHER : Chen_2024_Chem.Eng.J_481_148418
PubMedSearch : Chen_2024_Chem.Eng.J_481_148418
Gene_locus related to this paper: idesa-peth

Title : The role of the nucleus basalis of Meynert in neuromodulation therapy: a systematic review from the perspective of neural network oscillations - Jiao_2024_Front.Aging.Neurosci_16_1376764
Author(s) : Jiao L , Kang H , Geng Y , Liu X , Wang M , Shu K
Ref : Front Aging Neurosci , 16 :1376764 , 2024
Abstract : As a crucial component of the cerebral cholinergic system and the Papez circuit in the basal forebrain, dysfunction of the nucleus basalis of Meynert (NBM) is associated with various neurodegenerative disorders. However, no drugs, including existing cholinesterase inhibitors, have been shown to reverse this dysfunction. Due to advancements in neuromodulation technology, researchers are exploring the use of deep brain stimulation (DBS) therapy targeting the NBM (NBM-DBS) to treat mental and neurological disorders as well as the related mechanisms. Herein, we provided an update on the research progress on cognition-related neural network oscillations and complex anatomical and projective relationships between the NBM and other cognitive structures and circuits. Furthermore, we reviewed previous animal studies of NBM lesions, NBM-DBS models, and clinical case studies to summarize the important functions of the NBM in neuromodulation. In addition to elucidating the mechanism of the NBM neural network, future research should focus on to other types of neurons in the NBM, despite the fact that cholinergic neurons are still the key target for cell type-specific activation by DBS.
ESTHER : Jiao_2024_Front.Aging.Neurosci_16_1376764
PubMedSearch : Jiao_2024_Front.Aging.Neurosci_16_1376764
PubMedID: 38650866

Title : Construction of Virtual Compound Library and Screening of Acetylcholinesterase Inhibitor for the Medicinal Chemistry Laboratory - Yang_2024_J.Chem.Educ_101_1673
Author(s) : Yang J , Yuan Y , Wang N , Liu X , Gu J , Zeng R , Huang M , Zheng P , Wang Y , Huang C , Ouyang Q
Ref : Journal of Chemical Education , 101 :1673 , 2024
Abstract : The utilization of virtual compound libraries and virtual screening has become a routine method in drug discovery and has accelerated the research of pharmacy and translational medicine. With the development of computer-aided drug design (CADD), it is essential to incorporate virtual experiments into the education of medicinal chemistry. Herein, we describe a series of virtual experiments conducted by undergraduate students, including the construction of a virtual compound library, molecular docking, and the virtual screening of acetylcholinesterase inhibitors. Student feedback indicates that the virtual experiments are popular with students and effectively promote their interest in the drug discovery process.
ESTHER : Yang_2024_J.Chem.Educ_101_1673
PubMedSearch : Yang_2024_J.Chem.Educ_101_1673

Title : Ganshuang granule plays a pharmacological role in anti-alcoholic and anti-hangover via regulating alcohol metabolism and affecting neurotransmitters - Li_2024_Int.J.Neurosci__1
Author(s) : Li Q , Lu Y , Shang J , Song Q , Jiao J , Bi L , Jiang T , Liu X
Ref : International Journal of Neuroscience , :1 , 2024
Abstract : Background: To explore the effect of Ganshuang granule on anti-alcoholic and anti-hangover and its potential mechanism.Methods: SPF SD rats' drunken model and SPF Kunming mice's hangover model were used as models.Results: Ganshuang granule could significantly reduce sleep time, the time to climb in mice, and significantly prolong the tolerance time and shorten sleep time in rats (P < 0.05). The blood ethanol concentration of rats in each administration group was lower than that in the model group at each time point (P < 0.05). Compared with the control group, the activities of ADH and ALDH in the liver of the model group were significantly decreased (P < 0.05); the content of DA and 5-HT in the striatum of the model group was significantly increased (P < 0.05); and the activity of AchE in the hippocampus was significantly decreased (P < 0.05). The above processes could be improved and regulated in the drug administration group. Compared with the control group, there was no significant difference between ADH and ALDH in the serum of the model group (P > 0.05). However, the activities of ADH and ALDH in the liver of drunk rats could be upregulated by Ganshuang granule (P < 0.05).Conclusion: Ganshuang granule has the pharmacological effects of anti-alcoholic and anti-hangover, which is related to regulating the activities of ADH and ALDH in the liver, the contents of DA and 5-HT in striatum, and the activity of AchE in the hippocampus.
ESTHER : Li_2024_Int.J.Neurosci__1
PubMedSearch : Li_2024_Int.J.Neurosci__1
PubMedID: 38197183

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

Title : The acute neurotoxicity of inorganic mercury in Mactra chinensis philippi - Ma_2024_Aquat.Toxicol_270_106896
Author(s) : Ma B , Zhao X , Zhang X , Yang B , Cai Z , Xing Z , Xu M , Mi L , Zhang J , Wang L , Zhao Y , Liu X
Ref : Aquat Toxicol , 270 :106896 , 2024
Abstract : Inorganic mercury (IHg) is hazardous to marine organisms especially resulting in neurotoxicity, bivalves are sensitive to pollutants as "ocean sentinel", but data on the neurotoxicity of IHg in bivalves are sparse. So we chosed M. chinensis philippi with typical neural structures in bivalves to investigate the neurotoxicity of IHg, which could be helpful to understand the specificity of neural regulation and the response characteristics of bivalves. After acute exposed to IHg (HgCl(2)) for 24 h, the metabolites of ganglion tissues in M. chinensis philippi were evaluated using (1)H-nuclear magnetic resonance based metabolomics; Ca(2+), neurotransmitters (nitric oxide, glutamate, acetylcholine) and related enzymes (calcineurin, nitric oxide synthase and acetylcholinesterase) were measured using biochemical detection. Compared to the control group, the levels of the nitric oxide (81.04 +/- 12.84 micromol/g prot) and acetylcholine (30.93 +/- 12.57 microg/mg prot) in M. chinensis philippi of IHg-treated were decreased, while glutamate (2.11 +/- 0.61 mmol/L) increased significantly; the activity of nitric oxide synthase (679.34 +/- 135.33 U/mg prot) was increased, while acetylcholinesterase (1.39 +/- 0.44 U/mg prot) decreased significantly, and the activity of calcineurin (0.52 +/- 0.02 U/mg prot) had a statistically insignificant increasing tendency. The concentration of Ca(2+) (0.92 +/- 0.46 mmol/g prot) in the IHg-treated group was significantly higher than that in the control group. OPLS-DA was performed to reveal the difference in metabolites between the control and IHg-challenged groups, the metabolites of glucose, glutamine, inosine, succinate, glutamate, homarine, and alanine were sensitive to IHg, subsequently metabolic pathways that were affected including glucose metabolism, glutamine metabolism, nucleotide metabolism, Krebs cycle, amino acid metabolism and osmotic regulation. In our study, IHg interfered with metabolites in M. chinensis philippi, thus the corresponding metabolic pathways were changed, which influenced the neurotransmitters subsequently. Furthermore, Ca(2+)overload affected the synthesis or degradation of the neurotransmitters, and then the altered neurotransmitters involved in changes in metabolic pathways again. Overall, we hypothesized that the neurotoxic effects of IHg on bivalve were in close contact with metabolism, neurotransmitters, related enzymes and Ca(2+), which could be effective neurotoxic biomarkers for marine environmental quality assessment, and also provide effective data for the study of the regulatory mechanism of the nervous system in response to IHg in bivalves.
ESTHER : Ma_2024_Aquat.Toxicol_270_106896
PubMedSearch : Ma_2024_Aquat.Toxicol_270_106896
PubMedID: 38490093

Title : Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles - Tang_2024_Mater.Today.Bio_25_100988
Author(s) : Tang X , Zhang J , Sui D , Xu Z , Yang Q , Wang T , Li X , Liu X , Deng Y , Song Y
Ref : Mater Today Bio , 25 :100988 , 2024
Abstract : The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.
ESTHER : Tang_2024_Mater.Today.Bio_25_100988
PubMedSearch : Tang_2024_Mater.Today.Bio_25_100988
PubMedID: 38379935

Title : The alpha4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability - Andrew_2024_Toxics_12_
Author(s) : Andrew PM , Feng W , Calsbeek JJ , Antrobus SP , Cherednychenko GA , MacMahon JA , Bernardino PN , Liu X , Harvey DJ , Lein PJ , Pessah IN
Ref : Toxics , 12 : , 2024
Abstract : Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of alpha4, but not alpha7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that alpha4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the alpha4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.
ESTHER : Andrew_2024_Toxics_12_
PubMedSearch : Andrew_2024_Toxics_12_
PubMedID: 38668486

Title : Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea - Wang_2024_J.Agric.Food.Chem__
Author(s) : Wang Q , Wang X , Cai D , Yu J , Chen X , Niu W , Wang S , Liu X , Zhou D , Yin F , Wang T , Shi X , Wu Z , Zhang J , Hao J , Liu P
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.
ESTHER : Wang_2024_J.Agric.Food.Chem__
PubMedSearch : Wang_2024_J.Agric.Food.Chem__
PubMedID: 38226868 || 38634420

Title : Screening of efficient salicylaldoxime reactivators for DFP and paraoxon-inhibited acetylcholinesterase - Wei_2024_RSC.Med.Chem_15_1225
Author(s) : Wei Z , Zhang D , Liu X , Nie H , Ouyang Q , Zhang X , Zheng Z
Ref : RSC Med Chem , 15 :1225 , 2024
Abstract : Previously we reported two salicylaldoxime conjugates (L7R3 and L7R5) showing equal or even higher reactivating efficiency for both organophosphorus nerve agent and pesticide inhibited acetylcholinesterase in comparison to obidoxime and HI-6. In this study, L7R3 and L7R5 were selected as lead compounds and refined by employing a fragment-based drug design strategy, and a total of 32 novel salicylaldoxime conjugates were constructed and screened for DFP and paraoxon inhibited acetylcholinesterase. The findings demonstrate that the conjugate L73R3, which contains a 4-nitrophenyl group, exhibited a higher reactivation efficacy against paraoxon-inhibited acetylcholinesterase compared to obidoxime and HI-6. It was confirmed that the combination of a 4-pyridinyl or 4-nitrophenyl peripheral site ligand, a piperazine linker and a methyl or chloro-substituted salicylaldoxime could construct efficient nonquaternary oxime reactivators. The results hold promise for developing a new generation of highly effective antidotes for organophosphate poisoning.
ESTHER : Wei_2024_RSC.Med.Chem_15_1225
PubMedSearch : Wei_2024_RSC.Med.Chem_15_1225
PubMedID: 38665821

Title : Improvement of plant resistance to geminiviruses via protein de-S-acylation - Zhao_2024_Stress.Biol_4_23
Author(s) : Zhao Y , Li Z , Wang Z , Huang L , Li G , Liu X , Yuan M , Huang W , Ling L , Yang C , He Z , Lai J
Ref : Stress Biol , 4 :23 , 2024
Abstract : Geminiviruses are an important group of viruses that infect a variety of plants and result in heavy agricultural losses worldwide. The homologs of C4 (or L4) in monopartite geminiviruses and AC4 (or AL4) in bipartite geminiviruses are critical viral proteins. The C4 proteins from several geminiviruses are the substrates of S-acylation, a dynamic post-translational modification, for the maintenance of their membrane localization and function in virus infection. Here we initiated a screening and identified a plant protein ABAPT3 (Alpha/Beta Hydrolase Domain-containing Protein 17-like Acyl Protein Thioesterase 3) as the de-S-acylation enzyme of C4 encoded by BSCTV (Beet severe curly top virus). Overexpression of ABAPT3 reduced the S-acylation of BSCTV C4, disrupted its plasma membrane localization, inhibited its function in pathogenesis, and suppressed BSCTV infection. Because the S-acylation motifs are conserved among C4 from different geminiviruses, we tested the effect of ABAPT3 on the C4 protein of ToLCGdV (Tomato leaf curl Guangdong virus) from another geminivirus genus. Consistently, ABAPT3 overexpression also disrupted the S-acylation, subcellular localization, and function of ToLCGdV C4, and inhibited ToLCGdV infection. In summary, we provided a new approach to globally improve the resistance to different types of geminiviruses in plants via de-S-acylation of the viral C4 proteins and it can be extendedly used for suppression of geminivirus infection in crops.
ESTHER : Zhao_2024_Stress.Biol_4_23
PubMedSearch : Zhao_2024_Stress.Biol_4_23
PubMedID: 38662136
Gene_locus related to this paper: arath-At5g14390

Title : Toxicity comparison of benzophenone-3 and its metabolite benzophenone-8 in different tissues of zebrafish - Wang_2024_Aquat.Toxicol_268_106852
Author(s) : Wang Y , Shang Y , Liu X , Chen X , Xu G , Lu G
Ref : Aquat Toxicol , 268 :106852 , 2024
Abstract : Benzophenone-3 (BP-3) is a commonly used ultraviolet absorber that has the potential to accumulate in organisms, leading to toxicity. Benzophenone-8 (BP-8) is one of the major metabolites of BP-3. In this study, zebrafish were exposed to different concentrations of BP-3 and BP-8 (1 microg/L, 30 microg/L, and 300 microg/L) to investigate their accumulation and toxic effects in various tissues, including zebrafish brain, gut, and liver. The analysis focused on neurotoxicity, oxidative damage, inflammation, and gene expressions. The results showed that both BP-3 and BP-8 accumulated in the tissues, with the highest concentration observed in the gut, followed by the liver and brain. BP-8 exhibited a stronger ability to accumulate. In the brain, exposure to 1 microg/L of BP-3 and BP-8 promoted cortisol production, while higher exposures (30 microg/L and 300 microg/L) inhibited acetylcholinesterase activity and suppressed cortisol production. In the gut, both BP-3 and BP-8 exposures disrupted oxidative stress, inflammatory immunity, and apoptosis functions. In the liver, BP-3 and BP-8 affected hepatic metabolism, oxidative stress, apoptosis, and inflammatory immunity. Comparing gene expression in the brain, gut, and liver, it was found that BP-3 and BP-8 had a lower effect on gene expression in the brain, while the effect on the gut and liver was significantly higher. BP-8 generally had a higher effect than BP-3, which aligns with the observed accumulation pattern. These findings provide valuable insights for the risk assessment of BP-3 and BP-8 in the aquatic environment.
ESTHER : Wang_2024_Aquat.Toxicol_268_106852
PubMedSearch : Wang_2024_Aquat.Toxicol_268_106852
PubMedID: 38310667

Title : Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response - Gao_2024_Adv.Mater__e2312153
Author(s) : Gao G , Jiang YW , Chen J , Xu X , Sun X , Xu H , Liang G , Liu X , Zhan W , Wang M , Xu Y , Zheng J , Wang G
Ref : Adv Mater , :e2312153 , 2024
Abstract : The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate anti-tumor immunity, herein we rationally design a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic ciprofloxacin derivative (Cip-OH) and chemotherapeutic drug camptothecin (CPT) are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment. This article is protected by copyright. All rights reserved.
ESTHER : Gao_2024_Adv.Mater__e2312153
PubMedSearch : Gao_2024_Adv.Mater__e2312153
PubMedID: 38444205

Title : Excessive fat expenditure in MCT-induced heart failure rats is associated with BMAL1\/REV-ERBalpha circadian rhythmic loop disruption - Ma_2024_Sci.Rep_14_8128
Author(s) : Ma D , Qu Y , Wu T , Liu X , Cai L , Wang Y
Ref : Sci Rep , 14 :8128 , 2024
Abstract : Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBalpha circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light-dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light-dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBalpha protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA beta-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Ppargamma, Pgc-1alpha) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBalpha circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA beta oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBalpha circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.
ESTHER : Ma_2024_Sci.Rep_14_8128
PubMedSearch : Ma_2024_Sci.Rep_14_8128
PubMedID: 38584196

Title : Molecular mechanisms for selective action of afidopyropen to Myzus persicae and Coccinella septempunctata - Liu_2024_Pest.Manag.Sci__
Author(s) : Liu X , Wang Q , Xiao D , Liu TX , Liang P
Ref : Pest Manag Sci , : , 2024
Abstract : BACKGROUND: Afidopyropen is a novel insecticide with high selectivity between sucking insects such as the peach aphids Myzus persicae and natural enemies like the seven-spotted lady beetle Coccinella septempunctata. However, the mechanisms of selective action for afidopyropen remain unknown. RESULTS: The LC(50) values of afidopyropen to the 1st - 4th instar larvae and adult C. septempunctata were 372- to more than 7267-fold higher than that to adult M. persicae. Though the activity of cytochrome P450s in M. persicae was 6.1- to 7.5-fold higher than that in C. septempunctata, the latter has much higher activities of carboxylesterase (CarEs) and glutathione S-transferases (GSTs), and the crude enzyme of C. septempunctata and M. persicae showed similar metabolism efficiency to afidopyropen. Molecular docking results demonstrated that afdopyropen showed higher binding affinity to the vanilloid-type transient receptor potential (TRPV) channel of M. persicae (-9.1 kcal/mol) than to that of C. septempunctata (-8.2 kcal/mol). And the EC(50) value of afdopyropen to the TRPV channel of C. septempunctata (41360 nM) was 19885-fold higher than that in M. persicae (2.08 nM). CONCLUSIONS: Our results demonstrated that the significantly different sensitivity of M. persicae and C. septempunctata TRPV channel to afidopyropen play a key role in the high selectivity of afidopyropen. These findings provide new insights into the selective mechanisms of afidopyropen against insect pests and natural enemies as well as the theory support for coordinated application of chemical control and biological control. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2024_Pest.Manag.Sci__
PubMedSearch : Liu_2024_Pest.Manag.Sci__
PubMedID: 38511881

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

Title : Comparative study on the enzymatic degradation of phenolic esters: The HPLC-UV quantification of tyrosol and gallic acid liberated from tyrosol acyl esters and alkyl gallates by hydrolytic enzymes - Wang_2024_Food.Chem_442_138529
Author(s) : Wang X , Wang Q , Cai D , Yu J , Chen X , Guo X , Tong P , Liu X , Yin F , Zhou D
Ref : Food Chem , 442 :138529 , 2024
Abstract : HPLC-UV analysis was used to evaluate the enzymatic degradation characteristics of tyrosol acyl esters (TYr-Es) and alkyl gallates (A-GAs). Among various hydrolytic enzymes, TYr-Es can be hydrolyzed by pancrelipase, while A-GAs cannot be hydrolyzed by pancrelipase. Interestingly, carboxylesterase-1b (CES-1b), carboxylesterase-1c (CES-1c) and carboxylesterase-2 (CES-2) are able to hydrolyze TYr-Es and A-GAs, and thus to liberate tyrosol (TYr) and gallic acid (GA). By contrast, the degrees of hydrolysis (DHs) of TYr-Es and A-GAs by CES-1b and CES-1c were significantly higher than those by CES-2. Meanwhile, the DHs of TYr-Es were much higher than those of A-GAs. Especially, the DHs firstly increased and then decreased with the increasing alkyl chain length. Besides, DHs positively correlated with the unsaturation degree at the same chain length. Through regulating carbon length, unsaturation degree and the ester bond structure, controlled-release of phenolic compounds and fatty acids (or fatty alcohols) from phenolic esters will be easily achieved.
ESTHER : Wang_2024_Food.Chem_442_138529
PubMedSearch : Wang_2024_Food.Chem_442_138529
PubMedID: 38271912

Title : Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer's disease - Yu_2024_J.Enzyme.Inhib.Med.Chem_39_2313682
Author(s) : Yu C , Liu X , Ma B , Xu J , Chen Y , Dai C , Peng H , Zha D
Ref : J Enzyme Inhib Med Chem , 39 :2313682 , 2024
Abstract : Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer's disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC(50) = 4.68 nM; huBuChE IC(50) = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 microM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD(50) > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.
ESTHER : Yu_2024_J.Enzyme.Inhib.Med.Chem_39_2313682
PubMedSearch : Yu_2024_J.Enzyme.Inhib.Med.Chem_39_2313682
PubMedID: 38362862

Title : Novel LIPA-Targeted Therapy for Treating Ovarian Cancer - Collier_2024_Cancers.(Basel)_16_
Author(s) : Collier AB , Viswanadhapalli S , Gopalam R , Lee TK , Kassees K , Parra K , Sharma G , Reese TC , Liu X , Yang X , Ebrahimi B , Pratap UP , Mahajan M , Arnold WC , Baker A , Chen CY , Elmore ST , Subbarayalu P , Sareddy GR , Valente PT , Kost ER , Ahn JM , Vadlamudi RK
Ref : Cancers (Basel) , 16 : , 2024
Abstract : Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2alpha, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.
ESTHER : Collier_2024_Cancers.(Basel)_16_
PubMedSearch : Collier_2024_Cancers.(Basel)_16_
PubMedID: 38339252

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

Title : Genome-Wide Identification and Characterization of Effector Candidates with Conserved Motif in Falciphora oryzae - Dai_2024_Int.J.Mol.Sci_25_
Author(s) : Dai M , Su Z , Zhu X , Li L , Ye Z , Tan X , Kong D , Liu X , Lin F
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes. This research aims to discover the effector genes with conserved motifs in the genome of rice endophyte Falciphora oryzae. SignalP identified a total of 622 secreted proteins, out of which 227 were predicted as effector candidates by EffectorP. By utilizing HMM features, we discovered a total of 169 effector candidates with conserved motifs and three novel motifs. Effector candidates containing LysM, CFEM, DPBB_1, Cutinase, and Chitin_bind domains were conserved across species. In the transient expression assay, it was observed that one CFEM and one LysM activated cell death in tobacco leaves. Moreover, two CFEM and one Chitin_bind inhibited cell death induced by Bax protein. At various points during the infection, the genes' expression levels were increased. These results will help to identify functional effector proteins involving omics methods using new bioinformatics tools, thus providing a basis for the study of symbiosis mechanisms.
ESTHER : Dai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Dai_2024_Int.J.Mol.Sci_25_
PubMedID: 38203820

Title : Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects - Luo_2024_Pharmaceutics_16_
Author(s) : Luo X , Zhang Z , Mu R , Hu G , Liu L , Liu X
Ref : Pharmaceutics , 16 : , 2024
Abstract : Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and C(max) were within 0.5-2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients.
ESTHER : Luo_2024_Pharmaceutics_16_
PubMedSearch : Luo_2024_Pharmaceutics_16_
PubMedID: 38399287

Title : Abscisic acid ameliorates d-galactose -induced aging in mice by modulating AMPK-SIRT1-p53 pathway and intestinal flora - Zheng_2024_Heliyon_10_e28283
Author(s) : Zheng Y , Chen X , Ding C , Liu X , Chi L , Zhang S
Ref : Heliyon , 10 :e28283 , 2024
Abstract : Abscisic acid (ABA) is a plant hormone with various biological activities. Aging is a natural process accompanied by cognitive and physiological decline, and aging and its associated diseases pose a serious threat to public health, but its mechanisms remain insufficient. Therefore, the purpose of this study was to investigate the ameliorative effects of ABA on d-galactose (D-Gal)-induced aging in mice and to delve into its molecular mechanisms. Aging model was es-tablished by theintraperitoneal injection of D-Gal. We evaluated the oxidative stress by measuring superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) levels in serum. Proteins content in brain were determined by Western blot. D-Gal-induced brain damage was monitored by measuring the levels of acetylcholinesterase (AChE) content and hematoxylin-eosin staining (H&E). To evaluate the effects of ABA on aging, we measured the gut microbiota. The results demonstrated that ABA increased SOD, CAT and AChE, decreased MDA level. H&E staining showed that ABA could improve D-Gal-induced damage. In addition, ABA regulated the B-cell-lymphoma-2 (BCL-2) family and Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling pathway, while further regulating the acetylation of p53 protein by modulating the AMPK pathway and activating SIRT1 protein, thereby inhibiting the apoptosis of brain neurons and thus regulating the aging process. Interestingly, ABA improved the ratio of intestinal bacteria involved in regulating multiple metabolic pathways in the aging process, such as Bacteroides, Firmicutes, Lactobacillus and Ak-kermansia. In conclusion, the present study suggests that ABA may be responsible for improving and delaying the aging process by enhancing antioxidant activity, anti-apoptosis and regulating intestinal flora.
ESTHER : Zheng_2024_Heliyon_10_e28283
PubMedSearch : Zheng_2024_Heliyon_10_e28283
PubMedID: 38524603

Title : Development of biodegradable nanogels for lipase accelerated drug release of 5-aminolevulinic acid - Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
Author(s) : Liu X , Zhang Y , Zhang P , Ge K , Zhang R , Sun Y , Sheng Y , Bradley M
Ref : Colloids Surf B Biointerfaces , 225 :113268 , 2023
Abstract : Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers (L-lactide and sigma-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.
ESTHER : Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
PubMedSearch : Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
PubMedID: 36989818

Title : JH degradation pathway participates in hormonal regulation of larval development of Bombyx mori following lambda-cyhalothrin exposure - Su_2023_Chemosphere_349_140871
Author(s) : Su Y , Wang W , Dai Y , Qi R , Gu H , Guo X , Liu X , Ren Y , Li F , Li B , Sun H
Ref : Chemosphere , 349 :140871 , 2023
Abstract : lambda-Cyhalothrin (lambda-cyh), a widely utilized pyrethroid insecticide, poses serious threats to non-target organisms due to its persistence nature in the environment. Exposure to low concentrations of lambda-cyh has been observed to result in prolonged larval development in Bombyx mori, leading to substantial financial losses in sericulture. The present study was undertaken to elucidate the underlying mechanisms for prolonged development caused by lambda-cyh (LC(10)) exposure. The results showed that the JH titer was significantly increased at 24 h of lambda-cyh exposure, and the JH interacting genes Methoprene-tolerant 2, Steroid Receptor Co-activator, Krppel-homolog 1, and JH binding proteins were also up-regulated. Although the target of rapamycin (Tor) genes were induced by lambda-cyh, the biosynthesis of JH in the corpora allata was not promoted. Notably, 13 JH degradation genes were found to be significantly down-regulated in the midgut of B. mori. The mRNA levels and enzyme activity assays indicated that lambda-cyh had inhibitory effects on JH esterase, JH epoxide hydrolase, and JH diol kinase (JHDK). Furthermore, the suppression of JHDK (KWMTBOMO01580) was further confirmed by both western blot and immunohistochemistry. This study has offered a comprehensive perspective on the mechanisms underlying the prolonged development caused by insecticides, and our results also hold significant implications for the safe production of sericulture.
ESTHER : Su_2023_Chemosphere_349_140871
PubMedSearch : Su_2023_Chemosphere_349_140871
PubMedID: 38056714

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

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

Title : Complete bio-degradation of poly(butylene adipate-co-terephthalate) via engineered cutinases - Yang_2023_Nat.Commun_14_1645
Author(s) : Yang Y , Min J , Xue T , Jiang P , Liu X , Peng R , Huang JW , Qu Y , Li X , Ma N , Tsai FC , Dai L , Zhang Q , Liu Y , Chen CC , Guo RT
Ref : Nat Commun , 14 :1645 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h. We further show that the engineered cutinases, by applying a double mutation strategy to render a more flexible substrate-binding pocket exhibit higher decomposition rates. Notably, these variants produce TPA as a major end-product, which is beneficial feature for the future recycling economy. The crystal structures of wild type and double mutation of a cutinase from Thermobifida fusca in complex with a substrate analogue are also solved, elucidating their substrate-binding modes. These structural and biochemical analyses enable us to propose the mechanism of cutinase-mediated PBAT degradation.
ESTHER : Yang_2023_Nat.Commun_14_1645
PubMedSearch : Yang_2023_Nat.Commun_14_1645
PubMedID: 36964144
Gene_locus related to this paper: idesa-peth , thefu-q6a0i4

Title : Effects of monitoring exercise rehabilitation with target intensity on the patient with twice PCI: A case report - Liu_2023_Medicine.(Baltimore)_102_e33583
Author(s) : Liu X , Chen Y , Chen J , Li A , Zhong M , Zhou W , Tang L
Ref : Medicine (Baltimore) , 102 :e33583 , 2023
Abstract : RATIONALE: As the core of cardiac rehabilitation (CR), early exercise rehabilitation is beneficial for patients with coronary heart disease (CHD), and center-based CR with target intensity is superior to home-based CR. However, there was no research to observe the effects of exercise rehabilitation on cardiopulmonary exercise capacity, oxygen uptake efficiency slope, endothelial function evaluated as flow-mediated vasodilation (FMD), and blood plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) in CHD patients undergone percutaneous coronary intervention (PCI) for 3 months. PATIENT CONCERNS: A 57-year-old woman had been identified with triple vessel disease and undergone twice PCI for complete revascularization, however, there was no improvement in Lp-PLA2, FMD, and related indicators of cardiopulmonary exercise testing. DIAGNOSIS: Coronary angiography showed an 85% stenosis in the middle left anterior descending artery, an 85% stenosis in the proximity of a thick first-diagonal branch, a long 75 to 85% stenosis in the middle left circumflex artery, and a 90 to 95% stenosis in the proximal. The case was diagnosed as CHD. INTERVENTIONS: The patient obtained optimal medical therapy comprising therapeutic lifestyle changes, and began monitoring exercise rehabilitation with target intensity 3 months after the second PCI in the CR center. OUTCOMES: There were changes in cardiopulmonary exercise capacity, oxygen uptake efficiency slope, FMD, and Lp-PLA2 in the patient with 3 apparent stenotic coronary arteries who was done PCI twice, without or with postoperative exercise rehabilitation, respectively. LESSONS: We proved that monitoring exercise rehabilitation training with target intensity could improve the prognosis of chronic coronary syndrome patients, and it was never too late to do regular exercise rehabilitation.
ESTHER : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedSearch : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedID: 37083775

Title : Enzyme-targeted near-infrared fluorescent probe for organophosphorus pesticide residue detection - Luo_2023_Anal.Bioanal.Chem__
Author(s) : Luo S , Peng R , Wang Y , Liu X , Ren J , Li W , Xiong Y , Yi S , Wen Q
Ref : Anal Bioanal Chem , : , 2023
Abstract : Pesticide residues significantly affect food safety and harm human health. In this work, a series of near-infrared fluorescent probes were designed and developed by acylating the hydroxyl group of the hemicyanine skeleton with a quenching moiety for monitoring the presence of organophosphorus pesticides in food and live cells. The carboxylic ester bond on the probe was hydrolyzed catalytically in the presence of carboxylesterase and thereby the fluorophore was released with near-infrared emission. Notably, the proposed probe 1 exhibited excellent sensitivity against organophosphorus based on the carboxylesterase inhibition mechanism and the detection limit for isocarbophos achieved 0.1734 microg/L in the fresh vegetable sample. More importantly, probe 1 allowed for situ visualization of organophosphorus in live cells and bacteria, meaning great potential for tracking the organophosphorus in biological systems. Consequently, this study presents a promising strategy for tracking pesticide residues in food and biological systems.
ESTHER : Luo_2023_Anal.Bioanal.Chem__
PubMedSearch : Luo_2023_Anal.Bioanal.Chem__
PubMedID: 37433954

Title : Ultra-small magnetic Candida antarctica lipase B nanoreactors for enzyme synthesis of bixin-maltitol ester - Lv_2023_Food.Chem_421_136132
Author(s) : Lv D , Wang M , He W , Wu J , Liu X , Guan Y
Ref : Food Chem , 421 :136132 , 2023
Abstract : Bixin has desirable bioactivities but poor water solubility, which limits its practical applications. Enzymatic transesterification of methyl to alditol groups in bixin by Candida antarctica lipase B (CALB) improves bixin water solubility. Herein, magnetic CALB nanoreactors with diameter of 11.7 nm and CALB layer thickness of 3.5 nm were developed by covalently linking CALB onto silicon covered Fe(3)O(4) nanoparticles. The CALB loading capacity in nanoreactors achieved 30%. The Michaelis constant (Km) and maximum reaction rate of magnetic CALB nanoreactors were 56.1 mmol/L and 0.2 mmol/(L.min). Magnetic CALB nanoreactors could circularly catalyze bixin-maltitol ester synthesis and keep catalytic efficiency of 62.6% after eight repetitive enzymatic reactions. Additionally, the optimal bixin-maltitol ester synthesis procedure was heating bixin-maltitol mixture at molar ratio of 1:7 in anhydrous 2-methyl-2-butanol-dimethylsulfoxide (8:2, v/v) at 50 degreesC for 24 h. Bixin-maltitol ester showed improved water solubility at pH 5.5 and 7.0.
ESTHER : Lv_2023_Food.Chem_421_136132
PubMedSearch : Lv_2023_Food.Chem_421_136132
PubMedID: 37094396

Title : Sulfur-fluoride exchange (SuFEx)-enabled lead discovery of AChE inhibitors by fragment linking strategies - Zhang_2023_Eur.J.Med.Chem_257_115502
Author(s) : Zhang Z , Zhang SL , Wu C , Li HH , Zha L , Shi J , Liu X , Qin HL , Tang W
Ref : Eur Journal of Medicinal Chemistry , 257 :115502 , 2023
Abstract : SuFEx click chemistry has been a method for the rapid synthesis of functional molecules with desirable properties. Here, we demonstrated a workflow that allows for in situ synthesis of sulfonamide inhibitors based on SuFEx reaction for high-throughput testing of their cholinesterase activity. According to fragment-based drug discovery (FBDD), sulfonyl fluorides [R-SO(2)F] with moderate activity were identified as fragment hits, rapidly diversified into 102 analogs in SuFEx reactions, and the sulfonamides were directly screened to yield drug-like inhibitors with 70-fold higher potency (IC(50) = 94 nM). Moreover, the improved molecule J8-A34 can ameliorate cognitive function in Abeta(1-42)-induced mouse model. Since this SuFEx linkage reaction succeeds on picomole scale for direct screening, this methodology can accelerate the development of robust biological probes and drug candidates.
ESTHER : Zhang_2023_Eur.J.Med.Chem_257_115502
PubMedSearch : Zhang_2023_Eur.J.Med.Chem_257_115502
PubMedID: 37224761

Title : Variation in the HSL Gene and Its Association with Carcass and Meat Quality Traits in Yak - Wang_2023_Animals.(Basel)_13_
Author(s) : Wang X , Qi Y , Zhu C , Zhou R , Ruo Z , Zhao Z , Liu X , Li S , Zhao F , Wang J , Hu J , Shi B
Ref : Animals (Basel) , 13 : , 2023
Abstract : Hormone-sensitive lipase (HSL) is involved in the breakdown of triacylglycerols in adipose tissue, which influences muscle tenderness and juiciness by affecting the intramuscular fat content (IMF). This study analyzed the association between different genotypes and haplotypes of the yak HSL gene and carcass and meat quality traits. We used hybridization pool sequencing to detect exon 2, exon 8, and intron 3 variants of the yak HSL gene and genotyped 525 Gannan yaks via KASP to analyze the effects of the HSL gene variants on the carcass and meat quality traits in yaks. According to the results, the HSL gene is highly expressed in yak adipose tissue. Three single nucleotide polymorphisms (SNPs) were identified, with 2 of them located in the coding region and one in the intron region. Variants in the 2 coding regions resulted in amino acid changes. The population had 3 genotypes of GG, AG, and AA, and individuals with the AA genotype had lower WBSF values (p < 0.05). The H3H3 haplotype combinations could improve meat tenderness by reducing the WBSF values and the cooking loss rate (CLR) (p < 0.05). H1H1 haplotype combinations were associated with the increased drip loss rate (DLR) (p < 0.05). The presence of the H1 haplotype was associated the increased CLR in yaks, while that of the H2 haplotype was associated with the decreased DLR in yaks (p < 0.05). These results demonstrated that the HSL gene may influence the meat quality traits in yaks by affecting the IMF content in muscle tissues. Consequently, the HSL gene can possibly be used as a biomarker for improving the meat quality traits in yaks in the future.
ESTHER : Wang_2023_Animals.(Basel)_13_
PubMedSearch : Wang_2023_Animals.(Basel)_13_
PubMedID: 38067071

Title : A visualized sensor based on layered double hydroxides with peroxidase-like activity for sensitive acetylcholinesterase assay - Cheng_2023_Anal.Methods__
Author(s) : Cheng H , Wang Y , Ge L , Liu X , Li F
Ref : Anal Methods , : , 2023
Abstract : Acetylcholinesterase (AChE) plays a crucial role in biological neurotransmission. The aberrant expression of AChE is associated with various neurodegenerative diseases. Therefore, it is of great significance to develop a simple and highly sensitive AChE analysis platform. Herein, a simple colorimetric sensor was constructed for sensitive detection of AChE based on the peroxidase-like catalytic activity of Ni/Co layered double hydroxides (Ni/Co LDHs). In this sensor, the fabricated Ni/Co LDHs possess high peroxidase-like activity, enabling rapid catalysis of o-phenylenediamine (OPD) to produce yellow oxOPD in the presence of H(2)O(2). This peroxidase-like activity of Ni/Co LDHs was found to be effectively inhibited by the presence of AChE. It is speculated that the combination of AChE on the outer surface of Ni/Co LDHs through non-covalent interaction may cover the active sites and hinder their adsorption to the substrates, leading to the failure of OPD oxidation. As a result, the yellow color from oxOPD is related to the AChE concentration, enabling the direct AChE assay in an equipment-free manner. In addition, the fabricated Ni/Co LDHs could be modified on a paper surface to obtain a paper-based analytical device for visualized colorimetric detection of AChE. The as-proposed sensor shows high sensitivity to AChE with a detection limit down to 6.6 microU mL(-1). Therefore, this naked-eye paper-based sensor is capable of on-site and real-time detection of AChE, and has outstanding application prospects in clinical diagnosis and biomedical fields.
ESTHER : Cheng_2023_Anal.Methods__
PubMedSearch : Cheng_2023_Anal.Methods__
PubMedID: 37470116

Title : The potential of hydroxytyrosol fatty acid esters to enhance oral bioavailabilities of hydroxytyrosol and fatty acids: Continuous and slow-release ability in small intestine and blood - Wang_2023_Food.Chem_422_136246
Author(s) : Wang X , Wang Q , Yu J , Guo X , Tong P , Yin F , Liu X , Zhou D
Ref : Food Chem , 422 :136246 , 2023
Abstract : HPLC-UV analysis in rat everted gut sac and in vitro simulated digestion models indicated that hydroxytyrosol fatty acid esters (HTy-Es) could be hydrolyzed by pancreatic lipase to slow-release of free fatty acids (FAs) and HTy. Meanwhile, the HTy-Es, the liberated FAs and the HTy could cross the membrane and were transported into blood circulation. HTy-Es were further hydrolyzed by carboxylesterase in in vitro rat plasma hydrolysis model, which also showed slow-release of FAs (C1-C4) and HTy. Especially, the rates of hydrolysis and transport initially increased and then decreased with the increasing alkyl chain length. Besides, the above rates of the HTy-Es with a straight chain were greater than those of its isomer with a branched chain. Therefore, the above-mentioned continuous and slow-release of FAs and HTy in small intestine and blood clearly demonstrated that HTy-Es would be an effective approach to enhance oral bioavailabilities of free fatty acids and hydroxytyrosol.
ESTHER : Wang_2023_Food.Chem_422_136246
PubMedSearch : Wang_2023_Food.Chem_422_136246
PubMedID: 37126954

Title : Engineering a Bacillus subtilis esterase for selective hydrolysis of d, l-menthyl acetate in an organic solvent-free system - Qiao_2023_RSC.Adv_13_10468
Author(s) : Qiao J , Yang D , Feng Y , Wei W , Liu X , Zhang Y , Zheng J , Ying X
Ref : RSC Adv , 13 :10468 , 2023
Abstract : Esterase/lipase-catalyzed selective hydrolysis of d, l-menthyl esters has become one of the promising approaches for producing l-menthol, one of the most important flavoring chemicals with extensive uses. However, the activity and l-enantioselectivity of the biocatalyst are not sufficient for meeting the industrial requirements. Herein, a highly active para-nitrobenzyl esterase from Bacillus subtilis 168 (pnbA-BS) was cloned and then engineered to enhance its l-enantioselectivity. On the basis of the strategy tailoring the steric exclusion effect and structural flexibility of the region adjacent to the substrate, the substitution of Ala400 to Pro caused a remarkable improvement in the E value from 1.0 to 466.6. The variant A400P was purified and further confirmed with strict l-enantioselectivity in the selective hydrolysis of d, l-menthyl acetate, whereas the improved l-enantioselectivity caused decreased activity. To develop an efficient, easy-to-use, and green methodology, organic solvent was omitted and substrate constant feeding was integrated into the whole-cell catalyzed system. During the catalytic process, the selective hydrolysis of 1.0 M d, l-menthyl acetate in 14 h offered a conversion of 48.9%, e.e.(p) value of >99%, and space-time yield of 160.52 g (l d)(-1).
ESTHER : Qiao_2023_RSC.Adv_13_10468
PubMedSearch : Qiao_2023_RSC.Adv_13_10468
PubMedID: 37021103
Gene_locus related to this paper: 9baci-a0a2m8sv47

Title : Polystyrene nanoplastics induce lipid metabolism disorder and alter fatty acid composition in the hepatopancreas of Pacific whiteleg shrimp (Litopenaeus vannamei) - Li_2023_Sci.Total.Environ__167616
Author(s) : Li Y , Ye Y , Rihan N , Zhu B , Jiang Q , Liu X , Zhao Y , Che X
Ref : Sci Total Environ , :167616 , 2023
Abstract : The impact of nanoplastics (NPs) on environmental pollution and aquatic organisms has gradually attracted attention, but there are relatively few reports of the effects of NPs on the lipid metabolism of crustaceans. In this study, we exposed Pacific whiteleg shrimp (Litopenaeus vannamei) to different concentrations of polystyrene NPs (0, 0.1, 1, 5, and 10 mg/L) for 28 days. We then evaluated the effects of NP exposure on metabolite content, histology, lipid metabolism-related enzyme activity, and gene expression. Our results showed that with increasing NPs concentrations and exposure time, (1) the crude protein and crude fat content decreased and fatty acid composition changed; (2) the tissue structure was destroyed and the number of lipid droplets increased in the hepatopancreas; (3) the activities of acetyl-CoA carboxylase, fatty acid synthase, carnitine palmitoyl transferase-1, pyruvate kinase and low-density lipoprotein content tended to decrease and that of lipase and high-density lipoprotein content first increased and then decreased; the content of triglycerides and total carbohydrate first decreased and then increased; (4) the expression of fatty acid synthesis-related genes (Fas, SREBP, and FAD), fatty acid transport-related genes (FATP, FABP, and ACBP), and fatty acid decomposition-related genes (Ampk and lip1) first increased and then decreased. These results indicate that exposure to NPs can cause physiological disorders of fat metabolism in L. vannamei and that high concentrations of NPs have a negative impact on lipid metabolism. These results of this study provide valuable ecotoxicological data for better interpretation of the mechanism of action of NPs in crustaceans.
ESTHER : Li_2023_Sci.Total.Environ__167616
PubMedSearch : Li_2023_Sci.Total.Environ__167616
PubMedID: 37832676

Title : Enhancement degradation efficiency of pyrethroid-degrading esterase (Est816) through rational design and its application in bioremediation - Fan_2023_Chemosphere_319_138021
Author(s) : Fan X , Zhao M , Wen H , Zhang Y , Zhang J , Liu X
Ref : Chemosphere , 319 :138021 , 2023
Abstract : The pervasive use of pyrethroids is seriously hazardous to the environment and even human health. Enzymatic bioremediation is potentially a rapid and environmentally friendly technology to combat the pollution of pyrethroid pesticides. The hydrolysis of ester linkages is the initial and critical enzymatic step in microbial degradation pathways. Here, the versatile and thermostable esterase Est816 was cloned and its new function, pyrethroid-hydrolysis activity, was expanded. To further improve its pyrethroid-hydrolysis ability, Est816 was modified by rational design. After two rounds of mutation, the best-performing mutant, Est816(A216V/K238N/M97V,) was obtained, which could completely degrade 1 mg/L lambda-cyhalothrin, cypermethrin, and deltamethrin within 20 min, and efficiently degrade fenvalerate, reaching over 80% conversion. Degradation activity analyses showed that three substitutions (A216V, K238 N and M97V) were beneficial for enhancing the activity of Est816. Enzymatic characterization showed that Est816(A216V/K238N/M97V) inherited broad substrate specificity and possessed excellent stability and adaptability over wide ranges of temperature and pH, which is essential for bioremediation in frequently changing conditions. Furthermore, Est816(A216V/K238N/M97V) had the best degradation effect on all four pyrethroid residues in Panax notoginseng root, with more than 87% conversion after 24 h. Pyrethroid residues in tea, cucumber, and soil were reduced by more than 76%, 80%, and 76%, respectively. Taken together, these findings highlight the great potential of Est816(A216V/K238N/M97V) in the bioremediation of pyrethroid-contaminated soil and agricultural products.
ESTHER : Fan_2023_Chemosphere_319_138021
PubMedSearch : Fan_2023_Chemosphere_319_138021
PubMedID: 36731665
Gene_locus related to this paper: 9bact-i6yrg4

Title : Small molecular fluorescent probes for Alzheimer's disease associated active species - Tang_2023_Chemistry__e202300592
Author(s) : Tang F , Wang K , Liu X , Zhang X , Zhou W , Mu Z , Zhang T , Shu W , Liu Y , Xiao H
Ref : Chemistry , :e202300592 , 2023
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the main cause of dementia worldwide. As the pathogenesis of AD is quite complicated, there is continuous attention to AD-associated active species, such as amyloid-beta plaques, neurofibrillary tangles, metal ions, reactive oxygen/nitrogen/sulphurspecies, cholinesterase, viscosity, formaldehyde and so on. To this end, a series of small molecular fluorescent probes for these active species have been explored for early diagnosis and even remedy of AD. Herein, we systematacially summarize the versatile fluorescent probes mainly in recent three years, including the relationship between the structure and properties as well as the targeted diagnosis and imaging application of all these fluorescent probes. Moreover, the challenges and perspectives of the AD-related fluorescent probes are briefly explicated. We firmly expect this review may provide guidance for constructing new AD-relevant fluorescent probes and promote the clinical study of AD.
ESTHER : Tang_2023_Chemistry__e202300592
PubMedSearch : Tang_2023_Chemistry__e202300592
PubMedID: 37078523

Title : Nematicidal Coumarins from Cnidium monnieri Fruits and Angelica dahurica Roots and Their Physiological Effect on Pine Wood Nematode (Bursaphelenchus xylophilus) - Feng_2023_Molecules_28_
Author(s) : Feng J , Qin C , Liu X , Li R , Wang C , Li C , Du G , Guo Q
Ref : Molecules , 28 : , 2023
Abstract : Pine wood nematode (PWN), Bursaphelenchus xylophilus, is a major pathogen of pine wilt disease (PWD), which is a devastating disease affecting pine trees. Eco-friendly plant-derived nematicides against PWN have been considered as promising alternatives to control PWD. In this study, the ethyl acetate extracts of Cnidium monnieri fruits and Angelica dahurica roots were confirmed to have significant nematicidal activity against PWN. Through bioassay-guided fractionations, eight nematicidal coumarins against PWN were separately isolated from the ethyl acetate extracts of C. monnieri fruits and A. dahurica roots, and they were identified to be osthol (Compound 1), xanthotoxin (Compound 2), cindimine (Compound 3), isopimpinellin (Compound 4), marmesin (Compound 5), isoimperatorin (Compound 6), imperatorin (Compound 7), and bergapten (Compound 8) by mass and nuclear magnetic resonance (NMR) spectral data analysis. Coumarins 1-8 were all determined to have inhibitory effects on the egg hatching, feeding ability, and reproduction of PWN. Moreover, all eight nematicidal coumarins could inhibit the acetylcholinesterase (AChE) and Ca(2+) ATPase of PWN. Cindimine 3 from C. monnieri fruits showed the strongest nematicidal activity against PWN, with an LC(50) value of 64 microM at 72 h, and the highest inhibitory effect on PWN vitality. In addition, bioassays on PWN pathogenicity demonstrated that the eight nematicidal coumarins could effectively relieve the wilt symptoms of black pine seedlings infected by PWN. The research identified several potent botanical nematicidal coumarins for use against PWN, which could contribute to the development of greener nematicides for PWD control.
ESTHER : Feng_2023_Molecules_28_
PubMedSearch : Feng_2023_Molecules_28_
PubMedID: 37241850

Title : Carboxy-Functionalized Covalent Organic Framework as a Carrier for Lipase Immobilization and Its Application in Inhibitors Screening - Liu_2023_Appl.Biochem.Biotechnol__
Author(s) : Liu X , Wu J , Yang S , Li L , Ji Y
Ref : Appl Biochem Biotechnol , : , 2023
Abstract : Covalent organic frameworks (COFs) with large specific surface areas, high porosity, good stability, and designable structure are promising carriers for immobilized enzymes. It is important to explore lipase inhibitors from natural foods as lipase inhibitors are closely related to the treatment of obesity. In this work, a carboxyl functionalized covalent organic framework (TpBD-3COOH) was prepared by solvothermal method for covalent immobilization of porcine pancreatic lipase (PPL) and obtained the enzyme-decorated COF (PPL@COF). The immobilized lipase showed wider pH and temperature tolerance with the same optimal pH and temperature of 7.5 and 50 degC compared to free lipase. After 6 successive reuses, the PPL@COF maintained 53.0% of its original activity. Immobilized lipase also displayed enhanced storage stability (55.4% after 14 days at 4 degC). When p-nitrophenyl acetate was applied as the substrate, the calculated Michaelis constant was 3.57 mM and the half maximal inhibitory concentration of orlistat was 3.20 microM. Finally, the PPL@COF was used for enzyme inhibitors screening from natural foods combined with UV spectrophotometry, and Hawthorn was screened for excellent lipase inhibitory activity.
ESTHER : Liu_2023_Appl.Biochem.Biotechnol__
PubMedSearch : Liu_2023_Appl.Biochem.Biotechnol__
PubMedID: 37819460

Title : Chemical Composition and In Vitro Antioxidant Activity and Anti-Acetylcholinesterase Activity of Essential Oils from Tadehagi triquetrum (L.) Ohashi - Song_2023_Molecules_28_
Author(s) : Song W , Xu Z , Gao P , Liu X
Ref : Molecules , 28 : , 2023
Abstract : The present study aimed to determine the chemical compositions of essential oils (EOs) from Tadehagi triquetrum (L.) Ohashi and evaluate their antioxidant and anti-cholinesterase activity under the comprehensive influence of chemical components. The essential oils were extracted from T. triquetrum (L.) Ohashi by hydrodistillation. A total of 58 organic compounds were identified by GC-FID and GC-MS analysis. The major components of T. triquetrum (L.) Ohashi EOs were identified as palmitic acid (22.46%), 1-Octen-3-ol (14.07%), Caryophyllene (7.20%), (Z)-18-Octadec-9-enolide (6.04%), and 3-Hexen-1-ol (4.55%). The antioxidant activity of the essential oils was determined by using ABTS assay, DPPH assay, and FRAP assay, with IC(50) values of 2.12 +/- 0.05 mg/mL, 4.73 +/- 0.91 mg/mL against the ABTS, DPPH, and FRAP value 117.42 +/- 8.10 mM/g. The result showed that it had moderate antioxidant activities in the experiment, which why it is likely that it will be used as an antioxidant. At the same time, the EOs also showed moderate anti-acetylcholinesterase activity. This study expands the chemical and biological knowledge of the EOs of T. triquetrum.
ESTHER : Song_2023_Molecules_28_
PubMedSearch : Song_2023_Molecules_28_
PubMedID: 36985706

Title : Self-ratiometric fluorescent platform based on upconversion nanoparticles for on-site detection of chlorpyrifos - Zhao_2023_Food.Chem_439_138100
Author(s) : Zhao X , Lu Y , Li B , Kong M , Sun Y , Li H , Liu X , Lu G
Ref : Food Chem , 439 :138100 , 2023
Abstract : Chromobacterium sp. USM2, a locally isolated bacterium was found to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate), P(3HB-co-3HV) copolymer with high 3HV monomer composition. The PHA synthase gene was cloned and expressed in Cupriavidus necator PHB4 to investigate the possibilities of incorporating other monomer. The recombinant successfully incorporated 3-hydroxyhexanoate (3HHx) monomer when fed with crude palm kernel oil (CPKO) as the sole carbon source. Approximately 63 2 wt% of P(3HB-co-3HHx) copolymer with 4 mol% of 3HHx was synthesized from 5 g/L of oil after 48 h of cultivation. In addition, P(3HB-co-3HV-co-3HHx) terpolymer with 9 mol% 3HV and 4 mol% 3HHx could be synthesized with a mixture of CPKO and sodium valerate. The presence of 3HV and 3HHx monomers in the copolymer and terpolymer was further confirmed with +H-NMR analysis. This locally isolated PHA synthase has demonstrated its ability to synthesize P(3HB-co-3HHx) copolymer from a readily available and renewable carbon source; CPKO, without the addition of 3HHx precursors.
ESTHER : Zhao_2023_Food.Chem_439_138100
PubMedSearch : Zhao_2023_Food.Chem_439_138100
PubMedID: 38041885

Title : Exogenous methyl jasmonate induced cassava defense response and enhanced resistance to Tetranychus urticae - Zhang_2023_Exp.Appl.Acarol__
Author(s) : Zhang Y , Liu Y , Liang X , Wu C , Liu X , Wu M , Yao X , Qiao Y , Zhan X , Chen Q
Ref : Exp Appl Acarol , : , 2023
Abstract : Exogenous application of methyl jasmonate (MeJA) could activate plant defense response against the two-spotted spider mite (TSSM), Tetranychus urticae Koch,sin different plants. However, whether MeJA can also serve as an elicitor in cassava (Manihot esculenta Crantz) remains unknown. In this study, induced defense responses were investigated in TSSM-resistant cassava variety C1115 and TSSM-susceptible cassava variety KU50 when applied with MeJA. The performance of TSSM feeding on cassava plants that werespre-treated with various concentrations of MeJA was first evaluated. Subsequently, the activities of antioxidative enzymes (superoxide dismutase and catalase), detoxification enzymes (glutathione S-transferase, cytochrome P450 and carboxylesterase) and digestive enzymes (protease, amylase and invertase) in TSSM were analyzed at days 1, 2, 4 and 8 post-feeding. The results showed that MeJA treatment can induce cassava defense responses to TSSM in terms of reducing egg production and adult longevity as well as slowing development and prolonging thesegg stage. Noticeably, C1115 exhibited stronger inhibition of TSSM development and reproduction than KU50. In addition, the activities of all the tested enzymes were induced in both C1115 and KU50, the most in C1115. We conclude that exogenous methyl jasmonate can induce cassava defense responses and enhance resistance to TSSM.
ESTHER : Zhang_2023_Exp.Appl.Acarol__
PubMedSearch : Zhang_2023_Exp.Appl.Acarol__
PubMedID: 36635606

Title : Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters - Li_2023_Foods_12_1977
Author(s) : Li D , Guo J , Ma H , Pei L , Liu X , Wang H , Chen R , Zhao Z , Gao H
Ref : Foods , 12 :1977 , 2023
Abstract : Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor.
ESTHER : Li_2023_Foods_12_1977
PubMedSearch : Li_2023_Foods_12_1977
PubMedID: 37238795

Title : Rapid discovery and crystallography study of highly potent and selective butylcholinesterase inhibitors based on oxime-containing libraries and conformational restriction strategies - Jing_2023_Bioorg.Chem_134_106465
Author(s) : Jing L , Wei W , Meng B , Chantegreil F , Nachon F , Martinez A , Wu G , Zhao H , Song Y , Kang D , Brazzolotto X , Zhan P , Liu X
Ref : Bioorg Chem , 134 :106465 , 2023
Abstract : Butyrylcholinesterase is regarded as a promising drug target in advanced Alzheimer's disease. In order to identify highly selective and potent BuChE inhibitors, a 53-membered compound library was constructed via the oxime-based tethering approach based on microscale synthesis. Although A2Q17 and A3Q12 exhibited higher BuChE selectivity versus acetylcholinesterase, the inhibitory activities were unsatisfactory and A3Q12 did not inhibit Abeta1-42 peptide self-induced aggregation. With A2Q17 and A3Q12 as leads, a novel series of tacrine derivatives with nitrogen-containing heterocycles were designed based on conformation restriction strategy. The results demonstrated that 39 (IC50 = 3.49 nM) and 43 (IC50 = 7.44 nM) yielded much improved hBuChE inhibitory activity compared to the lead A3Q12 (IC50 = 63 nM). Besides, the selectivity indexes (SI = AChE IC50 / BChE IC50) of 39 (SI = 33) and 43 (SI = 20) were also higher than A3Q12 (SI = 14). The results of the kinetic study showed that 39 and 43 exhibited a mixed-type inhibition against eqBuChE with respective Ki values of 1.715 nM and 0.781 nM. And 39 and 43 could inhibit Abeta1-42 peptide self-induced aggregation into fibril. X-ray crystallography structures of 39 or 43 complexes with BuChE revealed the molecular basis for their high potency. Thus, 39 and 43 are deserve for further study to develop potential drug candidates for the treatment of Alzheimer's disease.
ESTHER : Jing_2023_Bioorg.Chem_134_106465
PubMedSearch : Jing_2023_Bioorg.Chem_134_106465
PubMedID: 36933339
Gene_locus related to this paper: human-BCHE

Title : Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation - Liu_2023_Embo.j__e112998
Author(s) : Liu X , Chen Z , Huang L , Ouyang Y , Wang Z , Wu S , Ye W , Yu B , Zhang Y , Yang C , Lai J
Ref : EMBO j , :e112998 , 2023
Abstract : Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk.
ESTHER : Liu_2023_Embo.j__e112998
PubMedSearch : Liu_2023_Embo.j__e112998
PubMedID: 37211868
Gene_locus related to this paper: arath-AT5G20520

Title : Genome-wide association study of 17 serum biochemical indicators in a chicken F(2) resource population - Song_2023_BMC.Genomics_24_98
Author(s) : Song H , Li W , Li Y , Zhai B , Guo Y , Chen Y , Han R , Sun G , Jiang R , Li Z , Yan F , Li G , Liu X , Zhang Y , Tian Y , Kang X
Ref : BMC Genomics , 24 :98 , 2023
Abstract : BACKGROUND: Serum biochemical indicators are often regarded as direct reflections of animal metabolism and health. The molecular mechanisms underlying serum biochemical indicators metabolism of chicken (Gallus Gallus) have not been elucidated. Herein, we performed a genome-wide association study (GWAS) to identify the variation associated with serum biochemical indicators. The aim of this research was to broaden the understanding of the serum biochemical indicators in chickens. RESULTS: A GWAS of serum biochemical indicators was carried out on 734 samples from an F2 Gushix Anka chicken population. All chickens were genotyped by sequencing, 734 chickens and 321,314 variants were obtained after quality control. Based on these variants, a total of 236 single-nucleotide polymorphisms (SNPs) on 9 chicken chromosomes (GGAs) were identified to be significantly (-log(10)(P) > 5.72) associated with eight of seventeen serum biochemical indicators. Ten novel quantitative trait locis (QTLs) were identified for the 8 serum biochemical indicator traits of the F2 population. Literature mining revealed that the ALPL, BCHE, GGT2/GGT5 genes at loci GGA24, GGA9 and GGA15 might affect the alkaline phosphatase (AKP), cholinesterase (CHE) and gamma-glutamyl transpeptidase (GGT) traits, respectively. CONCLUSION: The findings of the present study may contribute to a better understanding of the molecular mechanisms of chicken serum biochemical indicator regulation and provide a theoretical basis for chicken breeding programs.
ESTHER : Song_2023_BMC.Genomics_24_98
PubMedSearch : Song_2023_BMC.Genomics_24_98
PubMedID: 36864386

Title : Ferulic acid production from wheat bran by integration of enzymatic pretreatment and a cold-adapted carboxylesterase catalysis - Cao_2023_Bioresour.Technol__129435
Author(s) : Cao L , Xue D , Liu X , Wang C , Fang D , Zhang J , Gong C
Ref : Bioresour Technol , :129435 , 2023
Abstract : High-value chemical production from natural lignocellulose transformation is a reliable waste utilization approach. A gene encoding cold-adapted carboxylesterase in Arthrobacter soli Em07 was identified. The gene was cloned and expressed in Escherichia coli to obtain a carboxylesterase enzyme with a molecular weight of 37.2 KDa. The activity of the enzyme was determined using alpha-naphthyl acetate as substrate. Results showed that the optimum enzyme activity of carboxylesterase was at 10 degreesC and pH 7.0. It was also found that the enzyme could degrade 20 mg enzymatic pretreated de-starched wheat bran (DSWB) to produce 235.8 microg of ferulic acid under the same conditions, which was 5.6 times more than the control. Compared to the chemical strategy, enzymatic pretreatment is advantageous because it is environmentally friendly, and the by-products can be easily treated. Therefore, this strategy provides an effective method for high-value utilization of biomass waste in agriculture and industry.
ESTHER : Cao_2023_Bioresour.Technol__129435
PubMedSearch : Cao_2023_Bioresour.Technol__129435
PubMedID: 37399964

Title : Phytochemical Analysis, Antioxidant and Enzyme-Inhibitory Activities, and Multivariate Analysis of Insect Gall Extracts of Picea koraiensis Nakai - Wang_2023_Molecules_28_
Author(s) : Wang Y , Sun H , He X , Chen M , Zang H , Liu X , Piao H
Ref : Molecules , 28 : , 2023
Abstract : Picea koraiensis Nakai (PK) is an evergreen tree. It plays an important role in landscaping and road greening. Insect galls of PK are formed by parasitism of the adelgid Adelges laricis. Except for phenolics, other chemical constituents and biological activity of insect gall from PK are still unknown. Thus, here, we performed phytochemical and biological activity analyses of PK insect gall extracts, aiming to turn waste into treasure and serve human health. PK insect gall extracts were prepared using seven solvents. Antioxidant activities of the extracts were examined via antioxidant assays (radical and oxidizing substance quenching, metal chelating, and reducing power). The inhibitory activities of the extracts were determined toward the key human-disease-related enzymes alpha-glucosidase, alpha-amylase, cholinesterase, tyrosinase, urease, and xanthine oxidase. The content of numerous active constituents was high in the methanol and ethanol extracts of PK insect gall, and these extracts had the highest antioxidant and enzyme-inhibitory activities. They also showed excellent stability and low toxicity. These extracts have potential for use as stabilizers of olive and sunflower seed oils.
ESTHER : Wang_2023_Molecules_28_
PubMedSearch : Wang_2023_Molecules_28_
PubMedID: 37630273

Title : Fabrication and Enzymatic Disorganization of Multiresponse Worm-Like Micelles - Xu_2023_Langmuir__
Author(s) : Xu Y , Liu X
Ref : Langmuir , : , 2023
Abstract : How to fabricate multiresponse worm-like micelles (WLMs) and the corresponding green disposal is still challenging. A strategy of fabricating the surfactant-based WLMs that can respond simultaneously to light, heat, and pH was developed by using triple-response sodium (E)-2-(4-(phenyldiazenyl)phenoxy) acetate (AzoNa) and butyrylcholinesterase (BChE)-hydrolyzable palmitoylcholine bromide (PCB). Under the optimal molar ratio of AzoNa to PCB (-0.5), the PCB-AzoNa WLMs formed with a maximum zero-shear viscosity ((0)) value of about 2.1 x 10(5) mPa.s and an average diameter (D) of 4.1 +/- 0.6 nm under conditions of 37 degreesC and pH 7.4. After irradiated with 365 nm UV light for 80 min, AzoNa underwent the trans-to-cis transition, by which the PCB-AzoNa WLMs was destroyed; however, the PCB-AzoNa WLMs could be reformed upon the irradiation of 455 nm blue light for 18 h or heating at 70 degreesC for 45 min due to the cis-to-trans isomerization of AzoNa. When pH changed from 7.4 to 2.0, the PCB-AzoNa WLMs was destroyed rapidly because of the conversion of AzoNa to the acid form of AzoH, whereas the PCB-AzoNa WLMs could be reformed after pH was restored to 7.4. The multiple responsiveness of the PCB-AzoNa WLMs was reversible due to the reversible trans-cis isomerization or protonation of AzoNa. Besides, the average D values of light, heat, and pH-regenerated PCB-AzoNa WLMs were 4.2 +/- 0.7, 4.0 +/- 0.7, and 4.0 +/- 0.6 nm, respectively. Finally, the PCB-AzoNa WLMs could be enzymatically disorganized under conditions of 37 degreesC and pH 7.4 due to the BChE-catalyzed hydrolysis of PCB. We hope that the fabrication and enzymatic disorganization strategies for PCB-based multiresponse WLMs presented here will find potential applications in the formulation of antimicrobial household and personal care products containing PCB and in the green disposal of viscous waste containing PCB.
ESTHER : Xu_2023_Langmuir__
PubMedSearch : Xu_2023_Langmuir__
PubMedID: 38134447

Title : Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats - Zeng_2023_Scand.J.Rheumatol__1
Author(s) : Zeng M , Issotina Zibrila A , Li X , Liu X , Wang X , Zeng Z , Wang Z , He Y , Meng L , Liu J
Ref : Scand J Rheumatol , :1 , 2023
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
ESTHER : Zeng_2023_Scand.J.Rheumatol__1
PubMedSearch : Zeng_2023_Scand.J.Rheumatol__1
PubMedID: 37339380

Title : beta-cyclocitral, a novel AChE inhibitor, contributes to the defense of Microcystis aeruginosa against Daphnia grazing - Chen_2023_J.Hazard.Mater_465_133248
Author(s) : Chen W , Dou J , Xu X , Ma X , Chen J , Liu X
Ref : J Hazard Mater , 465 :133248 , 2023
Abstract : beta-cyclocitral is one of the major compounds in cyanobacterial volatile organic compound (VOCs) and can poison other aquatic organisms. To investigate the effect of beta-cyclocitral on cyanobacterial-grazer interactions, Daphnia sinensis was fed Microcystis aeruginosa and exposed to beta-cyclocitral. Our present study demonstrated that M. aeruginosa could significantly inhibit D. sinensis grazing. And the grazing inhibition by Microcystis aeruginosa results from the suppression of feeding rate, heart rate, thoracic limb activity and swimming speed of D. sinensis. In addition, M. aeruginosa could also induce intestinal peristalsis and emptying in D. sinensis. Interestingly, our present study found that the exposure to beta-cyclocitral could mimic a range of phenotypes induced by M. aeruginosa in D. sinensis. These results suggested that M. aeruginosa could release beta-cyclocitral to inhibit Daphnia grazing. To further examine the toxic mechanism of beta-cyclocitral in Daphnia, several in vivo and in vitro experiments displayed that beta-cyclocitral was a novel inhibitor of acetylcholinesterase (AChE). It could induce the accumulation of acetylcholine (ACh) by inhibiting AchE activity in D. sinensis. High level of endogenous Ach could inhibit feeding rate and induce intestinal peristalsis and emptying in D. sinensis.
ESTHER : Chen_2023_J.Hazard.Mater_465_133248
PubMedSearch : Chen_2023_J.Hazard.Mater_465_133248
PubMedID: 38147752
Gene_locus related to this paper: dapul-ACHE1

Title : Bioaccumulation, metabolism and toxicological effects of chiral insecticide malathion and its metabolites in zebrafish (Danio rerio) - Cui_2023_Chemosphere_318_137898
Author(s) : Cui J , Wei Y , Jiang J , Xiao S , Liu X , Zhou Z , Liu D , Wang P
Ref : Chemosphere , 318 :137898 , 2023
Abstract : The bioaccumulation, metabolism, tissue-specific distribution and toxicity of the widely used organophosphorous pesticide malathion to zebrafish were investigated on an enantiomeric level for evaluating the environmental risks. The metabolites were also monitored and evaluated. Malathion was metabolized by zebrafish very fast with the half-life of 0.12 d and showed a middle accumulation capacity in zebrafish with bioaccumulation factor (BCF) of 12.9 after a 15-d exposure. Brain could enrich higher concentration of malathion than other tissues. The metabolites malaoxon, malathion/malaoxon monocarboxylic acid (DMA), malathion/malaoxon dicarboxylic acid (DCA), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) were found, in which DMTP and DCA were in higher level, indicating the metabolism was mainly induced by carboxylesterase degradation. The accumulation of malathion and malaoxon was stereoselective in zebrafish tissues, exhibiting S-enantiomer preferentially enriched. The acute toxicity test showed rac-malathion was low toxic to zebrafish, which was 1.2 and 1.6 folds more toxic than S-malathion and R-malathion respectively. Malaoxon was highly toxic to zebrafish and approximately 32 times more toxic than malathion. The toxicity of other metabolites was lower than malathion. Malathion could cause an apparent developmental toxicity to zebrafish embryo, including bradycardia, hatchability reduction and deformity, and abnormal movement patterns in zebrafish larva. Chronic toxicity indicated that malathion and malaoxon induced oxidative damage and neurotoxicity in the liver, brain and gill of zebrafish, and malaoxon exhibited a relatively high injury to the zebrafish brain. The results can provide information for the comprehensive assessment of the potential risk of malathion to aquatic organisms and highlight the necessity of consideration of stereoselectivity and metabolites when systemically evaluating pesticides.
ESTHER : Cui_2023_Chemosphere_318_137898
PubMedSearch : Cui_2023_Chemosphere_318_137898
PubMedID: 36702415

Title : Low concentration of indoxacarb interferes with the growth and development of silkworm by damaging the structure of midgut cells - Wang_2023_Pestic.Biochem.Physiol_195_105567
Author(s) : Wang W , Su Y , Liu X , Qi R , Li F , Li B , Sun H
Ref : Pestic Biochem Physiol , 195 :105567 , 2023
Abstract : As an important economic insect, Bombyx mori plays an essential role in the development of the agricultural economy. Indoxacarb, a novel sodium channel blocker insecticide, has been widely used for the control of various pests in agriculture and forestry, and its environmental pollution caused by flight control operations has seriously affected the safe production of sericulture in recent years. However, the lethal toxicity and adverse effects of indoxacarb on silkworm remain largely unknown. In this study, the toxicity of indoxacarb on the 5th instar larvae of silkworm was determined, with an LC(50) (72 h) of 2.07 mg/L. Short-term exposure (24 h) to a low concentration of indoxacarb (1/2 LC(50)) showed significantly reduced body weight and survival rate of silkworm larvae. In addition, indoxacarb also led to decreased cocoon weight and cocoon shell weight, but had no significant effects on pupation, adult eclosion, and oviposition. Histopathological and ultrastructural analysis indicated that indoxacarb could severely damage the structure of the midgut epithelial cells, and lead to physiological impairment of the midgut. A total of 3883 differentially expressed genes (DEGs) were identified by midgut transcriptome sequencing and functionally annotated using GO and KEGG. Furthermore, the transcription level and enzyme activity of the detoxification related genes were determined, and our results suggested that esterases (ESTs) might play a major role in metabolism of indoxacarb in the midgut of B. mori. Future studies to examine the detoxification or biotransformation function of candidate genes will greatly enhance our understanding of indoxacarb metabolism in B. mori. The results of this study provide a theoretical basis for elucidating the mechanism of toxic effects of indoxacarb on silkworm by interfering with the normal physiological functions of the midgut.
ESTHER : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedSearch : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedID: 37666598

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

Title : Hydrolysis and transport characteristics of tyrosol-SCFA esters in rat intestine and blood: Two-step release of tyrosol and SCFAs to enhance the beneficial effects - Wang_2023_Food.Chem_414_135710
Author(s) : Wang X , Wang Q , Hu Y , Yin F , Liu X , Zhou D
Ref : Food Chem , 414 :135710 , 2023
Abstract : The models of rat everted gut sac and hydrolysis by rat plasma were used to clarify the hydrolysis and transport characteristics of tyrosol-SCFA esters (TYr-SEs). HPLC-UV results indicated that TYr-SEs could be hydrolyzed by intestinal lipase, which showed sustained release of SCFAs and TYr. Meanwhile, TYr-SEs and the liberated SCFAs and TYr could cross the membrane and were transported into blood circulation. TYr-SEs were further hydrolyzed by carboxylesterase in plasma. Obviously, the hydrolysis of TYr-SEs in blood also showed sustained release of SCFAs and TYr. Especially, the rates of hydrolysis and transport correlated positively with the acyl chain lengths. Besides, the above rates of the TYr-SE with a straight chain were greater than those of its isomer with a branched chain. Therefore, the above-mentioned two-step release of SCFAs and TYr clearly demonstrated that TYr-SEs would be an effective approach to enhance the beneficial health effects of SCFAs and TYr.
ESTHER : Wang_2023_Food.Chem_414_135710
PubMedSearch : Wang_2023_Food.Chem_414_135710
PubMedID: 36821923

Title : Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals - Xu_2023_Mol.Nutr.Food.Res__e2200816
Author(s) : Xu X , Song Y , Jiang M , Liu M , Zhang X , Wang D , Pan Y , Ren S , Liu X
Ref : Mol Nutr Food Res , :e2200816 , 2023
Abstract : SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.
ESTHER : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedSearch : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedID: 38018298

Title : New bysspectin A derivatives as potent inhibitors of human carboxylesterase 2A - Li_2023_Eur.J.Med.Chem_259_115708
Author(s) : Li W , Zhang Y , Wu Y , Zhu G , Liu X , Song Y , Ma B , Lin S , Ge G , Jiao X , Xie P
Ref : Eur Journal of Medicinal Chemistry , 259 :115708 , 2023
Abstract : Human carboxylesterase 2A (hCES2A), the most abundant carboxylesterase in the human gut, plays a crucial role in the metabolic clearance and activation of various ester-bearing drugs, environmental toxins and carcinogens. Inhibition of intestinal hCES2A can alleviate irinotecan-induced gut toxicity and modulate the oral bioavailability of hCES2A-substrate drugs. Bysspectin A, a natural product isolated from the endophytic fungus Byssochlamys spectabilis, has been identified as a highly selective hCES2A inhibitor. Herein, two sets of bysspectin A derivatives have been designed and synthesized, utilizing a Cu-catalyzed domino Sonogashira-cyclization as the key step. Following two rounds of structure activity relationship (SAR) studies and structural optimizations, compound 20w was identified as the most potent hCES2A inhibitor, with an IC(50) value of 1.6 nM, an approximately 1000-fold improvement over bysspectin A. Further investigation showed that 20w potently inhibited hCES2A in a mixed inhibition manner, while this agent could also potently inhibit intracellular hCES2A in living cells and exhibited suitable metabolic stability. In summary, our findings demonstrate that a new bysspectin A derivative (20w) is a promising candidate for the development of clinically used hCES2A inhibitor.
ESTHER : Li_2023_Eur.J.Med.Chem_259_115708
PubMedSearch : Li_2023_Eur.J.Med.Chem_259_115708
PubMedID: 37544184

Title : Plasma membrane association and resistosome formation of plant helper immune receptors - Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
Author(s) : Wang Z , Liu X , Yu J , Yin S , Cai W , Kim NH , El Kasmi F , Dangl JL , Wan L
Ref : Proc Natl Acad Sci U S A , 120 :e2222036120 , 2023
Abstract : Intracellular plant immune receptors, termed NLRs (Nucleotide-binding Leucine-rich repeat Receptors), confer effector-triggered immunity. Sensor NLRs are responsible for pathogen effector recognition. Helper NLRs function downstream of sensor NLRs to transduce signaling and induce cell death and immunity. Activation of sensor NLRs that contain TIR (Toll/interleukin-1receptor) domains generates small molecules that induce an association between a downstream heterodimer signalosome of EDS1 (EnhancedDisease Susceptibility 1)/SAG101 (Senescence-AssociatedGene 101) and the helper NLR of NRG1 (NRequired Gene 1). Autoactive NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector-induced NRG1 oligomerization are not well characterized. We demonstrate that helper NLRs require positively charged residues in their N-terminal domains for phospholipid binding and PM association before and after activation, despite oligomerization and conformational changes that accompany activation. We demonstrate that effector activation of a TIR-containing sensor NLR induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization. Alternatively, the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector-induced NRG1 resistosome formation.
ESTHER : Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
PubMedSearch : Wang_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2222036120
PubMedID: 37523563

Title : In vitro plasma hydrolysis of phenolic esters and their absorption kinetics in rats: Controlled release of phenolic compounds and enhanced health benefits - Wang_2023_Food.Chem_435_137647
Author(s) : Wang X , Wang Q , Cai D , Yu J , Liu X , Yin F , Zhou D
Ref : Food Chem , 435 :137647 , 2023
Abstract : Phenolic esters are considered as promising functional food ingredients. However, their digestion, absorption and metabolism are still unclear. Tyrosol acyl esters (TYr-Es), hydroxytyrosol acyl esters (HTy-Es) and alkyl gallates (A-GAs) were hydrolyzed by carboxylesterase in plasma and exhibited slow release of polyphenols (phenolic acids). In vitro hydrolysis degrees initially increased and then decreased with the increasing carbon chain length (C2-C16). TYr-Es exhibited higher hydrolysis degrees compared to HTy-Es, and hydrolysis degrees of TYr-Es and HTy-Es were markedly higher than those of A-GAs. Due to the fast hydrolysis rates of TYr-Es and HTy-Es, they were undetectable in all rat plasma samples collected at several times within 24 h after administration. Whereas, A-GAs could be detected in rat plasmas and three absorption peaks were found in the pharmacokinetic profiles. Importantly, the T(1/2), MRT, AUC(0-), AUC(0-t) in octyl gallate group were longer (or stronger) than those in propyl gallate and dodecyl gallate groups.
ESTHER : Wang_2023_Food.Chem_435_137647
PubMedSearch : Wang_2023_Food.Chem_435_137647
PubMedID: 37804730

Title : A Deep-Sea Bacterium Is Capable of Degrading Polyurethane - Gui_2023_Microbiol.Spectr__e0007323
Author(s) : Gui Z , Liu G , Liu X , Cai R , Liu R , Sun C
Ref : Microbiol Spectr , :e0007323 , 2023
Abstract : Plastic wastes have been recognized as the most common and durable marine contaminants, which are not only found in the shallow water, but also on the sea floor. However, whether deep-sea microorganisms have evolved the capability of degrading plastic remains elusive. In this study, a deep-sea bacterium Bacillus velezensis GUIA was found to be capable of degrading waterborne polyurethane. Transcriptomic analysis showed that the supplement of waterborne polyurethane upregulated the expression of many genes related to spore germination, indicating that the presence of plastic had effects on the growth of strain GUIA. In addition, the supplement of waterborne polyurethane also evidently upregulated the expressions of many genes encoding lipase, protease, and oxidoreductase. Liquid chromatography-mass spectrometry (LC-MS) results showed that potential enzymes responsible for plastic degradation in strain GUIA were identified as oxidoreductase, protease, and lipase, which was consistent with the transcriptomic analysis. In combination of in vitro expression and degradation assays as well as Fourier transform infrared (FTIR) analysis, we demonstrated that the oxidoreductase Oxr-1 of strain GUIA was the key degradation enzyme toward waterborne polyurethane. Moreover, the oxidoreductase Oxr-1 was also shown to degrade the biodegradable polybutylene adipate terephthalate (PBAT) film indicating its wide application potential. IMPORTANCE The widespread and indiscriminate disposal of plastics inevitably leads to environmental pollution. The secondary pollution by current landfill and incineration methods causes serious damage to the atmosphere, land, and rivers. Therefore, microbial degradation is an ideal way to solve plastic pollution. Recently, the marine environment is becoming a hot spot to screen microorganisms possessing potential plastic degradation capabilities. In this study, a deep-sea Bacillus strain was shown to degrade both waterborne polyurethane and biodegradable PBAT film. The FAD-binding oxidoreductase Oxr-1 was demonstrated to be the key enzyme mediating plastic degradation. Our study not only provided a good candidate for developing bio-products toward plastic degradation but also paved a way to investigate the carbon cycle mediated by plastic degradation in deep-sea microorganisms.
ESTHER : Gui_2023_Microbiol.Spectr__e0007323
PubMedSearch : Gui_2023_Microbiol.Spectr__e0007323
PubMedID: 36995243

Title : Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study - Jiang_2023_Reprod.Biol.Endocrinol_21_97
Author(s) : Jiang C , Chen M , Wu Y , Bai H , Liu X , Fan P
Ref : Reprod Biol Endocrinol , 21 :97 , 2023
Abstract : BACKGROUND: Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. METHODS: This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. RESULTS: Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. CONCLUSIONS: Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.
ESTHER : Jiang_2023_Reprod.Biol.Endocrinol_21_97
PubMedSearch : Jiang_2023_Reprod.Biol.Endocrinol_21_97
PubMedID: 37885002

Title : New Hydrolase from Aeromicrobium sp. HA for the Biodegradation of Zearalenone: Identification, Mechanism, and Application - Hu_2023_J.Agric.Food.Chem_71_2411
Author(s) : Hu J , Wang G , Hou M , Du S , Han J , Yu Y , Gao H , He D , Shi J , Lee YW , Mohamed SR , Dawood DH , Hong Q , Liu X , Xu J
Ref : Journal of Agricultural and Food Chemistry , 71 :2411 , 2023
Abstract : Zearalenone (ZEN) is an estrogenic mycotoxin most frequently found in cereals that can cause reproductive disorders in livestock and pose a severe threat to animal husbandry. In this study, we isolated a ZEN-degrading Aeromicrobium strain from soil and found that ZenH, a hydrolase, is responsible for the hydrolysis of ZEN through comparative proteomics and biochemical studies. ZenH exhibited the highest similarity with lactone hydrolase ZHD607 from Phialophora americana at 21.52%. ZenH displayed maximal enzymatic activity at pH 7.0 and 55 degreesC with a Michaelis constant of 12.64 microM. The catalytic triad of ZenH was identified as S117-D142-H292 by molecular docking and site-directed mutagenesis. ZenH catalyzed the hydrolysis of ZEN to a novel metabolite, (S,E)-4-hydroxy-2-(10-hydroxy-6-oxoundec-1-en-1-yl)-7-oxabicyclo[4.2.0]octa-1,3,5-trien-8-one, which exhibited significantly lower estrogenic toxicity than ZEN. This study illustrates a novel ZEN-degrading enzyme and reveals a new degradation product. Furthermore, the enzyme showed good potential for detoxifying ZEN during food processing.
ESTHER : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedSearch : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedID: 36701132

Title : Chemical Composition, In Vitro Antioxidant Activities, and Inhibitory Effects of the Acetylcholinesterase of Liparis nervosa (Thunb.) Lindl. Essential Oil - Zhao_2023_Biomolecules_13_
Author(s) : Zhao J , Xu Z , Gao P , Liu X
Ref : Biomolecules , 13 : , 2023
Abstract : The present study aimed to investigate the essential oil composition of Liparis nervosa (Thunb.) Lindl., grown in China, and to determine its antioxidant and inhibitory effects on acetylcholinesterase. The essential oil was obtained by hydrodistillation, and the chemical compounds were analyzed by GC-MS and GC-FID. We used 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing assay power (FRAP) to evaluate the antioxidant activity. The anti-acetylcholinesterase activity of the essential oil was also examined. Sixty-seven compounds were identified, representing 98.50 % of the total essential oil, which was shown to be rich in methyl (9E,11E)-octadeca-9,11-dienoate (31.69%), n-hexadecanoic acid (15.08%), isopropyl palmitate (12.44%), propyl tetradecanoate (7.20%), tetradecanoic acid (4.01%), 17-octadecynoic acid (3.71%), and pentacosane (2.24%). Its antioxidant ability was analyzed via ABTS (IC(50) = 721.95 +/- 9.93 microg/mL), DPPH scavenging capacity (IC(50) > 10,000 microg/mL), and the FRAP method (Trolox equivalent antioxidant concentration 39.64 +/- 3.38 microM/g). Acetylcholinesterase inhibition effects were evaluated and had an IC(50) value of 51.96 +/- 14.26 microg/mL. The results show that this essential oil has interesting biological potential, encouraging further investigations, especially regarding the mechanisms of action of its antioxidant and anti-acetylcholinesterase activity. This is the first time that the chemical composition, antioxidant activity, and acetylcholinesterase inhibition effects of essential oil from L. nervosa have been studied.
ESTHER : Zhao_2023_Biomolecules_13_
PubMedSearch : Zhao_2023_Biomolecules_13_
PubMedID: 37509125

Title : Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus - Meng_2023_Lipids.Health.Dis_22_219
Author(s) : Meng J , Yan R , Zhang C , Bai X , Yang X , Yang Y , Feng T , Liu X
Ref : Lipids Health Dis , 22 :219 , 2023
Abstract : BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I(2). Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.
ESTHER : Meng_2023_Lipids.Health.Dis_22_219
PubMedSearch : Meng_2023_Lipids.Health.Dis_22_219
PubMedID: 38082288

Title : In Vitro Gastrointestinal Digestion and Microbial Hydrolysis of Hydroxytyrosol-SCFA and Tyrosol-SCFA Acyl Esters: Controlled-Release of SCFAs and Polyphenols - Wang_2023_J.Agric.Food.Chem__
Author(s) : Wang X , Wang Q , Cai D , Guo X , Tong P , Yin F , Liu X , Zhou D
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Phenolipids such as hydroxytyrosol-SCFA acyl esters (HTy-SEs) and tyrosol-SCFA acyl esters (TYr-SEs) with various alkyl chains lengths (C1-C4) and different isomers (branched-chain and straight-chain) were successfully synthesized. All esters were hydrolyzed by pancreatic lipase to produce polyphenols (HTy and TYr) and SCFAs (iso-butyric acid, acetic acid, propionic acid, and n-butyric acid). Moreover, HTy-SEs (and TYr-SEs) could also be hydrolyzed to free HTy (and TYr) and SCFAs by gut microbiota and Lactobacillus from mice feces. Especially, the hydrolysis rates showed positive correlation with the carbon skeleton length, and the hydrolysis degree (DH) of ester with a branched-chain fatty acid was weaker than that of ester with a straight-chain fatty acid. Besides, the DH values of TYr -SEs were significantly higher than those of HTy-SEs. Therefore, through regulating the structures of polyphenols, carbon skeleton lengths, and isomers, controlled-release of polyphenols and SCFAs from phenolipids will be easily achieved.
ESTHER : Wang_2023_J.Agric.Food.Chem__
PubMedSearch : Wang_2023_J.Agric.Food.Chem__
PubMedID: 37294303

Title : Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes - Li_2023_Front.Pharmacol_14_1093696
Author(s) : Li Y , Liu X , Li L , Zhang T , Gao Y , Zeng K , Wang Q
Ref : Front Pharmacol , 14 :1093696 , 2023
Abstract : Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.
ESTHER : Li_2023_Front.Pharmacol_14_1093696
PubMedSearch : Li_2023_Front.Pharmacol_14_1093696
PubMedID: 36762117

Title : Development of novel 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as balanced multifunctional agents against Alzheimer's disease - Shi_2022_Eur.J.Med.Chem_230_114098
Author(s) : Shi Y , Zhang H , Song Q , Yu G , Liu Z , Zhong F , Tan Z , Liu X , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 230 :114098 , 2022
Abstract : Based on multitarget-directed ligands approach, through two rounds of screening, a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives were designed, synthesized and evaluated as innovative multifunctional agents against Alzheimer's disease. In vitro biological assays indicated that most of the hybrids were endowed with great AChE inhibitory activity, excellent antioxidant activity and moderate Abeta(1-42) aggregation inhibition. Taken both efficacy and balance into account, 12a was identified as the optimal multifunctional ligand with significant inhibition of AChE (EeAChE, IC(50) = 0.20 microM; HuAChE, IC(50) = 37.02 nM) and anti-Abeta activity (IC(50) = 1.92 microM for self-induced Abeta(1-42) aggregation; IC(50) = 1.80 microM for disaggregation of Abeta(1-42) fibrils; IC(50) = 2.18 microM for Cu(2+)-induced Abeta(1-42) aggregation; IC(50) = 1.17 microM for disaggregation of Cu(2+)-induced Abeta(1-42) fibrils; 81.7% for HuAChE-induced Abeta(1-40) aggregation). Moreover, it was equipped with the potential to serve as antioxidant (3.03 Trolox equivalents), metals chelator and anti-neuroinflammation agent for synergetic treatment. Finally, in vivo study demonstrated that 12a, with suitable BBB permeability (log BB = -0.61), could efficaciously ameliorate cognitive dysfunction on scopolamine-treated mice by regulating cholinergic system and oxidative stress simultaneously. Altogether, these results highlight the potential of 12a as an innovative balanced multifunctional candidate for Alzheimer's disease treatment.
ESTHER : Shi_2022_Eur.J.Med.Chem_230_114098
PubMedSearch : Shi_2022_Eur.J.Med.Chem_230_114098
PubMedID: 35026532

Title : Concurrent production of ferulic acid and glucose from wheat bran by catalysis of a putative bifunctional enzyme - Fang_2022_Bioresour.Technol__128393
Author(s) : Fang D , Xue D , Liu X , Cao L , Zhang J , Gong C
Ref : Bioresour Technol , :128393 , 2022
Abstract : The aim of this work is to study a bifunctional endoglucanase/carboxylesterase in Sphingobacterium soilsilvae Em02 and express it in soluble form in engineered Escherichia coli. The molecular weight of the recombinant protein of the bifunctional enzyme was 41 KDa. This research also determined the enzymatic activities of the bifunctional enzymes using microcrystalline cellulose and p-nitrophenyl butyrate as substrates and found 40 degreesC as the optimum temperature for their enzymatic activities. The optimal pH in dual function was 6.0 for endoglucanase and 7.0 for carboxylesterase. The bifunctional enzyme also exhibited enzymatic activities on the natural biomass by generating up to 3.94 mg of glucose and 49.4 microg of ferulic acid from 20 mg of destarched wheat bran. This indicates the broad application prospects of the bifunctional enzyme in agriculture and industry.
ESTHER : Fang_2022_Bioresour.Technol__128393
PubMedSearch : Fang_2022_Bioresour.Technol__128393
PubMedID: 36442604

Title : Characterization of a Novel Esterase Est33 From an Antarctic Bacterium: A Representative of a New Esterase Family - Liu_2022_Front.Microbiol_13_855658
Author(s) : Liu X , Zhou M , Sun R , Xing S , Wu T , He H , Chen J , Bielicki JK
Ref : Front Microbiol , 13 :855658 , 2022
Abstract : Studies of microorganisms from extreme environments can sometimes reveal novel proteins with unique properties. Here, we identified a novel esterase gene (Est33) from an Antarctic bacterium. The protein was expressed and purified for biochemical characterizations. Site-mutation variants including S94A, D205A, and H233A were constructed to explore the structure-function relationship of the catalytic triad of Est33, and we found mutating Ser(94), Asp(205), and His(233) residues lead to a complete loss of enzyme activity. In addition, the catalytic Ser(94) located in a conserved pentapeptide motif GVSWG. Phylogenetic analysis showed that Est33 and its closely related homologs belonged to an independent group apart from other known family members, indicating that Est33 represented a new family of esterase. The Est33 enzyme was found to be a cold-active esterase retaining 25%-100% activity from 10 degreesC to 30 degreesC and to have optimal catalytic activity toward p-nitrophenol acetate (30 degreesC and pH7.5). The serine modifying reagent phenylmethylsulfonyl fluoride inhibited the activity of Est33 by 77.34%, while thiol reagents such as dithiol threitol (DTT) activated the enzyme by 3-fold. Metal chelating reagents EDTA had no effects, indicating that Est33 is not a metalloenzyme. Collectively, these results indicate that Est33 constitutes the first member of a novel esterase family XXI that has been identified.
ESTHER : Liu_2022_Front.Microbiol_13_855658
PubMedSearch : Liu_2022_Front.Microbiol_13_855658
PubMedID: 35655995
Gene_locus related to this paper: psesp-Est33

Title : Synthesis and Characterization of Epoxidized Silkworm Pupae Oil and Its Application as Polyvinyl Chloride - Ji_2022_Appl.Biochem.Biotechnol_194_1290
Author(s) : Ji Y , Xu L , Xu Q , Liu X , Lin S , Liao S , Wang W , Lan D
Ref : Appl Biochem Biotechnol , 194 :1290 , 2022
Abstract : More and more industries demand environmental friendliness. Silkworm pupae oil (SPO), extracted from the desilked silkworm pupae, can serve as a promising substrate alternative to use in plasticization. This study aimed to prepare epoxidized silkworm pupae oil (ESPO) and investigate their effects on the thermal stability and plasticization of polyvinyl chloride (PVC) films. A chemo-enzymatic method of ESPO was developed in the presence of Lipase SMG1-F278N and H(2)O(2) in natural deep eutectic solvents (DESs). Lipase SMG1-F278N could initiate the epoxidation reaction effectively at room temperature with a negligible loss of activities 10 batches. A maximum oxirane value of 6.94% was obtained. The formation of oxirane ring in ESPO was confirmed by FTIR and (13)C NMR spectra. Moreover, ESPO showed a better thermal stability and lower freezing point than epoxidized soybean oil (ESO). It was demonstrated that ESPO had a good frost resistance. In addition, ESPO showed a significantly improved plasticizing effect on flexible polyvinyl chloride (PVC). Compared with ESO, ESPO could increase the tensile elongation at break effectively. A significantly lower migration rate of plasticizer was observed in PVC plasticized with ESPO.
ESTHER : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedSearch : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedID: 34677760
Gene_locus related to this paper: malgo-a8puy1

Title : Diterpenoid Caesalmin C Delays Abeta-Induced Paralysis Symptoms via the DAF-16 Pathway in Caenorhabditis elegans - Zhang_2022_Int.J.Mol.Sci_23_6871
Author(s) : Zhang ZP , Bai X , Cui WB , Chen XH , Liu X , Zhi DJ , Zhang ZX , Fei DQ , Wang DS
Ref : Int J Mol Sci , 23 :6871 , 2022
Abstract : Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Abeta-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Abeta-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Abeta monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_6871
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_6871
PubMedID: 35743309

Title : Design, synthesis and biological evaluation of novel coumarin derivatives as multifunctional ligands for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_242_114689
Author(s) : Liu W , Wu L , Tian L , Chen H , Wu Z , Wang N , Liu X , Qiu J , Feng X , Xu Z , Jiang X , Zhao Q
Ref : Eur Journal of Medicinal Chemistry , 242 :114689 , 2022
Abstract : Multi-targeted directed ligands (MTDLs) are emerging as promising Alzheimer's disease (AD) therapeutic possibilities. Coumarin is a multifunctional backbone with extensive bioactivity that has been utilized to develop innovative anti-neurodegenerative properties and is a desirable starting point for the construction of MTDLs. Herein, we explored and synthesized a series of novel coumarin derivatives and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3beta, and BACE1. Among these compounds, compound 30 displayed the multifunctional profile of targeting the AChE (IC(50) = 1.313 +/- 0.099 microM) with a good selectivity over BuChE (SI = 24.623), GSK-3beta (19.30% inhibition at 20 microM), BACE1 (IC(50) = 1.227 +/- 0.112 microM), along with moderate HepG2 cytotoxicity, SH-SY5Y cytotoxicity, low HL-7702 cytotoxicity, as well as good blood-brain barrier (BBB) permeability. Kinetic and docking studies indicated that compound 30 was a competitive AChE inhibitor. Furthermore, acute toxicity experiments revealed that it was non-toxic at a dosage of 1000 mg/kg. The ADME prediction results indicate that 30 has acceptable physicochemical properties. Collectively, these findings demonstrated that compound 30 would be a potential multifunctional candidate for AD therapy.
ESTHER : Liu_2022_Eur.J.Med.Chem_242_114689
PubMedSearch : Liu_2022_Eur.J.Med.Chem_242_114689
PubMedID: 36007469

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 : Methyl Jasmonate-Treated Pepper (Capsicum annuum L.) Depresses Performance and Alters Activities of Protective, Detoxification and Digestive Enzymes of Green Peach Aphid [Myzus persicae (Sulzer) (Hemiptera: Aphididae)] - Zhan_2022_J.Insect.Sci_22_
Author(s) : Zhan X , Liu Y , Liang X , Wu C , Liu X , Shui J , Zhang Y , Wang Y , Chen Q
Ref : J Insect Sci , 22 : , 2022
Abstract : Methyl jasmonate (MeJA) is a phytohormone that has been used to artificially induce plant resistance against multiple arthropod herbivores. However, it is still uncertain whether MeJA can trigger pepper plant resistance against Myzus persicae (Sulzer) (Hemiptera: Aphididae) (green peach aphid, GPA). In this study, we assessed the effects of different concentrations (0, 0.008, 0.04, 0.2, 1.0, and 5.0 mM) of MeJA-treated pepper on the development and reproduction performance of GPA to identify an appropriate concentration for vigorous resistance enhancement. MeJA dose was applied on the pepper to investigate the changes in activities of protective enzyme (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD and polyphenol oxidase, PPO), detoxification enzymes (acetylcholinesterase, AchE; glutathione S-transferase, GSTs; cytocrome P450, CYP450, and carboxylesterase, CarE), and digestive enzymes (protease, PRO and amylase, AMY) in GPA. The results showed that all concentrations of MeJA-treated pepper significantly suppressed GPA performance, wherein 0.2 mM was the optimal concentration, as it presented the lowest intrinsic rate of increase (rm), finite rate of increase (lambda), and the highest population doubling time (Dt) values. Furthermore, the protective enzymes (SOD and CAT), detoxification enzymes (GSTs, CYP450, and CarE), and AMY activities increased significantly in MeJA-treated groups than the control group, while the POD and PPO activities were remarkly inhibited under 0.2 mM treatment. These findings indicate that exogenous spraying of 0.2 mM of MeJA significantly enhanced pepper resistance against GPA. The result of this study suggests MeJA application can be used as a promising strategy in integrative management of this insect pest.
ESTHER : Zhan_2022_J.Insect.Sci_22_
PubMedSearch : Zhan_2022_J.Insect.Sci_22_
PubMedID: 36545895

Title : In Silico Investigation on KAR Signaling Reveals the Significant Dynamic Change of Its Receptor's Structure - Liu_2022_J.Chem.Inf.Model_62_1933
Author(s) : Liu X , Zhang J
Ref : J Chem Inf Model , 62 :1933 , 2022
Abstract : Karrikins (KARs) have been identified as a class of smoke-derived plant growth regulators widely functioning among angiosperms. However, little is known about the mechanism by which these molecules trigger the relevant signal transduction. In this research, conventional molecular dynamics simulations were used to investigate the dynamical behavior of the apo- and holo-forms of the KAR receptor KAI2. The results show that the dynamic binding conformation of KAR(1) in the active site is not completely consistent with that in the static crystal and is largely affected by the residue segment of the receptor, Tyr150-Asn180. The binding of the ligand with KAI2 changes the distribution of the electrostatic potential near the active site and drives the conformational transition of the Tyr150-Asn180 segment with strong internal positive correlation. A 'dual induction' signaling mechanism is proposed in view of the present calculations. Our work paves way for in-depth understanding of the KAR signal transduction mechanism and sheds light on further experimental and theoretical exploration.
ESTHER : Liu_2022_J.Chem.Inf.Model_62_1933
PubMedSearch : Liu_2022_J.Chem.Inf.Model_62_1933
PubMedID: 35389657

Title : Metal-Organic Frameworks-Based Immobilized Enzyme Microreactors Integrated with Capillary Electrochromatography for High-Efficiency Enzyme Assay - Liu_2022_Anal.Chem_94_6540
Author(s) : Liu R , Yi G , Ji B , Liu X , Gui Y , Xia Z , Fu Q
Ref : Analytical Chemistry , 94 :6540 , 2022
Abstract : Enzyme assays are important for studying enzyme-mediated biochemical reactions and for clinical diagnosis and drug development. The technique of an immobilized enzyme microreactor (IMER) integrated with capillary electrophoresis (CE) has been frequently utilized in online enzyme assays. However, the traditional approaches for IMER-CE enzyme analysis have some defects such as low loading capacity and poor stability. Herein, metal-organic frameworks (MOFs), which have enormous potential in the fields of enzyme immobilization and capillary electrochromatographic (CEC) separation, were first explored as novel support materials with good enzyme immobilization performance and stationary phases with excellent separation abilities to construct an integrated MOFs-IMER-CEC microanalysis system for a high-efficiency online enzyme assay. As a proof-of-concept demonstration, acetylcholinesterase (AChE) was immobilized on a densely packed UiO-66-NH(2) nanocrystal coating on a capillary inner surface with abundant intercrystalline mesoporosity and was employed as a highly effective and robust IMER for CEC-integrated online enzyme analysis. The excellent separation performance of the UiO-66-NH(2)-modified capillary was verified by high-efficiency separation of three types of neutral, acidic, and basic compounds. The Michaelis-Menten constant and enzyme inhibition kinetics of UiO-66-NH(2)-IMER were systematically assessed, exhibiting distinct advantages such as remarkably increased enzyme loadability, superior affinity for substrates, and greatly improved stability and repeatability compared to CE-integrated IMERs prepared by the traditional covalent bonding method. Furthermore, the developed method was successfully utilized for detecting organophosphorus pesticides in leguminous vegetable samples, demonstrating its strong practicality. The study not only proposed a novel support material and construction strategy for a high-performance microchannel-based IMER but also can be widely used in bioanalysis and biosensing research.
ESTHER : Liu_2022_Anal.Chem_94_6540
PubMedSearch : Liu_2022_Anal.Chem_94_6540
PubMedID: 35465669

Title : Discovery of novel beta-carboline-1,2,3-triazole hybrids as AChE\/GSK-3beta dual inhibitors for Alzheimer's disease treatment - Liu_2022_Bioorg.Chem_129_106168
Author(s) : Liu W , Tian L , Wu L , Chen H , Wang N , Liu X , Zhao C , Wu Z , Jiang X , Wu Q , Xu Z , Zhao Q
Ref : Bioorg Chem , 129 :106168 , 2022
Abstract : Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3beta (GSK-3beta), might be a breakthrough in the discovery of therapeutic success. Herein, 17 beta-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3beta inhibitory potential. The results indicated that compound 21 has the most potent inhibition against eeAChE (IC(50) = 0.20 +/- 0.02 microM), hAChE (IC(50) = 0.34 +/- 0.01 microM) and GSK-3beta (IC(50) = 1.14 +/- 0.05 microM) among these compounds. In addition, it inhibited hAChE in a mixed type manner and could occupy the binding pocket forming diverse interactions with the target of AChE and GSK-3beta. Moreover, compound 21 showed low cytotoxicity against SH-SY5Y and HepG2 cell lines and good BBB permeability. Compound 21 also attenuated the tau hyperphosphorylation in the Tau (P301L) 293T cell model. The ADME projection exhibited that compound 21 has acceptable physicochemical characteristics. This study provides new leads for the assessment of AChE and GSK-3beta dual inhibition as a promising strategy for AD treatment.
ESTHER : Liu_2022_Bioorg.Chem_129_106168
PubMedSearch : Liu_2022_Bioorg.Chem_129_106168
PubMedID: 36191431

Title : Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae - Li_2022_Front.Microbiol_13_853744
Author(s) : Li W , Liu X , Tsui W , Xu A , Li D , Zhang X , Li P , Bian X , Zhang J
Ref : Front Microbiol , 13 :853744 , 2022
Abstract : Klebsiella pneumoniae is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of K. pneumoniae pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of K. pneumoniae have not been fully elucidated. Among these mechanisms, the secretion systems encoded by strains of the bacteria confer adaptive advantages depending on the niche occupied. The type VI secretion system (T6SS) is a multi-protein complex that delivers effector proteins to the extracellular environment or directly to eukaryotic or prokaryotic cells. T6SSs are widely distributed in Gram-negative bacteria and play an important role in bacterial virulence and the interactions between bacteria and other microorganisms or the environment. This study aimed to enhance the understanding of the characteristics of T6SSs in K. pneumoniae through an in-depth comparative genomic analysis of the T6SS in 241 sequenced strains of K. pneumoniae. We identified the T6SS loci, the synteny of the loci in different species, as well as the effectors and core T6SS-related genes in K. pneumoniae. The presence of a T6SS was a common occurrence in K. pneumoniae, and two T6SS clusters are the most prevalent. The variable region downstream of the gene vgrG usually encodes effector proteins. Conserved domain analysis indicated that the identified putative effectors in K. pneumoniae had the functions of lipase, ribonuclease, deoxyribonuclease, and polysaccharide hydrolase. However, some effectors did not contain predicted functional domains, and their specific functions have yet to be elucidated. This in silico study represents a detailed analysis of T6SS-associated genes in K. pneumoniae and provides a foundation for future studies on the mechanism(s) of T6SSs, especially effectors, which may generate new insights into pathogenicity and lead to the identification of proteins with novel antimicrobial properties.
ESTHER : Li_2022_Front.Microbiol_13_853744
PubMedSearch : Li_2022_Front.Microbiol_13_853744
PubMedID: 35633723

Title : IrO(2) clusters loaded on dendritic mesoporous silica nanospheres with superior peroxidase-like activity for sensitive detection of acetylcholinesterase and its inhibitors - Xiao_2022_J.Colloid.Interface.Sci_635_481
Author(s) : Xiao W , Cai S , Wu T , Fu Z , Liu X , Wang C , Zhang W , Yang R
Ref : J Colloid Interface Sci , 635 :481 , 2022
Abstract : Nanomaterials-based enzyme mimics (nanozymes), by simulating enzyme catalysis, have shown potential in numerous biocatalytic applications, but nanozymes face significant challenges of catalytic activity and reusability that may restrict their practical uses. Herein, we report facile fabrication of surface-clean IrO(2) clusters supported on dendritic mesoporous silica nanospheres (DMSNs), which exhibit superior peroxidase-like activity, high thermal/long-term stability, and good recyclability. The IrO(2) clusters (1.4s+/-s0.2snm in size) are obtained by the laser ablation without any ligands and possess negative surface charge, which are efficiently loaded on the amino-functionalized DMSNs by electrostatic adsorption. Owing to morphological and structural advantages, the resulted DMSN/IrO(2) heterostructure displays outstanding peroxidase-like catalytic performance. Compared with horseradish peroxidase, it shows comparable affinities but higher reaction rate (2.95sxs10(-7)sM.s(-1)) towards H(2)O(2), resulting from rapid electron transfer during the catalysis. This value is also larger than those of mesoporous silicas supported metal or metal oxides nanoparticles/clusters in the previous studies. Benefitting from excellent peroxidase-catalysis of the DMSN/IrO(2), the colorimetric assays are further successfully established for the detection of acetylcholine esterase and its inhibitor, showing high sensitivity and selectivity. The work provides novel design of supported nanozymes for biosensing.
ESTHER : Xiao_2022_J.Colloid.Interface.Sci_635_481
PubMedSearch : Xiao_2022_J.Colloid.Interface.Sci_635_481
PubMedID: 36599245

Title : Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation - Fang_2022_Oxid.Med.Cell.Longev_2022_3773415
Author(s) : Fang Q , Liu X , Ding J , Zhang Z , Chen G , Du T , Wang Y , Xu R
Ref : Oxid Med Cell Longev , 2022 :3773415 , 2022
Abstract : BACKGROUND: Many patients with diabetes die from diabetic cardiomyopathy (DCM); however, effective strategies for the prevention or treatment of DCM have not yet been clarified. METHODS: Leptin receptor-deficient (db/db) mice were treated with either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. Cardiac structures and functions were analyzed using echocardiography and hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and high fat (HGHF) conditions were used to conduct in vitro loss-of-function assays after culture in the presence or absence of AUDA (1 microM). Fluorescence microscopy-based detection of mCherry-GFP-LC3 was performed to assess autophagic flux. RESULTS: The sEH inhibitor AUDA significantly attenuated ventricular remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice and the HGHF-treated cardiomyocytes. Additionally, AUDA increased autophagy and decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA promoted autophagic flux and elevated LC3-II protein level in the presence of bafilomycin A1. However, AUDA-induced autophagy was abolished, and the antiapoptotic effect was partially inhibited upon Nrf2 knockdown. CONCLUSION: Our findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and dysfunction in DCM via increasing autophagy and reducing apoptosis, which is relevant to activate Nrf2 signaling pathway.
ESTHER : Fang_2022_Oxid.Med.Cell.Longev_2022_3773415
PubMedSearch : Fang_2022_Oxid.Med.Cell.Longev_2022_3773415
PubMedID: 35378826

Title : Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress - Liu_2022_Nat.Cancer__
Author(s) : Liu X , Viswanadhapalli S , Kumar S , Lee TK , Moore A , Ma S , Chen L , Hsieh M , Li M , Sareddy GR , Parra K , Blatt EB , Reese TC , Zhao Y , Chang A , Yan H , Xu Z , Pratap UP , Liu Z , Roggero CM , Tan Z , Weintraub ST , Peng Y , Tekmal RR , Arteaga CL , Lippincott-Schwartz J , Vadlamudi RK , Ahn JM , Raj GV
Ref : Nat Cancer , : , 2022
Abstract : Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.
ESTHER : Liu_2022_Nat.Cancer__
PubMedSearch : Liu_2022_Nat.Cancer__
PubMedID: 35654861
Gene_locus related to this paper: human-LIPA

Title : Recombinant humanized IgG1 maintain liver triglyceride homeostasis through Arylacetamide deacetylase in ApoE(-\/-) mice - Xiao_2022_Int.Immunopharmacol_108_108741
Author(s) : Xiao S , Lin R , Duan R , Li Z , Tang D , Liu X , Liu Y , Zhao M
Ref : Int Immunopharmacol , 108 :108741 , 2022
Abstract : BACKGROUND & AIMS: Hyperlipidemia is a lipid metabolism disorder associated with elevated serum triglyceride (TG) and/or cholesterol. Over the years, studies have shown that hyperlipidemia is associated with combordities, incluing diabetes and obesity, gradually becoming a public health concern. Current treatment approaches remain limited due to the lack of effective drugs. Here we investigated the function of recombinant humanized IgG1 in maintaining liver TG homeostasis and the underlying mechanisms. METHODS: ApoE(-/-) mice were fed a high-fat diet (HFD) for 20 weeks to induce hyperlipidemia. RNA sequencing (RNA-Seq) was performed to identify differences in gene expression in different groups of ApoE(-/-) mice liver. In vitro lipid accumulation in primary mouse hepatocytes was induced using a free fatty acid (FFA) mixture. Gene and protein expression were assessed in primary mouse hepatocytes by qPCR and Western blot. Gene reporter assays and ChIP-PCR were used to determine arylacetamide deacetylase (Aadac) promoter activity. RESULTS: Recombinant humanized IgG1 could significantly decrease the serum level of TG and low-density lipoproteins (LDL-C). Moreover, hepatic TG and lipid droplets were also reduced compared to the HFD group. Mouse liver RNA-Seq revealed that administration of recombinant humanized IgG1 significantly elevated the expression of Aadac. In vitro, knock-down of Aadac could nullify the effect of recombinant humanized IgG1 on decreasing the lipid droplets induced by FFA in primary mouse hepatocytes. Gene Reporter assays and ChIP-PCR demonstrated that the foxa1 response element in the Aadac promoter played a key role in Aadac expression induced by recombinant humanized IgG1. Moreover, recombinant humanized IgG1 repressed phosphorylation of PKCdelta and resulted in foxa1 elevation. Finally, neonatal Fc receptor (FcRn) knock-down reversed the effect of recombinant humanized IgG1 on the expression of PKCdelta phosphorylation, foxa1 and Aadac. CONCLUSIONS: Our findings suggest that recombinant humanized IgG1 plays an important role in maintaining liver TG homeostasis via the FcRn/PKCdelta/foxa1/Aadac pathway.
ESTHER : Xiao_2022_Int.Immunopharmacol_108_108741
PubMedSearch : Xiao_2022_Int.Immunopharmacol_108_108741
PubMedID: 35397394

Title : BCHE as a Prognostic Biomarker in Endometrial Cancer and Its Correlation with Immunity - Liu_2022_J.Immunol.Res_2022_6051092
Author(s) : Liu J , Tian T , Liu X , Cui Z
Ref : J Immunol Res , 2022 :6051092 , 2022
Abstract : BACKGROUND: In developed countries, the most common gynecologic malignancy is endometrial carcinoma (EC), making the identification of EC biomarkers extremely essential. As a natural enzyme, butyrylcholinesterase (BCHE) is found in hepatocytes and plasma. There is a strong correlation between BCHE gene mutations and cancers and other diseases. The aim of this study was to analyze the role of BCHE in patients with EC. METHODS: A variety of analyses were conducted on The Cancer Genome Atlas (TCGA) data, including differential expression analysis, enrichment analysis, immunity, clinicopathology, and survival analysis. The Gene Expression Omnibus (GEO) database was used to validate outcomes. Using R tools, Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analyses revealed the potential mechanisms of BCHE in EC. Sangerbox tools were used to delve into the relations between BCHE expression and tumor microenvironment, including microsatellite instability (MSI), tumor neoantigen count (TNC), and tumor mutation burden (TMB). BCHE's genetic alteration analysis was conducted by cBioPortal. In addition, the Human Protein Atlas (HPA) was used to validate the outcomes by immunohistochemistry, and an analysis of the protein-protein interaction network (PPI) was performed with the help of the STRING database. RESULTS: Based on our results, BCHE was a significant independent prognostic factor for patients with EC. The prognosis with EC was affected by age, stage, grade, histological type, and BCHE. GSEA showed that BCHE was closely related to pathways regulating immune response, including transforming growth factor-beta (TGF-beta) signaling pathways and cancer immunotherapy through PD1 blockade pathways. The immune analysis revealed that CD4+ regulatory T cells (Tregs) were negatively correlated with BCHE expression and the immune checkpoint molecules CD28, ADORA2A, BTNL2, and TNFRSF18 were all significantly related to BCHE. BCHE expression was also associated with TMB by genetic alteration analysis. CONCLUSIONS: Identifying BCHE as a biomarker for EC might help predict its prognosis and could have important implications for immunotherapy.
ESTHER : Liu_2022_J.Immunol.Res_2022_6051092
PubMedSearch : Liu_2022_J.Immunol.Res_2022_6051092
PubMedID: 35915658

Title : Sublethal Effects of Thiamethoxam on Biological Traits and Detoxification Enzyme Activities in the Small Brown Planthopper, Laodelphax striatellus (Falln) - Cai_2022_J.Econ.Entomol__
Author(s) : Cai Y , Dou T , Gao F , Wang G , Dong Y , Song N , An S , Yin X , Liu X , Ren Y
Ref : J Econ Entomol , : , 2022
Abstract : The small brown planthopper (Laodelphax striatellus (Falln), Hemiptera: Delphacidae), is an important agricultural pest of rice, and neonicotinoid insecticides are commonly used for controlling L. striatellus. However, the sublethal effects of thiamethoxam on L. striatellus remain relatively unknown. In this study, an age-stage life table procedure was used to evaluate the sublethal effects of thiamethoxam on the biological parameters of L. striatellus. Additionally, activities of carboxylesterase, glutathione S-transferase, and cytochrome P450 monooxygenase in the third instar nymphs were analyzed. The results indicated that the survival time of F0 adults and the fecundity of female adults decreased significantly after the third instar nymphs were treated with sublethal concentrations of thiamethoxam (LC15 0.428 mg/liter and LC30 0.820 mg/liter). The developmental duration, adult preoviposition period, total preoviposition period, and mean generation time of the F1 generation increased significantly, whereas the fecundity of the female adults, intrinsic rate of increase (ri), and finite rate of increase (Lambda) decreased significantly. The oviposition period was significantly shorter for the insects treated with LC30 than for the control insects. Neither sublethal concentrations had significant effects on the adult longevity, net reproduction rate (R0), or gross reproduction rate (GRR) of the F1 generation. The activities of carboxylesterase, glutathione-S-transferase, and cytochrome P450 monooxygenase increased significantly after the thiamethoxam treatments. These results indicate that sublethal concentrations of thiamethoxam can inhibit L. striatellus population growth and enhance detoxification enzyme activities.
ESTHER : Cai_2022_J.Econ.Entomol__
PubMedSearch : Cai_2022_J.Econ.Entomol__
PubMedID: 36351784

Title : The benefit of exercise rehabilitation guided by 6-minute walk test on lipoprotein-associated phospholipase A2 in patients with coronary heart disease undergoing percutaneous coronary intervention: a prospective randomized controlled study - Liu_2022_BMC.Cardiovasc.Disord_22_177
Author(s) : Liu X , Zhou W , Fan W , Li A , Pang J , Chen Z , Li X , Hu X , Zeng Y , Tang L
Ref : BMC Cardiovasc Disord , 22 :177 , 2022
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been taken as a biomarker of inflammation in patients with acute coronary diseases. Regular exercise rehabilitation could attenuate inflammation and promote the rehabilitation of coronary heart disease (CHD). The level of Lp-PLA2 is negatively correlated with 6-min walk test (6-MWT). The exercise prescription of appropriate intensity is the basis of exercise rehabilitation. 6-MWT is associated with maximal oxygen consumption, and can be used to determine the intensity of exercise prescription guiding patients how to do exercise rehabilitation. The aim of this study was to observe the benefit of 6-MWT guided exercise rehabilitation on the level of Lp-PLA2 in patients with CHD undergoing percutaneous coronary intervention (PCI). METHODS: We prospectively, consecutively enrolled 100 patients between Dec 2018 and Dec 2020 in the fourth ward of the Department of Cardiology, Yuebei People's Hospital Affiliated to Shantou University. Eligible patients were 1:1 divided into Group A, with no exercise rehabilitation, and Group B, with regular exercise rehabilitation, using random number table method of simple randomization allocation. Clinical data such as general information, the profile of lipids and the level of Lp-PLA2 were collected at baseline and at 12-week follow-up. RESULTS: There were no statistically significant differences of the percentages of gender, hypertension, type-2 diabetes mellitus (T2DM), the profile of lipids and level of Lp-PLA2 between the groups at baseline (P > 0.05). The level of Lp-PLA2 decreased at 12-week follow-up, moreover, the decline of the Lp-PLA2 level in Group B was more significant than that in Group A (t = 2.875, P = 0.005). Multivariate linear regression analysis indicated that exercise rehabilitation was independently correlated with the level of Lp-PLA2 (beta' = - 0.258, t = - 2.542, P = 0.013). CONCLUSION: Exercise rehabilitation for 12 weeks guided by 6-MWT can further reduce the level of LP-PLA2 in patients with CHD undergoing PCI. Trial registration This trial was registered on the Chinese Clinical Trial Registry: ChiCTR2100048124, registered 3 July 2021- Retrospectively registered. The study protocol adheres to the CONSORT guidelines.
ESTHER : Liu_2022_BMC.Cardiovasc.Disord_22_177
PubMedSearch : Liu_2022_BMC.Cardiovasc.Disord_22_177
PubMedID: 35430800

Title : Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense - Hu_2022_J.Org.Chem__
Author(s) : Hu XY , Zhu SJ , Meng XH , Yu HF , Liu X , Zhang LY , Wei Y , Lei CW , Wei X , Zhou Y
Ref : J Org Chem , : , 2022
Abstract : Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (+/-)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.
ESTHER : Hu_2022_J.Org.Chem__
PubMedSearch : Hu_2022_J.Org.Chem__
PubMedID: 36354352

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

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

Title : MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR - Wang_2022_Front.Vet.Sci_9_948873
Author(s) : Wang J , Hao Z , Hu L , Qiao L , Luo Y , Hu J , Liu X , Li S , Zhao F , Shen J , Li M , Zhao Z
Ref : Front Vet Sci , 9 :948873 , 2022
Abstract : In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep.
ESTHER : Wang_2022_Front.Vet.Sci_9_948873
PubMedSearch : Wang_2022_Front.Vet.Sci_9_948873
PubMedID: 35990270

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

Title : Insecticidal Activity of a Component, (-)-4-Terpineol, Isolated from the Essential Oil of Artemisia lavandulaefolia DC. against Plutella xylostella (L.) - Huang_2022_Insects_13_
Author(s) : Huang X , Du L , Liu T , Ma R , Liu X , Yuan H , Liu S
Ref : Insects , 13 : , 2022
Abstract : Plutella xylostella (L.) is one of the most serious pests of cruciferous vegetables. Our previous work demonstrated that the essential oil of Artemisia lavandulaefolia DC. exhibits promising insecticidal activities against P. xylostella. This study further characterizes the key components that are responsible for the insecticidal effect. In total, 47 compounds (96.52% of the total compounds) were identified from the total oil using GC-MS, and the major compounds were eucalyptol (21.57%), D(+)-camphor (17.33%), (-)-4-terpineol (9.96%) and caryophyllene oxide (10.96%). Among them, (-)-4-terpineol showed significantly larvicidal and fumigant activities against P. xylostella. The LD(50) of (-)-4-terpineol was 43.15 mg/mL at 12 h and 31.22 mg/mL at 24 h for 3rd instar larvae, and the LC(50) for adults was 8.34 mg/mL at 12 h and 7.35 mg/mL at 24 h. In addition, the adults treated with (-)-4-terpineol showed varying degrees of inhibitory activity toward glutathione S-transferase, catalase, acetylcholinesterase and Na(+)/K(+)-ATPase at different post-treatment intervals and concentrations. The results indicate that (-)-4-terpineol has promising insecticidal activities against P. xylostella, and it has good inhibitory effects on the four enzymes of P. xylostella adults.
ESTHER : Huang_2022_Insects_13_
PubMedSearch : Huang_2022_Insects_13_
PubMedID: 36555036

Title : Anti-ischemic effect of monoterpene citronellol on experimental stroke models mediated by proinflammatroy cytokines - Liu_2022_Comb.Chem.High.Throughput.Screen__
Author(s) : Liu X , Zhu C , Yin Y
Ref : Comb Chem High Throughput Screen , : , 2022
Abstract : Background Phytomedicine are proven to treat various chronic diseases as these compounds are cost effective, render few or nil side effects. The elucidating the ameliorative effect of phytomedicine on cerebral ischemia may be potent alternative therapy. Citronellol, a monoterpene alcohol is one such phytocompound present is essential oils of Cymbopogon nardus, Pelargonium geraniums and has immense pharmacological properties such as antihyperalgesic, anticonvulsant and antinociceptive. Objective In the present work, the anti-ischemic effect of citronellol in both cellular and animal model of stroke was analyzed. Methods Citronellol pretreated SH-SY5Y cells were subjected to oxygen-glucose deprivation and reperfusion. The cells were assessed for cell viability and LDH quantification. Inflammatory cytokines were estimated in the cell lysate of citronellol pretreated OGD-R induced cells. Healthy young SD rats were pretreated with citronellol and induced with MCAO-R. Control group are sham operated rats treated with saline. Group II MCAO/R induced untreated rats. Group III and IV are rats prior treated with 10 mg/kg and 20 mg/kg citronellol respectively for 7 consecutive days and induced with MCAO/R. Brain edema was analysed by quantifying the water content and the percentage of infract was assessed using TTC staining technique. Acetylcholinesterase activity and the neurological scoring were performed to assess the neuroprotective activity of citronellol. Lipid peroxidation and antioxidant levels were quantified to evaluate the antioxidant activity of citronellol. The anti-inflammatory activity of citronellol was assessed by quantifying proinflammatory cytokines using commercially available ELISA kits. Results Citronellol treatment significantly ameliorated the neuronal damage in both cellular and animal stroke model. Prior treatment of citronellol significantly decreased the inflammatory cytokines and increased the antioxidants. Citronellol treatment effectively protected the rats from MCAO/R induced brain edema. Conclusion Our results confirm citronellol is an effective anti-ischemic drug with antioxidant, anti-inflammatory properties.
ESTHER : Liu_2022_Comb.Chem.High.Throughput.Screen__
PubMedSearch : Liu_2022_Comb.Chem.High.Throughput.Screen__
PubMedID: 36372917

Title : Branched poly(ethylenimine) carbon dots-MnO(2) nanosheets based fluorescent sensory system for sensing of malachite green in fish samples - Mu_2022_Food.Chem_394_133517
Author(s) : Mu X , Liu X , Ye X , Zhang W , Li L , Ma P , Song D
Ref : Food Chem , 394 :133517 , 2022
Abstract : Malachite green (MG) is an organic dye compound that is frequently used as a fungicide and antiseptic in aquaculture. However, human or animal exposure to MG causes carcinogenic, teratogenic and mutagenic effects. Herein, a novel fluorescent assay was designed for the detection of MG using manganese dioxide nanosheets (MnO(2) NS) as an energy acceptor to quench the fluorescence of branched poly(ethylenimine) carbon dots (BPEI-CDs) via Forster resonance energy transfer. When butyrylcholinesterase is introduced to form thiocholine in the presence of S-butyrylthiocholine iodide, MnO(2) NS can be recovered by thiocholine to Mn(2+), resulting in restoration of the fluorescence of BPEI-CDs. Exploiting these changes in fluorescence intensity in the above system, a fluorescence probe was successfully developed for the quantitative detection of MG. Besides, this assay was applied to fish samples, verifying the high potential for practical application of the proposed sensor for the monitoring of MG in aquatic products.
ESTHER : Mu_2022_Food.Chem_394_133517
PubMedSearch : Mu_2022_Food.Chem_394_133517
PubMedID: 35749877

Title : Cloning and Characterization of Three Novel Enzymes Responsible for the Detoxification of Zearalenone - Zhang_2022_Toxins.(Basel)_14_
Author(s) : Zhang Y , Liu X , Zhang X , Huang H
Ref : Toxins (Basel) , 14 : , 2022
Abstract : Zearalenone is a common mycotoxin contaminant in cereals that causes severe economic losses and serious risks to health of human and animals. Many strategies have been devised to degrade ZEN and keep food safe. The hydrolase ZHD101 from Clonostachys rosea, which catalyzes the hydrolytic degradation of ZEN, has been studied widely. In the current research, three new enzymes that have the capacity to detoxify ZEN were identified, namely CLA, EXO, and TRI, showing 61%, 63%, and 97% amino acids identities with ZHD101, respectively. Three coding genes was expressed as heterologous in Escherichia coli BL21. Through biochemical analysis, the purified recombinant CLA, EXO, TRI, and ZHD101 exhibited high activities of degrading ZEN with the specific activity of 114.8 U/mg, 459.0 U/mg, 239.8 U/mg, and 242.8 U/mg. The optimal temperatures of CLA, EXO, TRI, and ZHD101 were 40 degreesC, 40 degreesC, 40 degreesC, and 45 degreesC, and their optimum pH were 7.0, 9.0, 9.5, and 9.0, respectively. Our study demonstrated that the novel enzymes CLA, EXO, and TRI possessed high ability to degrade ZEN from the model solutions and could be the promising candidates for ZEN detoxification in practical application.
ESTHER : Zhang_2022_Toxins.(Basel)_14_
PubMedSearch : Zhang_2022_Toxins.(Basel)_14_
PubMedID: 35202110

Title : Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity - Huang_2022_Science_377_eabq3297
Author(s) : Huang S , Jia A , Song W , Hessler G , Meng Y , Sun Y , Xu L , Laessle H , Jirschitzka J , Ma S , Xiao Y , Yu D , Hou J , Liu R , Sun H , Liu X , Han Z , Chang J , Parker JE , Chai J
Ref : Science , 377 :eabq3297 , 2022
Abstract : Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR signaling requires helper NLRs N requirement gene 1 (NRG1) and Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1) that forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene101 (SAG101). Here, we show that TIR-containing proteins catalyze production of 2'-(5''-phosphoribosyl)-5'-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity.
ESTHER : Huang_2022_Science_377_eabq3297
PubMedSearch : Huang_2022_Science_377_eabq3297
PubMedID: 35857645
Gene_locus related to this paper: arath-eds1 , arath-PAD4

Title : Monoacylglycerol lipase from marine Geobacillus sp. showing lysophospholipase activity and its application in efficient soybean oil degumming - Liu_2022_Food.Chem_406_134506
Author(s) : Liu X , Wang W , Zhao Z , Xu L , Yang B , Lan D , Wang Y
Ref : Food Chem , 406 :134506 , 2022
Abstract : Enzymatic degumming is an essential refining process to improve oil quality. In this study, a monoacylglycerol lipase GMGL was derived from marine Geobacillus sp., and was found that not only took monoacylglycerol (MAG) as substrate, but also had activity toward lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and glycerolphosphatidylcholine (GPC). Binding free energy showed LPC and LPE could bind with enzyme stably as MAG. It presented great potential in the field of enzymatic degumming. The phosphorus content in crude soybean oil decreased from 680.50 to 2.01 mg/kg and the yield of oil reached to 98.80 % after treating with phospholipase A1 (Lecitase Ultra) combined with lipase GMGL. An ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was developed to identify 21 differential phospholipids between crude soybean oil and enzymatic treatment. This work might shed some light on understanding the catalytic mechanism of monoacylglycerol lipase and provide an effective strategy for enzymatic degumming.
ESTHER : Liu_2022_Food.Chem_406_134506
PubMedSearch : Liu_2022_Food.Chem_406_134506
PubMedID: 36463594

Title : Odor identification impairment and cholinesterase inhibitor treatment in Alzheimer's disease - Motter_2021_Alzheimers.Dement.(Amst)_13_e12158
Author(s) : Motter JN , Liu X , Qian M , Cohen HR , Devanand DP
Ref : Alzheimers Dement (Amst) , 13 :e12158 , 2021
Abstract : INTRODUCTION: This study evaluated acute change in odor identification following atropine nasal spray challenge, and 8-week change in odor identification ability, as a predictor of long-term improvement in patients with mild to moderate Alzheimer's disease (AD) who received open-label cholinesterase inhibitor treatment. METHODS: In patients with clinical AD, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Patients were then treated with donepezil for 52 weeks. RESULTS: In 21 study participants, acute atropine-induced decrease in UPSIT was not associated with change in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) or Selective Reminding Test (SRT). Decline in odor identification performance from baseline to week 8 was indicative of a future decline in cognitive performance over 52 weeks. DISCUSSION: Change in odor identification with atropine challenge is not a useful predictor of treatment response to cholinesterase inhibitors. Short-term change in odor identification performance needs further investigation as a potential predictor of cognitive improvement with cholinesterase inhibitor treatment.
ESTHER : Motter_2021_Alzheimers.Dement.(Amst)_13_e12158
PubMedSearch : Motter_2021_Alzheimers.Dement.(Amst)_13_e12158
PubMedID: 33816753

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

Title : Recent developments in the medicinal chemistry of single boron atom-containing compounds - Song_2021_Acta.Pharm.Sin.B_11_3035
Author(s) : Song S , Gao P , Sun L , Kang D , Kongsted J , Poongavanam V , Zhan P , Liu X
Ref : Acta Pharm Sin B , 11 :3035 , 2021
Abstract : Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.
ESTHER : Song_2021_Acta.Pharm.Sin.B_11_3035
PubMedSearch : Song_2021_Acta.Pharm.Sin.B_11_3035
PubMedID: 34729302

Title : Enhanced Production of (S)-2-arylpropionic Acids by Protein Engineering and Whole-Cell Catalysis - Liu_2021_Front.Bioeng.Biotechnol_9_697677
Author(s) : Liu X , Zhao M , Fan X , Fu Y
Ref : Front Bioeng Biotechnol , 9 :697677 , 2021
Abstract : Esterases are important biocatalysts for chemical synthesis. Several bHSL family esterases have been used to prepare (S)-2-arylpropionic acids with stronger anti-inflammatory effects via kinetic resolution. Here, we presented the discovery of key residues that controlled the enantioselectivity of bHSL family esterases to ethyl 2-arylpropionates, through careful analysis of the structural information and molecular docking. A new bHSL family esterase, Est924, was identified as a promising catalyst for kinetic resolution of racemic ethyl 2-arylpropionates with slight (R)-stereopreference. Using Est924 as the starting enzyme, protein engineering was conducted at hotspots, and the substitution of A203 was proved to enhance the enantioselectivity. The stereopreference of the mutant M1 (A203W) was inverted to ethyl (S)-2-arylpropionates, and this stereopreference was further improved in variant M3 (I202F/A203W/G208F). In addition, the optimal variant, M3, was also suitable for the resolution of ibuprofen ethyl ester and ketoprofen ethyl ester, and their efficient (S)-isomers were synthesized. Next, the whole-cell catalyst harboring M3 was used to prepare (S)-ketoprofen. (S)-ketoprofen with 86%ee was produced by whole-cell catalyst with a single freeze-thaw cycle, and the cells could be reused for at least five cycles. Our results suggested that Est924 variants could kinetically resolve economically important racemates for industrial production and further offer the opportunity for the rational design of enzyme enantioselectivity. Moreover, it is an economical process to prepare optically pure (S)-ketoprofen and (S)-naproxen by using an engineered strain harboring M3 as the catalyst.
ESTHER : Liu_2021_Front.Bioeng.Biotechnol_9_697677
PubMedSearch : Liu_2021_Front.Bioeng.Biotechnol_9_697677
PubMedID: 34307324
Gene_locus related to this paper: 9zzzz-Est924

Title : Computational redesign of a PETase for plastic biodegradation under ambient condition by the GRAPE strategy - Cui_2021_ACS.Catal_11_1340
Author(s) : Cui Y , Chen Y , Liu X , Dong S , Tian Y , Qiao Y , Mitra R , Han J , Li C , Han X
Ref : ACS Catal , 11 :1340 , 2021
Abstract : Nature has provided a fantastic array of enzymes that are responsible for essential biochemical functions but not usually suitable for technological applications. Not content with the natural repertoire, protein engineering holds promise to extend the applications of improved enzymes with tailored properties. However, engineering of robust proteins remains a difficult task since the positive mutation library may not cooperate to reach the target function in most cases owing to the ubiquity of epistatic effects. The main demand lies in identifying an efficient path of accumulated mutations. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to improve the robustness of a PETase from Ideonella sakaiensis. A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the redesign of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 C and a strikingly enhanced degradation toward semicrystalline poly(ethylene terephthalate) (PET) films (30%) at mild temperatures (over 300-fold). Complete biodegradation of 2 g/L microplastics to water-soluble products under mild conditions is also achieved, opening up opportunities to steer the biological degradation of uncollectable PET waste and further conversion of the resulting monomers to high-value molecules. The crystal structure revealed the individual mutation match with the design model. Concurrently, synergistic effects are captured, while epistatic interactions are alleviated during the accumulation process. We anticipate that our design strategy will provide a broadly applicable strategy for global optimization of enzyme performance.
ESTHER : Cui_2021_ACS.Catal_11_1340
PubMedSearch : Cui_2021_ACS.Catal_11_1340
Gene_locus related to this paper: idesa-peth

Title : Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K\/Akt\/m-TOR signaling pathway in the brains of mice - Zhang_2021_Int.Immunopharmacol_99_108035
Author(s) : Zhang Y , Ding C , Cai Y , Chen X , Zhao Y , Liu X , Zhang J , Sun S , Liu W
Ref : Int Immunopharmacol , 99 :108035 , 2021
Abstract : An increasing amount of evidence has shown that injection of D-galactose (D-gal) can mimic natural aging that typically is associated with brain injury. Oxidative stress and apoptosis has been shown to play an essential role in aging process. The purpose of this study was to investigate the protective effectsof astilbin (ASB) on D-Gal-induced agingin miceand to further explore the underlying mechanisms. We randomly divided 50 mice into 5 groups.To establish this model of aging, 40micewere intraperitoneally administered D-Gal (500 mg/kg). The mice in the treatmentgroupswere intragastricaly administratedASB at doses of 40 and 80 mg/kg. H&E and TUNEL staining were used to determine the effect of ASB on the number of apoptotic cells in the brain. Furthermore, biochemical indices of serum, oxidative stress factors, and apoptosis factors were determined to clarify the underlying mechanism using reagent test kits and western blotting. The results showed that varying doses of ASB could improve D-Gal-induced histopathological damageand significantly alleviatedthe aging induced by D-Galin mice. ASB remarkably decreased the activities of malondialdehyde (MDA)(p < 0.01)and Acetyl cholinesterase (AChE)(p < 0.05) and markedlyincreased the content of catalase (CAT)(p < 0.01)and superoxide dismutase (SOD)(p < 0.01), respectively. In addition, Western blotting revealed thatASB treatment (40 mg/kg)attenuated the D-gal-induced Bax and Caspase 3 protein expression(p < 0.01) and reversed the increase in Bcl-2protein expressionin brain. Moreover, ASB treatment significantly upregulated the protein expression ofp-PI3K/PI3K and altered the p-Akt/Akt ratio (p < 0.05), while inhibiting the expression of p-m-TOR relative to m-TOR(p < 0.05). Moreover, the expression of P53 tended to decreasein the low ASB treatmentgroup (40 mg/kg), whereas no change was observed in the high ASB treatmentgroup (80 mg/kg). In the intestinal flora, the richness of the normal group and the ASB group was higher than that of the D-Gal group. Heat map analysis also showed that ASB promoted Lactobacillus and other probiotics and also confirmed the advantages of ASB. The observed changes in intestinal flora further verified the efficacy of ASB.
ESTHER : Zhang_2021_Int.Immunopharmacol_99_108035
PubMedSearch : Zhang_2021_Int.Immunopharmacol_99_108035
PubMedID: 34435579

Title : An efficient phthalate ester-degrading Bacillus subtilis: Degradation kinetics, metabolic pathway, and catalytic mechanism of the key enzyme - Xu_2021_Environ.Pollut_273_116461
Author(s) : Xu Y , Liu X , Zhao J , Huang H , Wu M , Li X , Li W , Sun X , Sun B
Ref : Environ Pollut , 273 :116461 , 2021
Abstract : Phthalate ester pollution in the environment and food chain is frequently reported. Microbial treatment is a green and efficient method for solving this problem. The isolation and systematic investigation of microorganisms generally recognized as safe (GRAS) will provide useful resources. A GRAS Bacillus subtilis strain, BJQ0005, was isolated from Baijiu fermentation starter and efficiently degraded phthalate esters (PAEs). The half-lives for di-isobutyl phthalate, di-butyl phthalate and di-(2-ethylhexyl) phthalate were 3.93, 4.28, and 25.49 h, respectively, from the initial amount of 10 mg per 10 mL reaction mixture, which are records using wild-type strains. Genome sequencing and metabolic intermediate analysis generated the whole metabolic pathway. Eighteen enzymes from the alpha/beta hydrolase family were expressed. Enzymes GTW28_09400 and GTW28_13725 were capable of single ester bond hydrolysis of PAEs, while GTW28_17760 hydrolyzed di-ester bonds of PAEs. Using molecular docking, a possible mechanism affecting enzymatic ester bond hydrolysis of mono-butyl phthalate was proposed of GTW28_17760. The carboxyl group generated by the first hydrolysis step interacted with histidine in the catalytic active center, which negatively affected enzymatic hydrolysis. Isolation and systematic investigation of the PAE degradation characteristics of B. subtilis will promote the green and safe treatment of PAEs in the environment and food industry.
ESTHER : Xu_2021_Environ.Pollut_273_116461
PubMedSearch : Xu_2021_Environ.Pollut_273_116461
PubMedID: 33485001
Gene_locus related to this paper: bacsu-pnbae

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

Title : Background-free sensing platform for on-site detection of carbamate pesticide through upconversion nanoparticles-based hydrogel suit - Su_2021_Biosens.Bioelectron_194_113598
Author(s) : Su D , Zhao X , Yan X , Han X , Zhu Z , Wang C , Jia X , Liu F , Sun P , Liu X , Lu G
Ref : Biosensors & Bioelectronics , 194 :113598 , 2021
Abstract : On-site monitoring of carbamate pesticide in complex matrix remians as a challenge in terms of the real-time control of food safety and supervision of environmental quality. Herein, we fabricated robust upconversion nanoparticles (UCNPS)/polydopamine (PDA)-based hydrogel portable suit that precisely quantified carbaryl in complex tea samples with smartphone detector. UCNPS/PDA nanoprobe was developed by polymerization of dopamine monomers on the surface of NaErF(4): 0.5% Tm(3+)@NaYF(4) through electrostatic interaction, leading to efficient red luminescence quenching of UCNPS under near-infrared excitation, which circumvented autofluorescence and background interference in complicated environment. Such a luminescence quenching could be suppressed by thiocholine that was produced by acetylcholinesterase-mediated catalytic reaction, thus enabling carbaryl bioassay by inhibiting the activity of enzyme. Bestowed with the feasibility analysis of fluorescent output, portable platform was designed by integrating UCNPS-embedded sodium alginate hydrogel with 3D-printed smartphone device for quantitatively on-site monitoring of carbaryl in the range of 0.5-200 ng mL(-1) in tea sample, accompanied by a detection limit of 0.5 ng mL(-1). Owing to specific UCNPS signatures and hydrogel immobilization, this modular platform displayed sensitive response, portability and anti-interference capability in complex matrix analysis, thus holding great potential in point-of-care application.
ESTHER : Su_2021_Biosens.Bioelectron_194_113598
PubMedSearch : Su_2021_Biosens.Bioelectron_194_113598
PubMedID: 34507097

Title : Reshaping the active pocket of esterase Est816 for resolution of economically important racemates - Liu_2021_Catal.Sci.Technol__
Author(s) : Liu X , Zhao M , Fan XJ , Fu Y
Ref : Catal Sci Technol , : , 2021
Abstract : Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with high E values were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
ESTHER : Liu_2021_Catal.Sci.Technol__
PubMedSearch : Liu_2021_Catal.Sci.Technol__
Gene_locus related to this paper: 9bact-i6yrg4

Title : Phthalimide-(N-alkylbenzylamine) cysteamide hybrids as multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Zhang_2021_Chem.Biol.Drug.Des__
Author(s) : Zhang H , Song Q , Yu G , Cao Z , Qiang X , Liu X , Deng Y
Ref : Chemical Biology Drug Des , : , 2021
Abstract : The complex pathogenesis of Alzheimer's disease (AD) calls for multi-target approach for disease treatment. Herein, based on the MTDLs strategy, a series of phthalimide-(N-alkylbenzylamine) cysteamide hybrids were designed, synthesized and investigated in vitro for the purpose. Most of the target compounds were found to be potential multi-target agents. In vitro results showed that compound 9e was the representative compound in this series, endowed with high EeAChE and HuAChE inhibitory potency (IC(50) = 1.55microM and 2.23 microM, respectively), good inhibitory activity against self-induced Abeta(1-42) aggregation (36.08% at 25 microM) and moderate antioxidant capacity (ORAC-FL value was 0.68 Trolox equivalents). Molecular docking studies rationalized the binding mode of 9e in both PAS and CAS of AChE. Moreover, 9e displayed excellent ability to against H(2) O(2) -induced PC12 cell injury and penetrate BBB. Overall, these results highlighted that compound 9e was an effective and promising multi-target agent for further anti-AD drug development.
ESTHER : Zhang_2021_Chem.Biol.Drug.Des__
PubMedSearch : Zhang_2021_Chem.Biol.Drug.Des__
PubMedID: 34143938

Title : Antioxidant Effects of Sophora davidi (Franch.) Skeels on d-Galactose-Induced Aging Model in Mice via Activating the SIRT1\/p53 Pathway - Lin_2021_Front.Pharmacol_12_754554
Author(s) : Lin B , Xu D , Wu S , Qi S , Xu Y , Liu X , Zhang X , Chen C
Ref : Front Pharmacol , 12 :754554 , 2021
Abstract : This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on d-galactose-induced acute aging in mice. Ultra performance liquid chromatography coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), d-galactose (D-gal) model group, vitamin C (Vc) group (positive control), low-, medium-and high-dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activity in the liver and brain were measured. Immunohistochemistry was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor kappaB (NF-kappaB), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T-AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF-alpha, NF-kB, IL-1beta, and IL-6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathological changes of the liver and brain induced by D-gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D-gal. To summarize, SDE demonstrated clear anti-aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway.
ESTHER : Lin_2021_Front.Pharmacol_12_754554
PubMedSearch : Lin_2021_Front.Pharmacol_12_754554
PubMedID: 34938181

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

Title : Role of endocannabinoid signaling in a septohabenular pathway in the regulation of anxiety- and depressive-like behavior - Vickstrom_2021_Mol.Psychiatry_26_3178
Author(s) : Vickstrom CR , Liu X , Liu S , Hu MM , Mu L , Hu Y , Yu H , Love SL , Hillard CJ , Liu QS
Ref : Mol Psychiatry , 26 :3178 , 2021
Abstract : Enhancing endocannabinoid signaling produces anxiolytic- and antidepressant-like effects, but the neural circuits involved remain poorly understood. The medial habenula (MHb) is a phylogenetically-conserved epithalamic structure that is a powerful modulator of anxiety- and depressive-like behavior. Here, we show that a robust endocannabinoid signaling system modulates synaptic transmission between the MHb and its sole identified GABA input, the medial septum and nucleus of the diagonal band (MSDB). With RNAscope in situ hybridization, we demonstrate that key enzymes that synthesize or degrade the endocannabinoids 2-arachidonylglycerol (2-AG) or anandamide are expressed in the MHb and MSDB, and that cannabinoid receptor 1 (CB1) is expressed in the MSDB. Electrophysiological recordings in MHb neurons revealed that endogenously-released 2-AG retrogradely depresses GABA input from the MSDB. This endocannabinoid-mediated depolarization-induced suppression of inhibition (DSI) was limited by monoacylglycerol lipase (MAGL) but not by fatty acid amide hydrolase. Anatomic and optogenetic circuit mapping indicated that MSDB GABA neurons monosynaptically project to cholinergic neurons of the ventral MHb. To test the behavioral significance of this MSDB-MHb endocannabinoid signaling, we induced MSDB-specific knockout of CB1 or MAGL via injection of virally-delivered Cre recombinase into the MSDB of Cnr1(loxP/loxP) or Mgll(loxP/loxP) mice. Relative to control mice, MSDB-specific knockout of CB1 or MAGL bidirectionally modulated 2-AG signaling in the ventral MHb and led to opposing effects on anxiety- and depressive-like behavior. Thus, depression of synaptic GABA release in the MSDB-ventral MHb pathway may represent a potential mechanism whereby endocannabinoids exert anxiolytic and antidepressant-like effects.
ESTHER : Vickstrom_2021_Mol.Psychiatry_26_3178
PubMedSearch : Vickstrom_2021_Mol.Psychiatry_26_3178
PubMedID: 33093652

Title : Sequence and structure-based method to predict diacylglycerol lipases in protein sequence - Ali_2021_Int.J.Biol.Macromol__
Author(s) : Ali S , Liu X , Sen L , Lan D , Wang J , Hassan MI , Wang Y
Ref : Int J Biol Macromol , : , 2021
Abstract : Lipase enzymes play a central role in biotechnology and the food industry. Diacylglyceride lipases (DAG) have received considerable attention due to their physiological significance and potential industrial usage. However, compared to the wide application of triacylglycerol (TAG) lipases, DAG lipases have a limited application due to their low thermostability and specific activity. The molecular basis of substrate specificity of DAG lipases remains elusive, making structure-guided engineering of TAG to DAG lipase difficult. Besides, the number of available DAG lipases is limited compared to TAG lipases. In the current study, we identified structural consensus motifs of DAG lipases that contribute to their DAG specificity on a structural comparison of DAG and TAG lipases. To find potential DAG lipases, sequence motifs and predicted secondary structures were used to screen millions of protein sequences and predict new DAG lipases. In total, 83 new putative DAG lipases were identified. The predicted DAG lipases were validated by expression of randomly chosen putative DAG lipases followed by functional assay for their DAG and TAG specific activity. The reported method is efficient and cost-effective for discovering new DAG lipases used in the food industry after the required characterization to meet potential application needs.
ESTHER : Ali_2021_Int.J.Biol.Macromol__
PubMedSearch : Ali_2021_Int.J.Biol.Macromol__
PubMedID: 33836195

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

Title : Metabolism and Interspecies Variation of IMMH-010, a Programmed Cell Death Ligand 1 Inhibitor Prodrug - Wang_2021_Pharmaceutics_13_
Author(s) : Wang Y , Liu X , Zou X , Wang S , Luo L , Liu Y , Dong K , Yao X , Li Y , Chen X , Sheng L
Ref : Pharmaceutics , 13 : , 2021
Abstract : IMMH-010 is an ester prodrug of YPD-29B, a potent programmed cell death ligand 1 (PD-L1) inhibitor. The metabolism of IMMH-010 was investigated and compared in various species. Four metabolites of IMMH-010 were identified, and the major metabolite was the parent compound, YPD-29B, which was mainly catalyzed by carboxylesterase 1 (CES1). We observed IMMH-010 metabolism in the plasma of various species. IMMH-010 was rapidly metabolized to YPD-29B in rat and mouse plasma, whereas it remained stable in human and monkey plasma. In the liver S9 fractions of human, monkey, dog, and rat, IMMH-010 was quickly transformed to YPD-29B with no obvious differences among species. In addition, the transformation ratio of IMMH-010 to YPD-29B was low in rat and human intestines, which indicated that the intestine was not an important site for IMMH-010 hydrolysis. Moreover, we demonstrated the remarkable antitumor efficacy of IMMH-010 in B16F10 melanoma and MC38 colon carcinoma xenograft mouse models. We also compared the pharmacokinetic profiles of IMMH-010 in rodents and primates. After oral administration of IMMH-010, the general exposure of active metabolite YPD-29B was slightly lower in primates than in rodents, suggesting that data should be extrapolated cautiously from rodents to humans.
ESTHER : Wang_2021_Pharmaceutics_13_
PubMedSearch : Wang_2021_Pharmaceutics_13_
PubMedID: 33919384

Title : MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1 - Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
Author(s) : Luo Z , Fan Y , Liu X , Liu S , Kong X , Ding Z , Li Y , Wei L
Ref : Technol Cancer Research Treat , 20 :15330338211033074 , 2021
Abstract : BACKGROUND: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. METHODS: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. RESULTS: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3'UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. CONCLUSIONS: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.
ESTHER : Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
PubMedSearch : Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
PubMedID: 34355586
Gene_locus related to this paper: human-NDRG1

Title : Portable electrochemical biosensor based on laser-induced graphene and MnO(2) switch-bridged DNA signal amplification for sensitive detection of pesticide - Liu_2021_Biosens.Bioelectron_199_113906
Author(s) : Liu X , Cheng H , Zhao Y , Wang Y , Li F
Ref : Biosensors & Bioelectronics , 199 :113906 , 2021
Abstract : Developing portable, quantitative, and user-friendly analytical tools for sensitive pesticide assay is of significant importance for guaranteeing food safety. Herein, a novel electrochemical biosensor was constructed by integrating laser-induced graphene (LIG) electrode on polyimide (PI) foil and MnO(2) nanosheets loaded on the paper for point-of-care test (POCT) of organophosphorus (OPs) residues. The principle of this biosensor relied on acetylcholinesterase (AChE)-catalyzed hydrolytic product-triggered disintegration of MnO(2) nanosheets for releasing assistant DNA to initiate nicking enzyme-aided recycling amplification. In the presence of OPs, the activity of AChE was inhibited and could not initiate the cleavage of the electroactive molecules-labeled hairpin probe on the electrode, resulting in the maintenance of the electrochemical response to realize a "sign-on" determination of OPs. The proposed biosensor exhibited satisfactory analytical performance for OPs assay with a linear range from 3 to 4000 ng/mL and a limit of detection down to 1.2 ng/mL. Moreover, the biosensor was useful for evaluating the residual level of pesticides in the vegetables. Therefore, this novel biosensor holds great promise for OPs assay and opens a new avenue on the development of higher-performance POCT device for sensing applications in the environment and food safety fields.
ESTHER : Liu_2021_Biosens.Bioelectron_199_113906
PubMedSearch : Liu_2021_Biosens.Bioelectron_199_113906
PubMedID: 34968952

Title : Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway - Tan_2021_Drug.Des.Devel.Ther_15_1971
Author(s) : Tan Q , Hu J , Zhou Y , Wan Y , Zhang C , Liu X , Long X , Tan F , Zhao X
Ref : Drug Des Devel Ther , 15 :1971 , 2021
Abstract : AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.
ESTHER : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedSearch : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedID: 34007157

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

Title : Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-Alzheimer's disease agents - Ye_2021_Bioorg.Chem_111_104895
Author(s) : Ye C , Xu R , Cao Z , Song Q , Yu G , Shi Y , Liu Z , Liu X , Deng Y
Ref : Bioorg Chem , 111 :104895 , 2021
Abstract : A series of 4-aminoalkyl-1(2H)-phthalazinone derivatives was designed and synthesized as potential multifunctional agents for Alzheimer's disease (AD) treatment. In vitro biological assay results demonstrated that most synthesized compounds exhibited significant AChE inhibition, moderate to high MAOs inhibitory potencies and good anti-platelet aggregation abilities. Among them, compound 15b exhibited the highest inhibitory potencies towards MAO-B and MAO-A (IC(50) = 0.7 microM and 6.4 microM respectively), moderate inhibition towards AChE (IC(50) = 8.2 microM), and good activities against self- and Cu(2+)-induced Abeta(1-42) aggregation and platelet aggregation. Moreover, 15b also displayed antioxidant capacity, neuroprotective potency, anti-neuroinflammation and BBB permeability. These excellent results indicated that compound 15b could be worthy of further studies to be considered as a promising multifunctional candidate for the treatment of AD.
ESTHER : Ye_2021_Bioorg.Chem_111_104895
PubMedSearch : Ye_2021_Bioorg.Chem_111_104895
PubMedID: 33887586

Title : Identification and Biochemical Characterization of a Novel Hormone-Sensitive Lipase Family Esterase Est19 from the Antarctic Bacterium Pseudomonas sp. E2-15 - Liu_2021_Biomolecules_11_1552
Author(s) : Liu X , Zhou M , Xing S , Wu T , He H , Bielicki JK , Chen J
Ref : Biomolecules , 11 :1552 , 2021
Abstract : Esterases represent an important class of enzymes with a wide variety of industrial applications. A novel hormone-sensitive lipase (HSL) family esterase, Est19, from the Antarctic bacterium Pseudomonas sp. E2-15 is identified, cloned, and expressed. The enzyme possesses a GESAG motif containing an active serine (S) located within a highly conserved catalytic triad of Ser155, Asp253, and His282 residues. The catalytic efficiency (kcat/Km) of Est19 for the pNPC6 substrate is 148.68 s-1 mM-1 at 40 C. Replacing Glu154 juxtaposed to the critical catalytic serine with Asp (E154->D substitution) reduced the -activity and catalytic efficiency of the enzyme two-fold, with little change in the substrate affinity. The wild-type enzyme retained near complete activity over a temperature range of 10-60 C, while ~50% of its activity was retained at 0 C. A phylogenetic analysis suggested that Est19 and its homologs may represent a new subfamily of HSL. The thermal stability and stereo-specificity suggest that the Est19 esterase may be useful for cold and chiral catalyses.
ESTHER : Liu_2021_Biomolecules_11_1552
PubMedSearch : Liu_2021_Biomolecules_11_1552
PubMedID: 34827549
Gene_locus related to this paper: psesp-MT761613

Title : An ABHD17-like hydrolase screening system to identify de-S-acylation enzymes of protein substrates in plant cells - Liu_2021_Plant.Cell__
Author(s) : Liu X , Li M , Li Y , Chen Z , Zhuge C , Ouyang Y , Zhao Y , Lin Y , Xie Q , Yang C , Lai J
Ref : Plant Cell , : , 2021
Abstract : Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of ABHD17 (Alpha/Beta Hydrolase Domain-containing Protein 17)-like Acyl Protein Thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RIN4 (RPM1 Interacting Protein 4), which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation.
ESTHER : Liu_2021_Plant.Cell__
PubMedSearch : Liu_2021_Plant.Cell__
PubMedID: 34338800
Gene_locus related to this paper: arath-AT1G66900 , arath-AT2G24320 , arath-AT4G31020 , arath-AT5G20520 , arath-AT5G38220 , arath-F3C3.3 , arath-AT1G13610 , arath-At5g14390 , arath-F22K18.40 , arath-At3g01690 , arath-Q9LI62

Title : Carboxylesterases from bacterial enrichment culture degrade strobilurin fungicides - Wang_2021_Sci.Total.Environ__152751
Author(s) : Wang W , Zhao Z , Yan H , Zhang H , Li QX , Liu X
Ref : Sci Total Environ , :152751 , 2021
Abstract : Strobilurin fungicides are a class of persistent fungicides frequently detected in the environment. Microbes can effectively degrade strobilurins, but the mechanisms are complex and diverse. Compared with isolated strains, bacterial consortia are more robust in terms of the degradation of multiple pollutants. The enrichment culture XS19 is a group of bacterial strains enriched from soil and degrades six strobilurins at 50 mg/L within 8 d, including azoxystrobin, picoxystrobin, trifloxystrobin, kresoxim-methyl, pyraclostrobin and enestroburin. LC-Q-TOF-MS analysis confirmed that XS19 can demethylate these strobilurins via hydrolysis of the methyl ester group. Analysis of the bacterial communities suggested that Pseudomonas (69.8%), Sphingobacterium (21.2%), Delftia (6.3%), and Achromobacter (1.6%) spp. were highly associated with the removal of strobilurins in the system. Metagenomics-based comprehensive analysis of XS19 suggested that carboxylesterases in Pseudomonas and Sphingobacterium play a central role in the catabolism of strobilurins. Moreover, the carboxylesterase inhibitor bis-p-nitrophenyl phosphate inhibited the degradation activity of strobilurins in XS19. This work proved that XS19 or carboxylesterases can effectively hydrolyze strobilurins, providing a reliable bioremediation paradigm.
ESTHER : Wang_2021_Sci.Total.Environ__152751
PubMedSearch : Wang_2021_Sci.Total.Environ__152751
PubMedID: 34979227

Title : Structural Insights into a Novel Esterase from the East Pacific Rise and Its Improved Thermostability by a Semirational Design - Zhu_2021_J.Agric.Food.Chem__
Author(s) : Zhu C , Chen Y , Isupov MN , Littlechild JA , Sun L , Liu X , Wang Q , Gong H , Dong P , Zhang N , Wu Y
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : Lipolytic enzymes are essential biocatalysts in food processing as well as pharmaceutical and pesticide industries, catalyzing the cleavage of ester bonds in a variety of acyl chain substrates. Here, we report the crystal structure of an esterase from the deep-sea hydrothermal vent of the East Pacific Rise (EprEst). The X-ray structure of EprEst in complex with the ligand, acetate, has been determined at 2.03 resolution. The structure reveals a unique spatial arrangement and orientation of the helix cap domain and alpha/beta hydrolase domain, which form a substrate pocket with preference for short-chain acyl groups. Molecular docking analysis further demonstrated that the active site pocket could accommodate p-nitrophenyl (pNP) carboxyl ligands of varying lengths (>=6 C atoms), with pNP-butyrate ester predicted to have the highest binding affinity. Additionally, the semirational design was conducted to improve the thermostability of EprEst by enzyme engineering based on the established structure and multiple sequence alignment. A mutation, K114P, introduced in the hinge region of the esterase, which displayed increased thermostability and enzyme activity. Collectively, the structural and functional data obtained herein could be used as basis for further protein engineering to ultimately expand the scope of industrial applications of marine-derived lipolytic enzymes.
ESTHER : Zhu_2021_J.Agric.Food.Chem__
PubMedSearch : Zhu_2021_J.Agric.Food.Chem__
PubMedID: 33445864
Gene_locus related to this paper: 9bact-a0a2s1gux0

Title : Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats - Wang_2021_Front.Psychiatry_12_638328
Author(s) : Wang Q , Dong L , Wang M , Chen S , Li S , Chen Y , He W , Zhang H , Zhang Y , Pires Dias AC , Yang S , Liu X
Ref : Front Psychiatry , 12 :638328 , 2021
Abstract : Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.
ESTHER : Wang_2021_Front.Psychiatry_12_638328
PubMedSearch : Wang_2021_Front.Psychiatry_12_638328
PubMedID: 33841208

Title : TIR signal promotes interactions between lipase-like proteins and ADR1-L1 receptor and ADR1-L1 oligomerization - Wu_2021_Plant.Physiol_187_681
Author(s) : Wu Z , Tian L , Liu X , Zhang Y , Li X
Ref : Plant Physiol , 187 :681 , 2021
Abstract : TIR signaling promotes the interactions between lipase-like proteins EDS1/PAD4 and ADR1-L1 immune receptor, and oligomerization of ADR1-L1.
ESTHER : Wu_2021_Plant.Physiol_187_681
PubMedSearch : Wu_2021_Plant.Physiol_187_681
PubMedID: 34608964

Title : Triphenyl phosphate disturbs the lipidome and induces endoplasmic reticulum stress and apoptosis in JEG-3 cells - Wang_2021_Chemosphere_275_129978
Author(s) : Wang Y , Hong J , Shi M , Guo L , Liu L , Tang H , Liu X
Ref : Chemosphere , 275 :129978 , 2021
Abstract : Triphenyl phosphate (TPP) is a frequently used aryl organophosphate flame retardant. Epidemiological studies have shown that TPP and its metabolite diphenyl phosphate (DPP) can accumulate in the placenta, and positively correlated with abnormal birth outcomes. TPP can disturb placental hormone secretion through the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway. However, the extent and mechanism of placental toxicity mediation by TPP remains unknown. In this study, we used JEG-3 cells to investigate the role of PPARgamma-regulated lipid metabolism in TPP-mediated placental toxicity. The results of lipidomic analysis showed that TPP increased the production of triglycerides (TG), fatty acids (FAs), and phosphatidic acid (PA), but decreased the levels of phosphatidylethanol (PE), phosphatidylserine (PS), and sphingomyelin (SM). TG accumulation was accompanied by increased levels of sterol regulatory element binding transcription factor 1 (SREBP1), acetyl-coA carboxylase (ACC), and fatty acid transport protein (CD36). Although PPARgamma and its target CCAAT/enhancer binding proteins (C/EBPalpha) was decreased, the TG content and gene expression of SREBP1, ACC, and CD36 decreased when TPP was co-exposed to the PPARgamma antagonist GW9662. TPP also induced inflammatory responses, endoplasmic reticulum stress (ERS), and cell apoptosis. Expression of genes related to ERS and apoptosis were attenuated by GW9662. Together, these results show that TPP can disturb lipid metabolism and cause lipid accumulation through PPARgamma, induce ERS, and cell apoptosis. Our findings reveal that the developmental toxicity of TPP through placental toxicity should not be ignored.
ESTHER : Wang_2021_Chemosphere_275_129978
PubMedSearch : Wang_2021_Chemosphere_275_129978
PubMedID: 33662732

Title : Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota - Peng_2021_Phytomedicine_93_153772
Author(s) : Peng X , Hao M , Zhao Y , Cai Y , Chen X , Chen H , Zhang Y , Dong L , Liu X , Ding C , Liu W , Yang M , Luo Y
Ref : Phytomedicine , 93 :153772 , 2021
Abstract : BACKGROUND: Panax ginseng (PG) and red ginseng (RG) are considered to be effective anti-aging treatments. However, evidence of their therapeutic mechanisms and difference in anti-aging effects is lacking. PURPOSE: To explore the potential therapeutic mechanisms of RG and PG in brain damage in D-Gal-induced aging mice, and evaluate the difference in anti-aging effects caused by their compositional differences. METHODS: We first tested the chemical components in PG and RG. In D-Gal aging mouse model, RG and PG (800 mg/kg) were orally administered for 9 weeks. The mice performed the Radial Arm Maze (RAM) behavior test. We collected blood, brain tissue, and fecal samples and performed biochemical analysis, histological examination, western blot, and Illumina MiSeq sequencing analysis. RESULTS: The results of component analysis showed that the total polyphenols and rare ginsenosides were present in RG in 3.2, and 2.2 fold greater concentrations, respectively, compared to PG, while the proportion of non-starch polysaccharides in the crude polysaccharides of RG was 1.94 fold greater than that of PG. In D-Gal-induced aging mice, both PG and RG could prevent the increase in acetylcholinesterase (AChE), and malondialdehyde (MDA) levels, and improved the expression of superoxide dismutase (SOD), and catalase (CAT) in the serum. Meanwhile, both PG and RG could ameliorate brain tissue architecture and behavioral trial. In addition, the D-Gal-induced translocation of nuclear factor-kappaB (NF-kappaB), as well as activation of the pro-apoptotic factors Caspase-3 and the PI3K/Akt pathways were inhibited by PG and RG. Overall, both PG and RG exerted anti-aging effects, with RG stronger than PG. Finally, although both PG and RG regulated the diversity of gut microbes, RG appeared to aggravate the increase in probiotics, such as Bifidobacterium and Akkermania, and the decrease in inflammatory bacteria to a greater extent compared to PG. CONCLUSION: Our results suggest that RG is more conducive to delay the D-Gal-induced aging process than PG, with possible mechanisms including beneficial changes in brain structure, cognitive functions, oxidative stress inhibition, and gut microbiome structure and diversity than PG, These mechanisms may rely on the presence of more total polyphenols, rare ginsenosides and non-starch polysaccharides in RG.
ESTHER : Peng_2021_Phytomedicine_93_153772
PubMedSearch : Peng_2021_Phytomedicine_93_153772
PubMedID: 34753028

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

Title : Differential responses of larval zebrafish to the fungicide propamocarb: Endpoints at development, locomotor behavior and oxidative stress - Liu_2020_Sci.Total.Environ_731_139136
Author(s) : Liu X , Zhang R , Jin Y
Ref : Sci Total Environ , 731 :139136 , 2020
Abstract : The fungicide propamocarb (PM) is widely used to protect cucumbers, tomatoes and other plants from pathogens. According to previous studies, PM could be detected in the aquatic system in some area. However, the toxic effects of PM on zebrafish received very limited attention. In this study, we examined the toxic effects of various concentration of PM on the endpoints of development, locomotor behavior and oxidative stress in larval zebrafish. It was observed that PM exposure delayed embryonic development, inhibited hatchability at 60 and 72 h postfertilization and increased heart rate. After PM exposure, the larval zebrafish showed abnormal free swimming behavior and the swimming behavior in response to light-dark transition, indicating that PM had the potential to induce neurotoxicity. Moreover, PM exposure also affected the enzymatic activity of acetylcholinesterase and dopamine and the transcriptional level of genes related to neurotoxicity. In addition, PM exposure not only affects catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity but also affects the transcription level of various genes. We believed that PM induced oxidative stress was also a possible reason to cause neurotoxicity in larval zebrafish. In summary, our results suggested that PM could disturb the endpoints at development, locomotor behavior and oxidative stress in larval zebrafish.
ESTHER : Liu_2020_Sci.Total.Environ_731_139136
PubMedSearch : Liu_2020_Sci.Total.Environ_731_139136
PubMedID: 32438087

Title : Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study - Li_2020_Aging.Clin.Exp.Res__
Author(s) : Li M , Chen Y , Zhang Y , Liu X , Xie T , Yin J , Wang L , Gang S , Chen J , Liu L , Yang F , Geng T
Ref : Aging Clin Exp Res , : , 2020
Abstract : BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (>/= 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged >/= 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged >/= 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS.
ESTHER : Li_2020_Aging.Clin.Exp.Res__
PubMedSearch : Li_2020_Aging.Clin.Exp.Res__
PubMedID: 32067216

Title : Correlation between CYP1A1 polymorphisms and susceptibility to glyphosate-induced reduction of serum cholinesterase: A case-control study of a Chinese population - Cai_2020_Pestic.Biochem.Physiol_162_23
Author(s) : Cai W , Zhang F , Zhong L , Chen D , Guo H , Zhang H , Zhu B , Liu X
Ref : Pestic Biochem Physiol , 162 :23 , 2020
Abstract : Glyphosate (GLP) is one of the most common herbicides worldwide. The serum cholinesterase (ChE) may be affected when exposed to glyphosate. Reduction of serum ChE by herbicides is probably related to cytochrome P450 (CYP450) family polymorphisms. We suspect that the abnormal ChE caused by GLP could be correlated with the CYP family members. To determine whether CYP1B1 (rs1056827 and rs1056836) and CYP1A1 (rs1048943) gene polymorphisms and individual susceptibility to GLP-induced ChE abnormalities were interrelated in the Chinese Han population, we performed this genetic association study on a total of 230 workers previously exposed to GLP, including 115 cases with reduced serum ChE and 115 controls with normal serum ChE. Two even groups of cases and controls were enrolled. The CYP1A1 and CYP1B1 polymorphisms in both groups were genotyped using TaqMan. Subjects with the CYP1A1 rs619586 genotypes showed an increased risk of GLP-induced reduction of serum ChE, which was more evident in the following subgroups: female, > 35years old, history of GLP exposure time <10years and >10years, nonsmoker and nondrinker. The results show that CYP1A1 rs619586 was significantly associated with the GLP-induced reduction in serum ChE and could be a biomarker of susceptibility for Chinese GLP exposed workers. Because of a large number of people exposed to glyphosate, this study has a significance in protecting their health.
ESTHER : Cai_2020_Pestic.Biochem.Physiol_162_23
PubMedSearch : Cai_2020_Pestic.Biochem.Physiol_162_23
PubMedID: 31836050

Title : Design of Red Emissive Carbon Dots: Robust Performance for Analytical Applications in Pesticide Monitoring - Li_2020_Anal.Chem_92_3198
Author(s) : Li H , Su D , Gao H , Yan X , Kong D , Jin R , Liu X , Wang C , Lu G
Ref : Analytical Chemistry , 92 :3198 , 2020
Abstract : Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.0%) based on solvothermal treatment of citric acid and thiourea using dimethylformamide as solvent. Further investigations reveal that the conjugating sp(2)-domain controlling the incorporation of nitrogen and surface engineering are mainly responsible for the obtained red emission of CDs. Taking advantage of optical properties and abundant surface functional groups, CDs were considered to facilely construct a ratiometric fluorescent platform for quantifying trace levels of organophosphorus pesticides (OPs). Combining the acetylcholinesterase-mediated polymerization of dopamine and the inhibition of pesticide toward the enzyme, the degree of polymerization of dopamine rationally depends on the concentration of OPs. By measuring the fluorescence intensity ratio, the proposed platform exhibited highly selective and robust performance toward OPs, displaying ultrasensitive recognition in the pg L(-1) level. The multiexcitation format could efficiently shield background interference from complex samples by introducing a self-calibrated reference signal, which affords accurate and reliable quantitative information, endowing CDs as a universal candidate for a biosensing application by combining target-specific recognition elements.
ESTHER : Li_2020_Anal.Chem_92_3198
PubMedSearch : Li_2020_Anal.Chem_92_3198
PubMedID: 32008315

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

Title : Curcumin Alleviates the Side Effects of Cisplatin on Gastric Emptying of Mice by Inhibiting the Signal Changes of Acetylcholine and Interstitial Cells of Cajal - Li_2020_J.Med.Food_23_920
Author(s) : Li H , Xu W , Liu X , Ye J , Li P , Shang F , Yu X
Ref : J Med Food , 23 :920 , 2020
Abstract : Cisplatin is a widely used anticancer drug that has adverse effects on gastrointestinal function. Curcumin is a natural polyphenol extracted from the rhizome of turmeric that has a wide range of biological activities. The present study investigated the effects of cisplatin on gastric emptying in mice and examined whether these can be inhibited by curcumin. We found that pretreatment with curcumin (200mg/kg/day) for 10-30 days partly inhibited the decreases in gastric emptying rate and body weight induced by cisplatin. Furthermore, cisplatin reduced acetylcholine (ACh) concentration and the messenger RNA (mRNA) level of ACh receptor (AChR) as well as acetylcholinesterase activity in the stomach of mice; caused ultrastructural damage to interstitial cells of Cajal (ICC); and altered the expression of c-kit/stem cell factor and the gap junction protein connexin 43 in ICC. Curcumin pretreatment inhibited the effects of cisplatin on ACh indicators and ICC. These results demonstrate that curcumin can protect against cisplatin-induced gastric emptying disorder and thus has therapeutic potential for alleviating this condition in cancer patients receiving cisplatin chemotherapy.
ESTHER : Li_2020_J.Med.Food_23_920
PubMedSearch : Li_2020_J.Med.Food_23_920
PubMedID: 32833554

Title : Improving the production of AHL lactonase AiiO-AIO6 from Ochrobactrum sp. M231 in intracellular protease-deficient Bacillus subtilis - Xia_2020_AMB.Express_10_138
Author(s) : Xia R , Yang Y , Pan X , Gao C , Yao Y , Liu X , Teame T , Zhang F , Hu J , Ran C , Zhang Z , Liu-Clarke J , Zhou Z
Ref : AMB Express , 10 :138 , 2020
Abstract : Quorum quenching (QQ) blocks bacterial cell-to-cell communication (i.e., quorum sensing), and is a promising antipathogenic strategy to control bacterial infection via inhibition of virulence factor expression and biofilm formation. QQ enzyme AiiO-AIO6 from Ochrobactrum sp. M231 has several excellent properties and shows biotherapeutic potential against important bacterial pathogens of aquatic species. AiiO-AIO6 can be secretory expressed in Bacillus subtilis via a non-classical secretion pathway. To improve AiiO-AIO6 production, four intracellular protease-deletion mutants of B. subtilis 1A751 were constructed by individually knocking out the intracellular protease-encoding genes (tepA, ymfH, yrrN and ywpE). The AiiO-AIO6 expression plasmid pWB-AIO6BS was transformed into the B. subtilis 1A751 and its four intracellular protease-deletion derivatives. Results showed that all recombinant intracellular protease-deletion derivatives (BStepA, BSymfH, BSyrrN and BSywpE) had a positive impact on AiiO-AIO6 production. The highest amount of AiiO-AIO6 extracellular production of BSywpE in shake flask reached 1416.47 U/mL/OD(600), which was about 121% higher than that of the wild-type strain. Furthermore, LC-MS/MS analysis of the degrading products of 3-oxo-C8-HSL by purification of AiiO-AIO6 indicated that AiiO-AIO6 was an AHL-lactonase which hydrolyzes the lactone ring of AHLs. Phylogenetic analysis showed that AiiO-AIO6 was classified as a member of the alpha/beta hydrolase family with a conserved "nucleophile-acid-histidine" catalytic triad. In summary, this study showed that intracellular proteases were responsible for the reduced yields of heterologous proteins and provided an efficient strategy to enhance the extracellular production of AHL lactonase AiiO-AIO6.
ESTHER : Xia_2020_AMB.Express_10_138
PubMedSearch : Xia_2020_AMB.Express_10_138
PubMedID: 32757095
Gene_locus related to this paper: ocha4-a6wx49

Title : Interaction Mechanism of the Germination Stimulants Karrikins and Their Receptor ShKAI2iB - Zhang_2020_J.Phys.Chem.B_124_9812
Author(s) : Zhang JL , Liu X , Zhang HX
Ref : J Phys Chem B , 124 :9812 , 2020
Abstract : The significance of karrikins (KARs) in plant physiology opens a door for their application in the agricultural production. As the first event of the whole signaling pathway, the binding of smoke-derived signal molecules KARs to the receptor protein KAI2 triggers the germination of the primary dormant seeds of all angiosperms, not just the "fire-prone" taxa. In the present study, all-atom molecular dynamics simulations, along with the accurate estimation of the ligand-receptor binding free energy, were used to investigate the atomic level interaction of all the members of the KARs family (from KAR(1) to KAR(6)) with the receptor ShKAI2iB, an intermediate-evolving KAI2 from Striga hermonthica. The calculated binding energy value of KAR(1) to ShKAI2iB, -5.64 kcal/mol, is in good agreement with the available experimental data, -5.67 kcal/mol. The further analysis of the detailed interaction between each KAR and the protein reveals the primary reasons for the difference of the affinity of the diverse ligands with the receptor and displays the regional characteristics of the protein's active site. Our research will not only provide clues for the study of equivalent endogenous phytohormone, but also contribute to the development of synthetic germinating chemicals.
ESTHER : Zhang_2020_J.Phys.Chem.B_124_9812
PubMedSearch : Zhang_2020_J.Phys.Chem.B_124_9812
PubMedID: 33089685
Gene_locus related to this paper: strhe-ShHTL3

Title : Colorimetric Differentiation of Flavonoids Based on Effective Reactivation of Acetylcholinesterase Induced by Different Affnities between Flavonoids and Metal Ions - Li_2020_Anal.Chem_92_3361
Author(s) : Li S , Liu X , Liu QY , Chen Z
Ref : Analytical Chemistry , 92 :3361 , 2020
Abstract : Flavonoids are closely related to human health, and the distinguishiment of flavonoids is an important but difficult issue. We herein unveil a novel colorimetric sensor array for the rapid identification of 7 flavonoids (e.g., gallocatechin (GC), morin hydrate (MH), puerarin (Pu), epigallocatechin gallate (EGCG), catechin (C), rac Naringenin (rN), and Flavone (Fla)) for the first time. The colorimetric performances of gold nanoparticles (AuNPs) are characteristically correlated with thiocholine, which is issued from the enzymatic hydrolysis of acetylcholine (AcCh). Therefore, as a proof-of-concept design, three sensors (Cu2+/ acetylcholinesterase (AcChE)/AcCh/AuNPs, Zn2+/AcChE/AcCh/AuNPs, and Mn2+/AcChE/AcCh/AuNPs) were constructed to form our sensor array. The distinct affnities between flavonoids and metal ions would cause varying degrees of effective reactivation of AcChE, leading to unique colorimetric response patterns upon being challenged with the seven flavonoids for their pattern recognition, enabling an excellent identification of the seven flavonoids at a concentration of 20 nM and different concentrations of individual flavonoids, as well as mixtures of them.
ESTHER : Li_2020_Anal.Chem_92_3361
PubMedSearch : Li_2020_Anal.Chem_92_3361
PubMedID: 31983197

Title : Organocatalyzed solvent free and efficient synthesis of 2,4,5-trisubstituted imidazoles as potential acetylcholinesterase inhibitors for Alzheimer's disease - Pervaiz_2020_Chem.Biodivers__
Author(s) : Pervaiz S , Mutahir S , Khan IU , Ashraf M , Liu X , Tariq S , Zhou BJ , Khan MA
Ref : Chem Biodivers , : , 2020
Abstract : The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives. The compounds were synthesized by condensation reaction of substituted aromatic aldehydes, benzil and ammonium acetate ( 3a-3m ) in one pot in a good to excellent yield (74-96 %). These compounds were evaluated against acetylcholinesterase (AChE) enzyme activity to explore their potential against Alzheimer's disease. Among this series of compounds 3m bearing one ethoxy and a hydroxyl group on the phenyl ring on 2,4,5-trisubstituted imidazoles proved potent AChE inhibitor (102.56+/-0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the inhibitors 3m , 3e , 3k , 3c , 3a , 3d , 3j , and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the inhibitor 3m forms an H bond with the oxygen atom of the residue (i.e., THR121), and has a bond length of 3.051 A.
ESTHER : Pervaiz_2020_Chem.Biodivers__
PubMedSearch : Pervaiz_2020_Chem.Biodivers__
PubMedID: 31968151

Title : Synthesis, Biological Activity, Molecular Docking Studies of a Novel Series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives as the Acetylcholinesterase Inhibitors - Jin_2020_J.Biomol.Struct.Dyn__1
Author(s) : Jin Z , Zhang C , Liu M , Jiao S , Zhao J , Liu X , Lin H , Wan DC , Hu C
Ref : J Biomol Struct Dyn , :1 , 2020
Abstract : The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer's disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too.
ESTHER : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedSearch : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedID: 32266865

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

Title : Odor Identification Impairment and Change with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment - Devanand_2020_J.Alzheimers.Dis__
Author(s) : Devanand DP , Liu X , Chunga RE , Cohen H , Andrews H , Schofield PW , Stern Y , Huey ED , Choi J , Pelton GH
Ref : J Alzheimers Dis , : , 2020
Abstract : BACKGROUND: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease (AD) pathology, and short-term change in odor identification impairment with cholinesterase inhibitor (CheI) treatment may predict longer term cognitive outcomes. OBJECTIVE: In patients with mild cognitive impairment (MCI) treated prospectively with donepezil, a CheI, for 52 weeks, to determine if 1) acute decline in odor identification ability with anticholinergic challenge can predict cognitive improvement, and 2) change in odor identification over 8 weeks can predict cognitive improvement. METHODS: MCI was diagnosed clinically without AD biomarkers. At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and this dose was maintained for 52 weeks. Main outcomes were ADAS-Cog total score and Selective Reminding Test (SRT) total immediate recall score measured at baseline, 26 and 52 weeks. RESULTS: In 100 study participants, mean age 70.14 (SD 9.35) years, atropine-induced decrease in UPSIT score at baseline was not associated with change in ADAS-Cog or SRT scores over 52 weeks. Change in UPSIT score from 0 to 8 weeks did not show a significant association with change in the ADAS-Cog or SRT measures over 52 weeks. CONCLUSION: These negative findings in a relatively large sample of patients with MCI did not replicate results in much smaller samples. Change in odor identification with anticholinergic challenge, and over 8 weeks, may not be useful predictors of cognitive improvement with CheI in patients with MCI.
ESTHER : Devanand_2020_J.Alzheimers.Dis__
PubMedSearch : Devanand_2020_J.Alzheimers.Dis__
PubMedID: 32333591

Title : Comparison of Enzyme Secretion and Ferulic Acid Production by Escherichia coli Expressing Different Lactobacillus Feruloyl Esterases - Xu_2020_Front.Microbiol_11_568716
Author(s) : Xu Z , Kong J , Zhang S , Wang T , Liu X
Ref : Front Microbiol , 11 :568716 , 2020
Abstract : Construction of recombinant Escherichia coli strains carrying feruloyl esterase genes for secretory expression offers an attractive way to facilitate enzyme purification and one-step production of ferulic acid from agricultural waste. A total of 10 feruloyl esterases derived from nine Lactobacillus species were expressed in E. coli BL21 (DE3) to investigate their secretion and ferulic acid production. Extracellular activity determination showed all these Lactobacillus feruloyl esterases could be secreted out of E. coli cells. However, protein analysis indicated that they could be classified as three types. The first type presented a low secretion level, including feruloyl esterases derived from Lactobacillus acidophilus and Lactobacillus johnsonii. The second type showed a high secretion level, including feruloyl esterases derived from Lactobacillus amylovorus, Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus helveticus. The third type also behaved a high secretion level but easy degradation, including feruloyl esterases derived from Lactobacillus farciminis, Lactobacillus fermentum, and Lactobacillus reuteri. Moreover, these recombinant E. coli strains could directly release ferulic acid from agricultural waste. The highest yield was 140 g on the basis of 0.1 g de-starched wheat bran by using E. coli expressed L. amylovorus feruloyl esterase. These results provided a solid basis for the production of feruloyl esterase and ferulic acid.
ESTHER : Xu_2020_Front.Microbiol_11_568716
PubMedSearch : Xu_2020_Front.Microbiol_11_568716
PubMedID: 33329424
Gene_locus related to this paper: lacam-a0a1c9u7k7

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

Title : Effect of salt promote the muscle triglyceride hydrolysis during dry-salting by inducing the phosphorylation of adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and lipid droplets splitting - Zhao_2020_Food.Chem_327_127061
Author(s) : Zhao S , He L , Zhang M , Liu X , Jin G
Ref : Food Chem , 327 :127061 , 2020
Abstract : This study mainly investigated the effect of different salt concentrations (1, 3, or 5%) on triglycerides (TG) hydrolysis in muscle during salting by analyzing moisture distribution, TG hydrolysis, TG hydrolase activity, native and phosphorylated adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content, lipid droplets morphology, and muscle microstructure. The results showed that increasing salt concentration could significantly decrease T21 moisture proportion and relaxation time (p < 0.05), which was more beneficial to the lipase activity. The TG hydrolase activity increased first and then decreased with the salt concentration increasing during dry-salting process, and 3% salt concentration was the point of inflection. Western blot (WB) analysis detected both ATGL, HSL and their phosphorylated proteins, which were increased with the salt content increase. The microstructure analysis showed that the lipid droplets were split into small lipid droplets with the increase of salt content, which was more conducive to the triglycerides hydrolysis.
ESTHER : Zhao_2020_Food.Chem_327_127061
PubMedSearch : Zhao_2020_Food.Chem_327_127061
PubMedID: 32454271

Title : The Chromosome-Based Rubber Tree Genome Provides New Insights into Spurge Genome Evolution and Rubber Biosynthesis - Liu_2020_Mol.Plant_13_336
Author(s) : Liu J , Shi C , Shi CC , Li W , Zhang QJ , Zhang Y , Li K , Lu HF , Zhu ST , Xiao ZY , Nan H , Yue Y , Zhu XG , Wu Y , Hong XN , Fan GY , Tong Y , Zhang D , Mao CL , Liu YL , Hao SJ , Liu WQ , Lv MQ , Zhang HB , Liu Y , Hu-Tang GR , Wang JP , Wang JH , Sun YH , Ni SB , Chen WB , Zhang XC , Jiao YN , Eichler EE , Li GH , Liu X , Gao LZ
Ref : Mol Plant , 13 :336 , 2020
Abstract : The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the -1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by -65.88% (-970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains -15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.
ESTHER : Liu_2020_Mol.Plant_13_336
PubMedSearch : Liu_2020_Mol.Plant_13_336
PubMedID: 31838037
Gene_locus related to this paper: hevbr-a0a6a6mdr9

Title : Study on the Regulation of Earthworm Physiological Function under Cadmium Stress Based on a Compound Mathematical Model - Zhou_2020_Environ.Toxicol.Pharmacol__103499
Author(s) : Zhou H , Zhang T , Zhuang J , Xu M , Liu X , Shi Q , Zhou D
Ref : Environ Toxicol Pharmacol , :103499 , 2020
Abstract : A cadmium (Cd) stress test was carried out on Eisenia fetida in artificial soil. Six Cd concentration gradient solutions (0, 50, 100, 125, 250 and 500 mg/kg) were prepared. Two treatment groups, short-term stress and long-term stress, were established. The former lasted for 10 days, and the latter lasted for 30 days. The Biolog ECO-microplate culture method was used to determine the utilization of the 31 carbon sources by the microbes in earthworm homogenate. The total protein content (TP), peroxidase activity (POD), catalase activity (CAT), superoxide dismutase activity (SOD), glutathione peroxidase activity (GPX), glutathione-S-transferase activity (GST), malondialdehyde content (MDA) and acetylcholinesterase activity (AChE) in earthworm were determined in order to investigate the regulation of oxidative stress and the functional diversity of microbial communities in earthworms under Cd stress. By combining the entropy weight method (EW) and the technique for order preference by similarity to an ideal solution model (TOPSIS), the physiological functional indices of earthworms were assessed objectively and scientifically, and the physiological changes under the different stress periods were evaluated. The results showed that a Cd-tolerant dominant population appeared in the microbial community under Cd stress. In the short-term test, oxidative stress were more effective in coping with Cd stress than the microbial community, and oxidative stress regulated the microbial community functional diversity. Under long-term Cd stress, the regulatory effect was weak or non-existent. In this study, a new evaluation model was established to explore the regulation process of earthworm on its oxidation stress and the functional diversity of microbial communities under Cd stress, and provide a theoretical basis for revealing the detoxification mechanism of earthworms.
ESTHER : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedSearch : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedID: 32956818

Title : Near-infrared emission tracks inter-individual variability of carboxylesterase-2 via a novel molecular substrate - Liu_2020_Mikrochim.Acta_187_313
Author(s) : Liu X , Li X , Dong P , Wu Z , Gao J , Wang Q
Ref : Mikrochim Acta , 187 :313 , 2020
Abstract : A low-molecular-weight molecule (4-(2-(3-(dicyanomethyl)-5,5-dimethylcyclohex-1-en-1-yl)vinyl)phenyl-benzoate, DDPB) has been developed. The organic framework possesses very weak fluorescence . The feasibility of the signal transduction has been performed via fluorometric titrations in solution. DDPB gives rise to responses to carboxylesterase 2 (CES2) based on "off-on" responses. The red emission at 670 nm has been derived from the enzyme-induced hydrolysis of ester linkages, thus suppressing the intramolecular charge transfer (ICT) effect and thereby generating the fluorescent segment. The optical excitation window for this probe is extended to the visible light range (lambdaex = 516 nm), and it will induce less harmful influence on biological substances. The detection limit for the measurement of CES2 concentration is as low as 2.33 mU/mL. The conventional studies concerning the activation process are generally performed within only a single liveing cell system. In this study, it is the first time that expression of carboxylesterase 2 in five kinds of cell lines (HeLa > C1498 > active T cell > Jurkat > unactive T cell) has been clarified by flow cytometry, Western blotting, and confocal microscopy analysis. The elucidation of CES2 and its variability in a variety of cells will open new ways for drug metabolism and disease prevention. Graphical abstract We reported a new "substrate-mediated light-on" strategy based on an ester bond cleavage reaction. Most of prepared nanomaterials and organic fluorophores possessed short wavelength emissions in the blue or green region which will not be difficult for cellular imaging. In this study, a novel functional molecule (DDPB) was considered as the substrate for CES2 and the optical "off-on" response was realized. DDPB was cell permeable and possessed very low cytotoxicity. Moreover, the identification of CES2 and their subtle changes in five different cells afforded the sequence for carboxylesterase-2 as Hela > C1498 > Active T cell > Jurkat > Unactive T cell. Inhibition studies showed that the hydrolysis of DDPB was effectively suppressed by bis-p-nitrophenyl phosphate and the cellular tracking results firmly supported this point. To our knowledge, the inter-individual variability for the CES2 expressions in five different cell lines has never been reported via the substrate induced optical changes.
ESTHER : Liu_2020_Mikrochim.Acta_187_313
PubMedSearch : Liu_2020_Mikrochim.Acta_187_313
PubMedID: 32377952

Title : Identification of a Bacillus amyloliquefaciens H6 Thioesterase Involved in Zearalenone Detoxification by Transcriptomic Analysis - Xu_2020_J.Agric.Food.Chem_68_10071
Author(s) : Xu L , Sun X , Wan X , Li H , Yan F , Han R , Li Z , Tian Y , Liu X , Kang X , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 68 :10071 , 2020
Abstract : Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin produced by Fusarium graminearum, induces hyperestrogenic responses in mammals and can cause reproductive disorders in farm animals. In this study, a transcriptome analysis of Bacillus amyloliquefaciens H6, which was previously identified as a ZEA-degrading bacterium, was conducted with high-throughput sequencing technology, and the differentially expressed genes were subjected to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Among the 16 upregulated genes, BAMF_RS30125 was predicted to be the key gene responsible for ZEA degradation. The protein encoded by BAMF_RS30125 was then expressed in Escherichia coli, and this recombinant protein (named ZTE138) significantly reduced the ZEA content, as determined by the enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), and decreased the proliferating activity of ZEA in MCF-7 cells. What is more, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results showed that the relative molecular mass and the structure of ZEA also changed. Sequence alignment of the ZTE138 protein showed that it is a protease that belongs to the YBGC/FADM family of coenzyme A thioesterases, and thus, the protein can presumably cleave the ZEA lactone bond and break down its macrolide ring.
ESTHER : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedSearch : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedID: 32815728

Title : A facile microfluidic paper-based analytical device for acetylcholinesterase inhibition assay utilizing organic solvent extraction in rapid detection of pesticide residues in food - Jin_2020_Anal.Chim.Acta_1100_215
Author(s) : Jin L , Hao Z , Zheng Q , Chen H , Zhu L , Wang C , Liu X , Lu C
Ref : Anal Chim Acta , 1100 :215 , 2020
Abstract : The incompatibility of most organic solvents with acetylcholinesterase (AChE) inhibition assay normally limits pesticide extraction efficiency in sample pretreatment, which might cause false negatives in real world sample assessment. Herein, a novel method has been developed for an improved AChE inhibition assay via organic solvent extraction combined spontaneous in situ solvent evaporation on microfluidic paper-based analytical devices. Enzyme pre-immobilization procedure was spared and AChE was added to the system after sampling step until a complete in-situ solvent evaporation process was performed on chip. IC50 levels of the six investigated organophosphate and carbamate pesticides indicated a completely eliminated influence of solvents on AChE behavior with the new method. Most importantly, analytical performances were significantly improved in food sample measurements. Reduction in matrix effect was observed when acetonitrile was adopted for lettuce sample pretreatment instead of water. Studies on different pesticides suggested a remarkably decreased discrimination effect on recoveries from sample pretreatment with the new developed method. The recovery level for phoxim spiked head lettuce samples reached (107.5 +/- 14.2) %, in comparison with that of (18.6 +/- 1.4) % from water-based extraction. Spiked water and apple juice samples with carbaryl concentration of as low as 0.02 mg L(-1) were also successfully recognized with the present method by visual detection. This is the first report on direct sampling of organic extracts for AChE inhibition assay on-chip and it might provide a new perspective for real world sample assessments involving bio-reagents.
ESTHER : Jin_2020_Anal.Chim.Acta_1100_215
PubMedSearch : Jin_2020_Anal.Chim.Acta_1100_215
PubMedID: 31987143

Title : Structures and esterolytic reactivity of novel binuclear copper(ii) complexes with reduced l-serine Schiff bases as mimic carboxylesterases - Zhang_2020_Dalton.Trans_49_10261
Author(s) : Zhang Q , Shu J , Zhang Y , Xu Z , Yue J , Liu X , Xu B , Chen Z , Jiang W
Ref : Dalton Trans , 49 :10261 , 2020
Abstract : Three novel binuclear copper(ii) complexes with reduced l-serine Schiff bases were synthesized and their structures were analyzed with single-crystal X-ray diffraction and DFT calculations. The crystal data revealed that all of these binuclear complexes are chiral. Both 5-halogenated (bromo- and chloro-) binuclear complexes exhibit right-handed helix structural character. Interestingly, the 5-methyl-containing analogue has a two-dimensional pore structure. In this paper, the esterolysis reactivity of the as-prepared complexes shows that in the hydrolysis of p-nitrophenyl acetate (PNPA) these three complexes provide 26, 18, 40-fold rate acceleration as compared to the spontaneous hydrolysis of PNPA at pH 7.0, respectively. Under selected conditions, in excess buffered aqueous solution a rate enhancement by three orders of magnitude was observed for the catalytic hydrolysis of another carboxylic ester, p-nitrophenyl picolinate (PNPP). These complexes efficiently promoted PNPP hydrolysis in a micellar solution of cetyltrimethylammonium bromide (CTAB), giving rise to a rate enhancement in excess of four orders of magnitude, which is approximately 2.0-3.2 times higher than that in the buffer.
ESTHER : Zhang_2020_Dalton.Trans_49_10261
PubMedSearch : Zhang_2020_Dalton.Trans_49_10261
PubMedID: 32672259

Title : The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARgamma\/STAT1 Signaling Pathway - Dai_2020_Front.Pediatr_8_451
Author(s) : Dai N , Yang C , Fan Q , Wang M , Liu X , Zhao H , Zhao C
Ref : Front Pediatr , 8 :451 , 2020
Abstract : Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARgamma expression, while knockdown of PPARgamma blocked the cell growth and STAT1 expression inhibition induced by 100 mumol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-alpha, IL-1 beta, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-alpha, IL-1beta, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARgamma/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD.
ESTHER : Dai_2020_Front.Pediatr_8_451
PubMedSearch : Dai_2020_Front.Pediatr_8_451
PubMedID: 32903307

Title : The toxicity assessment of extract of Peganum harmala L. seeds in Caenorhabditis elegans - Miao_2020_BMC.Complement.Med.Ther_20_256
Author(s) : Miao X , Zhang X , Yuan Y , Zhang Y , Gao J , Kang N , Liu X , Wu J , Liu Y , Tan P
Ref : BMC Complement Med Ther , 20 :256 , 2020
Abstract : BACKGROUND: Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. METHODS: In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 degC in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P < 0.01), and the mean lifespan was significantly decreased (P < 0.01). We also observed that PHS exposure could induce the toxicity on body length, brood size, and locomotion behavior. CONCLUSION: Our study shows that the ethanol extract of PHS exerts obvious toxic effects on C. elegans, which would provide new ideas and methods for the biological evaluation of the toxicity of Chinese medicinal materials.
ESTHER : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedSearch : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedID: 32807143

Title : Triphenyl phosphate permeates the blood brain barrier and induces neurotoxicity in mouse brain - Liu_2020_Chemosphere_252_126470
Author(s) : Liu X , Zhao X , Wang Y , Hong J , Shi M , Pfaff D , Guo L , Tang H
Ref : Chemosphere , 252 :126470 , 2020
Abstract : Concerns have been raised over the neurotoxicity of triphenyl phosphate (TPP), but there have been few studies of the neurotoxic effects of TPP on mammals and the underlying mechanisms. In this study, weaned male mice (C57/BL6) were used and exposed to 0, 50, or 150 mg/kg TPP daily by oral gavage for 30 days. The blood brain barrier (BBB) permeability of TPP and its metabolite diphenyl phosphate (DPP) in the brain, and TPP induced metabolomic and transcriptomic changes of the brain were investigated. The results showed that TPP and DPP can cross the BBB of mice. Histopathological examination of the brain revealed abnormalities in the hippocampus, cortex and thalamus, and mice treated with high doses showed a potential inflammation in the thalamus and hippocampus. Untargeted metabolomic results revealed that the changed level of glutamic acid, N-acetyl CoA metabolites, and organic acid in the brain of treated mice, suggest that amino acid and lipid metabolism was interfered. RNA-seq data indicated that neuronal transcription processes and cell apoptosis pathway (forkhead box (FOXO), and mitogen-activated protein kinase (MAPK) signaling pathways) were significantly affected by TPP exposure. RT-PCR showed proinflammation cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)) levels were increased, while antioxidant genes including nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase1 (HO-1) and superoxide dismutase (SOD1) decreased. These results suggest that TPP could cause a degree of neurotoxicity by inducing neuroinflammation and neuronal apoptosis, which are related to oxidative stress. The potential implications for neurophysiology and behavioral regulation cannot be ignored.
ESTHER : Liu_2020_Chemosphere_252_126470
PubMedSearch : Liu_2020_Chemosphere_252_126470
PubMedID: 32443258

Title : Biodegradation of phthalate esters by Paracoccus kondratievae BJQ0001 isolated from Jiuqu (Baijiu fermentation starter) and identification of the ester bond hydrolysis enzyme - Xu_2020_Environ.Pollut_263_114506
Author(s) : Xu Y , Minhazul K , Wang X , Liu X , Li X , Meng Q , Li H , Zhang C , Sun X , Sun B
Ref : Environ Pollut , 263 :114506 , 2020
Abstract : Phthalate ester (PAE) pollution is an increasing problem globally. Paracoccus kondratievae BJQ0001 was isolated from the fermentation starter of Baijiu and showed an efficient degradation capability toward PAEs. To our poor knowledge, this is the first report of a P. kondratievae strain capable of degrading PAEs. The first complete genome sequence of P. kondratievae was presented without gaps, and composed of two circular chromosomes and one plasmid. The species simultaneously degraded di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP) and di-(2-ethylhexyl) phthalate (DEHP), with DMP and DEP as the preferred substrates. The half-life (t(1/2)) of DMP was only 6.34 h with an initial concentration of 200 mg/L. Combined with gene annotation and metabolic intermediate analysis, a metabolic pathway was proposed for the species. Benzoic acid, the intermediate of anaerobic PAE metabolism, was identified in the aerobic degradation process. Two key enzymes for alkyl ester bond hydrolysis were obtained, and belonged to families IV and VI of hydrolases, respectively. These results will promote the investigation of PAE degradation by P. kondratievae, and provide useful information for improving the quality control of food and environmental PAE treatment.
ESTHER : Xu_2020_Environ.Pollut_263_114506
PubMedSearch : Xu_2020_Environ.Pollut_263_114506
PubMedID: 32268225
Gene_locus related to this paper: 9rhob-a0a5p8jcg2 , 9rhob-a0a5p8jaa4

Title : Discovery and development of a novel short-chain fatty acid ester synthetic biocatalyst under aqueous phase from Monascus purpureus isolated from Baijiu - Xu_2020_Food.Chem_338_128025
Author(s) : Xu Y , Wang X , Liu X , Li X , Zhang C , Li W , Sun X , Wang W , Sun B
Ref : Food Chem , 338 :128025 , 2020
Abstract : Short-chain fatty acid esters are important flavor chemicals in Chinese traditional fermented Baijiu. Monascus purpureus was recognized as an important microorganism contributing to ester synthesis. However, the molecular basis for ester synthesis was still lacking. The present work combined genome sequencing, transcriptome sequencing, gene library construction, and enzyme engineering to discover a novel catalyst from M. purpureus (isolated from Baijiu fermentation starter). Enzyme LIP05, belonging to the alpha/beta hydrolase family, was identified to synthesize short-chain fatty acid esters under aqueous phase. After deleting the lid domain of LIP05, the synthesis of ethyl pentanoate, ethyl hexanoate, ethyl octanoate, or ethyl decanoate was achieved. Ethyl octanoate with the highest conversion ratio of 93.7% was obtained with the assistance of ultrasound. The study reveals the molecular basis for synthesizing short-chain fatty acid esters by M. purpureus and will promote the application of the species or the enzyme in food industry.
ESTHER : Xu_2020_Food.Chem_338_128025
PubMedSearch : Xu_2020_Food.Chem_338_128025
PubMedID: 32927200
Gene_locus related to this paper: monpu-a0a507qkl5

Title : An enhanced staining method K-B-2R staining for three-dimensional nerve reconstruction - Luo_2019_BMC.Neurosci_20_32
Author(s) : Luo P , Dong J , Qi J , Zhang Y , Liu X , Zhong Y , Xian CJ , Wang L
Ref : BMC Neurosci , 20 :32 , 2019
Abstract : BACKGROUND: Three-dimensional (3D) reconstruction of human peripheral nerves, as a useful tool to understand the nerve internal information and functional basis, has become an important area of research in the peripheral nerve field. METHODS: In this study, we proposed a two-dimensional (2D) Karnovsky-Roots toluidine blue ponceau 2R (K-B-2R) staining method based upon conventional Karnovsky-Roots staining. It significantly improved the ability to display nerve fascicles, motor and sensory nerve fiber textures. In this method, Karnovsky-Roots staining was carried out, followed by toluidine blue counterstain and ponceau 2R counterstain. RESULTS: Comparisons were conducted between the three methods in staining of median nerve sections, which showed similar distribution characters in acetylcholinesterase-positive sites. The additional counterstaining did not change the basis of Karnovsky-Roots staining. However, the resulting images from this new method significantly facilitated the subsequent 3D nerve reconstruction and 3D printing. CONCLUSIONS: These results show that the new staining method significantly enhanced the display qualities of nerve fascicle edges and fiber textures of motor and sensory nerves and facilitated 3D nerve reconstruction.
ESTHER : Luo_2019_BMC.Neurosci_20_32
PubMedSearch : Luo_2019_BMC.Neurosci_20_32
PubMedID: 31286881

Title : Cholinergic M4 receptors are involved in morphine-induced expression of behavioral sensitization by regulating dopamine function in the nucleus accumbens of rats - Ruan_2019_Behav.Brain.Res_360_128
Author(s) : Ruan H , Sun J , Liu X , Liu L , Cui R , Li X
Ref : Behavioural Brain Research , 360 :128 , 2019
Abstract : Repeated administration of morphine profoundly influences the dopaminergic and cholinergic systems in the nucleus accumbens [including the shell of the nucleus accumbens (NAcS)]. Further, dopamine release is regulated by the cholinergic system, especially the M4 receptor. Drug priming is one of the main factors that induces relapse in drug addiction. The present study first investigated how activation of the M4 receptor in the NAcS affects the expression of morphine-induced behavioral sensitization, through the administration of an M4 agonist (LY2033298) and antagonist (tropicamide), as well as a combination of an acetylcholinesterase inhibitor and M4 antagonist (huperzine-A + tropicamide). Additionally, the influence of a dopamine receptor agonist, in conjunction with an M4 agonist (i.e., SKF38393 + LY2033298), was also examined. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. The expression of behavioral sensitization was challenged by 5 mg/kg morphine. Results showed that (1) microinjection of the M4 receptor agonist LY2033298 (0.2 mug/side), but not the antagonist tropicamide (5, 10, or 20 muM/side) into the NAcS blocked the expression of behavioral sensitization; (2) tropicamide (20 muM/side) reversed the inhibition effect of huperzine-A on this behavior; and (3) SKF38393 (1 mug/side) reversed the inhibitory effect of LY2033298 on the expression of morphine-induced behavioral sensitization. These results suggest that the cholinergic M4 receptor in the NAcS plays an important role in the morphine-induced expression of behavioral sensitization through the regulation of dopamine function in rats.
ESTHER : Ruan_2019_Behav.Brain.Res_360_128
PubMedSearch : Ruan_2019_Behav.Brain.Res_360_128
PubMedID: 30529589

Title : Glucoconjugated Monoterpene Indole Alkaloids from Uncaria rhynchophylla - Guo_2019_J.Nat.Prod_82_3288
Author(s) : Guo Q , Si X , Shi Y , Yang H , Liu X , Liang H , Tu P , Zhang Q
Ref : Journal of Natural Products , 82 :3288 , 2019
Abstract : Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MS(n) behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 muM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE.
ESTHER : Guo_2019_J.Nat.Prod_82_3288
PubMedSearch : Guo_2019_J.Nat.Prod_82_3288
PubMedID: 31804070

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

Title : Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica - Qi_2019_J.Nat.Med_73_769
Author(s) : Qi B , Yang W , Ding N , Luo Y , Jia F , Liu X , Wang J , Wang X , Tu P , Shi S
Ref : J Nat Med , 73 :769 , 2019
Abstract : Six new pyrrole 2-carbaldehyde derived alkaloids, dahurines A-F (1-6), along with five known ones (7-11) and butyl 2-pyrrolidone-5-carboxylate (12) were isolated from the roots of Angelica dahurica. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Although compounds 7 and 8 have been chemically synthesized, they were obtained from natural materials for the first time. Compounds 2, 3, 4, 10, and 11 exhibited acetylcholinesterase inhibitory activity with IC50 values in the range of 47.5-52.5 muM. Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica.
ESTHER : Qi_2019_J.Nat.Med_73_769
PubMedSearch : Qi_2019_J.Nat.Med_73_769
PubMedID: 31209724

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

Title : Diacylglycerol Lipase-Alpha Regulates Hippocampal-Dependent Learning and Memory Processes in Mice - Schurman_2019_J.Neurosci_39_5949
Author(s) : Schurman LD , Carper MC , Moncayo LV , Ogasawara D , Richardson K , Yu L , Liu X , Poklis JL , Liu QS , Cravatt BF , Lichtman AH
Ref : Journal of Neuroscience , 39 :5949 , 2019
Abstract : Diacylglycerol lipase-alpha (DAGL-alpha), the principal biosynthetic enzyme of the endogenous cannabinoid 2-arachidonylglycerol (2-AG) on neurons, plays a key role in CB(1) receptor-mediated synaptic plasticity and hippocampal neurogenesis, but its contribution to global hippocampal-mediated processes remains unknown. Thus, the present study examines the role that DAGL-alpha plays on LTP in hippocampus, as well as in hippocampal-dependent spatial learning and memory tasks, and on the production of endocannabinoid and related lipids through the use of complementary pharmacologic and genetic approaches to disrupt this enzyme in male mice. Here we show that DAGL-alpha gene deletion or pharmacological inhibition disrupts LTP in CA1 of the hippocampus but elicits varying magnitudes of behavioral learning and memory deficits in mice. In particular, DAGL-alpha(-/-) mice display profound impairments in the Object Location assay and Morris Water Maze (MWM) acquisition engaging in nonspatial search strategies. In contrast, WT mice administered the DAGL-alpha inhibitor DO34 show delays in MWM acquisition and reversal learning, but no deficits in expression, extinction, forgetting, or perseveration processes in this task, as well as no impairment in Object Location. The deficits in synaptic plasticity and MWM performance occur in concert with decreased 2-AG and its major lipid metabolite (arachidonic acid), but increases of a 2-AG diacylglycerol precursor in hippocampus, PFC, striatum, and cerebellum. These novel behavioral and electrophysiological results implicate a direct and perhaps selective role of DAGL-alpha in the integration of new spatial information.SIGNIFICANCE STATEMENT Here we show that genetic deletion or pharmacologic inhibition of diacylglycerol lipase-alpha (DAGL-alpha) impairs hippocampal CA1 LTP, differentially disrupts spatial learning and memory performance in Morris water maze (MWM) and Object Location tasks, and alters brain levels of endocannabinoids and related lipids. Whereas DAGL-alpha(-/-) mice exhibit profound phenotypic spatial memory deficits, a DAGL inhibitor selectively impairs the integration of new information in MWM acquisition and reversal tasks, but not memory processes of expression, extinction, forgetting, or perseveration, and does not affect performance in the Objection Location task. The findings that constitutive or short-term DAGL-alpha disruption impairs learning and memory at electrophysiological and selective in vivo levels implicate this enzyme as playing a key role in the integration of new spatial information.
ESTHER : Schurman_2019_J.Neurosci_39_5949
PubMedSearch : Schurman_2019_J.Neurosci_39_5949
PubMedID: 31127001
Gene_locus related to this paper: mouse-q6wqj1

Title : Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa - Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
Author(s) : Liu X , Chen Q , Ali N , Zhang J , Wang M , Wang Z
Ref : Environ Sci Pollut Res Int , 26 :24695 , 2019
Abstract : The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems.
ESTHER : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedSearch : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedID: 31240645

Title : Nox4 and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells - Liu_2019_Vascul.Pharmacol_120_106544
Author(s) : Liu X , Qin Z , Liu C , Song M , Luo X , Zhao H , Qian D , Chen J , Huang L
Ref : Vascul Pharmacol , 120 :106544 , 2019
Abstract : BACKGROUND: Hyperhomocysteinemia leads to a vascular smooth muscle cell (VSMC) inflammatory response. Meanwhile, Nox4 dependent reactive oxygen species (ROS) signaling and soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids (EETs) are both involved in vascular inflammation. Herein, we hypothesized that Nox4 and soluble epoxide hydrolase cross regulated during homocysteine-induced VSMC inflammation. METHODS AND RESULTS: In cultured VSMCs, the expression of the inflammatory factors VCAM1 and ICAM1 was measured by real-time PCR and Western blotting, while supernatant MCP1 was measured by ELISA. Upon VSMC stimulation with 50 muMu homocysteine, we observed the VCAM1 and ICAM1 mRNA levels were increased by 1.15 and 1.0 folds, respectively. The MCP1 levels in the supernatant of cultured VSMCs treated with 100 muMu increased to 1.76 folds. As expected, homocysteine induced Nox4 expression and Nox4-dependent ROS generation. The sEH expression was also upregulated in the presence of homocysteine in a dose-dependent manner. Furthermore, we knocked down Nox4 with siRNA. Knockdown of Nox4 decreased ROS generation and homocysteine-induced sEH expression. Overexpression of Nox4 with an adenovirus stimulated sEH expression. Similarly, knockdown or chemical inhibition of sEH blunted the upregulation of Nox4 by homocysteine. In vivo, in homocysteine-fed mice, concomitant upregulation of Nox4 and sEH was associated with increased VCAM1 and ICAM1 expression in the aortic wall. CONCLUSIONS: The inflammatory response induced by homocysteine in VSMCs was accompanied by Nox4 and sEH upregulation. Nox4 and soluble epoxide hydrolase synergistically contribute to homocysteine-induced inflammation.
ESTHER : Liu_2019_Vascul.Pharmacol_120_106544
PubMedSearch : Liu_2019_Vascul.Pharmacol_120_106544
PubMedID: 30610956

Title : Two transcription factors cooperatively regulate DHN melanin biosynthesis and development in Pestalotiopsis fici - Zhang_2019_Mol.Microbiol_112_649
Author(s) : Zhang P , Zhou S , Wang G , An Z , Liu X , Li K , Yin WB
Ref : Molecular Microbiology , 112 :649 , 2019
Abstract : Fungal 1,8-dihydroxynaphthalene (DHN) melanin plays important roles in UV protection, oxidative stress and pathogenesis. However, knowledge of the regulatory mechanisms of its biosynthesis is limited. Previous studies showed two transcription factors, PfmaF and PfmaH, located in the DHN melanin biosynthetic gene cluster (Pfma) in Pestalotiopsis fici. In this study, deletion of PfmaH resulted in loss of melanin and affected conidia cell wall integrity. Specifically, PfmaH directly regulates the expression of scytalone dehydratase, which catalyzes the transition of scytalone to T(3) HN. However, PfmaF disruption using CRISPR/Cas9 system affected neither DHN melanin distribution nor conidia cell wall integrity in P. fici. Unexpectedly, overexpression of PfmaF leads to heavy pigment accumulation in P. fici hyphae. Transcriptome and qRT-PCR analyses provide insight into the roles of PfmaF and PfmaH in DHN melanin regulation. PfmaH, as a pathway specific regulator, mainly regulates melanin biosynthesis that contributes to cell wall development. Furthermore, PfmaF functions as a broad regulator to stimulate PfmaH expression in melanin production, secondary metabolism as well as fungal development.
ESTHER : Zhang_2019_Mol.Microbiol_112_649
PubMedSearch : Zhang_2019_Mol.Microbiol_112_649
PubMedID: 31116900
Gene_locus related to this paper: pesfw-pfmab , pesfw-pfmae

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

Title : Candida sp. 99-125 lipase-catalyzed synthesis of ergosterol linolenate and its characterization - He_2019_Food.Chem_280_286
Author(s) : He WS , Li L , Zhao J , Xu H , Rui J , Cui D , Li H , Zhang H , Liu X
Ref : Food Chem , 280 :286 , 2019
Abstract : As a major sterol in edible mushroom, ergosterol has gained much attention owing to its potential bioactivities. However, ergosterol has a high melting point, poor oil solubility and stability, which restrict its scope of application. In this study, an ergosterol ester of alpha-linolenic acid was successfully and efficiently prepared using Candida sp. 99-125 lipase as a biocatalyst. The desired product was confirmed to be ergosterol linolenate using MS, FT-IR, and NMR analyses. Using Candida sp. 99-125 lipase, the product conversion exceeded 92% in 12h under the following optimized parameters: 75mmol/L ergosterol, 40g/L lipase, 1:1.25 ergosterol-to-alpha-linolenic acid molar ratio, and 45 degrees C. The results confirmed that Candida sp. 99-125 lipase has good reusability and stability and is also relatively low cost, suggesting its great potential for large-scale production of ergosterol ester. Most importantly, the physiochemical properties (oil solubility and melting point) of ergosterol significantly improved after esterification with alpha-linolenic acid, thus facilitating its application in oil-based systems.
ESTHER : He_2019_Food.Chem_280_286
PubMedSearch : He_2019_Food.Chem_280_286
PubMedID: 30642499

Title : First Genome-wide Association Analysis for Growth Traits in the Largest Coral Reef-Dwelling Bony Fishes, the Giant Grouper (Epinephelus lanceolatus) - Wu_2019_Mar.Biotechnol.(NY)_21_707
Author(s) : Wu L , Yang Y , Li B , Huang W , Wang X , Liu X , Meng Z , Xia J
Ref : Mar Biotechnol (NY) , 21 :707 , 2019
Abstract : The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.
ESTHER : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedSearch : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedID: 31392592

Title : Capillary electrophoresis-immobilized enzyme microreactors for acetylcholinesterase assay with surface modification by highly-homogeneous microporous layer - Liu_2019_J.Chromatogr.A__460454
Author(s) : Liu X , Azhar I , Khan H , Qu Q , Tian M , Yang L
Ref : Journal of Chromatography A , :460454 , 2019
Abstract : We propose a new capillary electrophoresis (CE)-based open-tubular immobilized enzyme microreactor (OT-IMER) and its application in acetylcholinesterase (AChE) assays. The IMER is fabricated at the capillary inlet (reactor length of approximately 1cm) with the inner surface modified by a micropore-structured layer (thickness of approximately 220nm, pore size of approximately 15-20nm). The use of IMER accomplishes the enzymatic reaction and separation/detection of the products in the same capillary within 3 min. The feasibility of the proposed method is evaluated via online analysis of the activity and inhibition of AChE enzymes. Such method exhibits good reproducibility with relative standard deviation (RSD) of less than 4% for 20 runs, and the enzyme remains over 82% of the initial activity after usage of 7 days. The IMERs are successfully applied to detect the organophosphorus pesticide, paraoxon, in three types of vegetable juice samples with a limit of detection of as low as 61ng mL(-1). Results show that the spiked samples are in the range of 89.6-105.9% with RSD less than 2.7%, thereby indicating its satisfactory level of accurate and reliable analysis of real samples by using the proposed method. Our study indicates that, with combination of advantages of both porous-layer capillary and CE OT-IMER, the proposed method is capable to enhance enzymatic reactions and to achieve rapid analysis with simple instrumentation and operation, thus would pave the way for extensive application of CE-based IMERs in a variety of bioanalysis.
ESTHER : Liu_2019_J.Chromatogr.A__460454
PubMedSearch : Liu_2019_J.Chromatogr.A__460454
PubMedID: 31443966

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 : Insights into the improvement of the enzymatic hydrolysis of bovine bone protein using lipase pretreatment - Yao_2019_Food.Chem_302_125199
Author(s) : Yao Y , Wang M , Liu Y , Han L , Liu X
Ref : Food Chem , 302 :125199 , 2019
Abstract : Animal bones are a high-quality source of protein and comprehensive nutrients and improper handling can cause resource wasting and environmental issues. Pretreatment before enzymatic hydrolysis of bone could significantly improve the enzymolytic efficiency, which is an essential step to achieve high value-added utilization of bones. This study investigated the effect of lipase pretreatment on the enzymatic hydrolysis of bones. The degree of hydrolysis after lipase pretreatment was 12.58%, which was 8.19% higher than that without pretreatment. Lipase pretreatment was optimal at 9% substrate concentration and initial pH 7.5, with 0.08% lipase, followed by 4h incubation at 40 degrees C. Mechanism analysis indicated that lipase pretreatment improved the enzymolytic efficiency by significantly decreasing the lipid content, and changing the surface structure and surface element content of C, N, and O, promoting the attachment of alkaline protease onto the sample. Overall, lipase pretreatment was an effective method to reduce the costs of production.
ESTHER : Yao_2019_Food.Chem_302_125199
PubMedSearch : Yao_2019_Food.Chem_302_125199
PubMedID: 31400699

Title : A Flexible Acetylcholinesterase-Modified Graphene for Chiral Pesticide Sensor - Zhang_2019_J.Am.Chem.Soc_141_14643
Author(s) : Zhang Y , Liu X , Qiu S , Zhang Q , Tang W , Liu H , Guo Y , Ma Y , Guo X , Liu Y
Ref : Journal of the American Chemical Society , 141 :14643 , 2019
Abstract : Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 mug/L and 0.32 mug/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission.
ESTHER : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedSearch : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedID: 31448915

Title : Lycopodium alkaloids from Huperzia serrata - Jiang_2019_Fitoterapia__104277
Author(s) : Jiang F , Qi B , Ding N , Yang H , Jia F , Luo Y , Wang J , Liu X , Wang X , Tu P , Shi S
Ref : Fitoterapia , :104277 , 2019
Abstract : Five new Lycopodium alkaloids, huperzine Y1 (1), huperzine Y2 (2), huperzine Y3 (3), (+)-huperzine Z (4a) and (-)-huperzine Z (4b) as well as ten known alkaloids (5-14) were isolated from Huperzia serrata. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 4a and 4b were a pair of enantiomers successfully separated by chiral HPLC resolution. Compounds 2 and 3 indicated inhibitory activities against acetylcholinesterase with IC50 value of 57.1+/-1.6 and 32.7+/-1.0 muMu, respectively. However, no compound showed inhibitory effect on butyrocholinesterase at the concentration of 100 muMu.
ESTHER : Jiang_2019_Fitoterapia__104277
PubMedSearch : Jiang_2019_Fitoterapia__104277
PubMedID: 31351127

Title : Structural Features and Digestive Behavior of Fucosylated Chondroitin Sulfate from Sea Cucumbers Stichopus japonicus - Zhu_2019_J.Agric.Food.Chem_67_10534
Author(s) : Zhu Z , Dong X , Yan C , Ai C , Zhou D , Yang J , Zhang H , Liu X , Song S , Xiao H , Zhu B
Ref : Journal of Agricultural and Food Chemistry , 67 :10534 , 2019
Abstract : Fucosylated chondroitin sulfate from sea cucumber Stichopus japonicus (FCSSJ) has been demonstrated with various biological activities; however, its precise structure is still controversial, and digestive behavior remains poorly understood. FCSSJ was purified, and its detailed structure was elucidated mainly based on the NMR spectroscopic methods. Its main chain was characterized as -->4)-beta-d-GlcA-(1 --> 3)-beta-d-GalNAc-(1--> with GalNAc4S6S:GalNAc4S in a ratio of 1.5:1, and three types of sulfated fucosyl branches attaching C-3 of GlcA, namely, Fucp2S4S, Fucp3S4S, and Fucp4S, were found in a ratio of 2:1.5:1. The digestibility of FCSSJ was investigated in vitro, and the unchanged molecular weight and reducing sugar content indicated that FCSSJ was not broken down under salivary and gastrointestinal digestion. Furthermore, FCSSJ showed a significant inhibitory impact on pancreatic lipase dose-dependently but not on alpha-amylase, indicating that the inhibition of pancreatic lipase by FCSSJ might be a pathway for its hypolipidemic effect. These findings propose a fucosylated chondroitin sulfate and provide insight into the mechanism of its physiological effects in the digestion system.
ESTHER : Zhu_2019_J.Agric.Food.Chem_67_10534
PubMedSearch : Zhu_2019_J.Agric.Food.Chem_67_10534
PubMedID: 31464434

Title : Genome-wide association studies reveal genetic loci associated with plasma cholinesterase activity in ducks - Xu_2019_Anim.Genet_50_287
Author(s) : Xu Y , Liu H , Jiang Y , Fan W , Hu J , Zhang Y , Guo Z , Xie M , Huang W , Liu X , Zhou Z , Hou S
Ref : Anim Genet , 50 :287 , 2019
Abstract : Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck x mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.
ESTHER : Xu_2019_Anim.Genet_50_287
PubMedSearch : Xu_2019_Anim.Genet_50_287
PubMedID: 30994195
Gene_locus related to this paper: anapl-BCHE

Title : Contemporary medicinal-chemistry strategies for the discovery of selective butyrylcholinesterase inhibitors - Jing_2019_Drug.Discov.Today_24_629
Author(s) : Jing L , Wu G , Kang D , Zhou Z , Song Y , Liu X , Zhan P
Ref : Drug Discov Today , 24 :629 , 2019
Abstract : Butyrylcholinesterase (BChE) is considered a promising drug target for the treatment of moderate to severe Alzheimer's disease (AD). Here, we review medicinal-chemistry strategies that are currently available for the discovery of selective BChE inhibitors.
ESTHER : Jing_2019_Drug.Discov.Today_24_629
PubMedSearch : Jing_2019_Drug.Discov.Today_24_629
PubMedID: 30503804

Title : A Review of Danshen Combined with Clopidogrel in the Treatment of Coronary Heart Disease - Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
Author(s) : Zhang Z , Wang Y , Tan W , Wang S , Liu J , Liu X , Wang X , Gao X
Ref : Evid Based Complement Alternat Med , 2019 :2721413 , 2019
Abstract : Objective: Danshen, the root of Salvia miltiorrhiza Bunge, is a traditional herbal medicine in China, which has been used to treat irregular menstruation, cold hernia, and abdominal pain for thousands of years. Danshen is frequently used in combination with drugs to treat cardiovascular diseases. Clopidogrel is a commonly used drug for treating coronary heart disease, but clopidogrel resistance restricts its development. Therefore, the clinical efficacy of Danshen combined with clopidogrel treats coronary heart disease and the relationship between Danshen and clopidogrel metabolism enzymes is suggested for future investigations. Materials and Methods: The information was collected by searching online databases, and the RevMan 5.3 software was used to perform meta-analysis. Results: Twenty-two articles, including 2587 patients, were enrolled after the evaluation. Meta-analysis showed that Danshen combined with clopidogrel was more effective than clopidogrel alone in treating coronary heart disease by improving clinical curative effect, reducing the frequency of angina pectoris, improving electrocardiogram results, shortening the duration of angina pectoris, and easing adverse reactions. Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel. Conclusion: Danshen combined with clopidogrel may compensate for individual differences of clopidogrel resistance among individuals in the treatment of coronary heart disease. Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel.
ESTHER : Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
PubMedSearch : Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
PubMedID: 30911318

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

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

Title : Dental malocclusion stimulates neuromuscular circuits associated with temporomandibular disorders - Liu_2018_Eur.J.Oral.Sci_126_466
Author(s) : Liu X , Zhang C , Liu Q , Zhou K , Yin N , Zhang H , Shi M , Wang M
Ref : Eur J Oral Sci , 126 :466 , 2018
Abstract : Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)-trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA. The expression of vesicular glutamate transporter 1 (VGLUT1) in neurons of VII, XII, Amb, and SNA, and the expression of acetylcholinesterase (AChE) were measured in the stapedius, lingualis, palatopharyngeal, and sternocleidomastoid muscles. In BDA-treated rats, many BDA-labeled cell bodies in the Vme and terminals in VII, XII, Amb, and SNA were identified. Compared with control rats, rats with UAC showed higher expression of VGLUT1 in these nuclei, and statistically significantly higher expression of AChE in the stapedius, lingualis, and sternocleidomastoid muscles, but not in the palatopharyngeal muscle. These findings suggest that UAC activates orofacial, head, and cervical multimotor behaviors via connections between the Vme and the corresponding motor nuclei.
ESTHER : Liu_2018_Eur.J.Oral.Sci_126_466
PubMedSearch : Liu_2018_Eur.J.Oral.Sci_126_466
PubMedID: 30341927

Title : Pharmacological Basis for the Use of Evodiamine in Alzheimer's Disease: Antioxidation and Antiapoptosis - Zhang_2018_Int.J.Mol.Sci_19_
Author(s) : Zhang Y , Wang J , Wang C , Li Z , Liu X , Zhang J , Lu J , Wang D
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Evodiamine (Evo), a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus, has a wide range of pharmacological activities. The present study sought to explore the neuroprotective effects of Evo in l-glutamate (l-Glu)-induced apoptosis of HT22 cells, and in a d-galactose and aluminum trichloride-developed Alzheimer’s disease (AD) mouse model. Evo significantly enhanced cell viability, inhibited the accumulation of reactive oxygen species, ameliorated mitochondrial function, increased the B-cell lymphoma-2 protein content, and inhibited the high expression levels of Bax, Bad, and cleaved-caspase-3 and -8 in l-Glu-induced HT22 cells. Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the l-Glu-induced HT22 cells. In the AD mouse model, Evo reduced the aimless and chaotic movements, reduced the time spent in the central area in the open field test, and decreased the escape latency time in the Morris water maze test. Evo reduced the deposition of amyloid beta 42 (Aβ42) in the brain, and increased the serum level of Aβ42, but showed no significant effects on Aβ40. In addition, six weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels. In the central cholinergic system of AD mice, Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum, hypothalamus, and brain. Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases.
ESTHER : Zhang_2018_Int.J.Mol.Sci_19_
PubMedSearch : Zhang_2018_Int.J.Mol.Sci_19_
PubMedID: 29883380

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

Title : Biodegradation of pyraclostrobin by two microbial communities from Hawaiian soils and metabolic mechanism - Chen_2018_J.Hazard.Mater_354_225
Author(s) : Chen X , He S , Liang Z , Li QX , Yan H , Hu J , Liu X
Ref : J Hazard Mater , 354 :225 , 2018
Abstract : Pyraclostrobin has been widely and long-termly applicated to agricultural fields. The removal of pyraclostrobin from ecological environment has received wide attention. In this study, using sequential enrichments with pyraclostrobin as a sole carbon source, two microbial communities (HI2 and HI6) capable of catabolizing pyraclostrobin were obtained from Hawaiian soils. The microfloras analysis indicated that only Proteobacteria and Bacteroides could survive in HI2-soil after acclimatization, whereas the number of Proteobacteria in HI6-soil accounted for more than 99%. The percentages of Pseudomonas in the HI2 and HI6 microfloras were 69.3% and 59.3%, respectively. More than 99% of pyraclostrobin (C0=100mgL(-1)) was degraded by the HI2 and HI6 microorganisms within five days. A unique metabolite was identified by high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). A metabolic pathway involving carbamate hydrolysis was proposed. The tertiary amine group of pyraclostrobin was hydrolyzed to primary amine group with the decarboxylation, which facilitated pyraclostrobin detoxification because carboxylester was an important functional group. The metabolic mechanism suggested that Pseudomonas expressing carboxylesterase might be able to degrade carbamate chemicals. Therefore, Pseudomonas might be an ideal candidate for expression and cloning of carbamate-degrading gene in genomics studies. The current study would have important implications in detoxification and bioremediation of carbamates through the CN bond cleavage of methyl carbamate.
ESTHER : Chen_2018_J.Hazard.Mater_354_225
PubMedSearch : Chen_2018_J.Hazard.Mater_354_225
PubMedID: 29753191

Title : Soluble epoxide hydrolase inhibition alleviated cognitive impairments via NRG1\/ErbB4 signaling after chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis in mice - Hao_2018_Brain.Res_1699_89
Author(s) : Hao J , Chen Y , Yao E , Liu X
Ref : Brain Research , 1699 :89 , 2018
Abstract : Cerebral ischemic stroke is associated with a high rate of incidence, prevalence and mortality globally. Carotid artery stenosis, which is mainly caused by atherosclerosis plaque, results in chronic cerebral hypoperfusion and predominantly increases the risk of ischemic stroke. In the present study, we used bilateral common carotid artery stenosis (BCAS) model by placing microcoils of 0.18mm diameter encompassing both common carotid arteries respectively, to mimic the pathogenesis of carotid artery atherosclerosis and intensively explore the pathology. We found that BCAS injury for 1month impaired spatial cognitive functions significantly, and inhibited synaptic plasticity, including hippocampal long-term potentiation (LTP) inhibition, dendritic spine density reduction and synaptic associative proteins disorder. BCAS-induced cerebral hypoperfused mice treated with 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU), a potent soluble epoxide hydrolase (sEH) inhibitor, exhibited amelioration of cognitive dysfunction and improved synaptic plasticity. The neural protective effects of TPPU on BCAS-induced cerebral hypoperfusion might due to activation of neuregulin-1 (NRG1)/ErbB4 signaling, and triggered PI3K-Akt pathways subsequently. Our results suggested that sEH inhibition could exert multi-target protective effects and alleviate spatial cognitive dysfunctions after chronic cerebral hypoperfusion in mice.
ESTHER : Hao_2018_Brain.Res_1699_89
PubMedSearch : Hao_2018_Brain.Res_1699_89
PubMedID: 30343686

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 : Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro - Liu_2018_J.Insect.Sci_18_
Author(s) : Liu R , Wang W , Liu X , Lu Y , Xiang T , Zhou W , Wan Y
Ref : J Insect Sci , 18 : , 2018
Abstract : To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25 degrees C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.
ESTHER : Liu_2018_J.Insect.Sci_18_
PubMedSearch : Liu_2018_J.Insect.Sci_18_
PubMedID: 30395292

Title : Characterization of Tetrahydrolipstatin and Stereoderivatives on the Inhibition of Essential Mycobacterium tuberculosis Lipid Esterases - Goins_2018_Biochemistry_57_2383
Author(s) : Goins CM , Sudasinghe TD , Liu X , Wang Y , O'Doherty GA , Ronning DR
Ref : Biochemistry , 57 :2383 , 2018
Abstract : Tetrahydrolipstatin (THL) is a covalent inhibitor of many serine esterases. In mycobacteria, THL has been found to covalently react with 261 lipid esterases upon treatment of Mycobacterium bovis cell lysate. However, the covalent adduct is considered unstable in some cases because of the hydrolysis of the enzyme-linked THL adduct resulting in catalytic turnover. In this study, a library of THL stereoderivatives was tested against three essential Mycobacterium tuberculosis lipid esterases of interest for drug development to assess how the stereochemistry of THL affects respective enzyme inhibition and allows for cross enzyme inhibition. The mycolyltransferase Antigen 85C (Ag85C) was found to be stereospecific with regard to THL; covalent inhibition occurs within minutes and was previously shown to be irreversible. Conversely, the Rv3802 phospholipase A/thioesterase was more accepting of a variety of THL configurations and uses these compounds as alternative substrates. The reaction of the THL stereoderivatives with the thioesterase domain of polyketide synthase 13 (Pks13-TE) also leads to hydrolytic turnover and is nonstereospecific but occurs on a slower, multihour time scale. Our findings suggest the stereochemistry of the beta-lactone ring of THL is important for cross enzyme reactivity, while the two stereocenters of the peptidyl arm can affect enzyme specificity and the catalytic hydrolysis of the beta-lactone ring. The observed kinetic data for all three target enzymes are supported by recently published X-ray crystal structures of Ag85C, Rv3802, and Pks13-TE. Insights from this study provide a molecular basis for the kinetic modulation of three essential M. tuberculosis lipid esterases by THL and can be applied to increase potency and enzyme residence times and enhance the specificity of the THL scaffold.
ESTHER : Goins_2018_Biochemistry_57_2383
PubMedSearch : Goins_2018_Biochemistry_57_2383
PubMedID: 29601187
Gene_locus related to this paper: myctu-a85c , myctu-PKS13 , myctu-Rv3802c

Title : New 2-Aryl-9-methyl-beta-carbolinium salts as Potential Acetylcholinesterase Inhibitor agents: Synthesis, Bioactivity and Structure-Activity Relationship - Zhou_2018_Sci.Rep_8_1559
Author(s) : Zhou B , Zhang B , Li X , Liu X , Li H , Li D , Cui Z , Geng H , Zhou L
Ref : Sci Rep , 8 :1559 , 2018
Abstract : A series of 2-aryl-9-methyl-beta-carbolinium bromides (B) were synthesized and explored for anti-acetylcholinesterase (AChE) activities in vitro, action mechanism and structure-activity relationship. All the compounds B along with their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10 muM. Thirteen compounds B showed the excellent activity with IC50 values of 0.11-0.76 muM and high selectivity toward AChE relative to butyrylcholinesterase (BChE), superior to galantamine (IC50 = 0.79 muM), a selective AChE inhibitor drug. Kinetic analysis showed that the action mechanisms of both compounds B and A are a competitive inhibition model. Structure-activity relationship analyses showed that the C = N(+) moiety is a determinant for the activity. Substituents at 6, 7 or 4' site, the indole-N-alkyl and the aromatization of the C-ring can significantly improve the activity. Molecular docking studies showed that the compounds could combine with the active site of AChE by the pi-pi or cation-pi action between the carboline ring and the phenyl rings of the residues, and the beta-carboline moiety is embedded in a cavity surrounded by four aromatic residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, 2-aryl-9-methyl-beta-carboliniums emerged as novel and promising tool compounds for the development of new AChE inhibitor agents.
ESTHER : Zhou_2018_Sci.Rep_8_1559
PubMedSearch : Zhou_2018_Sci.Rep_8_1559
PubMedID: 29367595

Title : Impairment of Inhibitory Synapse Formation and Motor Behavior in Mice Lacking the NL2 Binding Partner LHFPL4\/GARLH4 - Wu_2018_Cell.Rep_23_1691
Author(s) : Wu M , Tian HL , Liu X , Lai JHC , Du S , Xia J
Ref : Cell Rep , 23 :1691 , 2018
Abstract : Normal brain functions depend on the balanced development of excitatory and inhibitory synapses. Our knowledge of the molecular mechanisms underlying inhibitory synapse formation is limited. Neuroligin-2 (NL2), a transmembrane protein at inhibitory postsynaptic sites, is capable of initiating inhibitory synapse formation. In an effort to search for NL2 binding proteins and the downstream mechanisms responsible for inhibitory synapse development, we identify LHFPL4/GARLH4 as a major NL2 binding partner that is specifically enriched at inhibitory postsynaptic sites. LHFPL4/GARLH4 and NL2 regulate the protein levels and synaptic clustering of each other in the cerebellum. Lhfpl4/Garlh4(-/-) mice display profound impairment of inhibitory synapse formation as well as prominent motor behavioral deficits and premature death. Our findings highlight the essential role of LHFPL4/GARLH4 in brain functions by regulating inhibitory synapse formation as a major NL2 binding partner.
ESTHER : Wu_2018_Cell.Rep_23_1691
PubMedSearch : Wu_2018_Cell.Rep_23_1691
PubMedID: 29742426

Title : Waterborne Zn influenced Zn uptake and lipid metabolism in two intestinal regions of juvenile goby Synechogobius hasta - Ling_2018_Ecotoxicol.Environ.Saf_148_578
Author(s) : Ling SC , Luo Z , Chen GH , Zhang DG , Liu X
Ref : Ecotoxicology & Environmental Safety , 148 :578 , 2018
Abstract : The present study explored the influence of Zn addition in the water on Zn transport and lipid metabolism of two intestinal regions in goby Synechogobius hasta. Zn contents in water were 0.004 (control), 0.181 and 0.361mg Zn L(-1), respectively. The experiment lasted for 28 days. TG and Zn contents, mRNA contents of genes of Zn transport and lipid metabolism, and enzyme activity from anterior and mid-intestine tissues were analyzed. In anterior intestine, Zn addition in the water increased Zn contents, and mRNA concentrations of ZIP4, ZIP5, ATGL, PPARalpha, ZNF202 and KLF7, decreased TG contents, 6PGD and G6PD activities, and mRNA contents of 6PGD, G6PD, FAS, PPARgamma, ICDH and KLF4. In mid-intestine tissue, the highest Zn and TG contents were observed for 0.18mg Zn/l group, in parallel with the highest expressions of ZnT1, ZIP4, ZIP5, 6PGD, FAS, ICDH, PPARgamma, PPARalpha, ZNF202, KLF4 and KLF7, and with the highest FAS, 6PGD and G6PD activities. Thus, in the anterior intestine, Zn addition increased lipolysis and decreased lipogenesis, and accordingly reduced TG content. However, the highest mid-intestinal TG content in 0.18mg Zn/l group was due to the up-regulated lipogenesis. Although lipolysis was also increased, the incremental lipid synthesis was enough to compensate for lipid degradation, which led TG accumulation. Our results, for the first time, show an anterior/mid functional regionalization of the intestine in lipid metabolism and Zn transport of S. hasta following Zn exposure.
ESTHER : Ling_2018_Ecotoxicol.Environ.Saf_148_578
PubMedSearch : Ling_2018_Ecotoxicol.Environ.Saf_148_578
PubMedID: 29127820
Gene_locus related to this paper: 9gobi-a0a067xh99

Title : Design, synthesis and evaluation of new classes of nonquaternary reactivators for acetylcholinesterase inhibited by organophosphates - Wei_2018_Bioorg.Chem_81_681
Author(s) : Wei Z , Bi H , Liu YQ , Nie HF , Yao L , Wang SZ , Yang J , Wang YA , Liu X , Zheng ZB
Ref : Bioorg Chem , 81 :681 , 2018
Abstract : A new series of nonquaternary conjugates for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. It was found that substituted salicylaldehydes conjugated to aminobenzamide through piperidine would produce efficient reactivators for sarin, VX and tabun inhibited hAChE, such as L6M1R3, L6M1R5 to L6M1R7, L4M1R3 and L4M1R5 to L4M1R7. The in vitro reactivation experiment for pesticides inhibited hAChE of these new synthesized oximes were conducted for the first time. Despite they were less efficient than obidoxime, some of them were highlighted as equal or more efficient reactivators in comparison to 2-PAM. It was found that introduction of peripheral site ligands could increase oximes' binding affinity for inhibited hAChE in most cases, which resulted in greater reactivation ability.
ESTHER : Wei_2018_Bioorg.Chem_81_681
PubMedSearch : Wei_2018_Bioorg.Chem_81_681
PubMedID: 30265992

Title : Joint toxic effects of triazophos and imidacloprid on zebrafish (Danio rerio) - Wu_2018_Environ.Pollut_235_470
Author(s) : Wu S , Li X , Liu X , Yang G , An X , Wang Q , Wang Y
Ref : Environ Pollut , 235 :470 , 2018
Abstract : Pesticide contamination is more often found as a mixture of different pesticides in water bodies rather than individual compounds. However, regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and joint toxicities of triazophos (TRI) and imidacloprid (IMI) to the zebrafish (Danio rerio) using acute indices and various sublethal endpoints. Results from 96-h semi-static test indicated that the LC50 values of TRI to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.49 (0.36-0.71) to 4.99 (2.06-6.81) mg a.i. L(-1), which were higher than those of IMI ranging from 26.39 (19.04-38.01) to 128.9 (68.47-173.6) mg a.i. L(-1). Pesticide mixtures of TRI and IMI displayed synergistic response to zebrafish embryos. Activities of carboxylesterase (CarE) and catalase (CAT) were significantly changed in most of the individual and joint exposures of pesticides compared with the control group. The expressions of 26 genes related to oxidative stress, cellular apoptosis, immune system, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis at the mRNA level revealed that zebrafish embryos were affected by the individual or joint pesticides, and greater changes in the expressions of six genes (Mn-sod, CXCL-CIC, Dio1, Dio2, tsh and vtg1) were observed when exposed to joint pesticides compared with their individual pesticides. Taken together, the synergistic effects indicated that it was highly important to incorporate joint toxicity studies, especially at low concentrations, when assessing the risk of pesticides.
ESTHER : Wu_2018_Environ.Pollut_235_470
PubMedSearch : Wu_2018_Environ.Pollut_235_470
PubMedID: 29316522

Title : Stereochemical Structure Activity Relationship Studies (S-SAR) of Tetrahydrolipstatin - Liu_2018_ACS.Med.Chem.Lett_9_274
Author(s) : Liu X , Wang Y , Duclos RI, Jr. , O'Doherty GA
Ref : ACS Med Chem Lett , 9 :274 , 2018
Abstract : Tetrahydrolipstatin (THL), its enantiomer, and an additional six diastereomers were evaluated as inhibitors of the hydrolysis of p-nitrophenyl butyrate by porcine pancreatic lipase. IC50s were found for all eight stereoisomers ranging from a low of 4.0 nM for THL to a high of 930 nM for the diastereomer with the inverted stereocenters at the 2,3,2'-positions. While the enantiomer of THL was also significantly less active (77 nM) the remaining five stereoisomers retained significant inhibitory activities (IC50s = 8.0 to 20 nM). All eight compounds were also evaluated against three human cancer cell lines (human breast cancers MCF-7 and MDA-MB-231, human large-cell lung carcinoma H460). No appreciable cytotoxicity was observed for THL and its seven diastereomers, as their IC50s in a MTT cytotoxicity assay were all greater than 3 orders of magnitude of camptothecin.
ESTHER : Liu_2018_ACS.Med.Chem.Lett_9_274
PubMedSearch : Liu_2018_ACS.Med.Chem.Lett_9_274
PubMedID: 29541373

Title : Single-Step In Situ Acetylcholinesterase-Mediated Alginate Hydrogelation for Enzyme Encapsulation in CE - Yang_2018_Anal.Chem_90_4071
Author(s) : Yang J , Hu X , Xu J , Liu X , Yang L
Ref : Analytical Chemistry , 90 :4071 , 2018
Abstract : A novel capillary electrophoresis-integrated immobilized enzyme reactor (CE-integrated IMER) is developed using single-step in situ acetylcholinesterase (AChE)-mediated alginate hydrogelation and enzyme encapsulation. Alginate hydrogelation with "egg-box" structure is triggered inside a capillary with releasing of Ca(2+) by changing the pH of the sol solution, which is accomplished in situ by AChE-catalyzed hydrolysis reaction of acetylthiocholine to produce acetic acid. AChE and any other enzyme initially contained in the sol solution [e.g., xanthine oxidase (XO)] are efficiently encapsulated as the hydrogel network grows, forming CE-integrated IMERs without any additional manipulation process. The proposed method facilitates the analysis of different kinds of enzymes using the same IMER depending on the substrate injected for CE analysis. Approximately 68% of the original enzyme in the sol mixture can be encapsulated, indicating high loading capacity for the CE-integrated IMERs. The IMERs exhibit excellent intraday and interday stability and batch-to-batch reproducibility, and these characteristics imply the reliability of the proposed IMERs for accurate online enzyme assays. Enzymatic activities and inhibition of immobilized AChE and XO are analyzed, and the results are compared with those using free enzymes. The feasibility of the proposed method for potential application in real sample analysis is demonstrated by the successful application of the IMERs in detecting organophosphorus pesticides in apple juice samples using AChE-catalyzed reactions. The proposed method is a simple, efficient, and universal approach for online CE assays with immobilized enzymes, which can be widely applied in bioanalysis.
ESTHER : Yang_2018_Anal.Chem_90_4071
PubMedSearch : Yang_2018_Anal.Chem_90_4071
PubMedID: 29469571

Title : Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy - Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
Author(s) : Zhang W , Teng M , Liu B , Liu Q , Liu X , Si Y , Li L
Ref : Gastroenterol Res Pract , 2018 :4136082 , 2018
Abstract : Objective: This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods: A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), alpha-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results: Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions: Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.
ESTHER : Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
PubMedSearch : Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
PubMedID: 30510572

Title : Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors - Wu_2018_Medchemcomm_9_149
Author(s) : Wu G , Gao Y , Kang D , Huang B , Huo Z , Liu H , Poongavanam V , Zhan P , Liu X
Ref : Medchemcomm , 9 :149 , 2018
Abstract : We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against Electrophorus electricus acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 muM and 3.61 muM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.
ESTHER : Wu_2018_Medchemcomm_9_149
PubMedSearch : Wu_2018_Medchemcomm_9_149
PubMedID: 30108908

Title : IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata - Wingfield_2018_IMA.Fungus_9_199
Author(s) : Wingfield BD , Bills GF , Dong Y , Huang W , Nel WJ , Swalarsk-Parry BS , Vaghefi N , Wilken PM , An Z , de Beer ZW , De Vos L , Chen L , Duong TA , Gao Y , Hammerbacher A , Kikkert JR , Li Y , Li H , Li K , Li Q , Liu X , Ma X , Naidoo K , Pethybridge SJ , Sun J , Steenkamp ET , van der Nest MA , van Wyk S , Wingfield MJ , Xiong C , Yue Q , Zhang X
Ref : IMA Fungus , 9 :199 , 2018
Abstract : Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi.
ESTHER : Wingfield_2018_IMA.Fungus_9_199
PubMedSearch : Wingfield_2018_IMA.Fungus_9_199
PubMedID: 30018880
Gene_locus related to this paper: 9helo-a0a370tge3 , 9helo-a0a3d8spg6 , 9euro-a0a3d8t2t6 , 9euro-a0a3d8t644 , 9helo-a0a370te58 , 9helo-a0a370tt42 , 9helo-a0a370u2s4 , 9helo-a0a3d8s0y2 , 9helo-a0a3d8stp9 , 9helo-a0a370u370 , 9euro-a0a3d8rk78 , 9helo-a0a370tat5 , 9helo-a0a3d8qpi0

Title : The Aegilops tauschii genome reveals multiple impacts of transposons - Zhao_2017_Nat.Plants_3_946
Author(s) : Zhao G , Zou C , Li K , Wang K , Li T , Gao L , Zhang X , Wang H , Yang Z , Liu X , Jiang W , Mao L , Kong X , Jiao Y , Jia J
Ref : Nat Plants , 3 :946 , 2017
Abstract : Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
ESTHER : Zhao_2017_Nat.Plants_3_946
PubMedSearch : Zhao_2017_Nat.Plants_3_946
PubMedID: 29158546
Gene_locus related to this paper: horvv-m0utz9 , wheat-a0a3b6c2m6 , wheat-a0a3b5zwb6 , wheat-a0a3b6bzs8 , wheat-a0a1d5zte7 , wheat-a0a1d5uwn5

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

Title : A cryptic pigment biosynthetic pathway uncovered by heterologous expression is essential for conidial development in Pestalotiopsis fici - Zhang_2017_Mol.Microbiol_105_469
Author(s) : Zhang P , Wang X , Fan A , Zheng Y , Liu X , Wang S , Zou H , Oakley BR , Keller NP , Yin WB
Ref : Molecular Microbiology , 105 :469 , 2017
Abstract : Spore pigmentation is very common in the fungal kingdom. The best studied pigment in fungi is melanin which coats the surface of single cell spores. What and how pigments function in a fungal species with multiple cell conidia is poorly understood. Here, we identified and deleted a polyketide synthase (PKS) gene PfmaE and showed that it is essential for multicellular conidial pigmentation and development in a plant endophytic fungus, Pestalotiopsis fici. To further characterize the melanin pathway, we utilized an advanced Aspergillus nidulans heterologous system for the expression of the PKS PfmaE and the Pfma gene cluster. By structural elucidation of the pathway metabolite scytalone in A. nidulans, we provided chemical evidence that the Pfma cluster synthesizes DHN melanin. Combining genetic deletion and combinatorial gene expression of Pfma cluster genes, we determined that the putative reductase PfmaG and the PKS are sufficient for the synthesis of scytalone. Feeding scytalone back to the P. fici deltaPfmaE mutant restored pigmentation and multicellular adherence of the conidia. These results cement a growing understanding that pigments are essential not simply for protection of spores from biotic and abiotic stresses but also for spore structural development.
ESTHER : Zhang_2017_Mol.Microbiol_105_469
PubMedSearch : Zhang_2017_Mol.Microbiol_105_469
PubMedID: 28517364
Gene_locus related to this paper: pesfw-pfmab , pesfw-pfmae

Title : The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice - Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Yang Y , Liu X
Ref : Evid Based Complement Alternat Med , 2017 :7426538 , 2017
Abstract : Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.
ESTHER : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedSearch : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedID: 28529531

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 : Muscarinic receptors in the nucleus accumbens shell play different roles in context-induced or morphine-challenged expression of behavioral sensitization in rats - Liu_2017_Eur.J.Pharmacol_819_51
Author(s) : Liu X , Tian L , Cui R , Ruan H , Li X
Ref : European Journal of Pharmacology , 819 :51 , 2017
Abstract : Both drug-related cues and drug priming are the main factors that induce relapse of drug addiction. Previous research has reported that blockade of the muscarinic receptors could significantly depress addictive behavior, suggesting that the muscarinic receptors might be involved in drug use and relapse behavior. The nucleus accumbens (NAc), especially the shell of the NAc, where the muscarinic receptors are expressed, is critical for craving and relapse. This study investigated the effects of microinfusion of the muscarinic receptor antagonist scopolamine into the NAc shell on context- and morphine-induced expression of behavioral sensitization. Behavioral sensitization was established by exposure to 5mg/kg morphine once daily for five consecutive days. Expression of behavioral sensitization was induced by saline challenge or 5mg/kg morphine challenge. The results showed that: (a) the muscarinic receptor antagonist scopolamine (10.8mug/rat) microinjected into the NAc shell blocked expression of conditional sensitization; (b) acetylcholinesterase inhibitor huperzine-A (0.5 and 0.1mug/rat), but not scopolamine (10.8mug/rat), microinjected into the NAc shell blocked morphine-induced expression of sensitization; and (c) pre-infusion of scopolamine (10.8mug/rat) reversed the inhibitory effect of huperzine-A (0.5mug/rat) on morphine-induced sensitization. Our findings suggest that muscarinic receptors in the NAc shell play different roles in context-induced and morphine-challenged expression of behavioral sensitization.
ESTHER : Liu_2017_Eur.J.Pharmacol_819_51
PubMedSearch : Liu_2017_Eur.J.Pharmacol_819_51
PubMedID: 29196177

Title : Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c - Long_2017_Molecules_22_
Author(s) : Long Y , Cui H , Liu X , Xiao Z , Wen S , She Z , Huang X
Ref : Molecules , 22 : , 2017
Abstract : One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 (9), and 1,2-dihydro-acetoxydehydroaustin B (10), were isolated from the mangrove endophytic fungus, Aspergillus sp. 16-5c. These structures were characterized by spectroscopic analysis, further the absolute configurations of stereogenic carbons for Compounds 1, 3, 4, 6, 7, 8, 9, and 10 were determined by single crystal X-ray diffraction analysis using Cu Kalpha radiation. Moreover, the absolute configurations of stereogenic carbons for Known Compounds 3, 7, 8, and 9 are identified here for the first time. Compounds 3, 7, and 8 showed acetylcholinesterase (AchE) inhibitory activity with IC50 values of 2.50, 0.40, and 3.00 muM, respectively.
ESTHER : Long_2017_Molecules_22_
PubMedSearch : Long_2017_Molecules_22_
PubMedID: 28467349

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

Title : Label-Free Homogeneous Electroanalytical Platform for Pesticide Detection Based on Acetylcholinesterase-Mediated DNA Conformational Switch Integrated with Rolling Circle Amplification - Liu_2017_ACS.Sens_2_562
Author(s) : Liu X , Song M , Hou T , Li F
Ref : ACS Sens , 2 :562 , 2017
Abstract : This study addresses the need for sensitive pesticide assay by reporting a new label-free and immobilization-free homogeneous electroanalytical strategy, which combines acetylcholinesterase (AChE)-catalyzed hydrolysis product-mediated DNA conformational switch and rolling circle amplification (RCA) to detect organophosphorous and carbamate pesticides in a "signal-on" mode. When target pesticides were present, AChE activity was inhibited and could not trigger the following DNA conformational change and the RCA reaction, which results in numerous methylene blue (MB) molecules in a free state, generating a strong electrochemical response. This proposed strategy was highly sensitive for omethoate detection with a detection limit as low as 2.1 mug/L and a linear range from 10 to 10000 mug/L. Furthermore, this strategy was demonstrated to be applicable for pesticide detection in real samples. Thus, this novel label-free homogeneous electroanalytical strategy holds great promise for pesticide detection and can be further exploited for sensing applications in the environment and the food safety field.
ESTHER : Liu_2017_ACS.Sens_2_562
PubMedSearch : Liu_2017_ACS.Sens_2_562
PubMedID: 28723196

Title : Does Resistance to Buprofezin Improve Heat and Cold Tolerance of Laodelphax striatellus (Hemiptera: Delphacidae)? - Li_2017_Environ.Entomol_46_988
Author(s) : Li Y , Zhang Y , Liu X , Guo H
Ref : Environ Entomol , 46 :988 , 2017
Abstract : There is ample evidence that insecticide resistance causes fitness costs and benefits in pests, while the impact of insecticide resistance on thermotolerance of pests is mostly unclear. The Laodelphax striatellus (Fallen), is an important rice insect pest, which has developed resistance to buprofezin in China. Here, we investigated differences in heat tolerance and cold tolerance among L. striatellus lines with variable buprofezin resistance. The lethal time for 50% of the individuals to die (LT50) at 40 degrees C increased with an increase in buprofezin resistance level, whereas both the survival rate under -22 degrees C and the supercooling point of planthoppers did not differ significantly between resistant and susceptible strains. The metabolic enzyme carboxylesterase was found to have an association with buprofezin resistance. Our research showed that buprofezin resistance was positively related with heat tolerance in L. striatellus, but it had no effect on cold tolerance. Insecticide resistance in L. striatellus may therefore have broader implications for the ecology of L. striatellus, and the management of buprofezin resistance in this pest may be challenging.
ESTHER : Li_2017_Environ.Entomol_46_988
PubMedSearch : Li_2017_Environ.Entomol_46_988
PubMedID: 28595288

Title : Aii810, a Novel Cold-Adapted N-Acylhomoserine Lactonase Discovered in a Metagenome, Can Strongly Attenuate Pseudomonas aeruginosa Virulence Factors and Biofilm Formation - Fan_2017_Front.Microbiol_8_1950
Author(s) : Fan X , Liang M , Wang L , Chen R , Li H , Liu X
Ref : Front Microbiol , 8 :1950 , 2017
Abstract : The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti-infection therapeutic strategy that does not rely on antibiotics. Here, a novel gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao-tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the highest activity at 20 degrees C, and it maintained 76.5% of activity at 0 degrees C and more than 50% activity at 0-40 degrees C. The optimal pH was 8.0. It was stable in both neutral and slightly alkaline conditions and at temperatures below 40 degrees C. The enzyme hydrolyzed several rho-nitrophenyl esters, but its best substrate was rho-nitrophenyl acetate. Its kcat and Km values were 347.7 S(-1) and 205.1 muM, respectively. It efficiently degraded N-butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, exceeding hydrolysis rates of 72.3 and 100%, respectively. Moreover, Aii810 strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase reported, which makes it an attractive enzyme for use as a therapeutic agent against P. aeruginosa infection.
ESTHER : Fan_2017_Front.Microbiol_8_1950
PubMedSearch : Fan_2017_Front.Microbiol_8_1950
PubMedID: 29067011
Gene_locus related to this paper: 9bact-Aii810

Title : Proprioceptive mechanisms in occlusion-stimulated masseter hypercontraction - Liu_2017_Eur.J.Oral.Sci_125_127
Author(s) : Liu X , Zhang C , Wang D , Zhang H , Li J , Wang M
Ref : Eur J Oral Sci , 125 :127 , 2017
Abstract : Neurons in the trigeminal mesencephalic nucleus (Vme) have an axon that branches peripherally to innervate the orofacial region and projects centrally to the trigeminal motor nucleus (Vmo). They function as the primary neurons conveying proprioceptive messages. The present study aimed to demonstrate the presence of a periodontal-Vme-Vmo circuit and to provide evidence for its involvement in an experimental unilateral anterior crossbite (UAC) model, which can induce osteoarthritis in the temporomandibular joint. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons in the Vmo. The levels of vesicular glutamate transporter 1 (VGLUT1) expressed in the periodontal region, Vme, Vmo, and masseter, and the level of acetylcholinesterase (AChE) expressed in the masseter, were assessed in UAC rats and controls. In CTb-treated rats, many CTb-labeled cell bodies and endings were identified in the Vme and in the Vmo, respectively. In UAC rats, VGLUT1 was expressed at a statistically significantly higher level in the periodontal ligament, Vme, Vmo, and masseter than it was in control rats. The level of AChE protein was 1.97 times higher in UAC rat masseter compared with control rat masseter. These findings reveal a trigeminal mechanism underlying masseter hyperactivity induced by an altered occlusion.
ESTHER : Liu_2017_Eur.J.Oral.Sci_125_127
PubMedSearch : Liu_2017_Eur.J.Oral.Sci_125_127
PubMedID: 28145597

Title : Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial - Xiao_2017_Age.Ageing__1
Author(s) : Xiao S , Wang T , Ma X , Qin Y , Li X , Zhao Z , Liu X , Wang X , Xie H , Jiang Q , Sun L , Luo B , Shang L , Chen W , Bai Y , Tang M , He M , Wu L , Ma Q , Hou D , He J
Ref : Age Ageing , :1 , 2017
Abstract : Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.
ESTHER : Xiao_2017_Age.Ageing__1
PubMedSearch : Xiao_2017_Age.Ageing__1
PubMedID: 28419192

Title : Dibenzo-alpha-pyrones: a new class of larvicidal metabolites against Aedes aegypti from the endophytic fungus Hyalodendriella sp. Ponipodef12 - Mao_2017_Pest.Manag.Sci_73_1478
Author(s) : Mao Z , Lai D , Liu X , Fu X , Meng J , Wang A , Wang X , Sun W , Liu ZL , Zhou L , Liu Y
Ref : Pest Manag Sci , 73 :1478 , 2017
Abstract : BACKGROUND: In our search for new agrochemicals from endophytic fungi, the crude extract of the endophytic Hyalodendriella sp. Ponipodef12 associated with the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. was found to possess larvicidal activity against Aedes aegypti.
RESULTS: Fractionation of the extract has led to the isolation of 11 dibenzo-alpha-pyrones (1-11), including three new congeners: hyalodendriols A-C (1-3). The structures of the new compounds were elucidated by comprehensive spectroscopic analyses, including the modified Mosher's method for the assignment of the absolute configuration. Compounds 2-7 showed potent larvicidal activities against the fourth-instar larvae of A. aegypti with IC50 values ranging from 7.21 to 120.81 microg mL-1 . Among them, penicilliumolide D (6) displayed the strongest activity (IC50 = 7.21 microg mL-1 ). A structure-larvicidal activity relationship was discussed. The possible mode of action of these compounds was assessed for their acetylcholinesterase inhibitory activities. In addition, hyalodendriol C (3) displayed antibacterial activity against Bacillus subtilis and Xanthomonas vesicatoria, and exhibited strong inhibition against the spore germination of Magnaporthe oryzae. CONCLUSION: Our study revealed dibenzo-alpha-pyrones to be a new class of larvicidal metabolites against A. aegypti. (c) 2016 Society of Chemical Industry.
ESTHER : Mao_2017_Pest.Manag.Sci_73_1478
PubMedSearch : Mao_2017_Pest.Manag.Sci_73_1478
PubMedID: 27862895

Title : Remarkable reactivity of alkoxide\/acetato-bridged binuclear copper(II) complex as artificial carboxylesterase - Xu_2017_J.Biol.Inorg.Chem_22_625
Author(s) : Xu B , Jiang W , Liu X , Liu F , Xiang Z
Ref : J Biol Inorg Chem , 22 :625 , 2017
Abstract : Bromo-containing binuclear Schiff base copper(II) complex, Cu2L(OAc), with an alkoxo/acetato-bridged moiety was employed as a model of carboxylesterases to promote the hydrolytic cleavage of p-nitrophenyl picolinate (PNPP). Furthermore, the reactivity of a mononuclear complex (CuHL) was evaluated for comparing it with that of binuclear one. The results reveal that the as-prepared binuclear Cu2L(OAc) efficiently accelerated the hydrolysis of PNPP, giving rise to excess four orders of magnitude rate enhancement in contrast to the un-catalyzed reaction. Cu2L(OAc) represented an enzyme-like bell-shaped pH-responsive kinetic behavior. Moreover, the binuclear one is more reactive than its mononuclear analogue (CuHL) by two orders of magnitude. The total efficiency of Cu2L(OAc) is about 61-fold than that of its mononuclear analogue, CuHL. In addition, a contrast experiment reveals that binuclear Cu2L(OAc) displayed good activity in the hydrolysis of PNPP as well another active ester, i.e., S-2-benzothiazolyl 2-amino-alpha-(methoxyimino)-4-thiazolethiolacetate (AE-active ester). Noteworthyly, it was found that mononuclear one inspired more obvious rate enhancement in the hydrolysis of AE-active ester relative to PNPP hydrolysis. The estimated pK a1 of bound water on the binuclear Cu2L(OAc) using second derivative method (SDM) is relatively smaller than that for CuHL by a gap of about 0.8 pK unit, which facilitates the hydrolysis of PNPP. Four orders of magnitude rate enhancement was observed for the catalytic hydrolysis of p-nitrophenyl picolinate (PNPP) by one mu-alkoxide/acetato-bridged binuclear copper(II) complex under physiological conditions. Substrate specificity of the resulting binuclear complexes was observed for the hydrolysis of PNPP and AE-active ester.
ESTHER : Xu_2017_J.Biol.Inorg.Chem_22_625
PubMedSearch : Xu_2017_J.Biol.Inorg.Chem_22_625
PubMedID: 28364223

Title : Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators - Flitter_2017_Proc.Natl.Acad.Sci.U.S.A_114_136
Author(s) : Flitter BA , Hvorecny KL , Ono E , Eddens T , Yang J , Kwak DH , Bahl CD , Hampton TH , Morisseau C , Hammock BD , Liu X , Lee JS , Kolls JK , Levy BD , Madden DR , Bomberger JM
Ref : Proc Natl Acad Sci U S A , 114 :136 , 2017
Abstract : Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8-driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.
ESTHER : Flitter_2017_Proc.Natl.Acad.Sci.U.S.A_114_136
PubMedSearch : Flitter_2017_Proc.Natl.Acad.Sci.U.S.A_114_136
PubMedID: 27980032
Gene_locus related to this paper: pseae-PA2934

Title : The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism - Liu_2017_Mol.Plant_10_975
Author(s) : Liu X , Liu Y , Huang P , Ma Y , Qing Z , Tang Q , Cao H , Cheng P , Zheng Y , Yuan Z , Zhou Y , Liu J , Tang Z , Zhuo Y , Zhang Y , Yu L , Huang J , Yang P , Peng Q , Zhang J , Jiang W , Zhang Z , Lin K , Ro DK , Chen X , Xiong X , Shang Y , Huang S , Zeng J
Ref : Mol Plant , 10 :975 , 2017
Abstract : The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding (13)C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.
ESTHER : Liu_2017_Mol.Plant_10_975
PubMedSearch : Liu_2017_Mol.Plant_10_975
PubMedID: 28552780
Gene_locus related to this paper: