Wang C

References (256)

Title : Identification and biochemical characterization of a carboxylesterase gene associated with beta-cypermethrin resistance in Dermanyssus gallinae - Zhang_2024_Poult.Sci_103_103612
Author(s) : Zhang X , Zhang Y , Xu K , Qin J , Wang D , Xu L , Wang C
Ref : Poult Sci , 103 :103612 , 2024
Abstract : Dermanyssus gallinae is a major hematophagous ectoparasite in layer hens. Although the acaricide beta-cypermethrin has been used to control mites worldwide, D. gallinae has developed resistance to this compound. Carboxylesterases (CarEs) are important detoxification enzymes that confer resistance to beta-cypermethrin in arthropods. However, CarEs associated with beta-cypermethrin resistance in D. gallinae have not yet been functionally characterized. Here, we isolated a CarE gene (Deg-CarE) from D. gallinae and assayed its activity. The results revealed significantly higher expression of Deg-CarE in the beta-cypermethrin-resistant strain (RS) than in the susceptible strain (SS) toward alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA). These findings suggest that enhanced esterase activities might have contributed to beta-cypermethrin resistance in D. gallinae. Quantitative real-time PCR analysis revealed that Deg-CarE expression levels were significantly higher in adults than in other life stages. Although Deg-CarE was upregulated in the RS, significant differences in gene copy numbers were not observed. Additionally, Deg-CarE expression was significantly induced by beta-cypermethrin in both the SS and RS. Moreover, silencing Deg-CarE via RNA interference decreased the enzyme activity and increased the susceptibility of the RS to beta-cypermethrin, confirming that Deg-CarE is crucial for beta-cypermethrin detoxification. Finally, recombinant Deg-CarE (rDeg-CarE) expressed in Escherichia coli displayed high enzymatic activity toward alpha/beta-NA. However, metabolic analysis indicated that rDeg-CarE did not directly metabolize beta-cypermethrin. The collective findings indicate that D. gallinae resistance to beta-cypermethrin is associated with elevated CarEs protein activity and increased Deg-CarE expression levels. These findings provide insights into the metabolic resistance of D. gallinae and offer scientific guidance for the management and control of D. gallinae.
ESTHER : Zhang_2024_Poult.Sci_103_103612
PubMedSearch : Zhang_2024_Poult.Sci_103_103612
PubMedID: 38492248

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

Title : Biotoxicity responses of Zebrafish in environmentally relevant concentration of Di (2-ethylhexyl) phthalate - Li_2024_Environ.Toxicol.Pharmacol__104423
Author(s) : Li X , Hu S , Jiang N , Yao X , Wang C , Wang Q , Yang Z , Wang J
Ref : Environ Toxicol Pharmacol , :104423 , 2024
Abstract : As an emerging environmental contaminant, di (2-ethylhexyl) phthalate (DEHP) is widely present in the aquatic environment, however, the effects and underlying mechanisms of DEHP on the aquatic organisms are poorly understood. This study systematically investigated the ecotoxicity induced by chronic exposure to environmental relevant concentrations of DEHP (0.03mg/L, 0.1mg/L, and 0.3mg/L) on zebrafish brain. Results indicated that DEHP exposure significantly increased the levels of ROS and disturbance of the antioxidant enzymes activities in the brain, which may further enhance lipid peroxidation and DNA damage. Furthermore, acetylcholinesterase activity was first stimulated and inhibited by exposure to DEHP, and the antioxidant and apoptosis related genes were mainly upregulated. Risk assessment indicated that the ecotoxicity of DEHP on the zebrafish showed an "enhancement-reduction" trend as the exposure time was prolonged. Overall, these results provided new insights and useful information to ecological risk assessment and environmental management of DEHP pollution.
ESTHER : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedSearch : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedID: 38521434

Title : ABHD7-mediated depalmitoylation of lamin A promotes myoblast differentiation - Shen_2024_Cell.Rep_43_113720
Author(s) : Shen Y , Zheng LL , Fang CY , Xu YY , Wang C , Li JT , Lei MZ , Yin M , Lu HJ , Lei QY , Qu J
Ref : Cell Rep , 43 :113720 , 2024
Abstract : LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase alpha/beta hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.
ESTHER : Shen_2024_Cell.Rep_43_113720
PubMedSearch : Shen_2024_Cell.Rep_43_113720
PubMedID: 38308845
Gene_locus related to this paper: human-EPHX4 , mouse-ephx4

Title : Acetylcholinesterase Inhibitors, AMD, and Alzheimer Disease -
Author(s) : Chen YH , Wang C , Kurth T
Ref : JAMA Ophthalmol , : , 2024
PubMedID: 38722653

Title : Overexpression of Fatty Acid Synthase Upregulates Glutamine-Fructose-6-Phosphate Transaminase 1 and O-Linked N-Acetylglucosamine Transferase to Increase O-GlcNAc Protein Glycosylation and Promote Colorectal Cancer Growth - Drury_2024_Int.J.Mol.Sci_25_
Author(s) : Drury J , Geisen ME , Tessmann JW , Rychahou PG , Kelson CO , He D , Wang C , Evers BM , Zaytseva YY
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently being tested in multiple clinical trials. However, the mechanisms behind the pro-oncogenic action of FASN are still not completely understood. Here, for the first time, we show that overexpression of FASN increases the expression of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) and O-linked N-acetylglucosamine transferase (OGT), enzymes involved in hexosamine metabolism, and the level of O-GlcNAcylation in vitro and in vivo. Consistently, expression of FASN significantly correlates with expression of GFPT1 and OGT in human CRC tissues. shRNA-mediated downregulation of GFPT1 and OGT inhibits cellular proliferation and the level of protein O-GlcNAcylation in vitro, and knockdown of GFPT1 leads to a significant decrease in tumor growth and metastasis in vivo. Pharmacological inhibition of GFPT1 and OGT leads to significant inhibition of cellular proliferation and colony formation in CRC cells. In summary, our results show that overexpression of FASN increases the expression of GFPT1 and OGT as well as the level of protein O-GlcNAcylation to promote progression of CRC; targeting the hexosamine biosynthesis pathway could be a therapeutic approach for this disease.
ESTHER : Drury_2024_Int.J.Mol.Sci_25_
PubMedSearch : Drury_2024_Int.J.Mol.Sci_25_
PubMedID: 38732103

Title : Molecular Mechanistic Insights into Dipeptidyl Peptidase-IV Inhibitory Peptides to Decipher the Structural Basis of Activity - Wang_2024_J.Agric.Food.Chem_72_11230
Author(s) : Wang C , Zheng L , Udenigwe CC , Lin L , Zhao M
Ref : Journal of Agricultural and Food Chemistry , 72 :11230 , 2024
Abstract : Dipeptidyl peptidase-IV (DPP-IV) inhibiting peptides have attracted increased attention because of their possible beneficial effects on glycemic homeostasis. However, the structural basis underpinning their activities has not been well understood. This study combined computational and in vitro investigations to explore the structural basis of DPP-IV inhibitory peptides. We first superimposed the Xaa-Pro-type peptide-like structures from several crystal structures of DPP-IV ligand-protein complexes to analyze the recognition interactions of DPP-IV to peptides. Thereafter, a small set of Xaa-Pro-type peptides was designed to explore the effect of key interactions on inhibitory activity. The intramolecular interaction of Xaa-Pro-type peptides at the first and third positions from the N-terminus was pivotal to their inhibitory activities. Residue interactions between DPP-IV and residues of the peptides at the fourth and fifth positions of the N-terminus contributed significantly to the inhibitory effect of Xaa-Pro-type tetrapeptides and pentapeptides. Based on the interaction descriptors, quantitative structure-activity relationship (QSAR) studies with the DPP-IV inhibitory peptides resulted in valid models with high R(2) values (0.90 for tripeptides; 0.91 for tetrapeptides and pentapeptides) and Q(2) values (0.33 for tripeptides; 0.68 for tetrapeptides and pentapeptides). Taken together, the structural information on DPP-IV and peptides in this study facilitated the development of novel DPP-IV inhibitory peptides.
ESTHER : Wang_2024_J.Agric.Food.Chem_72_11230
PubMedSearch : Wang_2024_J.Agric.Food.Chem_72_11230
PubMedID: 38709903

Title : Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS - Li_2024_Nat.Chem.Biol__
Author(s) : Li W , Liu Q , Qian Y , Wang C , Kong C , Sun L , Liu H , Zhang Y , Jiang D , Jiang C , Wang S , Xia P
Ref : Nat Chemical Biology , : , 2024
Abstract : Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1beta, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.
ESTHER : Li_2024_Nat.Chem.Biol__
PubMedSearch : Li_2024_Nat.Chem.Biol__
PubMedID: 38413746

Title : Naked-eye sensitive detection of nanoPET by pH-responsive colorimetric method based on dual-enzyme catalysis - Zhan_2024_Environ.Int_186_108598
Author(s) : Zhan W , Wang C , Yang X , Li H , Xiong S , Li X
Ref : Environ Int , 186 :108598 , 2024
Abstract : A pH-responsive colorimetric method based on dual-enzyme catalysis for rapid and facile detection and quantification of nanoPET at environment-dependent concentration is proposed. The nanoPET was hydrolyzed by the synergistic catalysis of cutinase and lipase to terephthalic acid which can be sensitive detected using bromocresol purple as the indicator. The color changed from purple to bright yellow as the nanoPET detection concentration increased from 0 mg/mL to 2 mg/mL which can be detected by UV-Vis. This naked-eye method has a high sensitivity for nanoPET detection with the visual detection cutoff of 31.00 microg/mL, and has a good linearity in the range of 0 - 1 mg/mL with LOD of 22.84 microg/mL. The reliability of this method is verified in the detection of nanoPET in lake water and beer samples, with an average recovery of 87.1 %. The as-developed dual-enzyme colorimetric chemosensor holds promising potential as a robust and effective platform for the sensitive detection of nanoPET.
ESTHER : Zhan_2024_Environ.Int_186_108598
PubMedSearch : Zhan_2024_Environ.Int_186_108598
PubMedID: 38531236

Title : Ameliorative effect of scopolamine-induced cognitive dysfunction by Fufangmuniziqi formula: The roles of alkaloids, saponins, and flavonoids - Zhao_2023_J.Ethnopharmacol__116792
Author(s) : Zhao X , Hu X , Xie Q , Qi S , Xiang Z , Sun X , Xie Z , Dang R , Zhou L , Liu W , Cheng X , Wang C
Ref : J Ethnopharmacol , :116792 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Fufangmuniziqi formula (FFMN), a traditional Uyghur medicine used in China, is derived from an ancient Uyghur medical book and consists of 13 herbs. The herbs of FFMN, such as Peganum harmala L., Glycyrrhiza uralensis Fisch., and Nigella glandulifera, have been demonstrated to have acetylcholinesterase (AChE) inhibitory, anti-neuroinflammatory, or antioxidant effects. Therefore, FFMN may have a good anti-Alzheimer's disease (AD) effect, but its specific action and mechanism need to be further proven. AIM OF THE STUDY: This study aims to investigate the anti-AD effects of FFMN and the role played by alkaloids, flavonoids, and saponins in anti-AD. MATERIALS AND METHODS: The alkaloids, flavonoids, and saponins fractions of FFMN were prepared by macroporous resin chromatography. The absorbed ingredients in the drug-containing serum were identified by UPLC-Q-TOF-MS. An AD mouse model was established by intraperitoneal injection of scopolamine (SCO). The role of different fractions of FFMN in the anti-AD process was examined by Morris water maze (MWM), in-vitro cell, and AChE inhibition assay. RESULTS: A total of 20 ingredients were identified in the serum samples collected after oral administration of FFMN, and seven compounds were selected as candidate active compounds. MWM experiments showed that different fractions of FFMN could significantly improve SCO-induced learning memory impairment in mice. The alkaloids fraction (ALK) regulated cholinergic function by inhibiting AChE activity, activating choline acetyltransferase activity, and protein expression. Flavonoids and saponins were more potent than the ALK in downregulating pro-inflammatory factors or inflammatory mediators, such as TNF-alpha, MPO, and nitric oxide. Western blot results further confirmed that flavonoids and saponins attenuated neuroinflammation by inhibiting the phosphorylation of IkappaB and NF-kappaB p65. This result was also verified by in-vitro cellular assays. FFMN enhanced antioxidant defense by increasing the activity of superoxide dismutase and reducing the production of MDA. Combined with cellular experiments, flavonoids and saponins were proven more protective against oxidative damage. CONCLUSION: FFMN improved cognitive and memory impairment in the SCO-induced AD mouse model. ALK mainly enhanced the function of the cholinergic system. Flavonoid and saponin fractions mainly attenuated neuroinflammation and oxidative stress by modulating the NF-kappaB pathway. All these findings strongly suggested that the combination of alkaloid, flavonoid, and saponin fractions derived from FFMN is a promising anti-AD agent that deserves further development.
ESTHER : Zhao_2023_J.Ethnopharmacol__116792
PubMedSearch : Zhao_2023_J.Ethnopharmacol__116792
PubMedID: 37356745

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

Title : DPP-IV Inhibitory Peptides from Coix Seed Prolamins: Release, Identification, and Analysis of the Interaction between Key Residues and Enzyme Domains - Zhang_2023_J.Agric.Food.Chem__
Author(s) : Zhang S , Li ZM , Feng Y , Yu S , Li Z , Zhang D , Wang C
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides can regulate type 2 diabetes by inhibiting the cleavage of glucagon-like peptide-1 andv prolonging its half-life. The development of DPP-IV inhibitory peptides is still a hot topic. The primary structure of coix seed prolamins contains peptide sequence fragments that potentially inhibit DPP-IV; however, limited information is available regarding the extraction of peptides from coix seeds and the analysis of their conformational relationships. In this study, novel coix seed prolamin-derived peptides were obtained through single hydrolysis and double-enzyme stepwise hydrolysis. The inhibitory activity of these peptides against DPP-IV was evaluated to explore new functional properties of coix seeds. The results evidenced that the step-by-step enzymolysis (papain and alcalase) compared to single enzymolysis promoted the secondary structure disruption of the hydrolysates, enhanced the beta-turn structure, significantly increased the content of peptides below 1 kDa, and exhibited a substantial increase in DPP-IV inhibitory activity (97% inhibition). Three nontoxic DPP-IV inhibitory peptides, namely, LPFYPN, TFFPQ, and ATFFPQ (IC(50) = 70.24, 176.87, 268.31 microM), were isolated and identified. All three peptides exhibited strong interactions with DPP-IV (all K(A) values >10(3)). LPFYPN exhibited competitive inhibition, while TFFPQ and ATFFPQ demonstrated mixed competitive-noncompetitive inhibition. Hydrogen bonding and hydrophobic interactions were the main contributors to the coix seed prolamin peptides binding to DPP-IV. The central residue was a key amino acid in the parent peptide sequence, forming a more stable Pi-Pi stacking with residues in the active pocket, which may facilitate peptide activity. This study provides theoretical support for the development of coix seed-derived hypoglycemic peptides.
ESTHER : Zhang_2023_J.Agric.Food.Chem__
PubMedSearch : Zhang_2023_J.Agric.Food.Chem__
PubMedID: 37748081

Title : Effects and mechanism of extracts rich in phenylpropanoids-polyacetylenes and polysaccharides from Codonopsis Radix on improving scopolamine-induced memory impairment of mice - Xie_2023_J.Ethnopharmacol__117106
Author(s) : Xie Q , Hu X , Zhao X , Xiang Z , Chen Q , Xie Z , Wang H , Zhao Y , Cheng X , Wang C
Ref : J Ethnopharmacol , :117106 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action. MATERIALS AND METHODS: C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated. RESULTS: Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-alpha, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity. CONCLUSION: EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.
ESTHER : Xie_2023_J.Ethnopharmacol__117106
PubMedSearch : Xie_2023_J.Ethnopharmacol__117106
PubMedID: 37652198

Title : Near-infrared-excitable acetylcholinesterase-activated fluorescent probe for sensitive and anti-interference detection of pesticides in colored food - Wu_2023_Biosens.Bioelectron_233_115341
Author(s) : Wu Z , Hao Z , Chai Y , Li A , Wang C , Zhang X , Chen H , Lu C
Ref : Biosensors & Bioelectronics , 233 :115341 , 2023
Abstract : The development of a common and anti-interference acetylcholinesterase (AChE) inhibition assay for plant-originated food samples has been of great challenge because of the prevalent and strong signal interferences from natural pigments. Plant pigments normally exhibit non-negligible absorbance in the UV-visible region. As a result, the signals of a typical near-infrared (NIR) fluorescent probe could be disturbed through primary inner filter effect if it is excited by UV-visible light during plant sample analysis. In this work, an NIR-excitable AChE-activated fluorescent probe was biomimetically designed and synthesized. And the NIR-excitation strategy was utilized for the anti-interference detection of organophosphate and carbamate pesticides in colored samples with this probe. Sensitive and rapid response to AChE and pesticides was achieved due to the high affinity of the biomimetic recognition unit in the probe. The limits of detection for four representative pesticides including dichlorvos, carbofuran, chlorpyrifos and methamidophos reached 0.0186 microg/L, 2.20 microg/L, 12.3 microg/L and 13.6 microg/L, respectively. Most importantly, fluorescent response to pesticide contents could be accurately measured in the coexistence of different plant pigments by this probe, and the measured results showed completely irrelevance to the plant pigments and their colors. Taking advantage of such probe, the new developed AChE inhibition assay showed good sensitivity and anti-interference ability in the detection of organophosphate and carbamate pesticides in real samples.
ESTHER : Wu_2023_Biosens.Bioelectron_233_115341
PubMedSearch : Wu_2023_Biosens.Bioelectron_233_115341
PubMedID: 37099980

Title : Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension - Guo_2023_Theranostics_13_1826
Author(s) : Guo Y , He Z , Chen Z , Chen F , Wang C , Zhou W , Liu J , Liu H , Shi R
Ref : Theranostics , 13 :1826 , 2023
Abstract : Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.
ESTHER : Guo_2023_Theranostics_13_1826
PubMedSearch : Guo_2023_Theranostics_13_1826
PubMedID: 37064881

Title : Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities - Gan_2023_Chin.J.Nat.Med_21_154
Author(s) : Gan D , Li C , Shu Y , Wang J , Wang C , Zhu L , Yang Y , Liu J , He B , Cai L , Ding Z
Ref : Chin J Nat Med , 21 :154 , 2023
Abstract : The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C(28)-steroid with an unusual beta- and gamma-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC(50) value of 2.61 +/- 0.05 micromol.L(-1). The beta-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 microg.mL(-1). Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 microg.mL(-1), respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC(50) values of 9.2 +/- 0.03 and 13.3 +/- 0.01 micromol.L(-1), respectively.
ESTHER : Gan_2023_Chin.J.Nat.Med_21_154
PubMedSearch : Gan_2023_Chin.J.Nat.Med_21_154
PubMedID: 36871983

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 : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : Toxic effects of the heavy metal Cd on Apis cerana cerana (Hymenoptera: Apidae): Oxidative stress, immune disorders and disturbance of gut microbiota - Li_2023_Sci.Total.Environ__169318
Author(s) : Li Z , Guo D , Wang C , Chi X , Liu Z , Wang Y , Wang H , Guo X , Wang N , Xu B , Gao Z
Ref : Sci Total Environ , :169318 , 2023
Abstract : Cadmium (Cd) is a toxic non-essential metal element that can enter the honey bee body through air, water and soil. Currently, there is a lack of sufficient research on the effects of Cd on A. cerana cerana, especially the potential risks of long-term exposure to sublethal concentrations. In order to ascertain the toxicological effects of the heavy metal Cd on bees, we performed laboratory-based toxicity experiments on worker bees and conducted analyses from three distinctive facets: antioxidative, immunological, and gut microbiota. The results showed that exposure of bees to high concentrations of Cd resulted in acute mortality, and the increase in mortality was concentration dependent. In long-term exposure to sublethal concentrations, Cd reduced the number of transcripts of antioxidant genes (AccSOD1, AccTPx3 and AccTPx4) and superoxide dismutase activity, causing an increase in malondialdehyde content. Simultaneously, the transcription of immune-related genes (AccAbaecin and AccApidaecin) and acetylcholinesterase activities was inhibited. Furthermore, Cd changes the structural characteristics of bacterial and fungal communities in the gut, disrupting the balance of microbial communities. In conclusion, the health and survival of honey bees are affected by Cd. This study provides a scientific basis for investigating the toxicological mechanisms and control strategies of the heavy metal Cd on honey bees, while facilitating a better understanding and protection of these valuable honey bees.
ESTHER : Li_2023_Sci.Total.Environ__169318
PubMedSearch : Li_2023_Sci.Total.Environ__169318
PubMedID: 38143006

Title : Rational design of a NIR fluorescent probe for carboxylesterase 1 detection during endoplasmic reticulum stress and drug-induced acute liver injury - Han_2023_Chem.Commun.(Camb)__
Author(s) : Han C , Zhao X , Huo X , Yu Z , Wang C , Feng L , Cui J , Tian X , Ma X
Ref : Chem Commun (Camb) , : , 2023
Abstract : An endoplasmic reticulum targeting NIR fluorescent probe (ERBM) was developed for real-time monitoring of carboxylesterase 1 (CES1) and exhibited excellent ER location in living cell imaging. In addition, ERBM was applied to illustrate the regulation characteristics of CES1 under ER stress and acute liver injury models at the cell and animal level.
ESTHER : Han_2023_Chem.Commun.(Camb)__
PubMedSearch : Han_2023_Chem.Commun.(Camb)__
PubMedID: 36594784

Title : Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment - Kumar_2023_Nat.Commun_14_557
Author(s) : Kumar S , Maniya N , Wang C , Senapati S , Chang HC
Ref : Nat Commun , 14 :557 , 2023
Abstract : Cardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple screening test for better biomarkers than the current lipid and lipoprotein profiles. We propose using a highly atheroprotective subset of HDL with colocalized PON1 (PON1-HDL) for superior cardiovascular risk assessment. However, direct quantification of HDL proteomic subclasses are complicated by the peroxides/antioxidants associated with HDL interfering with redox reactions in enzymatic calorimetric and electrochemical immunoassays. Hence, we developed an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform for quantification of PON1-HDL in plasma within 60 min, with a sub-picomolar limit of detection, 3-4 log dynamic range and without needing sample pretreatment or individual-sample calibration. Using NGEMS, we report our study on human plasma PON1-HDL as a cardiovascular risk marker with AUC~0.99 significantly outperforming others (AUC~0.6-0.8), including cholesterol/triglycerides tests. Validation for a larger cohort can establish PON1-HDL as a biomarker that can potentially reshape cardiovascular landscape.
ESTHER : Kumar_2023_Nat.Commun_14_557
PubMedSearch : Kumar_2023_Nat.Commun_14_557
PubMedID: 36732521

Title : MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain - Gu_2023_Mol.Med.Rep_27_
Author(s) : Gu C , Chen M , Li X , Geng D , Wang C
Ref : Mol Med Rep , 27 : , 2023
Abstract : Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces antiinflammatory and antinociceptive effects. However, the potential mechanism of MAGL in OA pain remains unclear. In the present study, the synovial tissues were removed from OA patients and mice. Immunohistochemical staining and western blotting were used to detect the expression of MAGL. M1 and M2 polarization markers were detected by flow cytometry and western blotting, and the mitophagy levels were detected by the immunofluorescence staining of mitochondrial autophagosomes with lysosomes and western blotting. The OA mice were intraperitoneally injected with MJN110 to inhibit MAGL once a day for a week. Mechanical and thermal pain thresholds were detected by electronic Von Frey and hot plate methods on days 0, 3, 7, 10, 14, 17, 21, and 28. The accumulation of MAGL in the synovial tissues of OA patients and mice promoted the polarization of macrophages towards an M1 phenotype. Pharmacological inhibition and siRNA knockdown of MAGL promoted polarization of M1 macrophages towards an M2 phenotype. MAGL inhibition increased the mechanical and thermal pain thresholds of OA mice and enhanced the mitophagy levels of M1 macrophages. In conclusion, in the present study, it was shown that MAGL regulated synovial macrophage polarization by inhibiting mitophagy in OA.
ESTHER : Gu_2023_Mol.Med.Rep_27_
PubMedSearch : Gu_2023_Mol.Med.Rep_27_
PubMedID: 37144506

Title : DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma - Chang_2023_Cancer.Res__
Author(s) : Chang K , Chen Y , Zhang X , Zhang W , Xu N , Zeng B , Wang Y , Feng T , Dai B , Xu F , Ye D , Wang C
Ref : Cancer Research , : , 2023
Abstract : The KEAP1-NRF2 axis is the principal regulator of cellular responses to oxidative and electrophilic stressors. NRF2 hyperactivation is frequently observed in many types of cancer and promotes cancer initiation, progression, metastasis, and resistance to various therapies. Here, we determined that dipeptidyl peptidase 9 (DPP9) is a regulator of the KEAP1-NRF2 pathway in clear cell renal cell carcinoma (ccRCC). DPP9 was markedly overexpressed at the mRNA and protein levels in ccRCC, and high DPP9 expression levels correlated with advanced tumor stage and poor prognosis in ccRCC patients. Protein affinity purification to identify functional partners of DPP9 revealed that it bound to KEAP1 via a conserved ESGE motif. DPP9 disrupted KEAP1-NRF2 binding by competing with NRF2 for binding to KEAP1 in an enzyme-independent manner. Upregulation of DPP9 led to stabilization of NRF2, driving NRF2-dependent transcription and thereby decreasing cellular reactive oxygen species (ROS) levels. Moreover, DPP9 overexpression suppressed ferroptosis and induced resistance to sorafenib in ccRCC cells, which was largely dependent on the NRF2 transcriptional target SLC7A11. Collectively, these findings indicate that the accumulation of DPP9 results in hyperactivation of the NRF2 pathway to promote tumorigenesis and intrinsic drug resistance in ccRCC.
ESTHER : Chang_2023_Cancer.Res__
PubMedSearch : Chang_2023_Cancer.Res__
PubMedID: 37713596
Gene_locus related to this paper: human-DPP9

Title : Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase\/transferase - Wang_2023_Nat.Commun_14_4795
Author(s) : Wang C , Liu C , Zhu X , Peng Q , Ma Q
Ref : Nat Commun , 14 :4795 , 2023
Abstract : Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the "Ser-His-Asp" catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a "catalytic site tuning" mechanism to expand the mechanistic paradigm of enzyme promiscuity.
ESTHER : Wang_2023_Nat.Commun_14_4795
PubMedSearch : Wang_2023_Nat.Commun_14_4795
PubMedID: 37558668

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

Title : Sitagliptin Extends Lifespan of Caenorhabditis elegans by Inhibiting IIS and Activating DR-like Signaling Pathways - Ye_2023_Gerontology__
Author(s) : Ye Q , Li Y , Wang C , Zheng J , Qiao J , Yang J , Wan QL
Ref : Gerontology , : , 2023
Abstract : INTRODUCTION: The discovery of longevity molecules that delay aging and prolong lifespan has always been a dream of humanity. Sitagliptin phosphate (SIT), an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, is an oral drug commonly used in the treatment of type 2 diabetes (T2D). In addition to being anti-diabetic, previous studies have reported that SIT has shown potential to improve health. However, whether SIT plays a role in the amelioration of aging and the underlying molecular mechanism remain undetermined. METHODS: Caenorhabditis elegans (C. elegans) was used as a model of aging. Lifespan assays were performed with adult-stage worms on NGM plates containing FUDR with or without the specific concentration of SIT. The period of fast body movement, body bending rates and pharyngeal pumping rates were recorded to assess the health-span of C. elegans. Gene expression was confirmed by GFP fluorescence signal of transgenic worms and qPCR. In addition, the intracellular ROS levels were measured using a free radical sensor H2DCF-DA. RESULTS: We found that SIT significantly extended lifespan and health-span of C. elegans. Mechanistically, we found that several age-related pathways and genes were involved in SIT-induced lifespan extension. The transcription factors DAF-16/FOXO, SKN-1/NRF2 and HSF-1 played important roles in SIT-induced longevity. Moreover, our findings illustrated that SIT induced survival benefits by inhibiting the insulin/insulin-like signaling (IIS) pathway and activating the dietary restriction (DR)-related and mitochondrial function-related signaling pathways. CONCLUSION: Our work may provide a theoretical basis for the development of anti-T2D drugs as anti-aging drugs, especially for the treatment of age-related disease in diabetic patients.
ESTHER : Ye_2023_Gerontology__
PubMedSearch : Ye_2023_Gerontology__
PubMedID: 37952525

Title : Visual evaluation of acetylcholinesterase inhibition by an easy-to-operate assay based on N-doped carbon nanozyme with high stability and oxidase-like activity - Zhang_2023_J.Mater.Chem.B__
Author(s) : Zhang M , Wang C , Wang Y , Li F , Zhu D
Ref : J Mater Chem B , : , 2023
Abstract : Acetylcholinesterase (AChE) is the key enzyme associated with neurotransmission, and thus many drugs have been explored for their inhibitory effect on AChE, such as donepezil for Alzheimer's disease and organophosphorus pesticides (OPs). Compared with clinical trials, in vitro screening bioassays for AChE inhibitors are preferable in terms of operability and cost. Herein, we developed an easy-to-operate nanozyme-based colorimetric assay for the evaluation of AChE inhibitory strength with excellent anti-interference ability and low dependence on professional equipment. The metal-free carbon nanozyme NC900 played an important role in the signal output due to its features of efficient oxidase-like activity, excellent water dispersibility, high stability and low color interference. Employing various AChE-targeted or non-targeted pesticides as examples, the as-proposed assay exhibited excellent distinguishing ability for different chemicals. The higher absorption intensity at 652 nm represents a stronger inhibitory effect, as well as blue color. In addition, this method was used to study the influence of pH on the degradation of prodrugs, and the efficiency of mixed pesticides. This work provides a simple and reliable assay to screen AChE inhibitors, which is promising for the preliminary evaluation of a large number of potential candidates.
ESTHER : Zhang_2023_J.Mater.Chem.B__
PubMedSearch : Zhang_2023_J.Mater.Chem.B__
PubMedID: 37067450

Title : Simple and novel icariin-loaded pro-glycymicelles as a functional food: physicochemical characteristics, in vitro biological activities, and in vivo experimental hyperlipidemia prevention evaluations - Cui_2023_Food.Funct__
Author(s) : Cui Q , Wang C , Zhou L , Wei Y , Liu Z , Wu X
Ref : Food Funct , : , 2023
Abstract : A novel functional food for hyperlipidemia named icariin (ICA) pro-glycymicelles (ICA-PGs) using glycyrrhizin as a phytonanomaterial was easily prepared with improved storage, pH, and salt stabilities. ICA-PGs can easily dissolve in water to self-assemble into a clear glycymicelle solution with high ICA encapsulation efficiency. The ICA in ICA-PGs exhibits significantly increased aqueous solubility, faster in vitro release, and higher bioaccessibility than bare ICA. The ICA-PGs exhibited improved in vitro activities including antioxidant, anti-alpha-glucosidase, anti-lipase, and anti-cholesterol esterase activities. The ICA-PG also demonstrated improved antioxidant activity in cells. In vivo evaluation confirmed that the ICA-PG demonstrated a significant protective effect against experimental hyperlipidemia in mice, exhibiting decreasing levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the serum, and restoring the hepatic morphology to the normal state. These results indicated that the ICA-PG could improve in vitro/in vivo profiles of ICA, providing a new concept and a promising functional food for hyperlipidemia.
ESTHER : Cui_2023_Food.Funct__
PubMedSearch : Cui_2023_Food.Funct__
PubMedID: 37853783

Title : Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones - Yi_2023_Plant.Physiol__
Author(s) : Yi F , An G , Song A , Cheng K , Liu J , Wang C , Wu S , Wang P , Zhu J , Liang Z , Chang Y , Chu Z , Cai C , Zhang X , Chen A , Xu J , Burritt DJ , Herrera-Estrella L , Tran LP , Li W , Cai Y
Ref : Plant Physiol , : , 2023
Abstract : Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.
ESTHER : Yi_2023_Plant.Physiol__
PubMedSearch : Yi_2023_Plant.Physiol__
PubMedID: 36718522

Title : Population performance and detoxifying and protective enzyme activities of four thrips species feeding on flowers of Magnolia grandiflora (Ranunculales: Magnolia) - Cao_2023_Pest.Manag.Sci__
Author(s) : Cao Y , Qi G , Jiang F , Meng Y , Wang C , Gu Z , Gao Y , Reitz SR , Li C
Ref : Pest Manag Sci , : , 2023
Abstract : BACKGROUND: Different thrips species can co-occur on the same flowers with different dominance degrees. To accurately evaluate the population performance on different thrips species on Magnolia grandiflora flowers, we investigated the diversity of thrips species and their population dynamics both in the field and laboratory. In addition, the activities of detoxifying and protective enzymes in thrips were also measured. RESULTS: Field investigations revealed that four thrips species (Thrips hawaiiensis, Thrips flavidulus, Frankliniella occidentalis, and Thrips coloratus) were coexisted on M. grandiflora flowers. They were ranked, from highest population density to lowest, as follows: T. hawaiiensis > T. flavidulus > F. occidentalis > T. coloratus. In laboratory investigations, the species were ranked, from fastest developmental rates to slowest, as follows: F. occidentalis > T. hawaiiensis > T. flavidulus > T. coloratus; and from largest population size to smallest, as follows: T. hawaiiensis > F. occidentalis > T. flavidulus > T. coloratus. Biochemistry assays showed that the four species differed in their activities of detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and cytochrome P450) and protective enzymes (superoxide dismutase, peroxidase) in both laboratory and field strains. CONCLUSION: Differences in population performance among these four thrips on M. grandiflora may be related to their activity levels of physiological enzymes. The variations in thrips population performance between the field and the laboratory could be due to differences in environmental conditions. T. hawaiiensis showed a strong host preference for M. grandiflora, and thus it has the potential to be a dangerous pest in horticultural plants. This article is protected by copyright. All rights reserved.
ESTHER : Cao_2023_Pest.Manag.Sci__
PubMedSearch : Cao_2023_Pest.Manag.Sci__
PubMedID: 37085951

Title : Static Binding and Dynamic Transporting-Based Design of Specific Ring-Chain-Ring Acetylcholinesterase Inhibitor: From Galantamine to Natural Product - Zhang_2023_Chemistry__e202203363
Author(s) : Zhang Z , Lv J , Wang Y , Yu H , Guo B , Zhai J , Wang C , Zhao Y , Fan F , Luo W
Ref : Chemistry , :e202203363 , 2023
Abstract : Acetylcholinesterase (AChE) is a key target for the current symptomatic treatment of Alzheimer's disease, and galantamine is a clinical anticholinesterase drug with transiently acting characteristic and good selectivity for AChE. The present theoretical-experimental work improves the drug's residence time without reducing inhibition effect, thus provides crucial breakthrough for modifying the inhibitor of AChE with better-kinetic behavior. The static binding and dynamic delivery properties acquired from atomic view reveal that the galantamine simply occupies catalytic anionic site, and its release from AChE needs only ~ 8.6 kcal/mol. Both of them may cause the short residence time of galantamine. The hotspots and most favorable transport mechanism are identified, and the hydrogen bond and aromatic stacking interactions are observed to play crucial roles for galantamine binding and release in AChE. The typical peripheral anionic site arisen at the delivery process would provide another key occupation to enhance the anti-release ability for inhibitors. The compound with "specific-ring-chain-ring" framework with detail beneficial modify scheme is summarized, which may improve the residence time of inhibitor in AChE. The thermodynamic and dynamic properties of galantamine derivatives are also studied. Based on dictamnine, a natural alkaloid, two novel eligible derivatives are designed, synthesized and evaluated, which verifies our prediction. Multiple computational approaches and experiment combination probably provide a train of thought from static and dynamic view to modify or design appropriate inhibitor on the basis of specific binding and transportation features.
ESTHER : Zhang_2023_Chemistry__e202203363
PubMedSearch : Zhang_2023_Chemistry__e202203363
PubMedID: 36826395

Title : PGC 1alpha-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure - Jin_2023_Biol.Pharm.Bull_46_563
Author(s) : Jin Q , Zhang Y , Cui Y , Shi M , Shi J , Zhu S , Shi T , Zhang R , Chen X , Zong X , Wang C , Li L
Ref : Biol Pharm Bull , 46 :563 , 2023
Abstract : This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and whether PGC-1alpha regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection. Then, liver damage was biochemically evaluated, and acetylcholinesterase (AChE) activity was also determined. Transmission electron microscopy (TEM) was performed to examine liver mitochondrial damage, and high-resolution respirometry was carried out for assessing mitochondrial respiration function. In addition, complex I-IV levels were quantitatively evaluated in isolated liver mitochondria by enzyme-linked immunosorbent assay (ELISA). PGC-1alpha levels were detected with a Jess capillary-based immunoassay device. Finally, oxidative stress was analyzed by quantifying superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and reactive oxygen species (ROS) levels. Repeated low-level soman exposure did not alter AChE activity, while increasing morphological damage of liver mitochondria and liver enzyme levels in rat homogenates. Complex I, II and I + II activities were 2.33, 4.95, and 5.22 times lower after treatment compared with the control group, respectively. Among complexes I-IV, I-III decreased significantly (p < 0.05), and PGC-1alpha levels were 1.82 times lower after soman exposure than in the control group. Subacute soman exposure significantly increased mitochondrial ROS production, which may cause oxidate stress. These findings indicated dysregulated mitochondrial energy metabolism involves PGC-1alpha protein expression imbalance, revealing non-cholinergic mechanisms for soman toxicity.
ESTHER : Jin_2023_Biol.Pharm.Bull_46_563
PubMedSearch : Jin_2023_Biol.Pharm.Bull_46_563
PubMedID: 37005300

Title : Study of Huperzine A derivatives with extended protection against soman intoxication - Cui_2023_Toxicol.Appl.Pharmacol__116646
Author(s) : Cui Y , Chen X , Shi J , Jin Q , Zhang R , Shi T , Wang C , Li L
Ref : Toxicol Appl Pharmacol , :116646 , 2023
Abstract : Pre-administration of huperzine A (Hup A) was validated to prevent poisoning from exposure to nerve agents (NAs) by reversibly inhibiting acetylcholinesterase (AChE). However, like the currently commonly used reversible inhibitors, Hup A has a short half-life and is unable to produce a long-term preventative effect. To extend the protective time of Hup A against NAs, 42 derivatives with a CN bond were designed based on the structure of Hup A in this study. All designed derivatives showed good binding capability with AChE via molecular docking. Six compounds (H3, H4, H11, H14, H16, and H25) with representative structures were selected for synthesis by Schiff base reaction, and their structures were stable. The modified Ellman's method showed the six compounds concentration-dependently inhibited AChE, and the half maximal inhibitory concentration (IC(50)) were higher than that of Hup A. Pretreatment of AChE with the derivatives significantly increased the IC(50) of soman. In vivo experiments demonstrated H3, H4, H14, H16, and H25 had longer protective capacities against 1 x LD(95) soman-induced death in mice than Hup A. The 12 h protective index showed that the protective ratios of H3, H4, H14 and H16 were 2.31, 1.85, 2.23 and 1.99 respectively, better than that of Hup A. The extended protection of the derivatives against soman may be explained by their transformation to Hup A in vivo. Furthermore, all six compounds showed lower acute oral toxicity than Hup A. Overall, our study provided an optional strategy to acquire pretreatment agents for NAs with extended action and low toxicity.
ESTHER : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedSearch : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedID: 37517785

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

Title : Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from Euphorbia fischeriana - Zhao_2022_Org.Biomol.Chem__
Author(s) : Zhao WY , Sun CP , Chang YB , Wang WY , Yan JK , Lv X , Wang C , Ma XC
Ref : Org Biomol Chem , : , 2022
Abstract : Biseuphoids A (1) and B (2), two unprecedented ent-abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from Euphorbia fischeriana, along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC(50) values of 8.17 and 5.61 microM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472.
ESTHER : Zhao_2022_Org.Biomol.Chem__
PubMedSearch : Zhao_2022_Org.Biomol.Chem__
PubMedID: 35266497

Title : FumDSB can alleviate the inflammatory response induced by fumonisin B(1) in growing pigs - Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
Author(s) : Liu Q , Huang L , Cui Z , Qiao B , Li F , Wang C
Ref : Food Additives & Contaminants Part A Chem Anal Control Expo Risk Assess , :1 , 2022
Abstract : Fumonisin B(1) (FB(1)) has the highest natural contamination rate among all fumonisin analogs and can inhibit food intake and weight gain of pigs. Under laboratory conditions, carboxylesterase FumDSB has a high FB(1) degradation rate and excellent pH and thermal stability. The present study sought to estimate the effects of FumDSB on growing pigs from the perspective of a brain-intestinal axis. Twenty-four growing pigs of similar weight were divided into Control, FB(1) (5mg FB(1)/kg feed), and FumDSB (5mg FB(1)/kg and 0.1% FumDSB in the feed) groups. After 42 days of feeding, hypothalamus and jejunum samples were collected for quantitative real-time fluorescence, western blotting, and immunohistochemistry. The results showed that FB(1) consumption can destruct the tissue structure of hypothalamus and jejunum, affect the expression and distribution of several appetite-related neuropeptides and inflammatory cytokines, thereby inducing neuroinflammatory responses and affecting food intake and weight gain. However, these anorexia effects and inflammatory responses are alleviated when FumDSB is added to the feed. In short, FumDSB can alleviate the inflammatory response induced by FB(1) in growing pigs.
ESTHER : Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
PubMedSearch : Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
PubMedID: 35858108
Gene_locus related to this paper: sphmc-FumD , 9sphn-a0a101vlk1

Title : Transcriptomic and metabolomic analyses reveal the antifungal mechanism of the compound phenazine-1-carboxamide on Rhizoctonia solani AG1IA - Zhang_2022_Front.Plant.Sci_13_1041733
Author(s) : Zhang Y , Li Q , Wang C , Liu S
Ref : Front Plant Sci , 13 :1041733 , 2022
Abstract : To explore the molecular mechanisms of the antifungal compound phenazine-1-carboxamide (PCN) inhibits Rhizoctonia solani and discover potential targets of action, we performed an integrated analysis of transcriptome and metabolome in R. solani mycelium by whether PCN treating or not. A total of 511 differentially expressed genes (DEGs) were identified between the PCN treatment and control groups. The fluorescence-based quantitative PCR (qPCR) got the accordant results of the gene expression trends for ten randomly selected DEGs. The Gene Ontology (GO) enrichment analysis revealed that fatty acid metabolic process, fatty acid oxidation, and lipid oxidation were among the most enriched in the biological process category, while integral component of membrane, plasma membrane, and extracellular region were among the most enriched in the cellular component category and oxidoreductase activity, cofactor binding, and coenzyme binding were among the most enriched in the molecular function category. KEGG enrichment analysis revealed the most prominently enriched metabolic pathways included ATP-binding cassette (ABC) transporters, nitrogen metabolism, aminobenzoate degradation. The DEGs related functions of cellular structures, cell membrane functions, cellular nutrition, vacuole-mitochondrion membrane contact site and ATPase activity, pH, anti-oxidation, were downregulated. A total of 466 differential metabolites were found between the PCN treatment and control groups after PCN treatment. KEGG enrichment found purine, arachidonic acid, and phenylpropanoid biosynthesis pathways were mainly affected. Further results proved PCN decreased the mycelial biomass and protein content of R. solani, and superoxide dismutase (SOD) activity reduced while peroxidase (POD) and cytochrome P450 activities increased. The molecule docking indicted that NADPH nitrite reductase, ATP-binding cassette transporter, alpha/beta hydrolase family domain-containing protein, and NADPH-cytochrome P450 reductase maybe the particular target of PCN. In conclusion, the mechanisms via which PCN inhibits R. solani AG1IA may be related to cell wall damage, cell membrane impairment, intracellular nutrient imbalance, disturbed antioxidant system, and altered intracellular pH, which laid foundation for the further new compound designing to improve antifungal efficacy.
ESTHER : Zhang_2022_Front.Plant.Sci_13_1041733
PubMedSearch : Zhang_2022_Front.Plant.Sci_13_1041733
PubMedID: 36483956

Title : Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) - Li_2022_BMC.Genomics_23_185
Author(s) : Li Z , Wu L , Wang C , Wang Y , He L , Wang Z , Ma X , Bai F , Feng G , Liu J , Jiang Y , Song F
Ref : BMC Genomics , 23 :185 , 2022
Abstract : BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
ESTHER : Li_2022_BMC.Genomics_23_185
PubMedSearch : Li_2022_BMC.Genomics_23_185
PubMedID: 35249536

Title : Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies - Sang_2022_Bioorg.Chem_127_106007
Author(s) : Sang Z , Bai P , Ban Y , Wang K , Wu A , Mi J , Hu J , Xu R , Zhu G , Wang J , Zhang J , Wang C , Tan Z , Tang L
Ref : Bioorg Chem , 127 :106007 , 2022
Abstract : Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy. Herein, a series of novel donepezil-chalone-rivastigmine hybrids was rationally designed and synthesized by fusing donepezil, chalone and rivastigmine. The in vitro bioactivity results displayed that compound 10c was a reversible huAChE (IC(50) = 0.87 microM) and huBuChE (IC(50) = 3.3 microM) inhibitor. It also presented significant anti-inflammation effects by suppressing the level of IL-6 and TNF-alpha production, and significantly inhibited self-mediated Abeta(1-42) aggregation (60.6%) and huAChE-mediated induced Abeta(1-40) aggregation (46.2%). In addition, 10c showed significant neuroprotective effect on Abeta(1-42)-induced PC12 cell injury and activated UPS pathway in HT22 cells to degrade tau and amyloid precursor protein (APP). Furthermore, compound 10c presented good stabilty in artificial gastrointestinal fluids and liver microsomes in vitro. The pharmacokinetic study showed that compound 10c was rapidly absorbed in rats and distributed in rat brain after intragastric administration. The PET-CT imaging demonstrated that [(11)C]10c could quickly enter the brain and washed out gradually in vivo. Further, compound 10c at a dose of 5 mg/kg improved scopolamine-induced memory impairment, deserving further investigations.
ESTHER : Sang_2022_Bioorg.Chem_127_106007
PubMedSearch : Sang_2022_Bioorg.Chem_127_106007
PubMedID: 35849893

Title : Pseudo toxicity abatement effect of norfloxacin and copper combined exposure on Caenorhabditis elegans - Liu_2022_Chemosphere_287_132019
Author(s) : Liu L , He S , Tang M , Zhang M , Wang C , Wang Z , Sun F , Yan Y , Li H , Lin K
Ref : Chemosphere , 287 :132019 , 2022
Abstract : The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 microM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 microM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 microM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 microM and 1.25 microM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 microM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.
ESTHER : Liu_2022_Chemosphere_287_132019
PubMedSearch : Liu_2022_Chemosphere_287_132019
PubMedID: 34450372

Title : Label-Free and Ultrasensitive Detection of Butyrylcholinesterase and Organophosphorus Pesticides by Mn(II)-Based Electron Spin Resonance Spectroscopy with a Zero Background Signal - Tang_2022_Anal.Chem__
Author(s) : Tang L , Wang C , Tian S , Zhang Z , Yu Y , Song D
Ref : Analytical Chemistry , : , 2022
Abstract : Mn(II)-based electron spin resonance (ESR) spectroscopy was used for detecting butyrylcholinesterase (BChE) and organophosphorus pesticides (OPs). MnO(2) nanosheets were synthesized with manganese chloride and hydrogen peroxide. With the catalysis of BChE, S-butyrylthiocholine iodide (BTCh) was hydrolyzed into thiocholine which has a reducing -SH group. In the presence of thiocholine, MnO(2) nanosheets were broken down and Mn(IV) in MnO(2) nanosheets was reduced into Mn(II). Mn(2+) is a paramagnetic ion and gives a good ESR signal. In contrast, MnO(2) nanosheets have no ESR signal and need not be separated from Mn(2+). Mn(2+) can be determined directly by ESR spectroscopy, and no further sensing probe is needed. ESR spectroscopy based on directly detecting Mn(2+) is much simpler than those using other probes besides MnO(2). The ESR signal of Mn(2+) is proportional to the catalytic activity of BChE. OPs which inhibit the activity of BChE can also be detected by probing the ESR signal of Mn(2+). Since there is no ESR signal of MnO(2) nanosheets, the background signal in the absence of BChE was close to zero. The limit of detection (LOD) of BChE was as low as 0.042 U L(-1). The standard curve for determining the OP paraoxon was established by measuring the inhibition of BChE by paraoxon, and the LOD of paraoxon was found to be 0.076 ng mL(-1). The spiked Chinese cabbage extract samples were analyzed, and the experimental results indicated that the recoveries were from 96.5 to 102.8%. The planted Chinese cabbage was sprayed with the paraoxon solution, and the residue amount of paraoxon in the extract was estimated by the method. The result obtained by the present method was consistent with that obtained by HPLC, which proved the practicability of this new method.
ESTHER : Tang_2022_Anal.Chem__
PubMedSearch : Tang_2022_Anal.Chem__
PubMedID: 36332200

Title : Neurotoxicity and transcriptome changes in embryonic zebrafish induced by halobenzoquinone exposure - Yang_2022_J.Environ.Sci.(China)_117_129
Author(s) : Yang X , Wang C , Yang L , Zheng Q , Liu Q , Wawryk NJP , Li XF
Ref : J Environ Sci (China) , 117 :129 , 2022
Abstract : Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) with a widespread presence in drinking water that exhibit much higher cytotoxicity than regulated DBPs. However, the developmental neurotoxicity of HBQs has not been studied in vivo. In this work, we studied the neurotoxicity of HBQs on zebrafish embryos, after exposure to varying concentrations (0-8 micromol/L) of three HBQs, 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ) for 4 to 120 hr post fertilization (hpf). HBQ exposure significantly decreased the locomotor activity of larvae, accompanied by significant reduction of neurotransmitters (dopamine and gamma-aminobutyric acid) and acetylcholinesterase activity. Furthermore, the expression of genes involved in neuronal morphogenesis (gfap, alpha1-tubulin, mbp, and syn-2alpha) were downregulated by 4.4-, 5.2-, 3.0-, and 4.5-fold in the 5 micromol/L 2,5-DCBQ group and 2.0-, 1.6-, 2.1-, and 2.3-fold in the 5 micromol/L 2,5-DBBQ group, respectively. Transcriptomic analysis revealed that HBQ exposure affected the signaling pathways of neural development. This study demonstrates the significant neurotoxicity of HBQs in embryonic zebrafish and provides molecular evidence for understanding the potential mechanisms of HBQ neurotoxicity.
ESTHER : Yang_2022_J.Environ.Sci.(China)_117_129
PubMedSearch : Yang_2022_J.Environ.Sci.(China)_117_129
PubMedID: 35725065

Title : Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020 - Ma_2022_Front.Public.Health_10_901485
Author(s) : Ma C , Wei D , Liu P , Fan K , Nie L , Song Y , Wang M , Wang L , Xu Q , Wang J , Shi J , Geng J , Zhao M , Jia Z , Huan C , Huo W , Wang C , Mao Z , Huang S , Zeng X
Ref : Front Public Health , 10 :901485 , 2022
Abstract : BACKGROUND: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. METHODS: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. RESULTS: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). CONCLUSION: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management.
ESTHER : Ma_2022_Front.Public.Health_10_901485
PubMedSearch : Ma_2022_Front.Public.Health_10_901485
PubMedID: 35757605

Title : Chlorphoxim induces neurotoxicity in zebrafish embryo through activation of oxidative stress - Xiong_2022_Environ.Toxicol__
Author(s) : Xiong Y , Wang C , Dong M , Li M , Hu C , Xu X
Ref : Environ Toxicol , : , 2022
Abstract : It is known that chlorphoxim is a broad-spectrum and high-effective pesticide. With the wide use in agricultural practice, chlorphoxim residue is also frequently detected in water, but its potential toxicity to aquatic life is still unclear. In this study, zebrafish is used as a model to detect the toxicity of chlorphoxim. Our results showed that exposure of high concentration of chlorphoxim at 96 h post-fertilization (hpf) resulted in a high mortality and pericardium edema rate, a low hatchability rate and heart rate. The nervous system damage, swimming behavior alteration and acetylcholinesterase (AChE) inhibition were measured in zebrafish embryos after a 6 days post-fertilization (dpf) of chlorphoxim exposure. The expression of neural-related genes is abnormal in zebrafish embryos. Chlorphoxim exposure significantly increases oxidative stress in zebrafish embryos by inhibiting antioxidant enzyme (SOD and CAT) and activating reactive oxygen species (ROS). As expected, chlorphoxim exposure induces apoptosis by enhancing the expression of apoptotic genes (Bax, Bcl2, and p53). Astaxanthin (ATX), an effective antioxidant, was found to be able to rescue the neurotoxicity of chlorphoxim through relieving oxidative stress and apoptosis. Altogether, the results showed that chlorphoxim exposure led to severe neurotoxicity to zebrafish embryos, which was contributed to a more comprehensive understanding of the safety use of the organophosphorus pesticide.
ESTHER : Xiong_2022_Environ.Toxicol__
PubMedSearch : Xiong_2022_Environ.Toxicol__
PubMedID: 36331003

Title : Effects of ABCG1 knockout on proteomic composition of HDL in mice on a chow diet and a high-fat diet - Wu_2022_Proteomics__e2100028
Author(s) : Wu Y , Chen L , Xie Z , Wang C , Zhang J , Yan X
Ref : Proteomics , :e2100028 , 2022
Abstract : ATP-binding cassette transporter G1 (ABCG1) is a cellular transmembrane protein that transports oxysterol efflux from cells to high-density lipoprotein (HDL) particles in the plasma. Previous studies have demonstrated that an ABCG1 deficiency exerts an antiatherosclerotic function through the effects of oxysterol accumulation in cells to enhance apoptosis and regulate inflammatory processes. However, whether the deficiency of ABCG1 and the corresponding changes in the efflux of oxysterols could take a series of impacts on the proteomic composition of HDL remains unclear. Here, plasma HDL of ABCG1(-/-) mice and their wild-type controls on a normal chow diet (NCD) or a high-fat diet (HFD) were isolated by ultracentrifugation. The proportion of 7-ketocholesterol and the proteomic composition of samples were comparatively analyzed by LC-MS/MS. In NCD-fed mice, lipid metabolism-related protein (arachidonate 12-lipoxygenase) and antioxidative protein (pantetheinase) exhibited increased accumulation, and inflammatory response protein (alpha-1-antitrypsin) was decreased in accumulation in ABCG1(-/-) mice HDL. In HFD-fed mice, fewer proteins were detected than that of NCD-fed mice. The ABCG1(-/-) mice HDL exhibited increased accumulation of lipid metabolism-related proteins (e.g., carboxylesterase 1C, apolipoprotein (apo)C-4) and decreased accumulation of alpha-1-antitrypsin, as well as significantly reduced proportion of 7-ketocholesterol. Additionally, positive correlations were found between 7-ketocholesterol and some essential proteins on HDL, such as alpha-1-antitrypsin, apoA-4, apoB-100, and serum amyloid A (SAA). These results suggest a detrimental impact of oxysterols on HDL composition, which might affect the antiatherosclerotic properties of HDL.
ESTHER : Wu_2022_Proteomics__e2100028
PubMedSearch : Wu_2022_Proteomics__e2100028
PubMedID: 35234362

Title : Pharmacokinetics of HupA-PLGA-NPs of different sizes in the mouse blood and brain determined by LC-MS\/MS - Zhang_2022_Eur.Rev.Med.Pharmacol.Sci_26_1183
Author(s) : Zhang RH , Wang C , Shi T , Chen XJ , Xu JF , Shi M , Li LQ
Ref : Eur Rev Med Pharmacol Sci , 26 :1183 , 2022
Abstract : OBJECTIVE: Huperzine A, which was extracted from a Chinese herb, is a reversible and selective inhibitor of acetylcholinesterase (AChE), which is used as an anti-Alzheimer's drug that exerts evident pretreatment effects against exposure to organophosphate chemical warfare agents or pesticides. The aims of this study were to establish an LC-MS/MS method for the detection of HupA in biological samples and to investigate the pharmacokinetics of HupA polylactic-co-glycolic acid nanoparticles (HupA-PLGA-NPs) with different diameters in mice. MATERIALS AND METHODS: The proposed LC-MS/MS method was established by optimizing the MS conditions and validating the specificity, linear range, lower limit, precision, accuracy, matrix effects, absolute recovery, and sample stability of the method. ICR mice were divided into three treatment groups: the HupA control group, the 46.4-nm HupA-PLGA-NP group and the 208.5-nm HupA-PLGA-NP group. All the mice in the three groups were administered 0.5 mg/kg HupA via the tail vein. The pharmacokinetic parameters in plasma and the brain were detected by LC-MS/MS. Pharmacokinetic parameters were analyzed using PKS pharmacokinetic software, and the relative bioavailability and brain-targeted drug targeting efficiency (DTE) were also calculated. RESULTS: The distributions of HupA-PLGA-NP groups showed marked changes compared with that of HupA in mice in vivo, and the particle size of nanodrugs exerted a significant effect on the pharmacokinetic parameters in mice. The half-life (T1/2) values in plasma of the 46.4- and 208.5-nm HupA-PLGA-NPs were 1.53- and 1.96-fold longer than that of the HupA at the same dose. The bioavailabilities of the two nanoparticles were 1.93- and 2.19-fold higher than that of HupA, respectively. In the brain, the Tmax values of the two HupA-PLGA-NPs of different sizes was 1.25 h, which was clearly longer than that of HupA (0.5 h), and the corresponding T1/2 values were 12.53 h and 8.47 h, which were 1.82- and 1.23-fold higher than that of HupA (6.89 h). In addition, the brain targeting index of the 46.40-nm HupA-PLGA-NPs was 1.48, which revealed an evident brain-targeting effect. CONCLUSIONS: The LC-MS/MS method has the advantages of good specificity, high sensitivity and needing a low sample amount and is economical and particularly suitable for determining the drug content in plasma and brain samples. The NP size is associated with the distribution patterns of nanodrugs. Therefore, a particular NP size can be selected to maximize the pharmacodynamics effects and control the toxicity of nanodrugs.
ESTHER : Zhang_2022_Eur.Rev.Med.Pharmacol.Sci_26_1183
PubMedSearch : Zhang_2022_Eur.Rev.Med.Pharmacol.Sci_26_1183
PubMedID: 35253175

Title : Strigolactone is involved in nitric oxide-enhanced the salt resistance in tomato seedlings - Liu_2022_J.Plant.Res__
Author(s) : Liu H , Li C , Yan M , Zhao Z , Huang P , Wei L , Wu X , Wang C , Liao W
Ref : J Plant Res , : , 2022
Abstract : Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during stress responses. At present, the interaction and mechanism of SLs and NO in tomato salt tolerance remain unclear. In the current study, tomato 'Micro-Tom' was used to study the roles and interactions of SLs and NO in salinity stress tolerance. The results show that 15 microM SLs synthetic analogs GR24 and 10 microM NO donor S-nitrosoglutathione (GSNO) promoted seedling growth under salt stress. TIS108 (an inhibitor of strigolactone synthesis) suppressed the positive roles of NO in tomato growth under salt stress, indicating that endogenous SLs might be involved in NO-induced salt response in tomato seedlings. Meanwhile, under salt stress, GSNO or GR24 treatment induced the increase of endogenous SLs content in tomato seedlings. Moreover, GR24 or GSNO treatment effectively increased the content of chlorophyll, carotenoids and ascorbic acid (ASA), and enhanced the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), glutathione reductase (GR) and cleavage dioxygenase (CCD) enzyme. Additionally, GSNO or GR24 treatment also up-regulated the expression of SLs synthesis genes (SlCCD7, SlCCD8, SlD27 and SlMAX1) and its signal transduction genes (SlD14 and SlMAX2) in tomato seedlings under salt stress. While, a strigolactone synthesis inhibitor TIS108 blocked the increase of endogenous SLs, chlorophyll, carotenoids and ASA content, and antioxidant enzyme, GR, CCD enzyme activity and SLs-related gene expression levels induced by GSNO. Thus, SLs may play an important role in NO-enhanced salinity tolerance in tomato seedlings by increasing photosynthetic pigment content, enhancing antioxidant capacity and improving endogenous SLs synthesis.
ESTHER : Liu_2022_J.Plant.Res__
PubMedSearch : Liu_2022_J.Plant.Res__
PubMedID: 35106650

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

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

Title : CRISPR-Cas12a based fluorescence assay for organophosphorus pesticides in agricultural products - Fu_2022_Food.Chem_387_132919
Author(s) : Fu R , Wang Y , Liu Y , Liu H , Zhao Q , Zhang Y , Wang C , Li Z , Jiao B , He Y
Ref : Food Chem , 387 :132919 , 2022
Abstract : Herein, we propose a sensitive fluorescent assay for organophosphorus pesticides (OPs) detection based on a novel strategy of activating the CRISPR-Cas12a system. Specifically, acetylcholinesterase (AChE) hydrolyzes acetylthiocholine into thiocholine (TCh). Subsequently, TCh induces the degradation of MnO(2) nanosheets and generates sufficient Mn(2+) ions to activate the Mn(2+)-dependent DNAzyme. Then, as the catalytic product of activated DNAzyme, the short DNA strand activates the CRISPR-Cas12a system to cleave the fluorophore-quencher-labeled DNA reporter (FQ) probe effectively; thus, increasing the fluorescence intensity (FI) in the solution. However, in the presence of OPs, the activity of AChE is suppressed, resulting in a decrease in FI. Under optimized conditions, the limits of detection for paraoxon, dichlorvos, and demeton were 270, 406, and 218 pg/mL, respectively. Benefiting from the outstanding MnO(2) nanosheets properties and three rounds of enzymatic signal amplification, the proposed fluorescence assay holds great potential for the detection of OPs in agricultural products.
ESTHER : Fu_2022_Food.Chem_387_132919
PubMedSearch : Fu_2022_Food.Chem_387_132919
PubMedID: 35421656

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

Title : Association between CES1 rs2244613 and the pharmacokinetics and safety of dabigatran: Meta-analysis and quantitative trait loci analysis - Li_2022_Front.Cardiovasc.Med_9_959916
Author(s) : Li H , Zhang Z , Weng H , Qiu Y , Zubiaur P , Zhang Y , Fan G , Yang P , Vuorinen AL , Zuo X , Zhai Z , Wang C
Ref : Front Cardiovasc Med , 9 :959916 , 2022
Abstract : OBJECTIVE: To date, the influence of the carboxylesterase 1 (CES1) rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran remains controversial. Hence, a systematic review was performed to study the association between CES1 rs2244613 genotype and the PKs and safety of dabigatran and CES1 relative expression. METHODS: In addition to the three English databases (Web of Science, PubMed, and Embase), two Chinese databases (CNKI and Wanfang) were thoroughly revised. The mean differences (MD) and corresponding 95% confidence intervals (CI) were applied to evaluate the differences in PKs between the CES1 rs2244613 genotype. Odds ratio (OR) was used to study the risk for bleeding events between the CES1 rs2244613 genotypes. Subsequent expression quantitative trait loci (eQTL) analyses were performed to evaluate genotype-specific expressions in human tissues. RESULTS: Ten studies (n = 2,777) were included. CES1 rs2244613 G allele carriers exhibited significantly lower dabigatran trough concentrations compared to T allele carriers (MD: -8.00 ng/mL; 95% CI: -15.08 to -0.92; p = 0.03). The risk for bleeding events was significantly lower in carriers of the G allele compared to T allele carriers (OR: 0.65; 95% CI: 0.44-0.96; p = 0.03). Subsequent eQTL analysis showed significant genome-wide expressions in two human tissues, whole blood (p = 5.1 x 10(-10)) and liver (p = 6.2 x 10(-43)). CONCLUSION: Our meta-analysis indicated a definite relation between the CES1 rs2244613 genotype and tolerability variations or pharmacokinetic fluctuations. The carriers of T allele showed higher dabigatran concentrations; therefore, they would benefit from a dose reduction. SYSTEMATIC REVIEW REGISTRATION: [], identifier [NPLASY202260027].
ESTHER : Li_2022_Front.Cardiovasc.Med_9_959916
PubMedSearch : Li_2022_Front.Cardiovasc.Med_9_959916
PubMedID: 35990949

Title : Genome-wide analysis of the strigolactone biosynthetic and signaling genes in grapevine and their response to salt and drought stresses - Yu_2022_PeerJ_10_e13551
Author(s) : Yu Y , Xu J , Wang C , Pang Y , Li L , Tang X , Li B , Sun Q
Ref : PeerJ , 10 :e13551 , 2022
Abstract : Strigolactones (SLs) are a novel class of plant hormones that play critical roles in regulating various developmental processes and stress tolerance. Although the SL biosynthetic and signaling genes were already determined in some plants such as Arabidopsis and rice, the information of SL-related genes in grapevine (Vitis vinifera L.) remains largely unknown. In this study, the SL-related genes were identified from the whole grapevine genome, and their expression patterns under salt and drought stresses were determined. The results indicated that the five genes that involved in the SL biosynthesis included one each of the D27, CCD7, CCD8, MAX1 and LBO genes, as well as the three genes that involved in the SL signaling included one each of the D14, MAX2, D53 genes. Phylogenetic analysis suggested that these SL-related proteins are highly conserved among different plant species. Promoter analysis showed that the prevalence of a variety of cis-acting elements associated with hormones and abiotic stress existed in the promoter regions of these SL-related genes. Furthermore, the transcription expression analysis demonstrated that most SL-related genes are involved in the salt and drought stresses response in grapevine. These findings provided valuable information for further investigation and functional analysis of SL biosynthetic and signaling genes in response to salt and drought stresses in grapevine.
ESTHER : Yu_2022_PeerJ_10_e13551
PubMedSearch : Yu_2022_PeerJ_10_e13551
PubMedID: 35712547

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Combined toxicity of chlorpyrifos, abamectin, imidacloprid, and acetamiprid on earthworms (Eisenia fetida) - Teng_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : Teng M , Zhao X , Wang C , Zhou L , Wu X , Wu F
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Mixed pesticides have been broadly used in agriculture. However, assessing the combined effects of pesticides in the environment is essential for potential risk assessment, though the task is far from complete. Median lethal concentrations of pesticides as well as acetylcholinesterase (AChE) levels and cellulose activities were measured in earthworms (Eisenia fetida) individually and jointly exposed to pesticides imidacloprid (IMI), acetamiprid (ACE), chlorpyrifos (CRF), and abamectin (ABM)). A 3:1 mixture of CRF and IMI had additive effects, while a 3:1 mixture of CRF and ACE had synergic effects. The joint effects of ABM with IMI or with ACE were synergistic. As CRF concentration increased, AChE activities were significantly decreased. For high concentrations of IMI, AChE activities under combined CRF and IMI applications were significantly inhibited following increased exposure time. Moreover, the cellulase activities under combined applications of CRF with IMI or with ACE had similar effects. This study provides basic data for scientifically evaluating the environmental risk and safety of combined uses of pesticides.
ESTHER : Teng_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Teng_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35297002

Title : Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor - Zhang_2022_PLoS.One_17_e0266608
Author(s) : Zhang C , Li W , Li X , Wan D , Mack S , Zhang J , Wagner K , Wang C , Tan B , Chen J , Wu CW , Tsuji K , Takeuchi M , Chen Z , Hammock BD , Pinkerton KE , Yang J
Ref : PLoS ONE , 17 :e0266608 , 2022
Abstract : Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.
ESTHER : Zhang_2022_PLoS.One_17_e0266608
PubMedSearch : Zhang_2022_PLoS.One_17_e0266608
PubMedID: 35443010

Title : Activation of cholinergic basal forebrain neurons improved cognitive functions in adult-onset hypothyroid mice - Xu_2022_Biomed.Pharmacother_153_113495
Author(s) : Xu YX , Wang C , Li XD , Guo WL , Liu GY , Zhang HB , Sun Y , Zhu DF , Xu Q
Ref : Biomed Pharmacother , 153 :113495 , 2022
Abstract : Cognitive dysfunction is common in hypothyroid patients, even after undergoing sufficient levothyroxine (LT4) replacement therapy for euthyroid. Our previous studies indicated that cholinergic neurons might contribute to the decline of cognition in adult-onset hypothyroidism. Nevertheless, the role of the cellular and neural control of basal forebrain (BF) cholinergic neurons in hypothyroidism-induced cognitive impairments is unknown. Using transgenic mice that specifically expressed chemogenetic activators in their BF cholinergic neurons, we systematically investigated the role of BF cholinergic neurons in hypothyroidism-induced cognitive dysfunction by the combined approaches of patch clamp electrophysiology, behavioral testing, and immunohistochemistry. The results showed that LT4 treatment in the adult-onset hypothyroid mice reversed only 78 % of the BF cholinergic neurons to their normal values of electrophysiological properties. LT4 monotherapy did not rehabilitate cognitive function in the hypothyroid mice. Chemogenetic selective activation of the BF cholinergic neurons combined with LT4 treatment significantly improved learning and memory functions in the hypothyroid mice. In addition, chemogenetic activation of the cholinergic neurons induced the robust expression of c-Fos protein in the BF, prefrontal cortex (PFC), and hippocampus. This indicated that the BF cholinergic neurons improved learning and memory functions in the hypothyroid mice via the BF-PFC and BF-hippocampus pathways. In the hypothyroid C57BL/6 J mice, combined treatment via LT4 and donepezil, a cholinesterase inhibitor, significantly increased cognitive functions. The results suggested that the BF cholinergic neurons are critical for regulating learning and memory and reveal a novel pathophysiological mechanism for hypothyroidism-induced cognitive impairments.
ESTHER : Xu_2022_Biomed.Pharmacother_153_113495
PubMedSearch : Xu_2022_Biomed.Pharmacother_153_113495
PubMedID: 36076509

Title : LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma - Wang_2022_J.Clin.Lab.Anal__e24824
Author(s) : Wang S , Chen Z , Lv H , Wang C , Wei H , Yu J
Ref : J Clin Lab Anal , :e24824 , 2022
Abstract : BACKGROUND: Although many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear. METHODS: TCGA, GEO, K-M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3. RESULTS: The expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance. CONCLUSIONS: LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD.
ESTHER : Wang_2022_J.Clin.Lab.Anal__e24824
PubMedSearch : Wang_2022_J.Clin.Lab.Anal__e24824
PubMedID: 36572999
Gene_locus related to this paper: human-LIPG

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

Title : Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination - Wang_2022_Curr.Drug.Metab__
Author(s) : Wang D , Zhao T , Zhao S , Chen J , Dou T , Ge G , Wang C , Sun H , Liu K , Meng Q , Wu J
Ref : Curr Drug Metab , : , 2022
Abstract : BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2.
ESTHER : Wang_2022_Curr.Drug.Metab__
PubMedSearch : Wang_2022_Curr.Drug.Metab__
PubMedID: 35114918

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

Title : Design, synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease - Zhu_2022_J.Enzyme.Inhib.Med.Chem_37_1375
Author(s) : Zhu G , Bai P , Wang K , Mi J , Yang J , Hu J , Ban Y , Xu R , Chen R , Wang C , Tang L , Sang Z
Ref : J Enzyme Inhib Med Chem , 37 :1375 , 2022
Abstract : Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC(50) = 0.32, 0.56, 0.54, 0.73, and 0.86 microM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Abeta(1-42) aggregation, and potent neuroprotective effect on Abeta(1-42)-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood-brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [(11)C]5f demonstrated that [(11)C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.
ESTHER : Zhu_2022_J.Enzyme.Inhib.Med.Chem_37_1375
PubMedSearch : Zhu_2022_J.Enzyme.Inhib.Med.Chem_37_1375
PubMedID: 35549612

Title : Improving Effect of the Policosanol from Ericerus pela Wax on Learning and Memory Impairment Caused by Scopolamine in Mice - Sun_2022_Foods_11_
Author(s) : Sun L , Li X , Ma C , He Z , Zhang X , Wang C , Zhao M , Gan J , Feng Y
Ref : Foods , 11 : , 2022
Abstract : Policosanol (PC) is a mixture of long-chain fatty alcohols that exhibits multiple biological activities, such as reducing blood lipid and cholesterol levels, lowering blood pressure, and extenuating liver inflammation. To assess PC's impact on cognitive behavior and function, PC was prepared from Ericerus pela wax using a reduction method and analyzed using gas chromatography (GC). A total of 60 mice were randomly divided into six groups of 10 animals each: control (0.5% CMC-Na solution, i.g.), model (0.5% CMC-Na solution, i.g.), donepezil (3 mg/kg, i.g.), PC low- (2 g/kg, i.g.), medium (4 g/kg, i.g.), and high- (6 g/kg, i.g.) dose groups. All the groups were administered daily for 28 consecutive days. There were four parameters-escape latency, crossings of platform, swimming distance, and time spent in the target quadrant-that were recorded to evaluate the cognitive performance of mice in the Morris Water Maze (MWM). After MWM testing, the levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) that were present in brain tissue were determined using assay kits. The GC data showed that PC consisted of four major components: tetracosanol (14.40%), hexacosanol (48.97%), octacosanol (25.40%), and triacontanol (4.80%). In the MWM test, PC significantly decreased the escape latency (p < 0.05) and increased the crossings of the platform (p < 0.05) and swimming distance (p < 0.05) and time in the target quadrant (p < 0.05) in rodents compared to that in the model group. Moreover, PC increased the levels of ACh, SOD, and GSH; inhibited AChE; and reduced MDA in the brain tissue of the tested animals. This is the first report to evaluate the efficacy of PC for cognitive behavior and function in animals. Our findings demonstrate that PC from E. pela wax is likely to exert an enhancing effect on learning and memory by promoting the cholinergic system and attenuating oxidative stress, which will provide a new insight into the efficacy of PC and expand its application in the food, nutraceutical, and beverage industries.
ESTHER : Sun_2022_Foods_11_
PubMedSearch : Sun_2022_Foods_11_
PubMedID: 35885338

Title : Repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus - Shi_2021_Toxicol.Lett_338_32
Author(s) : Shi M , Deng S , Cui Y , Chen X , Shi T , Song L , Zhang R , Zhang Y , Xu J , Shi J , Wang C , Li L
Ref : Toxicol Lett , 338 :32 , 2021
Abstract : Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4xLD(50) (16.8 microg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 +/- 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 +/- 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure.
ESTHER : Shi_2021_Toxicol.Lett_338_32
PubMedSearch : Shi_2021_Toxicol.Lett_338_32
PubMedID: 33253782

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

Title : Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene - Luo_2021_Front.Pediatr_9_679342
Author(s) : Luo X , Wang C , Lin L , Yuan F , Wang S , Wang Y , Wang A , Wu S , Lan X , Xu Q , Yin R , Cheng H , Zhang Y , Xi J , Zhang J , Sun X , Yan J , Zeng F , Chen Y
Ref : Front Pediatr , 9 :679342 , 2021
Abstract : The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14-15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14-15 deletion could cause CMS.
ESTHER : Luo_2021_Front.Pediatr_9_679342
PubMedSearch : Luo_2021_Front.Pediatr_9_679342
PubMedID: 34912755

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 : Natural soluble epoxide hydrolase inhibitors from Inula britanica and their potential interactions with soluble epoxide hydrolase: Insight from inhibition kinetics and molecular dynamics - Zhao_2021_Chem.Biol.Interact__109571
Author(s) : Zhao WY , Yan JJ , Zhang M , Wang C , Feng L , Lv X , Huo XK , Sun CP , Chen LX , Ma XC
Ref : Chemico-Biological Interactions , :109571 , 2021
Abstract : Soluble epoxide hydrolase (sEH) is a potential drug target to treat inammation and neurodegenerative diseases. In this study, we found that the extract of Inula britanica exhibited significantly inhibitory effects against sEH, therefore, we investigated its phytochemical constituents to obtain seven new compounds together with sixteen known ones (1-20), including two pairs of novel enantiomers, (2S,3S)-britanicafanin A (1a), (2R,3R)-britanicafanin A (1b), (2R,3S)-britanicafanin B (2a), and (2S,3R)-britanicafanin B (2b), and three new lignans britanicafanins C-E (3-5). Their structures were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. All the isolates were evaluated for their inhibitory effects against sEH, compounds 1-3, 5-7, 9, 10, 13, 14, and 17-20 showed significant inhibitory effects against sEH with IC(50) values from 3.56 microM to 26.93 microM. The inhibition kinetics results indicated that compounds 9, 10, 13, and 19 were all uncompetitive inhibitors, and their inhibition constants (K(i)) values were 7.11, 1.99, 4.06, and 8.78 microM, respectively. Their potential interactions were analyzed by molecular docking and molecular dynamics (MD), which suggested that amino acid residues Asp335 and Asn359, especially Gln384, played an important role in the inhibition of compounds 10 and 13 on sEH, and compounds 10 and 13 could be considered as the potential candidates for the development of sEH inhibitors.
ESTHER : Zhao_2021_Chem.Biol.Interact__109571
PubMedSearch : Zhao_2021_Chem.Biol.Interact__109571
PubMedID: 34217688

Title : ANGPTL8 in metabolic homeostasis: more friend than foe? - Guo_2021_Open.Biol_11_210106
Author(s) : Guo C , Wang C , Deng X , He J , Yang L , Yuan G
Ref : Open Biol , 11 :210106 , 2021
Abstract : ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.
ESTHER : Guo_2021_Open.Biol_11_210106
PubMedSearch : Guo_2021_Open.Biol_11_210106
PubMedID: 34582711

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

Title : Dynamic changes in chemical compositions and anti-acetylcholinesterase activity associated with steaming process of stem-leaf saponins of Panax notoginseng - Ma_2021_Biomed.Chromatogr__e5077
Author(s) : Ma C , Guan H , Lin Q , Liu C , Ju Z , Xue Y , Cheng X , Wang C
Ref : Biomedical Chromatography , :e5077 , 2021
Abstract : Stem-leaf saponins (SLS), the total saponins from aerial part of P. notoginseng, are by-products of notoginseng, a famous tradition Chinese medicine. SLS have been used as a health functional food in China, but its mild effects limited clinical applications in diseases. Inspired by steaming of notoginseng to enhance pharmacological activity, a steaming protocol was developed to deal SLS. SLS were steamed at 100 degreesC, 120 degreesC, and 140 degreesC for 1, 2, 3, and 4 h, respectively. The UPLC-Q-TOF and UPLC-MS/MS were applied to analyze the dynamic changes in chemical compositions. Anti-acetylcholinesterase activity of steamed SLS were assessed in vitro by directly determining the metabolic product of acetylcholine, choline. The components of SLS were significantly changed by steaming. Total 117 saponins and aglycones were characterized, and 35 of them were newly generated. The anti-acetylcholinesterase activity of steamed SLS gradually increased with the extension of steamed time and the increase of steamed temperature and reached the maximum after 140 degreesC for 3 h. Furthermore, ginsenosides Rk1 and Rg5, the main components of steamed SLS, showed dose-dependent anti-acetylcholinesterase activities with IC(50) values of 26.88 +/- 0.53 microM and 22.41 +/- 1.31 microM that were only 1.8- and 1.5-fold higher than donepezil, respectively.
ESTHER : Ma_2021_Biomed.Chromatogr__e5077
PubMedSearch : Ma_2021_Biomed.Chromatogr__e5077
PubMedID: 33475178

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 memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis - Du_2021_Eur.J.Med.Chem_223_113678
Author(s) : Du F , Sun W , Morisseau C , Hammock BD , Bao X , Liu Q , Wang C , Zhang T , Yang H , Zhou J , Xiao W , Liu Z , Chen G
Ref : Eur Journal of Medicinal Chemistry , 223 :113678 , 2021
Abstract : Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies. Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281. Among them, compound B401 significantly improved the inhibition potency with human and murine sEH IC(50) values as 0.4 nM and 0.5 nM, respectively. Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis.
ESTHER : Du_2021_Eur.J.Med.Chem_223_113678
PubMedSearch : Du_2021_Eur.J.Med.Chem_223_113678
PubMedID: 34218083

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

Title : Chemoproteomics-Enabled De Novo Discovery of Photoswitchable Carboxylesterase Inhibitors for Optically Controlled Drug Metabolism - Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
Author(s) : Dwyer BG , Wang C , Abegg D , Racioppo B , Qiu N , Zhao Z , Pechalrieu D , Shuster A , Hoch DG , Adibekian A
Ref : Angew Chem Int Ed Engl , 60 :3071 , 2021
Abstract : Herein, we report arylazopyrazole ureas and sulfones as a novel class of photoswitchable serine hydrolase inhibitors and present a chemoproteomic platform for rapid discovery of optically controlled serine hydrolase targets in complex proteomes. Specifically, we identify highly potent and selective photoswitchable inhibitors of the drug-metabolizing enzymes carboxylesterases 1 and 2 and demonstrate their pharmacological application by optically controlling the metabolism of the immunosuppressant drug mycophenolate mofetil. Collectively, this proof-of-concept study provides a first example of photopharmacological tools to optically control drug metabolism by modulating the activity of a metabolizing enzyme. Our arylazopyrazole ureas and sulfones offer synthetically accessible scaffolds that can be expanded to identify specific photoswitchable inhibitors for other serine hydrolases, including lipases, peptidases, and proteases. Our chemoproteomic platform can be applied to other photoswitches and scaffolds to achieve optical control over diverse protein classes.
ESTHER : Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
PubMedSearch : Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
PubMedID: 33035395

Title : Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism - Chen_2021_Chemosphere_286_131866
Author(s) : Chen X , Zheng J , Teng M , Zhang J , Qian L , Duan M , Cheng Y , Zhao W , Wang Z , Wang C
Ref : Chemosphere , 286 :131866 , 2021
Abstract : Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.
ESTHER : Chen_2021_Chemosphere_286_131866
PubMedSearch : Chen_2021_Chemosphere_286_131866
PubMedID: 34391112

Title : Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 - Zhao_2021_Curr.Drug.Metab__
Author(s) : Zhao T , Wang D , Shan Z , Chen J , Dou T , Ge G , Wang C , Meng Q , Sun H , Liu K , Wu J
Ref : Curr Drug Metab , : , 2021
Abstract : BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
ESTHER : Zhao_2021_Curr.Drug.Metab__
PubMedSearch : Zhao_2021_Curr.Drug.Metab__
PubMedID: 33568030

Title : FumDSB Can Reduce the Toxic Effects of Fumonisin B(1) by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs - Liu_2021_Toxins.(Basel)_13_874
Author(s) : Liu Q , Li F , Huang L , Chen W , Li Z , Wang C
Ref : Toxins (Basel) , 13 :874 , 2021
Abstract : Fumonisin B(1) (FB(1)) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB(1) ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB(1) group was supplemented with FB(1) at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB(1) group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB(1) can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB(1). After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB(1) were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB(1) by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.
ESTHER : Liu_2021_Toxins.(Basel)_13_874
PubMedSearch : Liu_2021_Toxins.(Basel)_13_874
PubMedID: 34941712
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : Data for the lipase catalyzed synthesis of cyano-containing multi-substituted indoles - Li_2021_Data.Brief_36_107045
Author(s) : Li F , Xu Y , Wang C , Zhao R , Wang L
Ref : Data Brief , 36 :107045 , 2021
Abstract : The data presented here are related to the research paper entitled "Efficient Synthesis of Cyano-containing Multi-substituted Indoles Catalyzed by Lipase" [1]. In this data article, the lipase catalyzed synthetic procedures for the preparation of multi-substituted indoles and their derivatives were described. In total, 11 compounds were obtained and the optimum pH, reaction time and substrate ratio were screened through this study.
ESTHER : Li_2021_Data.Brief_36_107045
PubMedSearch : Li_2021_Data.Brief_36_107045
PubMedID: 33997196

Title : Microbial halophilic lipases: A review - Qiu_2021_J.Basic.Microbiol__
Author(s) : Qiu J , Han R , Wang C
Ref : J Basic Microbiol , : , 2021
Abstract : Microbial lipases are commercially significant due to their versatile catalytic function of hydrolysis triacylglycerol. Among these, lipases from extremophiles are optimal for industrial application. Halophilic microorganisms living in a high salinity environment, such as the ocean, salt lakes, salt wells, and so on, produce halophilic lipases. In recent decades, many remarkable achievements have been made related to the properties and application of halophilic lipases. This review offers information collected over the last decades on halophilic lipase sources as well as advances in production, factors influencing activity, stability under various conditions, structural characteristics, progress in industrial applications such as food flavor modification, biodiesel production, and waste treatment, to provide theoretical and methodological references for the research in this direction.
ESTHER : Qiu_2021_J.Basic.Microbiol__
PubMedSearch : Qiu_2021_J.Basic.Microbiol__
PubMedID: 34096085

Title : Inhibition of monoacylglycerol lipase restrains proliferation, migration, invasion, tumor growth and induces apoptosis in cervical cancer - Wang_2021_J.Obstet.Gynaecol.Res__
Author(s) : Wang C , Li Z , Zhong L , Chen Y
Ref : J Obstet Gynaecol Res , : , 2021
Abstract : AIM: Cervical cancer is one of common diseases among women. There are limited therapies for patients with metastatic or recurrent cervical cancer. This study sought to explore the role of monoacylglycerol lipase (MAGL), an important metabolic enzyme, in cervical cancer progression. METHODS: In in vitro experiments, MAGL expression was inhibited by si-MAGL or JZL184 in cervical cancer cells. Quantitative real-time polymerase chain reaction and western blotting were performed to measure the expression of target molecules. Proliferation of cervical cancer cells was assessed by CCK-8 and colony formation assays. Apoptosis and cell cycle progression were evaluated by flow cytometry. The migration and invasion were detected by transwell assay. The in vivo tumor growth was detected in nude mice. TUNEL was utilized to observe apoptotic cells in tumor tissues. RESULTS: MAGL was upregulated in cervical cancer tissues and cells. Further, MAGL inhibition suppressed the growth of cervical cancer cells in vitro and in vivo. In addition, apoptosis and G1-phase cell cycle arrest were induced by MAGL knockdown. MAGL silencing-mediated upregulation of Bax and cleaved caspase-3, and downregulation of Bcl-2 was responsible for triggering apoptosis. More importantly, the migration and invasion of cervical cancer cells were restrained by MAGL depletion. CONCLUSIONS: MAGL drives the progression of cervical cancer, which can be a promising candidate to identify effective therapy for cervical cancer.
ESTHER : Wang_2021_J.Obstet.Gynaecol.Res__
PubMedSearch : Wang_2021_J.Obstet.Gynaecol.Res__
PubMedID: 34877750

Title : Susceptibility of Four Species of Aphids in Wheat to Seven Insecticides and Its Relationship to Detoxifying Enzymes - Gong_2020_Front.Physiol_11_623612
Author(s) : Gong P , Chen D , Wang C , Li M , Li X , Zhang Y , Zhu X
Ref : Front Physiol , 11 :623612 , 2020
Abstract : Sitobion avenae (Fabricius), Rhopalosiphum padi (Linnaeus), Schizaphis graminum (Rondani), and Metopolophium dirhodum (Walker) (Hemiptera: Aphididae) are important pests of wheat and other cereals worldwide. In this study, the susceptibilities of four wheat aphid species to seven insecticides were assessed. Furthermore, the activities of carboxylesterase (CarE), glutathione S-transferase (GSTs), and cytochrome P450 monooxygenase (P450s) were determined in imidacloprid treated and untreated aphids. The results showed that the susceptibilities of four wheat aphid species to tested insecticides are different and M. dirhodum has shown higher tolerance to most insecticides. Relatively higher CarE and GST activities were observed in M. dirhodum, and P450s activities increased significantly in response to imidacloprid treatment. Moreover, susceptibility to imidacloprid were increased by the oxidase inhibitor piperonyl butoxide in M. dirhodum (20-fold). The results we have obtained imply that P450s may play an important role in imidacloprid metabolic process in M. dirhodum. We suggest that a highly species-specific approach is essential for managing M. dirhodum.
ESTHER : Gong_2020_Front.Physiol_11_623612
PubMedSearch : Gong_2020_Front.Physiol_11_623612
PubMedID: 33536942

Title : Nose-to-brain delivery of drug nanocrystals by using Ca(2+) responsive deacetylated gellan gum based in situ-nanogel - Huang_2020_Int.J.Pharm__120182
Author(s) : Huang G , Xie J , Shuai S , Wei S , Chen Y , Guan Z , Zheng Q , Yue P , Wang C
Ref : Int J Pharm , :120182 , 2020
Abstract : The objective of this study is to use a carbohydrate polymer deacetylated gellan gum (DGG) as matrix to design nanocrystals based intranasal in situ gel (IG) for nose-to -brain delivery of drug. The harmine nanocrystals (HAR-NC) as model drug were prepared by coupling homogenization and spray-drying technology. The HAR-NC was redispersed in the(DGG)solutions and formed the ionic-triggered harmine nanocrystals based in situ gel(HAR-NC-IG). The crystal state of HAR remained unchanged during the homogenization and spray-drying. And the HAR-NC-IG with 0.5% DGG exhibited excellent in situ-gelation ability, water retention property and in vitro release behavior. The bioavailability in brain of intranasal HAR-NC-IG were 25-fold higher than that of oral HAR-NC, which could be attributed to nanosizing effect of HAR-NC and bioadhesive property of DGG triggered by nasal fluid. And the HAR-NC-IG could significantly inhibit the expression of acetylcholinesterase (AchE) and increase the content of acetylcholin (ACh) in brain compared with those of reference formulations (p <0.01). The DGG based nanocrystals-in situ gel was a promising carrier for nose-to-brain delivery of poorly soluble drug, which could prolong the residence time and improve the bioavailability of poorly soluble drugs in brain.
ESTHER : Huang_2020_Int.J.Pharm__120182
PubMedSearch : Huang_2020_Int.J.Pharm__120182
PubMedID: 33346126

Title : Design, synthesis and biological evaluation of novel O-carbamoyl ferulamide derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease - Sang_2020_Eur.J.Med.Chem_194_112265
Author(s) : Sang Z , Wang K , Bai P , Wu A , Shi J , Liu W , Zhu G , Wang Y , Lan Y , Chen Z , Zhao Y , Qiao Z , Wang C , Tan Z
Ref : Eur Journal of Medicinal Chemistry , 194 :112265 , 2020
Abstract : A novel series of O-carbamoyl ferulamide derivatives were designed by multitarget-directed ligands (MTDLs) strategy, the derivatives were synthesized and evaluated to treat Alzheimer's disease (AD). In vitro biological evaluation demonstrated that compound 4f was the best pseudo-irreversible hBChE (human butyrylcholinesterase) inhibitor with an IC50 value of 0.97 muM 4f was a potent selective MAO-B (monoamine oxidase-B) inhibitor (IC50 = 5.3 muM), and could inhibit (58.2%) and disaggregate (43.3%) self-mediated Abeta aggregation. 4f also could reduce the levels of pathological tau and APP clearance, and displayed a wide safe range hepatotoxicity on LO2 cells. The in vivo studies revealed that 4f exhibited fascinating dyskinesia recovery rate and response efficiency on AlCl3-mediated zebrafish, and demonstrated significant protective effect on vascular injury caused by Abeta1-40. PET-CT imaging demonstrated that [(11)C]4f exhibited high BBB penetration (especially could reach to hippocampus and striatum of brain) and had a fast brain uptake after intravenous bolus injection. Furthermore, compound 4f could improve scopolamine-induced cognitive impairment. Further, the metabolism in vitro of 4f was also investigated, and presented 3 metabolites in rat liver microsome metabolism, 4 metabolites in human liver microsome, and 4 metabolites in rat intestinal flora, providing previous data for the preclinical study. Therefore, these results implied that compound 4f was an advanced multi-function agent and deserved further preclinical study against mild-to-serve Alzheimer's disease.
ESTHER : Sang_2020_Eur.J.Med.Chem_194_112265
PubMedSearch : Sang_2020_Eur.J.Med.Chem_194_112265
PubMedID: 32240904

Title : Development of a whole-cell biocatalyst for diisobutyl phthalate degradation by functional display of a carboxylesterase on the surface of Escherichia coli - Ding_2020_Microb.Cell.Fact_19_114
Author(s) : Ding J , Zhou Y , Wang C , Peng Z , Mu Y , Tang X , Huang Z
Ref : Microb Cell Fact , 19 :114 , 2020
Abstract : BACKGROUND: Phthalic acid esters (PAEs) are widely used as plasticizers or additives during the industrial manufacturing of plastic products. PAEs have been detected in both aquatic and terrestrial environments due to their overuse. Exposure of PAEs results in human health concerns and environmental pollution. Diisobutyl phthalate is one of the main plasticizers in PAEs. Cell surface display of recombinant proteins has become a powerful tool for biotechnology applications. In this current study, a carboxylesterase was displayed on the surface of Escherichia coli cells, for use as whole-cell biocatalyst in diisobutyl phthalate biodegradation. RESULTS: A carboxylesterase-encoding gene (carEW) identified from Bacillus sp. K91, was fused to the N-terminal of ice nucleation protein (inpn) anchor from Pseudomonas syringae and gfp gene, and the fused protein was then cloned into pET-28a(+) vector and was expressed in Escherichia coli BL21(DE3) cells. The surface localization of INPN-CarEW/or INPN-CarEW-GFP fusion protein was confirmed by SDS-PAGE, western blot, proteinase accessibility assay, and green fluorescence measurement. The catalytic activity of the constructed E. coli surface-displayed cells was determined. The cell-surface-displayed CarEW displayed optimal temperature of 45 degrees C and optimal pH of 9.0, using p-NPC2 as substrate. In addition, the whole cell biocatalyst retained ~ 100% and ~ 200% of its original activity per OD600 over a period of 23 days at 45 degrees C and one month at 4 degrees C, exhibiting the better stability than free CarEW. Furthermore, approximately 1.5 mg/ml of DiBP was degraded by 10 U of surface-displayed CarEW cells in 120 min. CONCLUSIONS: This work provides a promising strategy of cost-efficient biodegradation of diisobutyl phthalate for environmental bioremediation by displaying CarEW on the surface of E. coli cells. This approach might also provide a reference in treatment of other different kinds of environmental pollutants by displaying the enzyme of interest on the cell surface of a harmless microorganism.
ESTHER : Ding_2020_Microb.Cell.Fact_19_114
PubMedSearch : Ding_2020_Microb.Cell.Fact_19_114
PubMedID: 32471417
Gene_locus related to this paper: bacsu-pnbae

Title : Eupholides A-H, abietane diterpenoids from the roots of Euphorbia fischeriana, and their bioactivities - Li_2020_Phytochemistry_183_112593
Author(s) : Li DW , Deng XP , He X , Han XY , Ma YF , Huang HL , Yu ZL , Feng L , Wang C , Ma XC
Ref : Phytochemistry , 183 :112593 , 2020
Abstract : The roots of Euphorbia fischeriana known as "Langdu" in traditional Chinese medicine have been used for the treatment of tuberculosis in China. Through a bioactive phytochemical investigation of the roots of E. fischeriana, 15 diterpenoids were obtained by various chromatographic techniques. On the basis of wide spectroscopic data, including NMR, UV, IR, HR-ESI-MS, ECD and X-ray crystallography, all of the isolated compounds were elucidated to be ent-abietane diterpenoid analogs, including undescribed eupholides A-H and seven known diterpenoids. In the bioassay for anti-tuberculosis, eupholides F-H moderately inhibited the proliferation of Mycobacterium tuberculosis H37Ra, with the MIC determined to be 50 M. Furthermore, eupholides G, ent-11alpha-hydroxyabieta-8(14), 13(15)-dien-16,12alpha-olide, and jolkinolide F significantly inhibited the lyase activity of human carboxylesterase 2 (HCE 2), with IC(50) values of 7.3, 150, and 34.5 nM, respectively.
ESTHER : Li_2020_Phytochemistry_183_112593
PubMedSearch : Li_2020_Phytochemistry_183_112593
PubMedID: 33341664

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

Title : 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 : Effect of Bariatric Surgery on Serum Enzyme Status in Obese Patients - Guan_2020_Obes.Surg__
Author(s) : Guan B , Chen Y , Chong TH , Peng J , Mak TK , Wang C , Yang J
Ref : Obes Surg , : , 2020
Abstract : BACKGROUND: Scarce data exists about serum enzyme in bariatric patients. We attempted to evaluate serum enzyme status in patients receiving Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and to identify related predictors. METHODS: We retrospectively reviewed the patients receiving RYGB and SG in our center from January 2013 to January 2018. Anthropometric data and serum enzyme data were collected preoperatively and 6 and 12 months postoperatively. RESULTS: Five hundred patients (201 RYGB, 299 SG) were included. Serum enzyme abnormalities were common preoperatively, with 50.8% for elevated alanine aminotransferase (ALT), 33.0% for elevated aspartate aminotransferase (AST), 36.6% for elevated gamma-glutamyltranspeptidase (gamma-GT), 17.6% for elevated creatine kinase (CK), 15.2% for elevated lactic dehydrogenase (LDH), 9.0% for elevated adenosine deaminase (ADA), 6.2% for elevated hydroxybutyrate dehydrogenase (HBDH), and 8.4% for decreased superoxide dismutase (SOD). After RYGB and SG, the prevalence of serum ALT, AST, gamma-GT, LDH, and HBDH abnormalities reduced. The levels of ALT, AST, gamma-GT, ADA, cholinesterase (CHE), LDH, CK, and HBDH reduced significantly, while amylase and SOD levels increased. Age and preoperative gamma-GT level were independent predictors of ALT, AST, gamma-GT, and LDH change 1 year postoperatively. Preoperative ALT, AST, ALP, LDH, and HBDH levels could predict postoperative change, respectively. Gender and surgical procedure could predict postoperative ALP change. CONCLUSION: Serum enzyme abnormalities are common in bariatric surgery candidates, with reduced prevalence of abnormalities postoperatively. RYGB and SG are related with reduced ALT, AST, gamma-GT, ADA, CHE, LDH, CK, and HBDH levels, as well as increased amylase and SOD levels.
ESTHER : Guan_2020_Obes.Surg__
PubMedSearch : Guan_2020_Obes.Surg__
PubMedID: 32180113

Title : A Bioluminescent Probe for Simultaneously Imaging Esterase and Histone Deacetylase Activity in a Tumor - Wang_2020_Anal.Chem_92_15275
Author(s) : Wang C , Du W , Zhang T , Liang G
Ref : Analytical Chemistry , 92 :15275 , 2020
Abstract : The monitoring of esterase (CES) and histone deacetylase (HDAC) activity in living cells has great potential for rapid diagnosis of malignant tumors. At present, using one bioluminescence (BL) probe to simultaneously detect (or image) these two enzymes' activity in tumors has not been reported. Herein, a bioluminescence "turn-on" probe AcAH-Luc (6-acetamidohexanoic acid-d-luciferin) was rationally designed for simultaneously imaging CES and HDAC activity with excellent sensitivity and selectivity. AcAH-Luc was successfully applied in vitro to selectively detect CES and HDAC6, a subtype of HDAC, at a linear concentration range of 0-100 and 0-120 nM with limits of detection (LODs) of 0.495 and 1.14 nM, respectively. In vivo results indicated that about 1/2 and 1/3 of the "turn-on" BL signal of AcAH-Luc was contributed by CES and HDAC activity in the tumors, respectively. We envision that AcAH-Luc might be applied to simultaneously measure (and image) CES and HDAC activity in the clinic for assisting with the precise diagnosis of malignant tumors in the near future.
ESTHER : Wang_2020_Anal.Chem_92_15275
PubMedSearch : Wang_2020_Anal.Chem_92_15275
PubMedID: 33170646

Title : Endothelial Lipase Exerts its Anti-Atherogenic Effect through Increased Catabolism of beta-VLDLs - Yan_2020_J.Atheroscler.Thromb__
Author(s) : Yan H , Niimi M , Wang C , Chen Y , Zhou H , Matsuhisa F , Nishijima K , Kitajima S , Zhang B , Yokomichi H , Nakajima K , Murakami M , Zhang J , Chen YE , Fan J
Ref : J Atheroscler Thromb , : , 2020
Abstract : AIM: Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect. METHODS: To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tg rabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis. RESULTS: With Tg and non-Tg rabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tg rabbits. Moreover, Tg rabbits exhibited faster clearance of DiI-labeled beta-VLDLs than non-Tg rabbits. CONCLUSION: The results of our study suggest that the enhancement of beta-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tg rabbits.
ESTHER : Yan_2020_J.Atheroscler.Thromb__
PubMedSearch : Yan_2020_J.Atheroscler.Thromb__
PubMedID: 32448826

Title : Transcriptome analysis of Spodoptera litura reveals the molecular mechanism to pyrethroids resistance - Xu_2020_Pestic.Biochem.Physiol_169_104649
Author(s) : Xu L , Mei Y , Liu R , Chen X , Li D , Wang C
Ref : Pestic Biochem Physiol , 169 :104649 , 2020
Abstract : Spodoptera litura is a destructive agricultural pest and has evolved resistance to multiple insecticides, especially pyrethroids. At present, the resistance mechanism to pyrethroids remains unclear. Four field-collected populations, namely CZ, LF, NJ and JD, were identified to have high resistance to pyrethroids comparing to pyrethroid-susceptible population (GX), with resistant ratio ranging from 11.5- to 9123.5-fold. To characterize pyrethroid resistance mechanism, the transcriptomes between two pyrethroid-resistant (LF and NJ) and a pyrethroid-susceptible (GX) populations were compared by RNA-sequencing. Results showed that multiple differentially expressed genes were enriched in metabolism-related GO terms and KEGG pathways. 35 up-regulated metabolism-related unigenes were selected to verify by qRT-PCR and 15 unigenes, including 4 cytochrome P450s (P450s), 5 glutathione S-transferase (GSTs), 1 UDP-glycosyltransferase (UGT), 4 carboxylesterases (COEs) and 1 and ATP-binding cassette transporters (ABC), were all up-regulated in the four pyrethroid-resistant populations. The expression levels of CYP3 and GST3, which were annotated as CYP6A13 and GSTE1, respectively, showed positive correlation with their pyrethroid resistance levels among the four pyrethroid-resistant populations. While the expression levels of CYP5, CYP12, COE4 and ABC5 showed good correlation with their pyrethroid resistance levels in at least three populations. UGT5 had the highest expression level among the tested UGT genes in the four pyrethroid-resistant populations. RNAi mediated silencing of CYP6 increased the cumulative mortality treated by beta cypermethrin and cyhalothrin significantly, while silencing of GST3 increased the cumulative mortality treated by fenvalerate significantly. CYP3, CYP5, CYP6, CYP12, GST3, COE4, UGT5 and ABC5 play important roles in pyrethroid resistance among the four pyrethroid-resistant populations. Our work provides a valuable clue for further study of pyrethroid resistance mechanisms in S. litura.
ESTHER : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedSearch : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedID: 32828367

Title : Efficient synthesis of cyano-containing multi-substituted indoles catalyzed by lipase - Li_2020_Bioorg.Chem_107_104583
Author(s) : Li F , Xu Y , Wang C , Zhao R , Wang L
Ref : Bioorg Chem , 107 :104583 , 2020
Abstract : BACKGROUND: Indoles are important bioactive compounds that have been extensively studied in organic chemistry. In this work, a green and efficient process for the synthesis of Indoles from 1,3-diketones with fumaronitrile was developed. RESULTS: Under optimal conditions (1,3-diketones (0.5 mmol), fumaronitrile (1 mmol), water (2 ml), lipase (15 mg), 30 degreesC, 24 h), high yields and satisfactory regioselectivity of cyano-containing multi-substituted indoles could be obtained when CRL (C. rugosa lipase) was used as the catalyst. CONCLUSION: This enzymatic method demonstrates the great potential for the synthesis of indoles and extends the application of enzyme in organic synthesis.
ESTHER : Li_2020_Bioorg.Chem_107_104583
PubMedSearch : Li_2020_Bioorg.Chem_107_104583
PubMedID: 33421956

Title : A Dual-Protein Cascade Reaction for the Regioselective Synthesis of Quinoxalines - Li_2020_Org.Lett__
Author(s) : Li F , Tang X , Xu Y , Wang C , Wang Z , Li Z , Wang L
Ref : Org Lett , : , 2020
Abstract : In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis.
ESTHER : Li_2020_Org.Lett__
PubMedSearch : Li_2020_Org.Lett__
PubMedID: 32337998

Title : Toxicity assessment of municipal sewage treatment plant effluent by an integrated biomarker response in the liver of crucian carp (Carassius auratus) - Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
Author(s) : Chang T , Wei B , Wang Q , He Y , Wang C
Ref : Environ Sci Pollut Res Int , 27 :7280 , 2020
Abstract : In this study, crucian carp (Carassius auratus) was exposed to the increasing concentrations of municipal sewage treatment plant effluent (MSTPE) for 15 days, and the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE), together with the contents of malondialdehyde (MDA) and glutathione (GSH) in the liver of C. auratus were investigated. Moreover, the integrated biomarker response (IBR) approach was applied to assess the adverse effects of MSTPE in freshwater. The aim of the study was to provide an effective biological indicator for evaluating the toxicity effects and ecological risks of MSTPE in the freshwater environment quantitatively. Results showed that MSTPE could cause oxidative damage to the liver of C. auratus, which reflected through the increasing MDA content over the exposure period. MSTPE also led to the biochemical responses of antioxidant defense in C. auratus liver, such as the enhancement of SOD, CAT, and GPx activities, as well as the inhibition of AChE activity and GSH content. It was found that MDA, SOD, GPx, and GSH could be used as the biomarkers for reflecting the adverse effects of MSTPE in the receiving freshwater on the 12th day of exposure. A significant increase of IBR values was observed as the increasing concentration of MSTPE, and the IBR values presented a significant positive correlation (r = 0.891, P < 0.05) with the increasing concentrations of MSTPE, indicating that IBR approach is a promising tool for assessing the toxicity effects of MSTPE in environmental freshwater.
ESTHER : Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
PubMedSearch : Chang_2020_Environ.Sci.Pollut.Res.Int_27_7280
PubMedID: 31883072

Title : Combined Omics Approach Identifies Gambogic Acid and Related Xanthones as Covalent Inhibitors of the Serine Palmitoyltransferase Complex - Hoch_2020_Cell.Chem.Biol_27_586
Author(s) : Hoch DG , Abegg D , Hannich JT , Pechalrieu D , Shuster A , Dwyer BG , Wang C , Zhang X , You Q , Riezman H , Adibekian A
Ref : Cell Chemical Biology , 27 :586 , 2020
Abstract : In this study, we identify the natural product gambogic acid as well as structurally related synthetic xanthones as first-in-class covalent inhibitors of the de novo sphingolipid biosynthesis. We apply chemoproteomics to determine that gambogic acid binds to the regulatory small subunit B of the serine palmitoyltransferase complex (SPTSSB). We then test structurally related synthetic xanthones to identify 18 as an equally potent but more selective binder of SPTSSB and show that 18 reduces sphingolipid levels in situ and in vivo. Finally, using various biological methods, we demonstrate that 18 induces cellular responses characteristic for diminished sphingosine-1-phosphate (S1P) signaling. This study demonstrates that SPTSSB may become a viable therapeutic target in various diseases with pathological S1P signaling. Furthermore, we believe that our compound will become a valuable tool for studying the sphingolipid metabolism and serve as a blueprint for the development of a new generation of sphingolipid biosynthesis inhibitors.
ESTHER : Hoch_2020_Cell.Chem.Biol_27_586
PubMedSearch : Hoch_2020_Cell.Chem.Biol_27_586
PubMedID: 32330443

Title : Molecular Dynamics Revealing a Detour-Forward Release Mechanism of Tacrine: Implication for the Specific Binding Characteristics in Butyrylcholinesterase - Zhang_2020_Front.Chem_8_730
Author(s) : Zhang Z , Fan F , Luo W , Zhao Y , Wang C
Ref : Front Chem , 8 :730 , 2020
Abstract : Butyrylcholinesterase (BChE) is a non-specific enzyme with clinical pharmacological and toxicological significance, which was a renewed interest as therapeutic target in Alzheimer's disease (AD) nowadays. Here, all-atom molecular dynamics simulations of butyrylcholinesterase with tacrine complex were designed to characterize inhibitor binding modes, strengths, and the hydrogen-bond dependent non-covalent release mechanism. Four possible release channels were identified, and the most favorable channel was determined by random acceleration molecular dynamics molecular dynamics (RAMD MD) simulations. The thermodynamic and dynamic properties as well as the corresponding Detour-forward delivery mechanism were determined according to the classical molecular dynamics (MD) simulations accompanied with umbrella sampling. The free energy barrier of the tacrine release process for the most beneficial pathway is about 10.95 kcal/mol, which is related to the non-covalent interactions from the surrounding residues, revealing the specific binding characteristics in the active site. The residues including Asp70, Ser79, Trp82, Gly116, Thr120, Tyr332, and His438 were identified to play major roles in the stabilization of tacrine in the pocket of BChE, where hydrogen bonding and Pi-Pi interactions are significant factors. Tyr332 and Asp70, which act as gate keepers, play crucial roles in the substrate delivery. The present results provide a basic understanding for the ligand transport mechanism depending on the BChE enzymatic environment, which is useful for the design of BChE inhibitors in the future.
ESTHER : Zhang_2020_Front.Chem_8_730
PubMedSearch : Zhang_2020_Front.Chem_8_730
PubMedID: 33195011

Title : An OliGreen-responsive fluorescence sensor for sensitive detection of organophosphorus pesticide based on its specific selectivity towards T-Hg(2+)-T DNA structure - Zhou_2020_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_247_119155
Author(s) : Zhou X , Wang C , Wu L , Wei W , Liu S
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 247 :119155 , 2020
Abstract : In this paper, it was found that OliGreen emitted much stronger fluorescence in rigid T-Hg(2+)-T DNA structure than that in the presence of poly T. Thus, an OliGreen-responsive label-free fluorescent sensor was proposed for sensitive detection of organophosphorus pesticides (OPs) by constructing T-Hg(2+)-T DNA structure. OliGreen emits strong fluorescence in T-Hg(2+)-T structures. The rigid DNA structure of T-Hg(2+)-T is prone to be destroyed by thiocholine (TCh) that hydrolyzed by acetylcholinesterase (AChE) because of the high affinity of TCh with Hg(2+). As a result, T-Hg(2+)-T DNA structure broke down and the fluorescence intensity of OliGreen decreased greatly. With the inhibition of AChE by OPs, fluorescence intensity of OliGreen remained strong because of the rigid T-Hg(2+)-T DNA structure. Thus, a "turn-on" fluorescent sensor which avoids synthesis of nanomaterials and complex label procedures is proposed based on the fluorescence intensity of OliGreen. DDVP were detected with a wide linear range from 0.005 to 25.0 ng/mL and the detection limit was 2.9 pg/mL, which is more sensitive than previously reported methods.
ESTHER : Zhou_2020_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_247_119155
PubMedSearch : Zhou_2020_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_247_119155
PubMedID: 33186818

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

Title : Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats - Sun_2020_J.Int.Med.Res_48_300060520936177
Author(s) : Sun Y , Zhao Z , Li Q , Wang C , Ge X , Wang X , Wang G , Qin Y
Ref : J Internal Medicine Res , 48 :300060520936177 , 2020
Abstract : OBJECTIVES: To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). METHODS: The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. RESULTS: The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. CONCLUSIONS: Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection.
ESTHER : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedSearch : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedID: 32644834

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 : Inhibition of Fatty Acid Synthase Upregulates Expression of CD36 to Sustain Proliferation of Colorectal Cancer Cells - Drury_2020_Front.Oncol_10_1185
Author(s) : Drury J , Rychahou PG , He D , Jafari N , Wang C , Lee EY , Weiss HL , Evers BM , Zaytseva YY
Ref : Front Oncol , 10 :1185 , 2020
Abstract : Fatty acid synthase, a key enzyme of de novo lipogenesis, is an attractive therapeutic target in cancer. The novel fatty acid synthase inhibitor, TVB-3664, shows anti-cancer activity in multiple cancers including colorectal cancer; however, it is unclear whether uptake of exogeneous fatty acids can compensate for the effect of fatty acid synthase inhibition. This study demonstrates that inhibition of fatty acid synthase selectively upregulates fatty acid translocase (CD36), a fatty acid transporter, in multiple colorectal cancer models including colorectal cancer cells with shRNA mediated knockdown of fatty acid synthase and genetically modified mouse tissues with heterozygous and homozygous deletion of fatty acid synthase. Furthermore, human colorectal cancer tissues treated with TVB-3664 show a significant and selective upregulation of CD36 mRNA. shRNA-mediated knockdown of CD36 and inhibition of CD36 via sulfosuccinimidyl oleate, a chemical inhibitor of CD36, decreased cell proliferation in vitro and reduced tumor growth in subcutaneous xenograft models. Isogenic cell populations established from patient derived xenografts and expressing high levels of CD36 show a significantly increased ability to grow tumors in vivo. The tumor-promoting effect of CD36 is associated with an increase in the levels of pAkt and survivin. Importantly, combinatorial treatment of primary and established colorectal cancer cells with TVB-3664 and sulfosuccinimidyl oleate shows a synergistic effect on cell proliferation. In summary, our study demonstrates that upregulation of CD36 expression is a potential compensatory mechanism for fatty acid synthase inhibition and that inhibition of CD36 can improve the efficacy of fatty acid synthase-targeted therapy.
ESTHER : Drury_2020_Front.Oncol_10_1185
PubMedSearch : Drury_2020_Front.Oncol_10_1185
PubMedID: 32850342

Title : Enhancing hydrogel-based long-lasting chemiluminescence by a platinum-metal organic framework and its application in array detection of pesticides and d-amino acids - Lu_2020_Nanoscale__
Author(s) : Lu Y , Wei M , Wang C , Wei W , Liu Y
Ref : Nanoscale , : , 2020
Abstract : Organophosphorus pesticides (OPs) are harmful to people's health and d-amino acids (d-AAs) in the human body are closely related to various diseases. So, detection of OPs in foods and d-AAs in serum is important for food safety and clinical diagnosis. Herein, a long-lasting chemiluminescence (CL) imaging sensor was constructed for the detection of OPs and d-AAs. The method was based on N-(4-aminobutyl)-N-ethylisoluminol/Co2+/chitosan (ABEI/Co2+/CS) hydrogels, where metal organic framework materials (MOF-Pt) were selected as catalysts to improve the sensitivity greatly. Under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), H2O2 was produced by using acetylcholine chloride (ACh) as a substrate, which was sensitive to the proposed CL system. OPs inhibited the activity of AChE and decreased the production of H2O2, reducing CL intensity. The linear range of the method for chlorpyrifos was 0.5 ng mL-1-1.0 mug mL-1, with a limit of detection (LOD) of 0.21 ng mL-1. Seventeen kinds of OPs can be visually and simultaneously discerned by the CL imager. On the other hand, d-AAs were catalyzed and oxidized by d-alpha-amino oxidase (DAAO) to produce H2O2. Thus, d-Ala in serum was used as a model to be detected by the proposed method. The linear range for d-Ala was 1.0 muM-10 mM, with an LOD of 0.12 muM.
ESTHER : Lu_2020_Nanoscale__
PubMedSearch : Lu_2020_Nanoscale__
PubMedID: 32053129

Title : Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: Challenge on monoamine oxidase and acetylcholinesterase inhibition - Jiang_2019_Phytomedicine_62_152967
Author(s) : Jiang B , Meng L , Zou N , Wang H , Li S , Huang L , Cheng X , Wang Z , Chen W , Wang C
Ref : Phytomedicine , 62 :152967 , 2019
Abstract : BACKGROUND: beta-Carboline alkaloid harmine (HAR) and harmaline (HAL) are monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors. However, whether HAR and HAL inhibit MAO or AChE selectively and competitively is unclear. PURPOSE: The purpose of this study was to investigate the potential competition inhibition of HAR and HAL on MAO and AChE in brain endothelial cells (RBE4) and in healthy rats to provide a basis for the application of the inhibitors in the treatment of patients with depression and with Parkinson's disease or Alzheimer's disease. STUDY DESIGN/METHODS: The transport properties of HAR and HAL by using blood-brain barrier models constructed with RBE4 were systematically investigated. Then, the modulation effects of HAR and HAL on CNS neurotransmitters (NTs) in healthy rat brains were determined by a microdialysis method coupled with LC-MS/MS. The competition inhibition of HAR and HAL on MAO and AChE was evaluated through real time-PCR, Western blot analysis, and molecular docking experiments. RESULTS: Results showed that HAL and HAR can be detected in the blood and striatum 300min after intravenous injection (1mg/kg). Choline (Ch), gamma-aminobutyric acid (GABA), glutamate (Glu), and phenylalanine (Phe) levels in the striatum decreased in a time-dependent manner after the HAL treatment, with average velocities of 1.41, 0.73, 3.86, and 1.10 (ng/ml)/min, respectively. The Ch and GABA levels in the striatum decreased after the HAR treatment, with average velocities of 1.16 and 0.22ng/ml/min, respectively. The results of the cocktail experiment using the human liver enzyme indicated that the IC50 value of HAL on MAO-A was 0.10 +/- 0.08microm and that of HAR was 0.38 +/- 0.21microm. Their IC50 values on AChE were not obtained. These findings indicated that HAL and HAR selectively acted on MAO in vitro. However, RT-PCR and Western blot analysis results showed that the AChE mRNA and protein expression decreased in a time-dependent manner in RBE4 cells after the HAR and HAL treatments. CONCLUSION: NT analysis results showed that HAL and HAR selectively affect AChE in vivo. HAL and HAR may be highly and suitably developed for the treatment of Alzheimer's disease.
ESTHER : Jiang_2019_Phytomedicine_62_152967
PubMedSearch : Jiang_2019_Phytomedicine_62_152967
PubMedID: 31154274

Title : Structure of lipoprotein lipase in complex with GPIHBP1 - Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
Author(s) : Arora R , Nimonkar AV , Baird D , Wang C , Chiu CH , Horton PA , Hanrahan S , Cubbon R , Weldon S , Tschantz WR , Mueller S , Brunner R , Lehr P , Meier P , Ottl J , Voznesensky A , Pandey P , Smith TM , Stojanovic A , Flyer A , Benson TE , Romanowski MJ , Trauger JW
Ref : Proc Natl Acad Sci U S A , 116 :10360 , 2019
Abstract : Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 A resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.
ESTHER : Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
PubMedSearch : Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
PubMedID: 31072929
Gene_locus related to this paper: human-LPL

Title : Potential Pharmacokinetic Drug(-)Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist - Zhang_2019_Molecules_24_
Author(s) : Zhang Y , Li S , Wang Y , Deng G , Cao N , Wu C , Ding W , Cheng X , Wang C
Ref : Molecules , 24 : , 2019
Abstract : Harmine (HAR) is a beta-carboline alkaloid widely distributed in nature. It exhibits psychopharmacological effects of improving learning and memory. However, excessive dose of HAR can cause central tremor toxicity, which may be related to the glutamate system. Memantine (MEM) is a non-competitive N-methyl-d-aspartate receptor antagonist. It can be used for the treatment of Alzheimer's disease and also can block the neurotoxicity caused by glutamate. Therefore, combination of HAR and MEM would be meaningful and the pharmacokinetics investigation of HAR and MEM in combination is necessary. A ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous quantitative determination of MEM, HAR and harmol (HOL), a main metabolite of HAR, in rat plasma after oral administration of HAR and MEM in combination (5.0 mg/kg of MEM combined with 20.0, 40.0, 80.0 mg/kg of HAR). The contents of HAR and HOL were determined after oral administration of HAR (20.0, 40.0 and 80.0 mg/kg), and the content of MEM was determined after oral administration of MEM (5.0 mg/kg). Blood samples were collected from each rat at 0 (pre-dose), 0.08, 0.17, 0.25, 0.33, 0.50, 0.75, 1.0, 2.0, 4.0, 8.0, 12.0 and 24.0 h after administration. The maximum peak concentration (Cmax) of MEM was obviously decreased, and the area under the plasma concentration versus time curve from zero to time t (AUC(0-t)) and mean residence time (MRT) were significantly increased after combination with HAR. The Cmax and AUC(0-t) of HAR and its metabolite HOL were increased after combination with MEM. These findings suggested that co-administration of HAR and MEM could extend their residence time in rats, and then might increase the efficacy for treatment of Alzheimer's disease. Therefore, this study will provide a basis for the rational combined application of HAR and MEM.
ESTHER : Zhang_2019_Molecules_24_
PubMedSearch : Zhang_2019_Molecules_24_
PubMedID: 30978991

Title : Bisphenol F-Induced Neurotoxicity toward Zebrafish Embryos - Yuan_2019_Environ.Sci.Technol_53_14638
Author(s) : Yuan L , Qian L , Qian Y , Liu J , Yang K , Huang Y , Wang C , Li Y , Mu X
Ref : Environ Sci Technol , 53 :14638 , 2019
Abstract : In this study, the influence of bisphenol F (BPF) toward central nervous system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity toward zebrafish embryos, including inhibited locomotion, reduced moving distance, and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. Peripheral motor neuron development was significantly inhibited by BPF at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-seq assay implied that the transcriptional changes were not mediated by ERalpha. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, and acetylcholine) or acetylcholinesterase (Ache) enzyme activity after BPF exposure, indicating that BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentration.
ESTHER : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedSearch : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedID: 31702913

Title : Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke - Yuan_2019_BMC.Neurol_19_236
Author(s) : Yuan M , Han B , Xia Y , Liu Y , Wang C , Zhang C
Ref : BMC Neurol , 19 :236 , 2019
Abstract : BACKGROUND: Brain ischemia activates the parasympathetic cholinergic pathway in animal models of human disease. However, it remains unknown whether activation of the cholinergic pathway impacts immune defenses and disease outcomes in patients with ischemic stroke. This study investigated a possible association between peripheral cholinergic activity, post-stroke infection, and mortality. METHODS: In this study, we enrolled 458 patients with acute ischemic stroke (< 24 h after onset), 320 patients with ischemic stroke on day 10, and 216 healthy subjects. Peripheral cholinergic activity, reflected by intracellular acetylcholine (ACh) content in human peripheral blood mononuclear cells (PBMCs), was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was measured by quantitative real-time PCR and western blot. Regression analyses were used to assess associations between peripheral cholinergic function and clinical outcomes. RESULTS: Within 24 h after the onset of acute ischemic stroke, there was a rapid increase in peripheral cholinergic activity that correlated with brain infarction volume (r = 0.67, P < 0.01). Specifically, lymphocyte-derived ACh levels were significantly higher in stroke patients with pneumonia (0.21 +/- 0.02 ng/10(6) PBMC versus 0.15 +/- 0.01 ng/10(6) PBMC, P = 0.03). Of note, lymphocytic AChE catalytic activity was significantly lower in these patients. One-year mortality was significantly greater in patients with higher intracellular ACh levels within the first 24 h after acute stroke. CONCLUSIONS: Lymphocytes produced increased amounts of ACh in patients with acute stroke, and pneumonia was a likely result. The association between this enhanced cholinergic activity and increased risk of pneumonia/mortality suggests that increased cholinergic activity may contribute to fatal post-stroke infection.
ESTHER : Yuan_2019_BMC.Neurol_19_236
PubMedSearch : Yuan_2019_BMC.Neurol_19_236
PubMedID: 31615442

Title : In vivo and in vitro metabolism and pharmacokinetics of cholinesterase inhibitor deoxyvasicine from aerial parts of Peganum harmala Linn in rats via UPLC-ESI-QTOF-MS and UPLC-ESI-MS\/MS - Deng_2019_J.Ethnopharmacol_236_288
Author(s) : Deng G , Liu W , Ma C , Rong X , Zhang Y , Wang Y , Wu C , Cao N , Ding W , Guan H , Cheng X , Wang C
Ref : J Ethnopharmacol , 236 :288 , 2019
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn are a Uighur traditional medicinal herb in China used to treat amnesia, bronchial asthma, and cough. Deoxyvasicine (DVAS), a potent cholinesterase inhibitor exhibiting anti-senile dementia activity, is one of the chief active ingredients in aerial parts of P. harmala and plays a key role in mediating the pharmacological effects of P. harmala. However, the metabolic profiling and in vivo pharmacokinetic characteristics of DVAS still remain unknown. AIM OF THE STUDY: The aim of this present study was to investigate the metabolism and pharmacokinetic properties of DVAS in rats by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS/MS) method. MATERIALS AND METHODS: The metabolic profiling of DVAS was evaluated in vitro and in vivo by rat liver microsomes (RLMs) incubation and by rat bio-specimens, such as urine, feces, plasma, and bile, after the oral administration of 45mg/kg DVAS. An efficient and sensitive UPLC-ESI-MS/MS method was developed and validated to simultaneously determine DVAS and its major four metabolites, namely, vasicine, deoxyvasicinone, vasicinone, and 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-beta-D-glucuronide in rat plasma. For pharmacokinetic studies, 32 Sprague-Dawley rats were randomly divided into four groups, namely, intravenous dosage group (2mg/kg DVAS) and three oral dosage groups (5, 15, and 45mg/kg DVAS). In addition, the activity of the components in plasma after intravenous administration of DVAS was evaluated by in vitro anti-butyrylcholinesterase (BChE) assays. RESULTS: A total of 23 metabolites were found in RLMs, plasma, urine, feces, and bile by UPLC-ESI-QTOF-MS. The metabolic pathway of DVAS in vivo and in vitro mainly involved hydroxylation, dehydrogenation, acetylation, methylation, glucuronidation, and O-sulphate conjugation, and the C-3 and C-9 sites were the main metabolic soft spots. All 23 metabolites were detected in the urine sample, and 13, 8, 22, and 6 metabolites were identified from rat feces, plasma, bile, and RLMs, respectively. The standard curves of DVAS and four metabolites in rat plasma showed good linearity in the concentration range of 0.82-524.00ng/mL with acceptable selectivity, precision, accuracy, recovery, and stability. DVAS exhibited linear dose-proportional pharmacokinetics at doses of 5, 15, and 45mg/kg after oral administration, and the average oral absolute bioavailability of DVAS was 47.46%. The in vitro anti-BChE assays implied that the inhibitive activities were mainly due to the different concentrations of prototype DVAS. CONCLUSIONS: DVAS can be rapidly absorbed and excreted by blood, and it is also extensively metabolized in vivo, and the anti-BChE activity in blood is mainly attributed to DVAS. These findings can lay a foundation for new drug development for DVAS.
ESTHER : Deng_2019_J.Ethnopharmacol_236_288
PubMedSearch : Deng_2019_J.Ethnopharmacol_236_288
PubMedID: 30872168

Title : Comparing and Contrasting the Multiple Roles of Butenolide Plant Growth Regulators: Strigolactones and Karrikins in Plant Development and Adaptation to Abiotic Stresses - Yang_2019_Int.J.Mol.Sci_20_
Author(s) : Yang T , Lian Y , Wang C
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Strigolactones (SLs) and karrikins (KARs) are both butenolide molecules that play essential roles in plant growth and development. SLs are phytohormones, with SLs having known functions within the plant they are produced in, while KARs are found in smoke emitted from burning plant matter and affect seeds and seedlings in areas of wildfire. It has been suggested that SL and KAR signaling may share similar mechanisms. The alpha/beta hydrolases DWARF14 (D14) and KARRIKIN INSENSITIVE 2 (KAI2), which act as receptors of SL and KAR, respectively, both interact with the F-box protein MORE AXILLARY GROWTH 2 (MAX2) in order to target SUPPRESSOR OF MAX2 1 (SMAX1)-LIKE/D53 family members for degradation via the 26S proteasome. Recent reports suggest that SLs and/or KARs are also involved in regulating plant responses and adaptation to various abiotic stresses, particularly nutrient deficiency, drought, salinity, and chilling. There is also crosstalk with other hormone signaling pathways, including auxin, gibberellic acid (GA), abscisic acid (ABA), cytokinin (CK), and ethylene (ET), under normal and abiotic stress conditions. This review briefly covers the biosynthetic and signaling pathways of SLs and KARs, compares their functions in plant growth and development, and reviews the effects of any crosstalk between SLs or KARs and other plant hormones at various stages of plant development. We also focus on the distinct responses, adaptations, and regulatory mechanisms related to SLs and/or KARs in response to various abiotic stresses. The review closes with discussion on ways to gain additional insights into the SL and KAR pathways and the crosstalk between these related phytohormones.
ESTHER : Yang_2019_Int.J.Mol.Sci_20_
PubMedSearch : Yang_2019_Int.J.Mol.Sci_20_
PubMedID: 31842355

Title : Acetylcholinesterase modified AuNPs-MoS2-rGO\/PI flexible film biosensor: Towards efficient fabrication and application in paraoxon detection - Jia_2019_Bioelectrochemistry_131_107392
Author(s) : Jia L , Zhou Y , Wu K , Feng Q , Wang C , He P
Ref : Bioelectrochemistry , 131 :107392 , 2019
Abstract : A flexible acetylcholinesterase (AChE) film biosensor, based on a AuNPs-MoS2-reduced graphene oxide/polyimide flexible film (rGO/PI) electrode, has been synthesized for paraoxon detection. In this study, the rGO/PI film acts as the flexible substrate and AuNPs are reduced by monolayer MoS2 under illumination. Transmission electron microscopy revealed that AuNPs are uniformly dispersed on the MoS2-rGO/PI electrode surface with a diameter ~10nm. X-ray photoelectron spectroscopy indicated that a strong binding force exists between reduced AuNPs and monolayer MoS2. The AChE modified AuNPs-MoS2-rGO/PI flexible film biosensor is used to hydrolyze acetylcholine chloride and obtain a large current response at 0.49V by differential pulse voltammetry, demonstrating successful immobilization of AChE. In view of the inhibition of paraoxon on the AChE, under optimal conditions, the AChE/AuNPs-MoS2-rGO/PI film biosensor shows a linear response over a concentration range 0.005-0.150mug/mL, a sensitivity of 4.44 uA/mugmL(-1), a detection limit of 0.0014mug/mL, acceptable reproducibility and stability to paraoxon. The flexible film biosensor has also proved used for detection of paraoxon in real samples.
ESTHER : Jia_2019_Bioelectrochemistry_131_107392
PubMedSearch : Jia_2019_Bioelectrochemistry_131_107392
PubMedID: 31707277

Title : Simultaneous determination of short-chain fatty acids in human feces by HPLC with ultraviolet detection following chemical derivatization and solid-phase extraction segmental elution - Wang_2019_J.Sep.Sci_42_2500
Author(s) : Wang HY , Wang C , Guo LX , Zheng YF , Hu WH , Dong TTX , Wang TJ , Tsim KWK
Ref : J Sep Sci , 42 :2500 , 2019
Abstract : Short-chain fatty acids are currently the most studied metabolites of gut microbiota, but the analysis of them, simultaneously, is still challenging due to their unique property and wide concentration range. Here, we developed a sensitive and versatile high-performance liquid chromatography with ultraviolet detection method, using pre-column derivatization and solid-phase extraction segmental elution, for the quantification of both major and trace amounts of short-chain fatty acids in human feces. Short-chain fatty acids were converted to 3-nitrophenylhydrazine-derived analytes, and then solid-phase extraction segmental elution was used for extraction of major analytes and enrichment of trace analytes. The method validation showed limits of quantitation <0.04 mM, and coefficient of determination > 0.998 at a wide range of 0.04-8.0 mM. The intra- and interday precision of analytes were all within accepted criteria, and the recoveries were 96.12 to 100.75% for targeted analytes in fecal samples. This method was successfully applied in quantification of eight analytes in human feces, which therefore could provide a sensitive and versatile high-performance liquid chromatography with ultraviolet detection method for precise and accurate quantitation of short-chain fatty acids in human feces.
ESTHER : Wang_2019_J.Sep.Sci_42_2500
PubMedSearch : Wang_2019_J.Sep.Sci_42_2500
PubMedID: 31115147

Title : Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease - Wang_2019_Int.J.Mol.Med_43_956
Author(s) : Wang C , Cai X , Hu W , Li Z , Kong F , Chen X , Wang D
Ref : Int J Mol Med , 43 :956 , 2019
Abstract : Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including antiapoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In lglutamatedamaged HT22 cells, 3h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase3 and increased the expression levels of Bcell lymphomaextra large, phosphorylated (P) protein kinase B and Pmammalian target of rapamycin compared with untreated cells. In mice with AD induced by dgalactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Abeta142 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Abeta142 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stressassociated apoptosis signaling pathway.
ESTHER : Wang_2019_Int.J.Mol.Med_43_956
PubMedSearch : Wang_2019_Int.J.Mol.Med_43_956
PubMedID: 30569175

Title : Investigating the Function of Cryptic Cytochalasan Cytochrome P450 Monooxygenases Using Combinatorial Biosynthesis - Wang_2019_Org.Lett_21_8756
Author(s) : Wang C , Becker K , Pfutze S , Kuhnert E , Stadler M , Cox RJ , Skellam E
Ref : Org Lett , 21 :8756 , 2019
Abstract : Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H deltaP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
ESTHER : Wang_2019_Org.Lett_21_8756
PubMedSearch : Wang_2019_Org.Lett_21_8756
PubMedID: 31644300
Gene_locus related to this paper: phano-phmG , aspcl-CCSE , aspfu-psoB , mago7-ORFZB , maggr-pyie

Title : Protective effects of enzyme degradation extract from Porphyra yezoensis against oxidative stress and brain injury in D-galactose-induced aging mice - Wang_2019_Br.J.Nutr__1
Author(s) : Wang C , Shen Z , Yu J , Yang J , Meng F , Jiang X , Zhu C
Ref : British Journal of Nutrition , :1 , 2019
Abstract : This study investigated the effects of Porphyra yezoensis enzyme degradation extract (PYEDE) on the brain injuries and neurodegenerative diseases due to oxidative stress. We used in vitro antioxidant systems to verify the antioxidant potential of PYEDE. The results indicated that PYEDE alleviated weight loss and organ atrophy, reduced the levels of lipid peroxidation and protein carbonylation, and elevated glutathione (GSH) content in the serum and brains of the D-gal-induced aging model mice. PYEDE also renewed the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total anti-oxidant capability (T-AOC) activities, downregulated the inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) levels, normalized the hippocampal neurons, and modulated multiple neurotransmitter systems by inhibiting the activities of acetylcholinesterase (AchE) and monoamine oxidase (MAO) in the upregulation of acetylcholine (Ach), dopamine (DA) and norepinephrine (NE) levels. Overall, PYEDE is a promising supplement for the alleviation of oxidative stress and age-associated brain diseases.
ESTHER : Wang_2019_Br.J.Nutr__1
PubMedSearch : Wang_2019_Br.J.Nutr__1
PubMedID: 31787131

Title : Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice - Deng_2019_Phytomedicine_63_153007
Author(s) : Deng G , Wu C , Rong X , Li S , Ju Z , Wang Y , Ma C , Ding W , Guan H , Cheng X , Liu W , Wang C
Ref : Phytomedicine , 63 :153007 , 2019
Abstract : BACKGROUND: Aerial parts of Peganum harmala Linn is used as a traditional medical herb for treatment of amnesia in Uighur medicine in China. Deoxyvasicine (DVAS) is one of the chief active ingredients in P. harmala, it possesses strong acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in vitro, but the therapeutic effect and mechanisms on amnesia in vivo are unclear. PURPOSE: The objective of this study was to investigate the improvement effect of DVAS from P. harmala in learning and memory deficits of scopolamine-induced mice and elucidate the underlying mechanisms involved. METHODS: Mice were pretreated with DVAS (5, 15 and 45mg/kg) and huperzine-A (0.2mg/kg) by gavage for 7 days, and subsequently were daily intraperitoneally injected with scopolamine (1mg/kg) to induce learning and memory deficits and behavioral performance was assessed by Morris water maze. To further evaluate the potential mechanisms of DVAS in improving learning and memory capabilities, pathological change, levels of various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation were examined. RESULTS: The results showed that DVAS could alleviate learning and memory deficits in scopolamine-treated mice. DVAS could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities and protein expressions. DVAS could induce brain-derived neurotrophic factor and protect hippocampal pyramidal cells against neuronal damage. DVAS also enhanced antioxidant defense via increasing the antioxidant enzyme level and activity of glutathione peroxidase, and anti-inflammatory function through suppressing tumor necrosis factor-alpha. Additionally, DVAS could regulate the neurotransmitters by elevating acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid and reducing 5-hydroxyindole-3-acetic acid and glutamic acid. CONCLUSION: Results illustrated that DVAS may be a promising candidate compound against amnesia via restoration of cholinergic function, regulating neurotransmitters, attenuating neuroinflammation and oxidative stress.
ESTHER : Deng_2019_Phytomedicine_63_153007
PubMedSearch : Deng_2019_Phytomedicine_63_153007
PubMedID: 31301537

Title : Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice - Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
Author(s) : Yao L , Cao B , Cheng Q , Cai W , Ye C , Liang J , Liu W , Tan L , Yan M , Li B , He J , Hwang SH , Zhang X , Wang C , Ai D , Hammock BD , Zhu Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , 316 :G527 , 2019
Abstract : Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.
ESTHER : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedSearch : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedID: 30789748

Title : Targeted Gene Inactivations Expose Silent Cytochalasans in Magnaporthe grisea NI980 - Wang_2019_Org.Lett_21_4163
Author(s) : Wang C , Hantke V , Cox RJ , Skellam E
Ref : Org Lett , 21 :4163 , 2019
Abstract : The biosynthetic gene cluster encoding the phytotoxin pyrichalasin H 5 was discovered in Magnaporthe grisea NI980, and the late-stage biosynthetic pathway of 5 was fully elucidated using targeted gene inactivations resulting in the isolation of 13 novel cytochalasans. This study reveals that the nonproteinogenic amino acid O-methyltyrosine is the true precursor of 5, and other cryptic cytochalasans and mutasynthesis experiments produce novel halogenated pyrichalasin H analogues.
ESTHER : Wang_2019_Org.Lett_21_4163
PubMedSearch : Wang_2019_Org.Lett_21_4163
PubMedID: 31099577
Gene_locus related to this paper: maggr-pyie

Title : Discovery and Evaluation of New Activity-Based Probes for Serine Hydrolases - Wang_2019_Chembiochem_20_2212
Author(s) : Wang C , Abegg D , Dwyer BG , Adibekian A
Ref : Chembiochem , 20 :2212 , 2019
Abstract : Serine hydrolases play crucial biological roles and are important therapeutic targets in many clinical applications. Activity-based protein profiling of serine hydrolases by using fluorophosphonate probes, pioneered by Cravatt and co-workers, has been a powerful tool for interrogating serine hydrolases in various biological systems. Herein, we present new phenyl phosphonate probes with an azide handle for click chemistry that offer remarkable improvements over the classical fluorophosphonate serine hydrolase activity-based probes including ease of preparation, excellent cell permeability, and distinct reactivity profiles, as controlled by the phenolate leaving group. Thus, these new activity-based serine hydrolase probes are valuable tools to further interrogate this important class of enzymes.
ESTHER : Wang_2019_Chembiochem_20_2212
PubMedSearch : Wang_2019_Chembiochem_20_2212
PubMedID: 30968522

Title : Combined toxicity of organophosphate flame retardants and cadmium to Corbicula fluminea in aquatic sediments - Li_2018_Environ.Pollut_243_645
Author(s) : Li D , Wang P , Wang C , Fan X , Wang X , Hu B
Ref : Environ Pollut , 243 :645 , 2018
Abstract : Organophosphate flame retardants (OPFRs), as alternatives to polybrominated biphenyl ethers (PBDEs), are frequently detected in various environmental matrices. Owing to urbanization and industrial pollution, co-contamination of OPFRs and heavy metals is ubiquitous in the environment. The toxicity of OPFRs in aqueous phase is a significant concern, but uncertainty still exists regarding the co-toxicity to benthic organisms of OPFRs and metals in sediments. Hence, we explored the physiological response of Corbicula fluminea to OPFRs and Cd in sediments. The results indicated that the antioxidant system in the clams was stimulated in the presence of OPFRs and Cd, and the oxidative stress increased with increasing concentrations of OPFRs. In contrast, the cytochrome P450 (CYP450) content and acetylcholinesterase (AChE) activity were reduced by exposure to both OPFRs and Cd. The cytochrome P450 4 family (CYP4) mRNA expression and OPFR toxicity were lower than those in previously reported experiments conducted in the water phase. Moreover, the expression levels of metallothionein (MT) and AChE mRNA decreased when OPFRs and Cd were present together. The highest integrated biomarker response (IBR) index (IBR=15.41) was observed in the presence of 45mgkg(-1) Cd + 200 mg kg(-1) OPFRs, rather than the 45mgkg(-1) Cd + 400 mg kg(-1) OPFRs treatment (IBR=9.48). In addition, CYP450 and AChE in the digestive glands of C. fluminea exhibited significant correlations with the concentration of the OPFR/Cd mixture (p<0.01) and could be effective biomarkers for OPFR and Cd co-contamination. The results potentially contribute to more realistic predictions and evaluations of the environmental risks posed by OPFRs in aquatic sediments contaminated with heavy metals, particularly with respect to the risk to benthic organisms.
ESTHER : Li_2018_Environ.Pollut_243_645
PubMedSearch : Li_2018_Environ.Pollut_243_645
PubMedID: 30219590

Title : Activatable Near-Infrared Fluorescent Probe for Dipeptidyl Peptidase IV and Its Bioimaging Applications in Living Cells and Animals - Liu_2018_Anal.Chem_90_3965
Author(s) : Liu T , Ning J , Wang B , Dong B , Li S , Tian X , Yu Z , Peng Y , Wang C , Zhao X , Huo X , Sun C , Cui J , Feng L , Ma X
Ref : Analytical Chemistry , 90 :3965 , 2018
Abstract : Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.
ESTHER : Liu_2018_Anal.Chem_90_3965
PubMedSearch : Liu_2018_Anal.Chem_90_3965
PubMedID: 29493228

Title : Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo - Zhu_2018_Eur.J.Pharm.Sci_123_459
Author(s) : Zhu Y , Liu W , Qi S , Wang H , Wang Y , Deng G , Zhang Y , Li S , Ma C , Cheng X , Wang C
Ref : Eur J Pharm Sci , 123 :459 , 2018
Abstract : Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer's disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results, the glucuronidation metabolic rate of l-VAS was faster than d-VAS in human liver microsomes and isoenzymes tests, and it was proved that the UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B15 were the major metabolic enzymes for glucuronidation of l-VAS, while only UGT1A9 for d-VAS, which take responsibility of the significantly less metabolic affinity of d-VAS than l-VAS in HLM and rhUGT1A9. The plasma exposure of d-VAS in rats was 1.3-fold and 1.6-fold higher than that of l-VAS after intravenous and oral administration of d-VAS and l-VAS, respectively. And the plasma exposure of the major glucuronidation metabolite d-VASG was one of tenth of l-VASG or more less, no matter by intravenous or oral administration. Both d-VAS and l-VAS were exhibited promising acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and the BChE inhibitory activity of d-VAS with IC50 of 0.03+/-0.001muM was significantly stronger than that of l-VAS with IC50 of 0.98+/-0.19muM. The molecular docking results indicated that d-VAS and l-VAS could bind to the catalytic active site (CAS position) either of human AChE and BChE, and the BChE combing ability of d-VAS (the score of GBI/WAS dG -7.398) was stronger than that of l-VAS (the score of GBI/WAS dG -7.135). Both d-VAS and l-VAS could improving the learning and memory on scopolamine-induced memory deficits in mice. The content of acetylcholine (ACh) after oral administration d-VAS increased more than that of l-VAS in mice cortex, through inhibiting cholinesterase (ChE) and increasing choline acetyltransferase (ChAT). In addition, the LD50 value of d-VAS ( was slight lower than l-VAS ( These results indicated that VAS enantiomers displayed significantly stereoselective metabolic, pharmacokinetics, anti-amnesic effect and toxic properties in vitro and in vivo. The d-VAS might be the dominant configuration for treating Alzheimer's disease.
ESTHER : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedSearch : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedID: 30077712

Title : Protective effects of evodiamine in experimental paradigm of Alzheimer's disease - Wang_2018_Cogn.Neurodyn_12_303
Author(s) : Wang D , Wang C , Liu L , Li S
Ref : Cogn Neurodyn , 12 :303 , 2018
Abstract : Evodiamine, a major component of Evodia rutaecarpa, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidative stress, and neuroprotective effects. Our previous study has shown that the potential effects of evodiamine on the learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). The present study was designed to investigate neuroprotective mechanism and therapeutic potential of evodiamine against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic Alzheimer's disease in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily oral administration with evodiamine (50 or 100 mg/kg per day) starting from the first dose of STZ for 21 days showed an improvement in STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze test. Evodiamine significantly decreased STZ induced elevation in acetylcholinesterase activity and malondialdehyde level, and significantly increased STZ induced reduction in glutathione activities and superoxide dismutase activities in the hippocampus compared to control. Furthermore, evodiamine inhibited significantly glial cell activation and neuroinflammation (TNF-alpha, IL-1beta, and IL-6 levels) in the hippocampus. Moreover, evodiamine increased the activity of AKT/GSK-3beta signalling pathway and inhibited the activity of nuclear factor kappaB. In summary, our study suggests that evodiamine can be a novel therapeutic agent for the management of sporadic AD.
ESTHER : Wang_2018_Cogn.Neurodyn_12_303
PubMedSearch : Wang_2018_Cogn.Neurodyn_12_303
PubMedID: 29765479

Title : Midgut transcriptomal response of the rice leaffolder, Cnaphalocrocis medinalis (Guenee) to Cry1C toxin - Yang_2018_PLoS.One_13_e0191686
Author(s) : Yang Y , Xu H , Lu Y , Wang C , Lu Z
Ref : PLoS ONE , 13 :e0191686 , 2018
Abstract : Cnaphalocrocis medinalis (Guenee) is one of the important insect pests in rice field. Bt agents were recommended in the C. medinalis control and Bt rice is bred as a tactic to control this insect. However, the tolerance or resistance of insect to Bt protein is a main threat to the application of Bt protein. In order to investigate the response of C. medinalis transcriptome in defending a Cry1C toxin, high-through RNA-sequencing was carried in the C. medinalis larvae treated with and without Cry1C toxin. A total of 35,586 high-quality unigenes was annotated in the transcriptome of C. medinalis midgut. The comparative analysis identified 6,966 differently expressed unigenes (DEGs) between the two treatments. GO analysis showed that these genes involved in proteolysis and extracellular region. Among these DEGs, carboxylesterase, glutathione S-transferase and P450 were differently expressed in the treated C. medinalis midgut. Furthermore, trypsin, chymotrypsin, and carboxypeptidase were identified in DEGs, and most of them up-regulated. In addition, thirteen ABC transporters were downregulated and three upregulated in Cry1C-treated C. medinalis midgut. Based on the pathway analysis, antigen processing and presentation pathway, and chronic myeloid leukemia pathway were significant in C. medinalis treated with Cry1C toxin. These results indicated that serine protease, detoxification enzymes and ABC transporter, antigen processing and presentation pathway, and chronic myeloid leukemia pathway may involved in the response of C. medinalis to Cry1C toxin. This study provides a transcriptomal foundation for the identification and functional characterization of genes involved in the toxicity of Bt Cry protein against C. medinalis, and provides potential clues to the studies on the tolerance or resistance of an agriculturally important insect pest C. medinalis to Cry1C toxin.
ESTHER : Yang_2018_PLoS.One_13_e0191686
PubMedSearch : Yang_2018_PLoS.One_13_e0191686
PubMedID: 29360856

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 : Tacrine(10)-hupyridone, a dual-binding acetylcholinesterase inhibitor, potently attenuates scopolamine-induced impairments of cognition in mice - Chen_2018_Metab.Brain.Dis_33_1131
Author(s) : Chen H , Xiang S , Huang L , Lin J , Hu S , Mak SH , Wang C , Wang Q , Cui W , Han Y
Ref : Metabolic Brain Disease , 33 :1131 , 2018
Abstract : Tacrine(10)-hupyridone (A10E) was designed as a dual-binding acetylcholinesterase (AChE) inhibitor from the modification of tacrine and a fragment of huperzine A. We have found that A10E effectively inhibited AChE in a mixed competitive manner, with an IC50 of 26.4 nM, which is more potent than those of tacrine and huperzine A. Most importantly, we have shown, for the first time that A10E attenuated scopolamine-induced cognitive impairments without affecting motor function in mice. A10E effectively attenuated impairments of learning and memory to a similar extent as donepezil, an inhibitor of AChE used for treating Alzheimer's disease (AD). In addition, A10E significantly decreased AChE activity in the brain of mice, suggesting that A10E might cross the brain blood-barrier. Taken together, our results demonstrated that A10E, a designed dual-binding AChE inhibitor, could effectively reverse cognitive impairments, indicating that A10E might provide therapeutic efficacy for AD treatment.
ESTHER : Chen_2018_Metab.Brain.Dis_33_1131
PubMedSearch : Chen_2018_Metab.Brain.Dis_33_1131
PubMedID: 29564727

Title : [Effect of enteral nutrition tolerance assessment standardized process management on ventilator associated pneumonia and prognosis in patients with tracheotomy and long-term mechanical ventilation in intensive care unit] - Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
Author(s) : Wang C , Wang J , Wang B , Jing X , Huang Y
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 30 :1173 , 2018
Abstract : OBJECTIVE: To investigate the effect of enteral nutrition (EN) tolerance assessment standardized process management on nosocomial infection and prognosis in patients with tracheotomy and long-term mechanical ventilation (MV) in intensive care unit (ICU). METHODS: A prospective cohort study was conducted. Forty-six patients who required long-term MV due to tracheotomy admitted to ICU of Changzhou First People's Hospital from January 2015 to December 2017 were enrolled. Taking the standardized process management of EN tolerance assessment from June 30th, 2016 as the time spot, patients admitted from January 1st, 2015 to June 30th, 2016 were taken as the control group (25 cases) and patients admitted from July 1st, 2016 to December 31st, 2017 as the observation group (21 cases). The two groups were all given conventional EN treatment and conventional symptomatic supportive treatment. Patients in the observation group was given the EN tolerance standardized process management, and received the nutritional risk screening score. While the control group was given a conventional EN management protocol (nurses routinely reported to the doctor and then gave further action). The nutritional support related indicators within 30 days of treatment (including serum albumin, serum pre-albumin, serum cholinesterase), the EN feeding tolerance index (the average amount of gastrointestinal motility drugs used within 30 days, the average EN interruption time per patient, and the incidence of gastrointestinal bleeding) and the prognosis-related indicators [including the incidence of ventilator-associated pneumonia (VAP), the monthly average hospitalization cost, the proportion of drugs, and the ratio of antibiotics to drugs] were compared. RESULTS: Compared with the control group, serum albumin, pre-albumin and cholinesterase were significantly increased in the observation group [albumin (g/L): 32.86+/-4.83 vs. 28.16+/-3.62, pre-albumin (mg/L): 186.42+/-62.84 vs. 163.26+/-73.49, cholinesterase (U/L): 3 482.34+/-369.92 vs. 2 986.86+/-491.49, all P < 0.05], the average use of gastrointestinal motility drugs was significantly reduced (mg: 11.20+/-3.86 vs. 15.23+/-5.68, P < 0.05), the average EN interruption time was significantly longer in each patient (hours: 6.38+/-3.59 vs. 4.96+/-2.28, P < 0.05), and the incidence of gastrointestinal bleeding was significantly decreased (19.04% vs. 24.00%, P < 0.05), the incidence of VAP was significantly decreased (18.64% vs. 21.36%, P < 0.05), and the antibiotics accounted for a significant decrease (62.43% vs. 76.59%, P < 0.05), but there was no significant difference in the proportion of drugs and monthly average hospitalization expenses [drug ratio: 36.88% vs. 38.42%, monthly average hospitalization cost (ten thousand yuan): 4.36+/-0.57 vs. 4.39+/-0.49, both P > 0.05]. CONCLUSIONS: For the patients with tracheotomy and long-term MV of ICU, the enteral nutrition tolerance assessment standardized process management can improve the nutritional status, reduce the incidence of nosocomial infections, and improve the prognosis of the patients.
ESTHER : Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
PubMedSearch : Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173
PubMedID: 30592953

Title : Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) - Wang_2018_Chem.Biol.Drug.Des_91_756
Author(s) : Wang J , Wang C , Wu Z , Li X , Xu S , Liu J , Lan Q , Zhu Z , Xu J
Ref : Chemical Biology Drug Des , 91 :756 , 2018
Abstract : A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer's disease agents.
ESTHER : Wang_2018_Chem.Biol.Drug.Des_91_756
PubMedSearch : Wang_2018_Chem.Biol.Drug.Des_91_756
PubMedID: 29112799

Title : miR-1b overexpression suppressed proliferation and migration of RSC96 and increased cell apoptosis - Liu_2018_Neurosci.Lett_687_137
Author(s) : Liu YP , Xu P , Guo CX , Luo ZR , Zhu J , Mou FF , Cai H , Wang C , Ye XC , Shao SJ , Guo HD
Ref : Neuroscience Letters , 687 :137 , 2018
Abstract : Peripheral nerve injury (PNI) is a global problem that leads to severe disability and high healthcare expenditure. Accumulating evidence suggested that the phenotypes of Schwann cells (SCs) could be regulated by microRNAs (miRNAs) and expressions of various miRNAs are altered after PNI. In this study, the expression of miR-1b in the injured nerve and hypoxia-treated SCs was detected through qRT-PCR. The target genes of miR-1b were predicted by bioinformatics prediction and dual-luciferase reporter assay and verified through qRT-PCR and western blot. The effects of miR-1b and its specific target gene on the proliferation, migration and apoptosis of SCs were determined and the regulation of miR-1b on peripheral nerve regeneration after PNI was further investigated in vivo. We found that miR-1b was obviously downregulated in the injured nerve in a rat sciatic nerve transection model and directly targeted N-myc downstream-regulated gene 3 (NDRG3) by binding to its 3'-UTR and caused both mRNA degradation and translation suppression of NDRG3. Overexpression of miR-1b or knockdown of NDRG3 decreased the proliferation and migration as well as increased the apoptosis of SCs. NDRG3 reversed the effects of miR-1b overexpression on proliferation/migration/apoptosis of RSC96. In addition, injection of miR-1b antagomir promoted the expression of NDRG3 in the injured nerve following sciatic nerve injury. Compared to the model group, the rats treated with miR-1b agomir had lower functional recovery rate, and downregulation of miR-1b through injection of specific antagomir improved the functional recovery rate according to the results of sciatic functional index and nerve conduction velocity. Overall, our results will contribute to the development of novel targets for promoting nerve regeneration after PNI.
ESTHER : Liu_2018_Neurosci.Lett_687_137
PubMedSearch : Liu_2018_Neurosci.Lett_687_137
PubMedID: 30261232

Title : Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China - Dong_2018_Mol.Neurodegener_13_36
Author(s) : Dong EL , Wang C , Wu S , Lu YQ , Lin XH , Su HZ , Zhao M , He J , Ma LX , Wang N , Chen WJ , Lin X
Ref : Mol Neurodegener , 13 :36 , 2018
Abstract : BACKGROUND: Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both the clinical and mutational spectrum of Chinese patients with HSP remained unclear. In this study, we aim to perform a comprehensive analysis of clinical phenotypes and genetic distributions in a large cohort of Chinese HSP patients, and to elucidate the primary pathogenesis in this population. METHODS: We firstly performed next-generation sequencing targeting 149 genes correlated with HSP in 99 index cases of our cohort. Multiplex ligation-dependent probe amplification testing was further carried out among those patients without known disease-causing gene mutations. We simultaneously performed a retrospective study on the reported patients exhibiting HSP in other Chinese cohorts. All clinical and molecular characterization from above two groups of Chinese HSP patients were analyzed and summarized. Eventually, we further validated the cellular changes in fibroblasts of two major spastic paraplegia (SPG) patients (SPG4 and SPG11) in vitro. RESULTS: Most patients of ADHSP (94%) are pure forms, whereas most patients of ARHSP (78%) tend to be complicated forms. In ADHSP, we found that SPG4 (79%) was the most prevalent, followed by SPG3A (11%), SPG6 (4%) and SPG33 (2%). Subtle mutations were the common genetic cause for SPG4 patients and most of them located in AAA cassette domain of spastin protein. In ARHSP, the most common subtype was SPG11 (53%), followed by SPG5 (32%), SPG35 (6%) and SPG46 (3%). Moreover, haplotype analysis showed a unique haplotype was shared in 14 families carrying c.334C > T (p.R112(*)) mutation in CYP7B1 gene, suggesting the founder effect. Functionally, we observed significantly different patterns of mitochondrial dynamics and network, decreased mitochondrial membrane potential (deltam), increased reactive oxygen species and reduced ATP content in SPG4 fibroblasts. Moreover, we also found the enlargement of LAMP1-positive organelles and abnormal accumulation of autolysosomes in SPG11 fibroblasts. CONCLUSIONS: Our study present a comprehensive clinical spectrum and genetic landscape for HSP in China. We have also provided additional evidences for mitochondrial and autolysosomal-mediated pathways in the pathogenesis of HSP.
ESTHER : Dong_2018_Mol.Neurodegener_13_36
PubMedSearch : Dong_2018_Mol.Neurodegener_13_36
PubMedID: 29980238

Title : Effects of a novel neonicotinoid insecticide cycloxaprid on earthworm, Eisenia fetida - Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
Author(s) : Qi S , Wang D , Zhu L , Teng M , Wang C , Xue X , Wu L
Ref : Environ Sci Pollut Res Int , 25 :14138 , 2018
Abstract : Cycloxaprid (CYC) is a novel neonicotinoid insecticide with high activity against resistant pests but is safe for mammals. The toxic effects of CYC on earthworms (Eisenia fetida) were studied in this paper. The 14-day exposure results showed that CYC is potentially toxic to earthworms, with a 14d-LC50 of 10.21 mg/kg dry soil, and that it induced tissue damage to the epidermis, gut, and neurochord at sublethal doses. During a 21-day exposure, CYC induced oxidative stress in earthworms, and both enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were impacted. In addition, expression of the genes Cat and Sod were down- and upregulated, respectively. The activity of the enzyme acetylcholinesterase (AChE) was increased at day 7 but decreased at day 21 after CYC exposure, while expression of the signal transduction-related genes was significantly regulated. Our study shows for the first time that negative impacts could be induced by CYC on earthworms under both acute and chronic exposure through oxidative stress and gene regulation. The present study provides a database for assessing the environmental risk to non-target organisms resulting from the use of CYC.
ESTHER : Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
PubMedSearch : Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
PubMedID: 29520554

Title : Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y - Bogaert_2018_Proc.Natl.Acad.Sci.U.S.A_115_302
Author(s) : Bogaert AF , Skorska MN , Wang C , Gabrie J , MacNeil AJ , Hoffarth MR , VanderLaan DP , Zucker KJ , Blanchard R
Ref : Proc Natl Acad Sci U S A , 115 :302 , 2018
Abstract : We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.
ESTHER : Bogaert_2018_Proc.Natl.Acad.Sci.U.S.A_115_302
PubMedSearch : Bogaert_2018_Proc.Natl.Acad.Sci.U.S.A_115_302
PubMedID: 29229842
Gene_locus related to this paper: human-NLGN4Y

Title : Z-Ligustilide Exerted Hormetic Effect on Growth and Detoxification Enzymes of Spodoptera litura Larvae - Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
Author(s) : Yi Y , Dou G , Yu Z , He H , Wang C , Li L , Zhou J , Liu D , Shi J , Li G , Pang L , Yang N , Huang Q , Qi H
Ref : Evid Based Complement Alternat Med , 2018 :7104513 , 2018
Abstract : Plants have evolved a variety of phytochemicals to defense insect feeding, whereas insects have also evolved diverse detoxification enzymes, which are adaptively induced as a prosurvival mechanism. Herein, Z-ligustilide in Ligusticum chuanxiong Hort. was found to exhibit a similar trend in the accumulation from December to May as the occurrence of Spodoptera litura (Fabricius) larvae. Importantly, S. litura larvae feeding enhanced Z-ligustilide level in the stem and leaf (p < 0.01). Moreover, Z-ligustilide ranging from 1 to 5 mg.g(-1) exhibited remarkable larvicidal activity, antifeedant activity, and growth inhibition against S. litura larvae. The LC50 values of larvicidal activity for phthalides in L. chuanxiong were compared as follows: Z-ligustilide > levistilide A > senkyunolide A > 3-butylidenephthalide > senkyunolide I, implicating the critical role of conjugated structure. Notably, there was a biphasic dose response for glutathione S-transferase (GST), cytochrome P450 (CYP) 450, Acetylcholinesterase (AChE), and Carboxylesterase (CarE) activities and GSTs1, cytochrome P450 (CYP) 4S9, and CYP4M14 mRNA expression. Particularly, low dose (0.1 mg.g(-1)) of Z-ligustilide conferred the resistance of S. litura larvae against chlorpyrifos (p < 0.05). Together, our data suggest that Z-ligustilide may function in a hormetic way in the chemical defense of L. chuanxiong against S. litura larvae.
ESTHER : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedSearch : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedID: 30057645

Title : Duplication of a Pks gene cluster and subsequent functional diversification facilitate environmental adaptation in Metarhizium species - Zeng_2018_PLoS.Genet_14_e1007472
Author(s) : Zeng G , Zhang P , Zhang Q , Zhao H , Li Z , Zhang X , Wang C , Yin WB , Fang W
Ref : PLoS Genet , 14 :e1007472 , 2018
Abstract : The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection. Different upstream signaling pathways were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1-MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive selection and synthesize different secondary metabolites. PKS1 is involved in synthesis of an anthraquinone derivative, and contributes to conidial pigmentation, which plays an important role in fungal tolerance to UV radiation and extreme temperatures. Disruption of the Pks2 gene delayed formation of infectious structures and increased the time taken to kill insects, indicating that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene cluster and its subsequent functional diversification has increased the adaptive flexibility of Metarhizium species.
ESTHER : Zeng_2018_PLoS.Genet_14_e1007472
PubMedSearch : Zeng_2018_PLoS.Genet_14_e1007472
PubMedID: 29958281
Gene_locus related to this paper: metaq-pks1 , metra-pks2 , metmf-pks2 , metaf-pks1 , metbs-pks2 , metas-pks1 , metaq-pks2

Title : Substrates for Paraoxonase - Mu_2018_Curr.Pharm.Des_24_615
Author(s) : Mu X , Yi X , Xiao S , Wang C , Chen G , Li Y
Ref : Curr Pharm Des , 24 :615 , 2018
Abstract : BACKGROUND: Paraoxonase (PON) is a family of calcium-dependent hydrolases, which is related to many diseases. Elucidation of PON physiological roles, active center and all applications in medical fields are dependent on its substrates. OBJECTIVE: The reports about PON substrates scattered in a long span of period are collected to afford clue for drug design, diagnosis of PON status and other academic purposes. METHOD: PON substrates from 133 references are classified and compared. Structurally, PON substrates are generally classified as organic phosphorous esters, lactones and arylesters. Some phosphoramidates, organophosphorous obidoximes, aryl carboxylic acid amides and special fatty alcohol esters as PON substrates are also included. RESULTS: The electron nature, steric hindrance and hydrophilicity of substrate substituents affecting the PON catalytic ability, binding ability and specificities are discussed. Drugs, prodrugs and naturally endogenous molecules in life processes activated or inactivate by PON are reviewed. Interestingly, some organophosphate and lactone substrates are preferably hydrolyzed by one of the PON1R192Q allozymes, and such a substrate is generally essential for differentiating the three PON1192R phenotypes by using a dual-substrate method. Intricately, some chiral substrates are hydrolyzed by PON stereoselectively. CONCLUSION: As more substrates are synthesized and characterized, more facts about PON structure and catalytic properties (including PON active center and catalytic mechanism) will be revealed, and therefore the use of PON as a drug target or as an accurate disease marker will be achieved.
ESTHER : Mu_2018_Curr.Pharm.Des_24_615
PubMedSearch : Mu_2018_Curr.Pharm.Des_24_615
PubMedID: 29237378

Title : Identification and characterization of a novel carboxylesterase (FpbH) that hydrolyzes aryloxyphenoxypropionate herbicides - Wang_2017_Biotechnol.Lett_39_553
Author(s) : Wang C , Qiu J , Yang Y , Zheng J , He J , Li S
Ref : Biotechnol Lett , 39 :553 , 2017
Abstract : OBJECTIVE: To identify and characterize a novel aryloxyphenoxypropionate (AOPP) herbicide-hydrolyzing carboxylesterase from Aquamicrobium sp. FPB-1.
RESULTS: A carboxylesterase gene, fpbH, was cloned from Aquamicrobium sp. FPB-1. The gene is 798 bp long and encodes a protein of 265 amino acids. FpbH is smaller than previously reported AOPP herbicide-hydrolyzing carboxylesterases and shares only 21-35% sequence identity with them. FpbH was expressed in Escherichia coli BL21(DE3) and the product was purified by Ni-NTA affinity chromatography. The purified FpbH hydrolyzed a wide range of AOPP herbicides with catalytic efficiency in the order: haloxyfop-P-methyl > diclofop-methyl > fenoxaprop-P-ethyl > quizalofop-P-ethyl > fluazifop-P-butyl > cyhalofop-butyl. The optimal temperature and pH for FpbH activity were 37 degrees C and 7, respectively.
CONCLUSIONS: FpbH is a novel AOPP herbicide-hydrolyzing carboxylesterase; it is a good candidate for mechanistic study of AOPP herbicide-hydrolyzing carboxylesterases and for bioremediation of AOPP herbicide-contaminated environments.
ESTHER : Wang_2017_Biotechnol.Lett_39_553
PubMedSearch : Wang_2017_Biotechnol.Lett_39_553
PubMedID: 28058522
Gene_locus related to this paper: burvg-a4jl51

Title : Neonicotinoid insecticides imidacloprid, guadipyr, and cycloxaprid induce acute oxidative stress in Daphnia magna - Qi_2017_Ecotoxicol.Environ.Saf_148_352
Author(s) : Qi S , Wang D , Zhu L , Teng M , Wang C , Xue X , Wu L
Ref : Ecotoxicology & Environmental Safety , 148 :352 , 2017
Abstract : Cycloxaprid (CYC) and guadipyr (GUA) are two new and promising neonicotinoid insecticides whose effects on Daphnia magna are as yet unknown. In this study, the acute toxicities of CYC and GUA to D. magna, including immobilization and embryo-hatching inhibition, and their effects on antioxidant enzymes and related gene expression were determined after a 48-h exposure. Imidacloprid (IMI) was evaluated at the same time as a reference agent. The 48-h EC50 values of IMI, GUA, and CYC for neonate immobilization were 13.0-16.5mg/L and for embryo hatching were 11.3-16.2mg/L. The specific activity of the enzymes superoxide dismutase (SOD) and catalase (CAT) were interfered by IMI, but not by GUA and CYC, while the activity of acetylcholinesterase (AChE) was significantly increased by IMI, but inhibited by GUA and CYC. The relative expressions of the Sod-Cu/Zn, Sod-Mn, Cat, and Ache genes were usually inhibited by IMI, GUA, and CYC, except for Cat by CYC, Ache by GUA, and Sods by IMI. For vitellogenin genes with a SOD-like domain (Vtg1/2-sod), relative expression was increased by IMI and inhibited by GUA and CYC, indicating that IMI, GUA, and CYC have potential toxicity toward reproduction. CYC and GUA are highly active against IMI-resistant pests, and considering the similar toxicity of IMI to D. magna, CYC and GUA are suitable for use in future integrated pest management systems.
ESTHER : Qi_2017_Ecotoxicol.Environ.Saf_148_352
PubMedSearch : Qi_2017_Ecotoxicol.Environ.Saf_148_352
PubMedID: 29096261

Title : Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits - Wang_2017_Arterioscler.Thromb.Vasc.Biol_37_1282
Author(s) : Wang C , Nishijima K , Kitajima S , Niimi M , Yan H , Chen Y , Ning B , Matsuhisa F , Liu E , Zhang J , Chen YE , Fan J
Ref : Arterioscler Thromb Vasc Biol , 37 :1282 , 2017
Abstract : OBJECTIVE: Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. APPROACH AND
RESULTS: We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates.
CONCLUSIONS: Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis.
ESTHER : Wang_2017_Arterioscler.Thromb.Vasc.Biol_37_1282
PubMedSearch : Wang_2017_Arterioscler.Thromb.Vasc.Biol_37_1282
PubMedID: 28546217
Gene_locus related to this paper: human-LIPG

Title : Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice - Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
Author(s) : Li N , Liu C , Jing S , Wang M , Wang H , Sun J , Wang C , Chen J , Li H
Ref : Evid Based Complement Alternat Med , 2017 :8632016 , 2017
Abstract : Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement.
ESTHER : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedSearch : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedID: 28814961

Title : Diterpenoids from the roots of Euphorbia ebracteolata and their inhibitory effects on human carboxylesterase 2 - Wang_2017_Phytochemistry_146_82
Author(s) : Wang AH , Tian XG , Cui YL , Huo XK , Zhang BJ , Deng S , Feng L , Ma XC , Jia JM , Wang C
Ref : Phytochemistry , 146 :82 , 2017
Abstract : A chemical investigation of the roots of Euphorbia ebracteolata identified eighteen diterpenoids and glycosides. On the basis of spectroscopic data, they were determined to be ent-kauranes, ent-atisanes, tigliane derivatives, ingenane, and ent-abietanes, among which were eleven previously undescribed diterpenoids. The inhibitory effects of the isolated compounds against human carboxylesterase 2 (hCE-2) were evaluated in vitro, which revealed moderate inhibitory effects with IC50 values<50muM. Next, the inhibitory kinetics were evaluated for the putative hCE-2 inhibitor 4beta,9alpha,16,20-tetrahydroxy-14(13-->12)-abeo-12alphaH-1,6-tigliadiene-3,13-di one (IC50 3.88muM), and results indicated competitive inhibition with Ki 4.94muM. Additionally, none of the diterpenoids showed cytotoxic effects against five human tumor cell lines as determined by MTT assays.
ESTHER : Wang_2017_Phytochemistry_146_82
PubMedSearch : Wang_2017_Phytochemistry_146_82
PubMedID: 29253734

Title : Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity - Cen_2017_Eur.J.Med.Chem_144_128
Author(s) : Cen J , Guo H , Hong C , Lv J , Yang Y , Wang T , Fang D , Luo W , Wang C
Ref : Eur Journal of Medicinal Chemistry , 144 :128 , 2017
Abstract : A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced beta-amyloid (Abeta) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation.
ESTHER : Cen_2017_Eur.J.Med.Chem_144_128
PubMedSearch : Cen_2017_Eur.J.Med.Chem_144_128
PubMedID: 29268129

Title : A bioactive new protostane-type triterpenoid from Alisma plantago-aquatica subsp. orientale (Sam.) Sam - Wang_2017_Nat.Prod.Res__1
Author(s) : Wang YL , Zhao JC , Liang JH , Tian XG , Huo XK , Feng L , Ning J , Wang C , Zhang BJ , Chen G , Li N , Sun CP
Ref : Nat Prod Res , :1 , 2017
Abstract : A new protostane-type triterpenoid, 5beta,29-dihydroxy alisol A (1) was isolated from Alisma plantago-aquatica subsp. orientale (Sam.) Sam. as well as 12-deoxyphorbol-13alpha-pentadecanoate (2). We first report the presence of compound 2 in the genus Alisma. Their structures were established on the basis of 1D and 2D NMR, and HRESIMS spectroscopic analyses. All the isolated compounds were assayed for their inhibitory effects against human carboxylesterase 2 (HCE-2). Compounds 1 and 2 displayed inhibitory activities against HCE-2 with IC50 values of 29.2 and 4.6 muM, respectively. The interaction mechanisms of HCE-2 with compounds 1 and 2 were investigated by molecular docking, respectively.
ESTHER : Wang_2017_Nat.Prod.Res__1
PubMedSearch : Wang_2017_Nat.Prod.Res__1
PubMedID: 29183156

Title : A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum - Li_2017_J.Ethnopharmacol_203_127
Author(s) : Li S , Cheng X , Wang C
Ref : J Ethnopharmacol , 203 :127 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. AIM OF THE REVIEW: The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research. MATERIALS AND
METHODS: Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS's dissertations.
RESULTS: The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory.
CONCLUSIONS: Based on this review, there is some evidence for extracts' pharmacological effects on Alzheimer's and Parkinson's diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding many aspects of the genus such as mechanisms of actions, metabolism, pharmacokinetics, toxicology, potential drug interactions with standard-of-care medications is still limited which call for additional studies particularly in humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices.
ESTHER : Li_2017_J.Ethnopharmacol_203_127
PubMedSearch : Li_2017_J.Ethnopharmacol_203_127
PubMedID: 28359849

Title : Chemical characteristics of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesterase - Wei_2017_J.Asian.Nat.Prod.Res__1
Author(s) : Wei JC , Wang AH , Wei YL , Huo XK , Tian XG , Feng L , Ma XC , Wang C , Huang SS , Jia JM
Ref : J Asian Nat Prod Res , :1 , 2017
Abstract : The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 muM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE.
ESTHER : Wei_2017_J.Asian.Nat.Prod.Res__1
PubMedSearch : Wei_2017_J.Asian.Nat.Prod.Res__1
PubMedID: 28944681

Title : Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice - Liu_2017_J.Ethnopharmacol_204_95
Author(s) : Liu W , Zhu Y , Wang Y , Qi S , Ma C , Li S , Jiang B , Cheng X , Wang Z , Xuan Z , Wang C
Ref : J Ethnopharmacol , 204 :95 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND
METHODS: The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.
RESULTS: The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group.
CONCLUSIONS: EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
ESTHER : Liu_2017_J.Ethnopharmacol_204_95
PubMedSearch : Liu_2017_J.Ethnopharmacol_204_95
PubMedID: 28442406

Title : The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure - Ren_2017_J.Toxicol_2017_3265727
Author(s) : Ren Q , Zhao R , Wang C , Li S , Zhang T , Ren Z , Yang M , Pan H , Xu S , Zhu J , Wang X
Ref : J Toxicol , 2017 :3265727 , 2017
Abstract : The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE) in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The behavior responses of D. magna in DM (13.36 mug/L and 33.40 mug/L) and MT (19.66 mug/L and 49.15 mug/L) suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.
ESTHER : Ren_2017_J.Toxicol_2017_3265727
PubMedSearch : Ren_2017_J.Toxicol_2017_3265727
PubMedID: 29201050
Gene_locus related to this paper: dapul-ACHE1

Title : Effects of monocrotophos pesticide on cholinergic and dopaminergic neurotransmitter systems during early development in the sea urchin Hemicentrotus pulcherrimus - Zhang_2017_Toxicol.Appl.Pharmacol_328_46
Author(s) : Zhang X , Li S , Wang C , Tian H , Wang W , Ru S
Ref : Toxicol Appl Pharmacol , 328 :46 , 2017
Abstract : During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae. At the blastula stages, MCP disrupted DA metabolism but not 5-HT metabolism, resulting in abnormal development. High ChAT and AChE activity were observed at the gastrulation-completed stage and the two-armed pluteus stage, respectively, MCP inhibited ChAT activity and AChE activity/distribution and resulted in developmental defects of the plutei. From the gastrula stage to the two-armed pluteus stage, we found ubiquitous disrupting effects of MCP on ACh, DA, and 5-HT metabolism, particularly at critical periods during the development of these neurotransmitter systems. Therefore, we propose that this disruption is one of the main mechanisms of MCP-related developmental neurotoxicity, which would contribute better understanding insight into the mechanism of MCP pesticide's toxic effects.
ESTHER : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedSearch : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedID: 28479505

Title : Phenolic glycosides and monoterpenoids from the roots of Euphorbia ebracteolata and their bioactivities - Wang_2017_Fitoterapia_121_175
Author(s) : Wang AH , Huo XK , Feng L , Sun CP , Deng S , Zhang HL , Zhang BJ , Ma XC , Jia JM , Wang C
Ref : Fitoterapia , 121 :175 , 2017
Abstract : The bioactive substance investigation of Euphorbia ebracteolata obtained 17 compounds by various chromatographic techniques. Their structures were elucidated using widely spectroscopic data, including ESI-MS, HRESI-MS, CD, 1D- and 2D-NMR, which gave 5 new phenolic glucosides and 4 new monoterpenoids. The phenolic glucosides and monoterpenoids showed the inhibitory effect against the human carboxylesterase-2 (hCE-2) using a fluorescence bioassay in vitro, with the strongest inhibitor compound 4 (IC50 7.17muM). The antioxidant effects of these isolated compounds were evaluated using a DPPH scavenging assay. All of the phenolic acids displayed the DPPH scavenging effect, especially that eight compounds have better effect than vitamin C, with the IC50 values ranging from 4.52 to 7.52muM. Additionally, compounds 1-17 showed no cytotoxic effect against five human cancer cell lines by MTT assay.
ESTHER : Wang_2017_Fitoterapia_121_175
PubMedSearch : Wang_2017_Fitoterapia_121_175
PubMedID: 28760607

Title : Metabolic Profile of 3-Acetyl-11-Keto-beta-Boswellic Acid and 11-Keto-beta-Boswellic Acid in Human Preparations In Vitro, Species Differences, and Bioactivity Variation - Cui_2016_AAPS.J_18_1273
Author(s) : Cui Y , Tian X , Ning J , Wang C , Yu Z , Wang Y , Huo X , Jin L , Deng S , Zhang B , Ma X
Ref : AAPS J , 18 :1273 , 2016
Abstract : 3-Acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-beta-boswellic acid (KBA) are widely used in the clinic as anti-inflammatory drugs. However, these drugs have the poor bioavailability, which may be caused by their extensive metabolism. In this study, we systemically characterized both phase I and II metabolism of AKBA and KBA in vitro. In total, four major metabolites were firstly biosynthesized and identified using 1D and 2D NMR spectroscopy. Among them, three metabolites were novel. The kinetic parameters (K m , V max , CL int, and K i ) were also analyzed systematically in various biological samples. Finally, the deacetylation of AKBA and hydroxylation of KBA were confirmed to be the major metabolic pathways based on their large CL int and the high amounts of KBA (46.7%) and hydroxylated KBA (50.8%) along with a low amount of AKBA (2.50%) in human primary hepatocytes. Carboxylesterase 2 (CE2) selectively catalyzed the deacetylation of AKBA to form KBA. Although CYP3A4, CYP3A5, and CYP3A7 catalyzed the metabolism of KBA, CYP3A4 played a predominant role in the hydroxylation reaction of KBA in human. Notably, deacetylation and regioselective hydroxylation exhibited considerable species differences. Deacetylation was only observed in human liver microsomes and primary human hepatocytes; 21- and 20-mono-hydroxylation of KBA were primarily observed in human, monkey, and dog; and 16- and 30-mono-hydroxylation were observed in other species. More importantly, all four mono-hydroxylation metabolites exhibited a moderate anti-inflammatory activity. The 21- and 20-hydroxylation metabolites inhibited the expression of iNOS, the LPS-induced activation of IkBalpha and p65 phosphorylation, and suppressed p65 nuclear translocation in RAW264.7 cells.
ESTHER : Cui_2016_AAPS.J_18_1273
PubMedSearch : Cui_2016_AAPS.J_18_1273
PubMedID: 27329304

Title : High expression of NDRG3 associates with positive lymph node metastasis and unfavourable overall survival in laryngeal squamous cell carcinoma - Ma_2016_Pathology_48_691
Author(s) : Ma J , Liu S , Zhang W , Zhang F , Wang S , Wu L , Yan R , Wang C , Zha Z , Sun J
Ref : Pathology , 48 :691 , 2016
Abstract : N-myc downstream-regulated gene 3 (NDRG3), which belongs to the NDRG family, is believed to play important roles in human cancer. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (qPCR) and western blotting tests with 10 fresh-frozen laryngeal squamous cell carcinoma (LSCC) samples and immunohistochemistry (IHC) analysis in 109 LSCC cases were performed to investigate the relationship between NDRG3 expression and the clinicopathological characteristics of LSCC. Results demonstrated that NDRG3 mRNA and protein expression levels were statistically higher in LSCC tissues than that in non-cancerous tissues (all p<0.05). IHC data showed that the NDRG3 protein expression was remarkably correlated with lymph node metastasis (p=0.043). Univariate and multivariate survival analysis implied that high NDRG3 expression (p=0.004), lymph node metastasis (p=0.044) and TNM stage (p=0.020) were independently associated with the unfavourable overall survival of patients with LSCC. The above findings suggested that NDRG3 may be identified as a novel biomarker predicting the prognosis of LSCC.
ESTHER : Ma_2016_Pathology_48_691
PubMedSearch : Ma_2016_Pathology_48_691
PubMedID: 27780595

Title : Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae - Shen_2016_Sci.Rep_6_33905
Author(s) : Shen H , Zhu Y , Wang C , Yan H , Teng M , Li X
Ref : Sci Rep , 6 :33905 , 2016
Abstract : Hda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 A. The ARB2 domain displays an alpha/beta sandwich architecture with an arm protruding outside. Two ARB2 domain molecules form a compact homo-dimer via the arm elements, and assemble as an inverse "V" shape. The pull-down and ITC results reveal that the ARB2 domain possesses the histone binding ability, recognizing both the H2A-H2B dimer and H3-H4 tetramer. Perturbation of the dimer interface abolishes the histone binding ability of the ARB2 domain, indicating that the unique dimer architecture of the ARB2 domain coincides with the function for anchoring to histone. Collectively, our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda1 HDAC complex.
ESTHER : Shen_2016_Sci.Rep_6_33905
PubMedSearch : Shen_2016_Sci.Rep_6_33905
PubMedID: 27665728
Gene_locus related to this paper: yeast-hda1

Title : Soluble epoxide hydrolase: A potential target for metabolic diseases - He_2016_J.Diabetes_8_305
Author(s) : He J , Wang C , Zhu Y , Ai D
Ref : J Diabetes , 8 :305 , 2016
Abstract : Epoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non-alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti-inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega-6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega-3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti-inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega-3 and omega-6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH.
ESTHER : He_2016_J.Diabetes_8_305
PubMedSearch : He_2016_J.Diabetes_8_305
PubMedID: 26621325

Title : Suppressive subtractive hybridization reveals different gene expression between high and low virulence strains of Cladosporium cladosporioides - Gu_2016_Microb.Pathog_100_276
Author(s) : Gu Y , Liu Y , Cao S , Huang X , Zuo Z , Yu S , Deng J , Ding C , Yuan M , Shen L , Wu R , Wen Y , Ren Z , Zhao Q , Peng G , Zhong Z , Wang C , Ma X
Ref : Microb Pathog , 100 :276 , 2016
Abstract : Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the unigenes in the forward library corresponded to 5 different pathways and the reverse library unigenes were involved in 3 different pathways. The qRT-PCR results indicated that expressions of APL1, GUD1, CSE1, SPBC3E7.04c and MFS were significantly different between Z20 and Zt strains, while genes encoding the senescence-associated proteins, pse1, nup107, mip1, pex2, icl1 and alpha/beta hydrolase exhibited no significant differences between the two strains. In addition, we found that 5 unigenes encoding mip1, chk1, icl1, alpha/beta hydrolase and beta-glucosidase may be associated with pathogenicity. One unigene (MFS) may be related to the resistance to 14 alpha-demethylase inhibitor fungicides, and 5 unigenes (PEX2, NUP107, PSE1, APL1, and SPBC3E7.04c) may be related to either low spore yield or earlier aging of the Zt strain. Our study may help better understand the molecular mechanism of C. cladosporioides infection, and therefore improve the treatment and prevention of C. cladosporioides induced diseases.
ESTHER : Gu_2016_Microb.Pathog_100_276
PubMedSearch : Gu_2016_Microb.Pathog_100_276
PubMedID: 27744104

Title : A novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improves Abeta25-35-impaired mouse cognitive function - Zhang_2016_Psychopharmacology.(Berl)_233_599
Author(s) : Zhang Z , Chen R , An W , Wang C , Liao G , Dong X , Bi A , Yin Z , Luo L
Ref : Psychopharmacology (Berl) , 233 :599 , 2016
Abstract : RATIONALE: The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy. OBJECTIVES: We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Abeta25-35-injected mice, and the potential mechanisms.
METHODS: AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Abeta25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Abeta25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12.
RESULTS: SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Abeta25-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Abeta25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Abeta25-35-induced signal cascade in neurons.
CONCLUSIONS: All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy.
ESTHER : Zhang_2016_Psychopharmacology.(Berl)_233_599
PubMedSearch : Zhang_2016_Psychopharmacology.(Berl)_233_599
PubMedID: 26554390

Title : Divergent and Convergent Evolution of Fungal Pathogenicity - Shang_2016_Genome.Biol.Evol_8_1374
Author(s) : Shang Y , Xiao G , Zheng P , Cen K , Zhan S , Wang C
Ref : Genome Biol Evol , 8 :1374 , 2016
Abstract : Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.
ESTHER : Shang_2016_Genome.Biol.Evol_8_1374
PubMedSearch : Shang_2016_Genome.Biol.Evol_8_1374
PubMedID: 27071652
Gene_locus related to this paper: 9hypo-a0a162hs49 , 9hypo-a0a162hub8 , 9hypo-a0a162i1u8 , 9euro-a0a162iix1 , 9hypo-a0a162ima8 , 9hypo-a0a162jas9 , 9hypo-a0a162jfj3 , 9hypo-a0a162jhb9 , 9hypo-a0a162jmg2 , cordf-a0a162k2a2 , 9hypo-a0a162k3b2 , 9hypo-a0a162k3t2 , cordf-a0a162kne2 , cordf-a0a162kwz0 , 9hypo-a0a162m4x7 , cordf-a0a162mwk4 , 9hypo-a0a166nct4 , 9euro-a0a166nl14 , 9hypo-a0a166v6u3 , 9hypo-a0a166wlx9 , 9hypo-a0a166wxz0 , 9hypo-a0a166yda3 , 9hypo-a0a166ymi5 , 9hypo-a0a166z511 , 9hypo-a0a167fcg1 , 9hypo-a0a167gu64 , 9hypo-a0a167gyk2 , 9hypo-a0a167kjz5 , 9hypo-a0a167m3a6 , 9pezi-a0a167nge5 , 9hypo-a0a167qnf7 , 9pezi-a0a167qz56 , 9pezi-a0a167sfr8 , 9pezi-a0a167snk4 , 9hypo-a0a167tjx1 , 9hypo-a0a167tm61 , 9pezi-a0a167u5l8 , 9pezi-a0a167uqx6 , 9hypo-a0a167v4i2 , 9euro-a0a167vcq2 , 9pezi-a0a167vqe2 , 9hypo-a0a167vzl7 , 9euro-a0a167w192 , cordf-a0a167wrl9 , 9pezi-a0a167wyb6 , 9euro-a0a167xzp3 , 9euro-a0a167y0h7 , 9hypo-a0a167yg81 , 9pezi-a0a167z9i1 , cordf-a0a167zqi5 , 9hypo-a0a168are5 , cordf-a0a168bcu5 , 9hypo-a0a168bsl8 , cordf-a0a168cqs1 , cordf-a0a168crk3 , 9hypo-a0a168d6j2 , 9hypo-a0a168enh0 , 9hypo-a0a168eu39 , cordf-a0a168g0e1 , cordf-a0a168g1t1 , cordf-a0a168g678 , cordf-a0a168hsg3 , cordf-a0a168j527 , cordf-a0a168jr90 , cordf-a0a168l178 , 9hypo-a0a167x7j9 , beaba-a0a2s7xwt2 , 9hypo-a0a167xk24 , cordf-a0a168j0y7 , 9hypo-a0a167es80 , 9pezi-a0a162mh01 , 9hypo-a0a168b790 , 9hypo-a0a166uph8 , 9hypo-a0a168enk0 , 9hypo-a0a167dlr2 , cordf-a0a168hsf0 , 9hypo-a0a167hq40 , metrr-a0a166ygn0 , cordf-a0a179ib68 , corfa-a0a167q5m2 , metrr-a0a162jas4 , cordf-a0a168fit9

Title : A Novel Radiotracer for Imaging Monoacylglycerol Lipase in the Brain Using Positron Emission Tomography - Wang_2016_ACS.Chem.Neurosci_7_484
Author(s) : Wang C , Placzek MS , Van de Bittner GC , Schroeder FA , Hooker JM
Ref : ACS Chem Neurosci , 7 :484 , 2016
Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerols to glycerol and fatty acid and plays an important role in neuroinflammation. MAGL inhibitors are a class of molecules with therapeutic potential for human diseases of the central nervous system (CNS), in areas such as pain and inflammation, immunological disorders, and neurological and psychiatric conditions. Development of a noninvasive imaging probe would elucidate the distribution and functional roles of MAGL in the brain and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot rodent imaging of a novel MAGL imaging agent, [(11)C]SAR127303. Our imaging results demonstrate the high specificity, good selectivity, and appropriate kinetics and distribution of [(11)C]SAR127303, validating its utility for imaging MAGL in the brain. Our findings support the translational potential for human CNS MAGL imaging.
ESTHER : Wang_2016_ACS.Chem.Neurosci_7_484
PubMedSearch : Wang_2016_ACS.Chem.Neurosci_7_484
PubMedID: 26694017

Title : Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice - Huang_2016_ACS.Chem.Neurosci_7_1047
Author(s) : Huang L , Lin J , Xiang S , Zhao K , Yu J , Zheng J , Xu D , Mak SH , Hu S , Nirasha S , Wang C , Chen X , Zhang J , Xu S , Wei X , Zhang Z , Zhou D , Zhou W , Cui W , Han YF , Hu Z , Wang Q
Ref : ACS Chem Neurosci , 7 :1047 , 2016
Abstract : Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice.
ESTHER : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedSearch : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedID: 27046396

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

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

Title : In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor - Liu_2015_PLoS.One_10_e0122366
Author(s) : Liu W , Shi X , Yang Y , Cheng X , Liu Q , Han H , Yang B , He C , Wang Y , Jiang B , Wang Z , Wang C
Ref : PLoS ONE , 10 :e0122366 , 2015
Abstract : Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer's disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity.
ESTHER : Liu_2015_PLoS.One_10_e0122366
PubMedSearch : Liu_2015_PLoS.One_10_e0122366
PubMedID: 25849329

Title : Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation - Yang_2015_J.Ethnopharmacol_168_279
Author(s) : Yang Y , Cheng X , Liu W , Chou G , Wang Z , Wang C
Ref : J Ethnopharmacol , 168 :279 , 2015
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. AIM OF THE STUDY: The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). MATERIALS AND
METHODS: For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline.
RESULTS: The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine (10), 2-carboxyl-3,4-dihydroquinazoline (19), one syringin structure analog 1-O-beta-D-xylopyranose sinapyl alcohol (22), and along with 19 known compounds. Compounds acetylnorharmine (6), harmic acid methy ester (7), harmine N-oxide (13), 6-methoxyindoline (14), syringin (21) were first found from genus Peganum and compounds 3-hydroxylated harmine (4), 1-hydroxy-7-methoxy-beta-carboline (5) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine (10) has a potential inbibitive effect on both AChE and BChE with IC50 values of 12.35+/-0.24 and 5.51+/-0.33microM, respectively. Deoxyvasicine (15) and vasicine (16) showed the strongest BChE inhibitory activity with IC50 values of 0.04+/-0.01 and 0.1+/-0.01microM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for beta-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity.
CONCLUSIONS: Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala. These results are in agreement with the traditional uses of the seeds of P. harmala.
ESTHER : Yang_2015_J.Ethnopharmacol_168_279
PubMedSearch : Yang_2015_J.Ethnopharmacol_168_279
PubMedID: 25862961

Title : Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis - Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_135
Author(s) : Wang HF , Yu JT , Tang SW , Jiang T , Tan CC , Meng XF , Wang C , Tan MS , Tan L
Ref : Journal of Neurology Neurosurg Psychiatry , 86 :135 , 2015
Abstract : OBJECTIVE: Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB.
METHODS: We searched Cochrane Dementia and Cognitive Improvement Group Specialised Register, Pubmed, Embase, and other sources for eligible trials. We selected global impression and cognitive function as primary efficacy outcomes, and dropouts and adverse events as safety outcomes. Furthermore, Meta-analysis and trial sequential analysis (TSA) were used here.
RESULTS: Ten trials were included in this study. Cholinesterase inhibitors and memantine produced small global efficacy on clinicians' global impression of change (CGIC), from a weighted mean difference of -0.40 (95% CI -0.77 to -0.03) to -0.65 (95% CI -1.28 to -0.01); however, cholinesterase inhibitors but not memantine significantly improved cognition on Mini-Mental State Examination (MMSE), from 1.04 (95% CI 0.43 to 1.65) to 2.57 (95% CI 0.90 to 4.23). Additionally, both of them had good safety outcomes, although rivastigmine showed an increased risk on adverse events than placebo (risk ratio, RR 1.19, TSA adjusted 95% CI 1.04 to 1.36), these events were usually mild or moderate, and the risk disappeared on serious adverse events.
CONCLUSIONS: Cholinesterase inhibitors and memantine slightly improve global impression; however, only cholinesterase inhibitors enhance cognitive function. Besides, all the drugs have good safety outcomes. But the limited trials precluded the generalisation of these outcomes.
ESTHER : Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_135
PubMedSearch : Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_135
PubMedID: 24828899

Title : Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis - Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_101
Author(s) : Wang J , Yu JT , Wang HF , Meng XF , Wang C , Tan CC , Tan L
Ref : Journal of Neurology Neurosurg Psychiatry , 86 :101 , 2015
Abstract : BACKGROUND: A wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting. OBJECTIVES: To quantify the efficacy and safety of pharmacological treatment on neuropsychiatric symptoms in AD patients.
METHODS: Systematic review and meta-analysis of RCTs comparing pharmacological agents with placebo on Neuropsychiatric Inventory (NPI) and safety outcomes in AD patients with neuropsychiatric symptoms.
RESULTS: Cholinesterase inhibitors (ChEIs) and atypical antipsychotics improved NPI total scores (ChEIs: standardised mean difference (SMD) -0.12; 95% CI -0.23 to -0.02; atypical antipsychotics: SMD -0.21; 95% CI -0.29 to -0.12), but antidepressants (95% CI -0.35 to 0.37) and memantine (95% CI -0.27 to 0.03) did not. However, ChEIs and atypical antipsychotics increased risk of dropouts due to adverse events (ChEIs: risk ratio (RR) 1.64; 95% CI 1.12 to 2.42; atypical antipsychotics: RR 2.24; 95% CI 1.53 to 3.26) and on incidence of adverse events (ChEIs: RR 1.08; 95% CI 1.01 to 1.17; atypical antipsychotics: RR 1.17; 95% CI 1.05 to 1.31). For typical antipsychotics, no study was included.
CONCLUSIONS: ChEIs and atypical antipsychotics could improve neuropsychiatric symptoms in AD patients, but with bad safety outcomes.
ESTHER : Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_101
PubMedSearch : Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_101
PubMedID: 24876182

Title : Development of self-assembling peptide nanovesicle with bilayers for enhanced EGFR-targeted drug and gene delivery - Liang_2015_Biomaterials_82_194
Author(s) : Liang X , Shi B , Wang K , Fan M , Jiao D , Ao J , Song N , Wang C , Gu J , Li Z
Ref : Biomaterials , 82 :194 , 2015
Abstract : Development of rational vectors for efficient drug and gene delivery is crucial for cancer treatment. In this study, epidermal growth factor receptor (EGFR)-binding peptide amphiphile (PA) were used as the primary bilayer skeleton material to construct ultra-stable self-assembling peptide nanovesicle (SPV). The resulted EGFR-targeted SPV (ESPV) could efficiently encapsulate therapeutic cargos (drugs or small interfering RNAs [siRNAs]) or labelled fluorescent cargo (quantum dots [QDs]) and exhibited excellent affinity for EGFR-positive cancer cells. Moreover, ESPV could deliver more drug or plasmid DNA to tumour sites and promote gene expression (a three-fold ratio of ESPVs vs cationic liposomes). Notably, the individual delivery or co-delivery of doxorubicin (DOX) and the acetylcholinesterase (AChE) gene via the ESPVs resulted in excellent drug/gene delivery both in vitro and in vivo and exerted a significant growth-suppressing effect on a liver cancer xenograft. This nanoscale, targeted cargo-packaging technology may provide a new strategy for the design of highly targeted cancer therapy vectors.
ESTHER : Liang_2015_Biomaterials_82_194
PubMedSearch : Liang_2015_Biomaterials_82_194
PubMedID: 26763734

Title : Properties of a newly identified esterase from Bacillus sp. K91 and its novel function in diisobutyl phthalate degradation - Ding_2015_PLoS.One_10_e0119216
Author(s) : Ding J , Wang C , Xie Z , Li J , Yang Y , Mu Y , Tang X , Xu B , Zhou J , Huang Z
Ref : PLoS ONE , 10 :e0119216 , 2015
Abstract : The widely used plasticizer phthalate esters (PAEs) have become a public concern because of their effects on environmental contamination and toxicity on mammals. However, the biodegradation of PAEs, especially diisobutyl phthalate (DiBP), remains poorly understood. In particular, genes involved in the hydrolysis of these compounds were not conclusively identified. In this study, the CarEW gene, which encodes an enzyme that is capable of hydrolyzing ro-nitrophenyl esters of fatty acids, was cloned from a thermophilic bacterium Bacillus sp. K91 and heterologously expressed in Escherichia coli BL21 using the pEASY-E2 expression system. The enzyme showed a monomeric structure with a molecular mass of approximately 53.76 kDa and pI of 4.88. The enzyme exhibited maximal activity at pH 7.5 and 45 degreesC, with ro-NP butyrate as the best substrate. The enzyme was fairly stable within the pH range from 7.0 to 8.5. High-pressure liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) were employed to detect the catabolic pathway of DiBP. Two intermediate products were identified, and a potential biodegradation pathway was proposed. Altogether, our findings present a novel DiBP degradation enzyme and indicate that the purified enzyme may be a promising candidate for DiBP detoxification and for environmental protection.
ESTHER : Ding_2015_PLoS.One_10_e0119216
PubMedSearch : Ding_2015_PLoS.One_10_e0119216
PubMedID: 25746227
Gene_locus related to this paper: bacsu-pnbae

Title : Insights into the origin and evolution of the plant hormone signaling machinery - Wang_2015_Plant.Physiol_167_872
Author(s) : Wang C , Liu Y , Li SS , Han GZ
Ref : Plant Physiol , 167 :872 , 2015
Abstract : Plant hormones modulate plant growth, development, and defense. However, many aspects of the origin and evolution of plant hormone signaling pathways remain obscure. Here, we use a comparative genomic and phylogenetic approach to investigate the origin and evolution of nine major plant hormone (abscisic acid, auxin, brassinosteroid, cytokinin, ethylene, gibberellin, jasmonate, salicylic acid, and strigolactone) signaling pathways. Our multispecies genome-wide analysis reveals that: (1) auxin, cytokinin, and strigolactone signaling pathways originated in charophyte lineages; (2) abscisic acid, jasmonate, and salicylic acid signaling pathways arose in the last common ancestor of land plants; (3) gibberellin signaling evolved after the divergence of bryophytes from land plants; (4) the canonical brassinosteroid signaling originated before the emergence of angiosperms but likely after the split of gymnosperms and angiosperms; and (5) the origin of the canonical ethylene signaling pathway postdates shortly the emergence of angiosperms. Our findings might have important implications in understanding the molecular mechanisms underlying the emergence of land plants.
ESTHER : Wang_2015_Plant.Physiol_167_872
PubMedSearch : Wang_2015_Plant.Physiol_167_872
PubMedID: 25560880

Title : Organelle-Specific Nitric Oxide Detection in Living Cells via HaloTag Protein Labeling - Wang_2015_PLoS.One_10_e0123986
Author(s) : Wang J , Zhao Y , Wang C , Zhu Q , Du Z , Hu A , Yang Y
Ref : PLoS ONE , 10 :e0123986 , 2015
Abstract : Nitric oxide (NO) is a membrane-permeable signaling molecule that is constantly produced, transferred, and consumed in vivo. NO participates and plays important roles in multiple biological processes. However, spatiotemporal imaging of NO in living cells is challenging. To fill the gap in currently used techniques, we exploited the versatility of HaloTag technology and synthesized a novel organelle-targetable fluorescent probe called HTDAF-2DA. We demonstrate the utility of the probe by monitoring subcellular NO dynamics. The developed strategy enables precise determination of local NO function.
ESTHER : Wang_2015_PLoS.One_10_e0123986
PubMedSearch : Wang_2015_PLoS.One_10_e0123986
PubMedID: 25923693

Title : Protostane Triterpenoids from the Rhizome of Alisma orientale Exhibit Inhibitory Effects on Human Carboxylesterase 2 - Mai_2015_J.Nat.Prod_78_2372
Author(s) : Mai ZP , Zhou K , Ge GB , Wang C , Huo XK , Dong PP , Deng S , Zhang BJ , Zhang HL , Huang SS , Ma XC
Ref : Journal of Natural Products , 78 :2372 , 2015
Abstract : Twelve new and 10 known protostane triterpenoids were isolated from the rhizome of Alisma orientale. Their structures were elucidated based on physical data analyses, including UV, HRESIMS, NMR experiments ((1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, and NOESY), and induced electronic circular dichroism. New compounds 1-12 were classified as protostanes (1-10), 29-norprotostane (11), and 24-norprotostane (12) by structure analyses. Furthermore, the inhibitory effects on human carboxylesterases (hCE-1, hCE-2) of compounds 1-22 were evaluated. Compounds 2, 6, 9, and 11 showed moderate inhibitory activities and were selective toward hCE-2 enzymes, with IC50 values of 8.68, 4.72, 4.58, and 2.02 muM, respectively. The inhibition kinetics of compound 11 toward hCE-2 were established, and the Ki value was determined as 1.76 muM using a mixed inhibition model. The interaction of bioactive compound 11 with hCE-2 was shown using molecular docking.
ESTHER : Mai_2015_J.Nat.Prod_78_2372
PubMedSearch : Mai_2015_J.Nat.Prod_78_2372
PubMedID: 26425784

Title : Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products - Wang_2015_BMC.Genomics_16_28
Author(s) : Wang X , Zhang X , Liu L , Xiang M , Wang W , Sun X , Che Y , Guo L , Liu G , Wang C , Yin WB , Stadler M , Liu X
Ref : BMC Genomics , 16 :28 , 2015
Abstract : BACKGROUND: In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics.
RESULTS: Here, we report the genome sequence of the endophytic fungus of tea Pestalotiopsis fici W106-1/CGMCC3.15140. The abundant carbohydrate-active enzymes especially significantly expanding pectinases allow the fungus to utilize the limited intercellular nutrients within the host plants, suggesting adaptation of the fungus to endophytic lifestyle. The P. fici genome encodes a rich set of secondary metabolite synthesis genes, including 27 polyketide synthases (PKSs), 12 non-ribosomal peptide synthases (NRPSs), five dimethylallyl tryptophan synthases, four putative PKS-like enzymes, 15 putative NRPS-like enzymes, 15 terpenoid synthases, seven terpenoid cyclases, seven fatty-acid synthases, and five hybrids of PKS-NRPS. The majority of these core enzymes distributed into 74 secondary metabolite clusters. The putative Diels-Alderase genes have undergone expansion. CONCLUSION: The significant expansion of pectinase encoding genes provides essential insight in the life strategy of endophytes, and richness of gene clusters for secondary metabolites reveals high potential of natural products of endophytic fungi.
ESTHER : Wang_2015_BMC.Genomics_16_28
PubMedSearch : Wang_2015_BMC.Genomics_16_28
PubMedID: 25623211
Gene_locus related to this paper: 9pezi-w3wud0 , 9pezi-w3xja3 , pesfw-w3wz53 , pesfw-w3x341 , pesfw-w3whp0 , pesfw-w3xc39 , pesfw-w3wrn9 , pesfw-pfmab , pesfw-pfmae

Title : Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke - Lin_2015_Neurology_85_1585
Author(s) : Lin J , Zheng H , Cucchiara BL , Li J , Zhao X , Liang X , Wang C , Li H , Mullen MT , Johnston SC , Wang Y
Ref : Neurology , 85 :1585 , 2015
Abstract : OBJECTIVE: To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke.
METHODS: We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days.
RESULTS: The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 +/- 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase).
CONCLUSIONS: Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events.
ESTHER : Lin_2015_Neurology_85_1585
PubMedSearch : Lin_2015_Neurology_85_1585
PubMedID: 26311748

Title : Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents - Zhang_2015_Acta.Pharm.Sin.B_5_67
Author(s) : Zhang X , Wang J , Hong C , Luo W , Wang C
Ref : Acta Pharm Sin B , 5 :67 , 2015
Abstract : A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 2.75 mumol/L, which was better than that of rivastigmine (5.60 mumol/L). Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10 mumol/L.
ESTHER : Zhang_2015_Acta.Pharm.Sin.B_5_67
PubMedSearch : Zhang_2015_Acta.Pharm.Sin.B_5_67
PubMedID: 26579427

Title : CYP2C8 rs17110453 and EPHX2 rs751141 two-locus interaction increases susceptibility to ischemic stroke - Yi_2015_Gene_565_85
Author(s) : Yi X , Zhang B , Wang C , Liao D , Lin J , Chi L
Ref : Gene , 565 :85 , 2015
Abstract : AIMS: Ischemic stroke (IS) is a multifactorial disease caused by a combination of environmental risk factors and genetic susceptibilities. However, few studies have assessed the effects of gene-gene interactions among cytochrome P450 (CYP) pathway genes on the risk of stroke. The present study investigated the association of seven variants of six CYP pathway genes with IS in a Chinese population. MAIN
METHODS: A total of 396 patients with IS and 378 controls were genotyped for seven variants from six CYP pathway genes, including CYP2J2 rs10889160, CYP2C8 rs17110453, CYP2C8 rs1934980, CYP2C9 rs1799853, CYP2C9 rs1057910, and CYP3A5 rs776746, as well as epoxide hydrolase 2 (EPHX2) rs751141, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) methods. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. KEY FINDINGS: Single-gene variant analysis showed no significant differences in the genotype distributions of the seven variants between IS patients and healthy volunteers. However, GMDR analysis showed a significant gene-gene interaction between rs17110453 and rs751141, with scores of 10 and 9 for the cross-validation consistency and sign test, respectively (P=0.0167). A 1.86-fold increased risk for IS was detected in individuals carrying the genotypes of rs17110453CC and rs751141GG (adjusted for age, hypertension, and diabetes mellitus; 95% CI: 1.216-2.896, P=0.005). SIGNIFICANCE: The CYP2C8 rs17110453 and EPHX2 rs751141 two-locus interaction confers a significantly higher risk for IS. The combinational analysis used in this study may be helpful in the elucidation of genetic risk factors for common and complex diseases such as IS.
ESTHER : Yi_2015_Gene_565_85
PubMedSearch : Yi_2015_Gene_565_85
PubMedID: 25839935

Title : Fungal biosynthesis of the bibenzoquinone oosporein to evade insect immunity - Feng_2015_Proc.Natl.Acad.Sci.U.S.A_112_11365
Author(s) : Feng P , Shang Y , Cen K , Wang C
Ref : Proc Natl Acad Sci U S A , 112 :11365 , 2015
Abstract : Quinones are widely distributed in nature and exhibit diverse biological or pharmacological activities; however, their biosynthetic machineries are largely unknown. The bibenzoquinone oosporein was first identified from the ascomycete insect pathogen Beauveria bassiana>50 y ago. The toxin can also be produced by different plant pathogenic and endophytic fungi with an array of biological activities. Here, we report the oosporein biosynthetic machinery in fungi, a polyketide synthase (PKS) pathway including seven genes for quinone biosynthesis. The PKS oosporein synthase 1 (OpS1) produces orsellinic acid that is hydroxylated to benzenetriol by the hydroxylase OpS4. The intermediate is oxidized either nonenzymatically to 5,5'-dideoxy-oosporein or enzymatically to benzenetetrol by the putative dioxygenase OpS7. The latter is further dimerized to oosporein by the catalase OpS5. The transcription factor OpS3 regulates intrapathway gene expression. Insect bioassays revealed that oosporein is required for fungal virulence and acts by evading host immunity to facilitate fungal multiplication in insects. These results contribute to the known mechanisms of quinone biosynthesis and the understanding of small molecules deployed by fungi that interact with their hosts.
ESTHER : Feng_2015_Proc.Natl.Acad.Sci.U.S.A_112_11365
PubMedSearch : Feng_2015_Proc.Natl.Acad.Sci.U.S.A_112_11365
PubMedID: 26305932
Gene_locus related to this paper: beab2-ops1

Title : Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida - Wang_2015_Bull.Environ.Contam.Toxicol_95_475
Author(s) : Wang K , Qi S , Mu X , Chai T , Yang Y , Wang D , Li D , Che W , Wang C
Ref : Bulletin of Environmental Contamination & Toxicology , 95 :475 , 2015
Abstract : Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.
ESTHER : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedSearch : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedID: 26293707

Title : Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors - Wang_2015_Bioorg.Med.Chem.Lett_25_5212
Author(s) : Wang C , Wu Z , Cai H , Xu S , Liu J , Jiang J , Yao H , Wu X , Xu J
Ref : Bioorganic & Medicinal Chemistry Lett , 25 :5212 , 2015
Abstract : A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.9nM and high AChE/BuChE selectivity (SI>230). Kinetic and molecular modeling studies suggested that compound 9d was mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. Besides, the preliminary structure-activity relationships were discussed.
ESTHER : Wang_2015_Bioorg.Med.Chem.Lett_25_5212
PubMedSearch : Wang_2015_Bioorg.Med.Chem.Lett_25_5212
PubMedID: 26454504

Title : Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors - Xu_2015_Sci.Rep_5_14261
Author(s) : Xu S , Zhang T , Kompella SN , Yan M , Lu A , Wang Y , Shao X , Chi C , Adams DJ , Ding J , Wang C
Ref : Sci Rep , 5 :14261 , 2015
Abstract : Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting alphaD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of alphaD-GeXXA, GeXXA-CTD, retains inhibitory activity against the alpha9alpha10 nAChR subtype. Furthermore, we identified that His7 of the rat alpha10 nAChR subunit determines the species preference of alphaD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that alphaD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of alphaD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds.
ESTHER : Xu_2015_Sci.Rep_5_14261
PubMedSearch : Xu_2015_Sci.Rep_5_14261
PubMedID: 26395518

Title : Toxicity of a neonicotinoid insecticide, guadipyr, in earthworm (Eisenia fetida) - Wang_2015_Ecotoxicol.Environ.Saf_114C_17
Author(s) : Wang K , Mu X , Qi S , Chai T , Pang S , Yang Y , Wang C , Jiang J
Ref : Ecotoxicology & Environmental Safety , 114C :17 , 2015
Abstract : Neonicotinoid insecticides are new class of pesticides and it is very meaningful to evaluate the toxicity of guadipyr to earthworm (Eisenia fetida). In the present study, effects of guadipyr on reproduction, growth, catalase(CAT), superoxide dismutase (SOD), acetylcholinesterase (AChE) and DNA damage in earthworm were assessed using an artificial soil medium. Guadipyr showed low toxicity to earthworms and did not elicit an effect on earthworm reproduction or growth in artificial soils at concentrations <100mg/kg. However, after exposure to guadipyr, the activity of SOD and CAT in earthworm increased and then decreased to control level. AChE activity decreased at day 3 at 50 and 100mg/kg and then increased to control level. Our data indicate that guadipyr did not induce DNA damage in earthworms at concentration of <100mg/kg.
ESTHER : Wang_2015_Ecotoxicol.Environ.Saf_114C_17
PubMedSearch : Wang_2015_Ecotoxicol.Environ.Saf_114C_17
PubMedID: 25594687

Title : Biosynthesis of non-melanin pigment by a divergent polyketide synthase in Metarhizium robertsii - Chen_2015_Fungal.Genet.Biol_81_142
Author(s) : Chen Y , Feng P , Shang Y , Xu YJ , Wang C
Ref : Fungal Genet Biol , 81 :142 , 2015
Abstract : Fungal polyketide synthases (PKSs) and their related gene clusters are highly diversified at both inter- and intra-specific levels. The most well characterized PKS enzymes include those responsible for the biosynthesis of polyketide pigments such as melanins. The genome of the insect pathogenic fungus Metarhizium robertsii contains 20 type I PKSs but none has been functionally characterized. In this study, two PKS genes (designated as MrPks1 and MrPKs2) showing homologies to those counterparts for the biosynthesis of heptaketide pigments and dihydroxynaphthalene (DHN)-melanins, respectively, were deleted in two different strains of M. robertsii. The results indicated that disruption of MrPks1 but not MrPks2 impaired fungal culture pigmentation and cell wall structure. In addition to the negative effect of the DHN-melanin pathway inhibitor, it was postulated that DHN-melanin would not be produced by M. robertsii. Various assays revealed that the stress resistance abilities against ultraviolet radiation, heat shock and oxidants, as well as virulence against insects were not impaired in deltaMrPks1 and deltaMrPks2 isolates when compared with the wild-type strain. Thus, the non-melanin pigment(s) produced by the fungus do not contribute to cell damage protection and pathogenicity in M. robertsii. Physiological differences were evident in the two examined wild-type strains. The results from this study advance the understanding of functional divergence of fungal PKSs.
ESTHER : Chen_2015_Fungal.Genet.Biol_81_142
PubMedSearch : Chen_2015_Fungal.Genet.Biol_81_142
PubMedID: 25445307
Gene_locus related to this paper: metra-pks2 , metaf-pks1

Title : Improvement of the activation of lipase from Candida rugosa following physical and chemical immobilization on modified mesoporous silica - Wang_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_45_261
Author(s) : Wang C , Li Y , Zhou G , Jiang X , Xu Y , Bu Z
Ref : Mater Sci Eng C Mater Biol Appl , 45 :261 , 2014
Abstract : Lipase from Candida rugosa (CRL) was chemically and physically immobilized onto four types of rod-shaped mesoporous silica (RSMS). RSMS prepared using surfactant P123 and poly(ethylene glycol) as co-templates was functionalized with (3-aminopropyl)triethoxysilane (APTES) to obtain P-RSMS by post-synthesis grafting. Tetraethoxysilane was hydrothermally co-condensed with APTES to obtain C-RSMS. A two-step process using APTES and glutaraldehyde was also performed to obtain G-RSMS. The effects of modification methods (including post-synthesis grafting and co-condensation) and glutaraldehyde on the mesoscopic order, interplanar spacing d100, cell parameter a0, mesoporous structure, and wall thickness of RSMS were studied in detail. Results showed that all samples were mesoporous materials with 2D mesostructures (p6mm). Pore size and d100 decreased, whereas the wall thickness increased after different modifications. CRL was used as a model enzyme to determine the effect of physical and chemical adsorption on loading amount and enzymatic activity. The possible mechanism of CRL immobilization on G-RSMS by chemical adsorption was systematically investigated. The chemical immobilization of CRL on G-RSMS increased the loading amount, hydrolytic activity, thermal stability, and reusability. Moreover, immobilized CRL was employed to catalyze the resolution of 2-octanol by esterification with caprylic acid. The enantiomeric excess of 2-octanol was 45.8% when the reaction was catalyzed by G-RSMS-CRL and decreased to about 38%-39% using the physically immobilized CRL, after 48h of reaction in hexane.
ESTHER : Wang_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_45_261
PubMedSearch : Wang_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_45_261
PubMedID: 25491828

Title : Electroacupuncture at PC6 or ST36 Influences the Effect of Tacrine on the Motility of Esophagus - Wang_2014_Evid.Based.Complement.Alternat.Med_2014_263489
Author(s) : Wang C , Chen X , Xie PY
Ref : Evid Based Complement Alternat Med , 2014 :263489 , 2014
Abstract : Aim. To investigate the mechanisms of gastrointestinal side effects of tacrine, and find treatment methods with electroacupuncture (EA). Methods. Twenty-five healthy cats were randomly divided into 5 groups: gastric-distention group (model group), tacrine group (cholinesterase inhibitor), tacrine + sham acupoint group (control group), tacrine + PC6 (neiguan) group, and tacrine + ST36 (zusanli) group, with 5 cats in each group. Saline 2 mL i.p. was given 30 min before gastric distention in model group. Tacrine 5.6 mg/kg i.p. was given 30 minutes before gastric distention in the other groups. Tacrine + sham acupoint group (control group), tacrine + PC6 group, and tacrine + ST36 group received EA at corresponding acupoints during gastric distention. The frequency of TLESRs and LESP were recorded by using a perfused sleeve assembly. Results. Compared with the model group, tacrine significantly increased the frequency of gastric distention-induced TLESR (P < 0.05) but did not influence the rate of common cavity during TLESR. Tacrine significantly increased the LESP, which could not remain during gastric distention. EA at PC6 could decrease the frequency of TLESR and maintain the increase of LESP, but EA at ST36 did not have these effects. Conclusion. Tacrine can significantly increase the gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs). Electroacupuncture (EA) at PC6 may reverse the above side effect.
ESTHER : Wang_2014_Evid.Based.Complement.Alternat.Med_2014_263489
PubMedSearch : Wang_2014_Evid.Based.Complement.Alternat.Med_2014_263489
PubMedID: 24808917

Title : A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 - Wang_2014_Appl.Environ.Microbiol_80_3811
Author(s) : Wang C , Chen Q , Wang R , Shi C , Yan X , He J , Hong Q , Li S
Ref : Applied Environmental Microbiology , 80 :3811 , 2014
Abstract : Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.
ESTHER : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedSearch : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedID: 24747891
Gene_locus related to this paper: 9sphn-q0kjt3 , sphwj-a0a059u2z8

Title : Chrysin attenuates experimental autoimmune neuritis by suppressing immuno-inflammatory responses - Xiao_2014_Neurosci_262_156
Author(s) : Xiao J , Zhai H , Yao Y , Wang C , Jiang W , Zhang C , Simard AR , Zhang R , Hao J
Ref : Neuroscience , 262 :156 , 2014
Abstract : Guillain-Barre syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. This study was designed to investigate the anti-inflammatory and neuroprotective properties of preventative and therapeutic chrysin treatment in EAN rats. For preventative treatment, chrysin was administered orally from day 1 to day 16 (50mg/kg once daily) while, for therapeutic treatment, rats received chrysin from day 7 to day 16 at the same dose once daily. Control animals received the same volume of the vehicle (phosphate-buffered saline/2% dimethylsulfoxide). Regardless of the treatment regimen, chrysin attenuated the severity and duration of the clinical course of EAN and reduced inflammatory cell infiltration and demyelination of sciatic nerves. In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1beta, interleukin-2, interleukin-6, inteleukin-12, interferon gamma and tumor necrosis factor alpha, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.
ESTHER : Xiao_2014_Neurosci_262_156
PubMedSearch : Xiao_2014_Neurosci_262_156
PubMedID: 24412705

Title : Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease: a systematic review and meta-analysis - Tan_2014_J.Alzheimers.Dis_41_615
Author(s) : Tan CC , Yu JT , Wang HF , Tan MS , Meng XF , Wang C , Jiang T , Zhu XC , Tan L
Ref : J Alzheimers Dis , 41 :615 , 2014
Abstract : Background: The role of currently available drugs for Alzheimer's disease (AD) has been controversial, with some national formularies restricting their use, and health economists questioning whether the small clinical effects are economically worthwhile. Objective: To estimate the efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of AD. Methods: Double-blind, placebo-controlled, with random assignment to a cholinesterase inhibitor or memantine trials were included into the pooled studies. Results: Cognitive effects were significant for all drugs, ranging from a -1.29 points mean difference (95% CI -2.30 to -0.28) in the 20 mg daily memantine trials to -3.20 points (95% CI -3.28 to -3.12) in the 32 mg daily galantamine group. Only memantine had no effect on the Clinicians' Global Impression of Change scale. No behavioral benefits were observed, except for -2.72 (95% CI -4.92 to -0.52) in the 10 mg daily donepezil group and -1.72 (95% CI -3.12 to -0.33) for 24 mg daily galantamine trial. Only 5 mg daily donepezil had no effect on the function outcome. Compared with placebo, more dropouts and adverse events occurred with the cholinesterase inhibitors, but not with memantine. Conclusions: Cholinesterase inhibitors and memantine are able to stabilize or slow decline in cognition, function, behavior, and global change.
ESTHER : Tan_2014_J.Alzheimers.Dis_41_615
PubMedSearch : Tan_2014_J.Alzheimers.Dis_41_615
PubMedID: 24662102

Title : A visible light photoelectrochemical biosensor coupling enzyme-inhibition for organophosphates monitoring based on a dual-functional Cd(0.5)Zn(0.5)S-reduced graphene oxide nanocomposite - Liu_2014_Analyst_139_1121
Author(s) : Liu Q , Cai J , Huan J , Dong X , Wang C , Qiu B , Wang K
Ref : Analyst , 139 :1121 , 2014
Abstract : A novel visible light photoelectrochemical (PEC) platform coupled with enzyme-inhibition for rapid and sensitive determination of organophosphates (OPs) was constructed based on a dual-functional Cd0.5Zn0.5S-reduced graphene oxide (Cd0.5Zn0.5S-rGO) nanocomposite. Due to the inherent biocompatibility of the Cd0.5Zn0.5S-rGO nanocomposite, acetylcholinesterase (AChE) immobilized on the Cd0.5Zn0.5S-rGO modified electrode can hydrolyze acetylthiocholine chloride into thiocholine, which could increase the photocurrent of the enzyme electrode, and the further inhibition of OPs on the enzyme electrode could decrease the photocurrent response. Based on the notable change in the PEC response of the AChE-Cd0.5Zn0.5S-rGO modified electrode and using Dursban as a model, a simple and effective way for PEC monitoring of OPs is proposed, which showed a wide linear range of 0.001-1 mug mL(-1) with a low detection limit of 0.3 ng mL(-1) (S/N = 3). Moreover, the biosensor was successfully challenged with water samples, demonstrating a new method for rapid and sensitive screening/evaluating exposure to organophosphorus pesticides and other hazardous substances.
ESTHER : Liu_2014_Analyst_139_1121
PubMedSearch : Liu_2014_Analyst_139_1121
PubMedID: 24416761

Title : Design of activated serine-containing catalytic triads with atomic-level accuracy - Rajagopalan_2014_Nat.Chem.Biol_10_386
Author(s) : Rajagopalan S , Wang C , Yu K , Kuzin AP , Richter F , Lew S , Miklos AE , Matthews ML , Seetharaman J , Su M , Hunt JF , Cravatt BF , Baker D
Ref : Nat Chemical Biology , 10 :386 , 2014
Abstract : A challenge in the computational design of enzymes is that multiple properties, including substrate binding, transition state stabilization and product release, must be simultaneously optimized, and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate reactivity. Following optimization by yeast display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest that the designs could provide the basis for a new class of organophosphate capture agents.
ESTHER : Rajagopalan_2014_Nat.Chem.Biol_10_386
PubMedSearch : Rajagopalan_2014_Nat.Chem.Biol_10_386
PubMedID: 24705591

Title : Rapid and sensitive detection of the inhibitive activities of acetyl- and butyryl-cholinesterases inhibitors by UPLC-ESI-MS\/MS - Liu_2014_J.Pharm.Biomed.Anal_94_215
Author(s) : Liu W , Yang Y , Cheng X , Gong C , Li S , He D , Yang L , Wang Z , Wang C
Ref : J Pharm Biomed Anal , 94 :215 , 2014
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are legitimate therapeutic targets for Alzheimer's disease. The classical approach for screening potential AChE/BChE inhibitors was developed by Ellman. However, the background color of compounds or plant extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Rapid, selective, and sensitive ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry method was developed and used for the detection of AChE and BChE inhibition by directly determining the common product, choline (Ch). Proper separation was achieved for choline and chlormequat (internal standard) within 1.2min via isocratic elution (0.1% fromic acid:methanol=98:2) on an HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of the intra- and inter-day precisions were below 7.34 and 9.09%, respectively, whereas the mean accuracy for the quality control samples was 100.31+/-10.93%. The method exhibited the advantages of small total reaction volume (100muL), short analysis time (1.2min), high sensitivity (LOQ of 0.036muM for Ch), and low cost (little consumption enzymes of 0.0035 and 0.008unitmL(-1) for AChE and BChE, and substrates of 5.505 and 7.152muM for ACh and BCh in individual inhibition, respectively), and without matrix effect (90.00-105.03%). The developed method was successfully applied for detecting the AChE and BChE inhibitive activities for model drugs, including galanthamine, tacrine, neostigmine methylsulfate, eserine, as well as beta-carboline and quinazoline alkaloids from Peganum harmala.
ESTHER : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedSearch : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedID: 24631841

Title : Valeriana amurensis improves Amyloid-beta 1-42 induced cognitive deficit by enhancing cerebral cholinergic function and protecting the brain neurons from apoptosis in mice - Wang_2014_J.Ethnopharmacol_153_318
Author(s) : Wang Q , Wang C , Shu Z , Chan K , Huang S , Li Y , Xiao Y , Wu L , Kuang H , Sun X
Ref : J Ethnopharmacol , 153 :318 , 2014
Abstract : ETHNOPHAMACOLOGICAL RELEVANCE: Valeriana amurensis, a perennial medicinal herb, has been widely used as anxiolytic, antidepressant, antispasmodic, and sedative in traditional Chinese medicines (TCMs). Moreover, it has been used to treat dementia in Mongolia preparations. In our previous study, we reported that AD-effective fraction of Valeriana amurensis (AD-EFV) has protective effect on Abeta-induced toxicity in PC12 cells. Up to now, however, the therapeutic effect of Valeriana amurensis on Alzheimer disease (AD) has not been explored. This study was designed to determine whether the AD-EFV could improve the Amyloid-beta (Abeta)-induced cognitive deficit and to explore the mechanism of AD-EFV improves cognitive deficit in intact animals. MATERIALS AND
METHODS: The constituents of AD-EFV were isolated with silica gel, octadecyl silica gel (ODS) column chromatography (CC) and preparative HPLC. The structures of compounds were determined by detailed NMR and ESI-MS data analyses. AD mice model was established by injecting Abeta1-42 (1muL, 200mumol) into the bilateral ventricle. Cognitive performance was evaluated by the Morris water maze (MWM) test. The level of cerebral acetylcholine (ACh), the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were investigated using Enzyme-linked immunoassay (ELISA) kits. Brain sections were processed and neuronal apoptosis in hippocampus were evaluated by Hematoxylin and Eosin (HE), Nissl, and Tunel stainings. The analyses of p-ERK/ERK and Bcl-2/Bax protein expression by western blot assay were used to explore the anti-neuronal apoptosis mechanism of AD-EFV.
RESULTS: Seventeen compounds (15 lignans and two iridoids) were isolated from AD-EFV. A significant improvement in cognitive function was observed in administrated AD-EFV AD model mice. AD-EFV increased the ACh level by enhancing the ChAT activity but has no effect on AChE activity in the cerebral cortex and hippocampus in mice. Moreover, the histological injury in hippocampus CA1 induced by Abeta1-42 was inhibited following administration of the AD-EFV. As well as the expression ratios of Bcl-2 to Bax and p-ERK to ERK were increased significantly in the mice which were administrated AD-EFV. CONCLUSION: These findings suggest that AD-EFV could ameliorate Abeta induced cognitive dysfunction through two underlying mechanisms: AD-EFV enhances the cerebral cholinergic function by increasing the secretion of ACh and enhancing the ChAT activity, and AD-EFV protects the brain neurons from Abeta induced apoptosis via activating the p-ERK and Bcl-2 signaling and suppressing the Bax pathways. Besides, the main constituents of AD-EFV are lignans which might be responsible for the AD-activity of Valeriana amurensis.
ESTHER : Wang_2014_J.Ethnopharmacol_153_318
PubMedSearch : Wang_2014_J.Ethnopharmacol_153_318
PubMedID: 24269774

Title : Mutatomics analysis of the systematic thermostability profile of Bacillus subtilis lipase A - Tian_2014_J.Mol.Model_20_2257
Author(s) : Tian F , Yang C , Wang C , Guo T , Zhou P
Ref : J Mol Model , 20 :2257 , 2014
Abstract : Use of point mutagenesis technique to improve protein thermostability is a routine strategy in the protein engineering community and directed evolution approach has been widely utilized to fulfill this. However, directed evolution often does not assure a minimalist design for obtaining a desired property in proteins, and other traditional methods such as error-prone PCR and iterative saturation mutagenesis are also too time-consuming and expensive to carry out a systemic search for protein mutation space. In the current study, we performed mutatomics analysis of the systematic thermostability profile of Bacillus subtilis lipase A (LipA) using a virtual scanning strategy. In the procedure, a new characterization method was proposed to describe structural variations upon protein residue mutation, and the generated descriptors were then statistically correlated with protein thermostability change associated with the mutation based on a large panel of structure-solved, melting temperature-known protein mutation data. As a result, linear and nonlinear quantitative structure-thermostability relationship (QSTR) models were built and their statistical quality was verified rigorously through internal cross-validation and external blind test. It is suggested that the nonlinear support vector machine (SVM) performed much better than linear partial least squares (PLS) regression in correlating protein structure and thermostability information. Thus, the SVM model was employed to systematically scan the complete mutation profile of LipA protein, resulting in a 181x19 matrix that characterizes the change in theoretical thermostability of LipA due to the mutation of wild-type residue at each of the 181 sequence sites to other 19 amino acid types. From the profile most mutations were predicted to (i) destabilize LipA structure and (ii) address modest effect on LipA thermostability. Satisfactorily, several known thermostable mutations such as G80V, G111D, M134D, and N161Y were identified properly and, expectedly, a number of mutations including L55Y, A75V, and S162P that have never been reported previously were inferred as hotspot mutations that have high potential to enhance LipA thermostability. The structural basis and energetic property of the five promising mutations were further examined in detail using atomistic molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann/surface area (MM-PB/SA) analysis, revealing intensive nonbonded interaction networks created by these mutations.
ESTHER : Tian_2014_J.Mol.Model_20_2257
PubMedSearch : Tian_2014_J.Mol.Model_20_2257
PubMedID: 24827611

Title : Highly sensitive assay for acetylcholinesterase activity and inhibition based on a specifically reactive photonic nanostructure - Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
Author(s) : Tian T , Li X , Cui J , Li J , Lan Y , Wang C , Zhang M , Wang H , Li G
Ref : ACS Appl Mater Interfaces , 6 :15456 , 2014
Abstract : Assays for acetylcholinesterase (AChE) with high sensitivity and high selectivity as well as facile manipulation have been urgently required in various fields. In this work, a reaction-based photonic strategy was developed for the efficient assay of AChE activity and inhibition based on the synergetic combination of the specific thiol-maleimide addition reaction with photonic porous structure. It was found that various applications including detection of AChE activity, measurement of the related enzymatic kinetics, and screening of inhibitors could be efficiently implemented using such strategy. Remarkably, the unique photonic nanostructure endows the constructed sensing platform with high sensitivity with a limit of detection (LOD) of 5 mU/mL for AChE activity, high selectivity, and self-reporting signaling. Moreover, the label-free solid film-based sensing approach described here has advantages of facile manipulation and bare-eye readout, compared with conventional liquid-phase methods, exhibiting promising potential in practical application for the AChE assay.
ESTHER : Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
PubMedSearch : Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
PubMedID: 25130420

Title : The treatment of Alzheimer's disease using Chinese Medicinal Plants: From disease models to potential clinical applications - Su_2014_J.Ethnopharmacol_152_403
Author(s) : Su Y , Wang Q , Wang C , Chan K , Sun Y , Kuang H
Ref : J Ethnopharmacol , 152 :403 , 2014
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports. MATERIAL AND
METHODS: Literature survey was performed via electronic search (SciFinder(R), Pubmed(R), Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries.
RESULTS: This review mainly introduces the current research on the Chinese Material Medica (CMM) theoretical research on Alzheimer's disease (AD), anti-AD active constituent of CMM, anti-AD effects on AD models, anti-AD mechanism of CMM, and anti-AD effect of CMM formula. CONCLUSION: Scholars around the world have made studies on the anti-AD molecular mechanism of CMM from different pathways, and have made substantial progress. The progress not only enriched the anti-AD theory of CMM, but also provided clinical practical significance and development prospects in using CMM to treat AD. Western pure drugs cannot replace the advantages of CMM in the anti-AD aspect. Therefore, in the near future, the development of CMM anti-AD drugs with a more clearly role and practical data will be a major trend in the field of AD drug development, and it will promote the use of CMM.
ESTHER : Su_2014_J.Ethnopharmacol_152_403
PubMedSearch : Su_2014_J.Ethnopharmacol_152_403
PubMedID: 24412377

Title : Comparative genomics and transcriptomics analyses reveal divergent lifestyle features of nematode endoparasitic fungus Hirsutella minnesotensis - Lai_2014_Genome.Biol.Evol_6_3077
Author(s) : Lai Y , Liu K , Zhang X , Li K , Wang N , Shu C , Wu Y , Wang C , Bushley KE , Xiang M , Liu X
Ref : Genome Biol Evol , 6 :3077 , 2014
Abstract : Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism.
ESTHER : Lai_2014_Genome.Biol.Evol_6_3077
PubMedSearch : Lai_2014_Genome.Biol.Evol_6_3077
PubMedID: 25359922
Gene_locus related to this paper: 9hypo-a0a0f7zjg7 , 9hypo-a0a0f7zm48 , 9hypo-a0a0f7zrk5 , 9hypo-a0a0f7ztt4 , 9hypo-a0a0f7ztz3 , 9hypo-a0a0f7zun4 , 9hypo-a0a0f7zus6 , 9hypo-a0a0f7zx75 , 9hypo-a0a0f7zy63 , 9hypo-a0a0f8a122 , 9hypo-a0a0f8a341 , 9hypo-a0a0f8a483 , 9hypo-a0a0f8a644 , 9hypo-a0a0f8a655 , 9hypo-a0a0f8a6k2 , 9hypo-a0a0f7zgk0 , 9hypo-a0a0f7zy10 , 9hypo-a0a0f7zmp5

Title : Trajectory and genomic determinants of fungal-pathogen speciation and host adaptation - Hu_2014_Proc.Natl.Acad.Sci.U.S.A_111_16796
Author(s) : Hu X , Xiao G , Zheng P , Shang Y , Su Y , Zhang X , Liu X , Zhan S , St Leger RJ , Wang C
Ref : Proc Natl Acad Sci U S A , 111 :16796 , 2014
Abstract : Much remains unknown regarding speciation. Host-pathogen interactions are a major driving force for diversification, but the genomic basis for speciation and host shifting remains unclear. The fungal genus Metarhizium contains species ranging from specialists with very narrow host ranges to generalists that attack a wide range of insects. By genomic analyses of seven species, we demonstrated that generalists evolved from specialists via transitional species with intermediate host ranges and that this shift paralleled insect evolution. We found that specialization was associated with retention of sexuality and rapid evolution of existing protein sequences whereas generalization was associated with protein-family expansion, loss of genome-defense mechanisms, genome restructuring, horizontal gene transfer, and positive selection that accelerated after reinforcement of reproductive isolation. These results advance understanding of speciation and genomic signatures that underlie pathogen adaptation to hosts.
ESTHER : Hu_2014_Proc.Natl.Acad.Sci.U.S.A_111_16796
PubMedSearch : Hu_2014_Proc.Natl.Acad.Sci.U.S.A_111_16796
PubMedID: 25368161
Gene_locus related to this paper: metan-a0a086npb7 , 9hypo-a0a0b2wj22 , 9hypo-a0a0b2wjv9 , 9hypo-a0a0b2wph9 , 9hypo-a0a0b2wpk8 , 9hypo-a0a0b2wpu7 , 9hypo-a0a0b2wwt8 , 9hypo-a0a0b2wyt3 , 9hypo-a0a0b2x1p9 , metan-a0a0b4es34 , 9hypo-a0a0b4g6h7 , 9hypo-a0a0b4gae9 , 9hypo-a0a0b4gyw4 , 9hypo-a0a0b4gzy5 , 9hypo-a0a0b4hfr4 , 9hypo-a0a0b4hi37 , 9hypo-a0a0b4hin0 , 9hypo-a0a0b4fk47 , 9hypo-a0a0b4g7m5 , 9hypo-a0a0b4i0i8 , 9hypo-a0a0b4ie69 , 9hypo-a0a0b4if28 , 9hypo-a0a0b4h1h6 , 9hypo-a0a0b4hlm2 , metan-a0a0d9pev7 , metas-a0a0b2wy97 , metas-a0a0b2wk60 , metra-e9ewg3 , metaq-pks1 , metra-pks2 , metmf-pks2 , metaf-pks1 , metbs-pks2 , metas-pks1

Title : SET-mediated NDRG1 inhibition is involved in acquisition of epithelial-to-mesenchymal transition phenotype and cisplatin resistance in human lung cancer cell - Liu_2014_Cell.Signal_26_2710
Author(s) : Liu H , Gu Y , Yin J , Zheng G , Wang C , Zhang Z , Deng M , Liu J , Jia X , He Z
Ref : Cell Signal , 26 :2710 , 2014
Abstract : Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) have been shown to play roles in resistance to chemotherapy. Here, we utilized a proteomics-based method and identified a significant downregulation of the metastasis suppressor NDRG1 in drug resistant lung cancer cells. We showed that downregulation of DNRG1 constitutes a mechanism for acquisition of EMT phenotype and endows lung cancer cells with an increased resistance to cisplatin. We also identified a signal cascade, namely, SET--- PP2A---| c-myc---| NDRG1, in which upregulation of SET is critical for inhibition of NDRG1. We also found that blockade of SET (or reactivation of PP2A) by FTY720 reverted EMT, restored drug sensitivity, and inhibited invasiveness and growth of lung tumor xenografts. Together, our results indicated a functional link between SET-mediated NDRG1 regulation and acquisition of EMT phenotype and drug resistance, and provided an evidence that blockade of SET-driven EMT can overcome drug resistance and inhibit tumor progression.
ESTHER : Liu_2014_Cell.Signal_26_2710
PubMedSearch : Liu_2014_Cell.Signal_26_2710
PubMedID: 25152373

Title : Genome survey uncovers the secrets of sex and lifestyle in caterpillar fungus. - Hu_2013_Chin.Sci.Bull_58_2846
Author(s) : Hu X , Zhang Y , Xiao G , Zheng P , Xia Y , Zhang X , St Leger R.J , Liu X , Wang C
Ref : Chin Sci Bull , 58 :2846 , 2013
Abstract : The caterpillar fungus Ophiocordyceps sinensis (best known as Cordyceps sinensis) mummifies ghost moth larvae exclusively in Tibetan Plateau alpine ecosystems. Touted as -YHimalayan Viagra, the fungus is highly prized due to its medical benefits and dwindling supplies. Attempts to culture the sexual fruiting-body have failed and the huge market demand has led to severe devastation of local ecosystems and to the fungus heading towards extinction. By genome sequencing, we establish that unlike related insect pathogens O. sinensis contains two compatible mating-type genes in its genome and is self-fertile, i.e. homothallic. However, sexual processes are only initiated under native environmental conditions. O. sinensis resembles biotrophic plant pathogens in having a genome shaped by retrotransposon-driven expansions. The resulting changes in gene content suggest that O. sinensis has a biphasic pathogenic mechanism beginning with stealth pathogenesis in early host instars. O. sinensis is the first psychrophilic fungus sequenced and is adapted to extreme cold with putative antifreeze proteins and mechanisms for increasing lipid accumulation and fatty acid unsaturation. We hypothesize that for the inbreeding O. sinensis the massive proliferation of retrotransposons provides a tradeoff between the advantages of increased genetic variation independent of sexual recombination and deletion of genes dispensable for its specialized pathogenic lifestyle.
ESTHER : Hu_2013_Chin.Sci.Bull_58_2846
PubMedSearch : Hu_2013_Chin.Sci.Bull_58_2846
Gene_locus related to this paper: ophsc-t5ap86 , ophsc-t5abc7 , ophsc-t5acw5 , ophsc-t5ajn1 , ophsc-t5aqy1

Title : Toxicity assessments with Daphnia magna of Guadipyr, a new neonicotinoid insecticide and studies of its effect on acetylcholinesterase (AChE), glutathione S-transferase (GST), catalase (CAT) and chitobiase activities - Qi_2013_Ecotoxicol.Environ.Saf_98_339
Author(s) : Qi S , Wang C , Chen X , Qin Z , Li X
Ref : Ecotoxicology & Environmental Safety , 98 :339 , 2013
Abstract : Guadipyr is a novel neonicotinoid insecticide, developed by the China Agricultural University. This work investigated its aquatic toxicity on Daphnia magna. The acute immobilization test showed that guadipyr was slightly toxic to daphnids, with a 48h EC50 of 13.01mg/L. In addition, guadipyr significantly enhanced the acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity (per gram of protein), but had no obvious impact on catalase (CAT) activity within 48h. The 21d chronic exposure of D. magna to guadipyr induced a significant decrease in body growth and reproduction; both share the same lowest observed effect concentration (LOEC) at 0.10mg/L. In the 14d chronic test, a significant increase in chitobiase activity in test media was observed at day 8 (days to the first breeding), while a significant decrease was observed from days 10 to 14, which might be due to the endocrine imbalance resulting from guadipyr stress. These results demonstrated that guadipyr can induce notable negative ecotoxicological impacts on the aquatic system in long-term exposure at a sub-lethal dose. Further research in environmental behaviors is needed to regulate guadipyr use in the future.
ESTHER : Qi_2013_Ecotoxicol.Environ.Saf_98_339
PubMedSearch : Qi_2013_Ecotoxicol.Environ.Saf_98_339
PubMedID: 24075643

Title : Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens - Liu_2013_PLoS.One_8_e55185
Author(s) : Liu G , Zhang L , Wei X , Zou G , Qin Y , Ma L , Li J , Zheng H , Wang S , Wang C , Xun L , Zhao GP , Zhou Z , Qu Y
Ref : PLoS ONE , 8 :e55185 , 2013
Abstract : Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.
ESTHER : Liu_2013_PLoS.One_8_e55185
PubMedSearch : Liu_2013_PLoS.One_8_e55185
PubMedID: 23383313
Gene_locus related to this paper: peno1-s7zjd1 , peno1-s8aym9 , peno1-s7zcd7 , peno1-s8aui7 , peno1-s7zba9 , peno1-s7z7w2 , peno1-s7zkn6 , peno1-s8ak78 , peno1-s7z721 , peno1-s8ajn6 , peno1-s7zqw4 , peno1-s8bba0 , peno1-s8b4w2 , peno1-s7zta4 , peno1-s8a1h3 , peno1-s8aiq5 , peno1-s8ba66 , peno1-s7zxp5 , penox-poxo

Title : Contamination by metals and pharmaceuticals in northern Taihu Lake (China) and its relation to integrated biomarker response in fish - Lu_2013_Ecotoxicology_22_50
Author(s) : Lu G , Yang X , Li Z , Zhao H , Wang C
Ref : Ecotoxicology , 22 :50 , 2013
Abstract : Taihu Lake is the largest shallow freshwater lake in eastern China and is suffering not only from an increasingly serious threat of eutrophication but also potential ecological risk due to the input of emerging contaminants. Active biomonitoring was conducted in Taihu Lake using transplanted goldfish (Carassius auratus) to determine the contamination by pharmaceuticals and metals and to assess the potential ecological risk. A suite of biomarkers including acetylcholinesterase, ethoxyresorufin O-deethylase, glutathione S-transferase, glutathione peroxidase and superoxide dismutase activities in fish after 7, 14, 21 and 28 days of exposure in situ, as well as pharmaceuticals and metals in water, were determined during the field exposure period. The results indicate that pharmaceuticals exist mainly in Zhushan Bay and Meiliang Bay, while metals are present mainly in Gong Bay. An integrated biomarker response (IBR) was calculated and used to evaluate the ecological risk of the polluted area of Taihu Lake. It was found that Zhushan Bay might present higher risk to fish, followed by Meiliang Bay. IBR values were in good agreement with copper and caffeine concentrations.
ESTHER : Lu_2013_Ecotoxicology_22_50
PubMedSearch : Lu_2013_Ecotoxicology_22_50
PubMedID: 23053787

Title : [Impacts that dimethoate inhibited the benchmark dose of acetylcholinesterase based on experimental designs] - He_2013_Wei.Sheng.Yan.Jiu_42_999
Author(s) : He X , Li T , Yi N , Wu H , Zhao M , Yao X , Wang C
Ref : Wei Sheng Yan Jiu , 42 :999 , 2013
Abstract : OBJECTIVE: To obtain the impacts of experimental design on benchmark dose (BMD), and the result was applied to test the computer simulation by software Slob (optimal method to calculate the BMD: for a certain sample capacity, to add the experimental groups by reducing the amount of animals in each group) , consequently, this method can be widely used in the future.
METHODS: Eighty adult female SD rats were ig given dimethoate 0.5, 1, 2, 4, 8, 16 and 32 mg/kg for 21 d, respectively. Rats were sacrificed, and acetylcholinesterase (AChE) activity in the hippocampus, cerebral cortex and serum of rats was determined after dimethoate was ig given to rats for 21 d. And then, the software package PROAST28.1 was applied to calculate the BMD. The four does groups of 10 animals (4 x 10 design) and 8 x 5 design were selected from 8 x 10 design to study the impacts of experimental design on BMD.
RESULTS: Comparing with the normal control, the significant decline of AChE in hippocampus was observed in 2, 4, 8, 16 and 32 mg/kg groups (P < 0.05), whereas the significant decrease was obtained in 0.5, 1, 2, 4, 8, 16 and 32 mg/kg groups (P < 0.05). Taking the 8 x 10 design as the standard, the confidence interval of BMD calculated by both of 4 x 10 design and 8 x 5 design covered the BMD by 8 x 10 design. And also, confidence interval of BMD, calculated by design scheme 1, 2, 3, 4 and 6 of 4 x 10 design, wider than that of 8 x 5 design, but its scheme 5 narrower than 8 x 5 design. CONCLUSION: To add experimental groups in a certain sample capacity was the optimal method to calculate BMD, but was not the common toxicity experimental design (e. g. set four groups including control, low-dose, moderate-dose, high-dose group).
ESTHER : He_2013_Wei.Sheng.Yan.Jiu_42_999
PubMedSearch : He_2013_Wei.Sheng.Yan.Jiu_42_999
PubMedID: 24459918

Title : Cell debris self-immobilized thermophilic lipase: a biocatalyst for synthesizing aliphatic polyesters - Sun_2013_Appl.Biochem.Biotechnol_170_399
Author(s) : Sun Y , Yang Y , Wang C , Liu J , Shi W , Zhu X , Lu L , Li Q
Ref : Appl Biochem Biotechnol , 170 :399 , 2013
Abstract : The paper explored the catalytic activity of a cell debris self-immobilized thermophilic lipase for polyester synthesis, using the ring-opening polymerization of sigma-caprolactone as model. Effects of biocatalyst concentration, temperature, and reaction medium on monomer conversion and product molecular weight were systematically evaluated. The biocatalyst displayed high catalytic activity at high temperatures (70-90 degreesC), with 100 % monomer conversion. High monomer conversion values (>90 %) were achieved in both hydrophobic and hydrophilic solvents, and also in solvent-free system, with the exception of dichloromethane. Poly(sigma-caprolactone) was obtained in 100 % monomer conversion, with a number-average molecular weight of 1,680 g/mol and a polydispersity index of 1.35 in cyclohexane at 70 degreesC for 72 h. Furthermore, the biocatalyst exhibited excellent operational stability, with monomer conversion values exceeding 90 % over the course of 15 batch reactions.
ESTHER : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedSearch : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedID: 23536248

Title : Poster: Novel strategy of blocking nAChR revealed by dissecting a dimeric conotoxin alphaD-GeXXA -
Author(s) : Kompella SN , Xu S , Zhang T , Yan M , Shao X , Chi C , Ding J , Wang C , Adams DJ
Ref : Biochemical Pharmacology , 86 :1229 , 2013

Title : On the evolutionary history, population genetics and diversity among isolates of Salmonella Enteritidis PFGE pattern JEGX01.0004 - Allard_2013_PLoS.One_8_e55254
Author(s) : Allard MW , Luo Y , Strain E , Pettengill J , Timme R , Wang C , Li C , Keys CE , Zheng J , Stones R , Wilson MR , Musser SM , Brown EW
Ref : PLoS ONE , 8 :e55254 , 2013
Abstract : Facile laboratory tools are needed to augment identification in contamination events to trace the contamination back to the source (traceback) of Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis). Understanding the evolution and diversity within and among outbreak strains is the first step towards this goal. To this end, we collected 106 new S. Enteriditis isolates within S. Enteriditis Pulsed-Field Gel Electrophoresis (PFGE) pattern JEGX01.0004 and close relatives, and determined their genome sequences. Sources for these isolates spanned food, clinical and environmental farm sources collected during the 2010 S. Enteritidis shell egg outbreak in the United States along with closely related serovars, S. Dublin, S. Gallinarum biovar Pullorum and S. Gallinarum. Despite the highly homogeneous structure of this population, S. Enteritidis isolates examined in this study revealed thousands of SNP differences and numerous variable genes (n = 366). Twenty-one of these genes from the lineages leading to outbreak-associated samples had nonsynonymous (causing amino acid changes) changes and five genes are putatively involved in known Salmonella virulence pathways. While chromosome synteny and genome organization appeared to be stable among these isolates, genome size differences were observed due to variation in the presence or absence of several phages and plasmids, including phage RE-2010, phage P125109, plasmid pSEEE3072_19 (similar to pSENV), plasmid pOU1114 and two newly observed mobile plasmid elements pSEEE1729_15 and pSEEE0956_35. These differences produced modifications to the assembled bases for these draft genomes in the size range of approximately 4.6 to 4.8 mbp, with S. Dublin being larger ( approximately 4.9 mbp) and S. Gallinarum smaller (4.55 mbp) when compared to S. Enteritidis. Finally, we identified variable S. Enteritidis genes associated with virulence pathways that may be useful markers for the development of rapid surveillance and typing methods, potentially aiding in traceback efforts during future outbreaks involving S. Enteritidis PFGE pattern JEGX01.0004.
ESTHER : Allard_2013_PLoS.One_8_e55254
PubMedSearch : Allard_2013_PLoS.One_8_e55254
PubMedID: 23383127
Gene_locus related to this paper: salty-STY1441 , salty-ycfp , salen-l6rcw4

Title : Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs - Keane_2013_FEBS.Open.Bio_4_43
Author(s) : Keane FM , Yao TW , Seelk S , Gall MG , Chowdhury S , Poplawski SE , Lai JH , Li Y , Wu W , Farrell P , Vieira de Ribeiro AJ , Osborne B , Yu DM , Seth D , Rahman K , Haber P , Topaloglu AK , Wang C , Thomson S , Hennessy A , Prins J , Twigg SM , McLennan SV , McCaughan GW , Bachovchin WW , Gorrell MD
Ref : FEBS Open Bio , 4 :43 , 2013
Abstract : The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was approximately 20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.
ESTHER : Keane_2013_FEBS.Open.Bio_4_43
PubMedSearch : Keane_2013_FEBS.Open.Bio_4_43
PubMedID: 24371721

Title : Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis - Chen_2013_BMC.Genomics_14_339
Author(s) : Chen L , Yue Q , Zhang X , Xiang M , Wang C , Li S , Che Y , Ortiz-Lopez FJ , Bills GF , Liu X , An Z
Ref : BMC Genomics , 14 :339 , 2013
Abstract : BACKGROUND: The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868.
RESULTS: The pneumocandin biosynthetic gene cluster contains a NRPS (GLNRPS4) and a PKS (GLPKS4) arranged in tandem, two cytochrome P450 monooxygenases, seven other modifying enzymes, and genes for L-homotyrosine biosynthesis, a component of the peptide core. Thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin B gene cluster. Disruption mutants of GLNRPS4 and GLPKS4 no longer produced the pneumocandins (A0 and B0), and the Deltaglnrps4 and Deltaglpks4 mutants lost antifungal activity against the human pathogenic fungus Candida albicans. In addition to pneumocandins, the G. lozoyensis genome encodes a rich repertoire of natural product-encoding genes including 24 PKSs, six NRPSs, five PKS-NRPS hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases.
CONCLUSIONS: Characterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. Whole genome estimation of the secondary metabolite-encoding genes from G. lozoyensis provides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom.
ESTHER : Chen_2013_BMC.Genomics_14_339
PubMedSearch : Chen_2013_BMC.Genomics_14_339
PubMedID: 23688303
Gene_locus related to this paper: glal2-s3cg73 , glal2-s3d2r4 , glal2-s3dmm6 , glal2-s3e306 , glal2-s3dl45 , glal2-s3d1r9 , glal2-s3e4a7 , glal2-s3ddr1 , glal2-s3ctz6 , glal2-s3dy35 , glal2-s3dws5 , glal2-s3df31 , glal2-s3d7q5 , glal2-s3cwz5 , glal2-s3dcn7 , glal2-s3dhj7 , glal2-s3dm96 , glal2-s3d6q1 , glal2-s3cv25 , glal2-s3e8v9 , glal2-s3crh2 , glal2-s3dde8 , glal2-s3cxt6 , glal2-s3da89 , glal2-s3ckn8 , glal2-s3d4y3 , glal2-s3ddw6 , glal2-s3dk02 , glal2-s3d048 , glal2-s3de12

Title : Genome Sequences of Two Emerging Non-O157 Shiga Toxin-Producing Escherichia coli Strains - Cao_2013_Genome.Announc_1_E00200
Author(s) : Cao G , Ju W , Rump L , Zhao S , Zou L , Wang C , Strain E , Luo Y , Timme R , Allard M , Brown E , Meng J
Ref : Genome Announc , 1 :E00200 , 2013
Abstract : Shiga toxin-producing Escherichia coli (STEC) causes severe illness in humans, including hemorrhagic colitis and hemolytic uremic syndrome. A parallel evolutionary model was proposed in which E. coli strains of distinct phylogenies independently integrate Shiga toxin-encoding genes and evolve into STEC. We report the draft genomes of two emerging non-O157 STEC strains.
ESTHER : Cao_2013_Genome.Announc_1_E00200
PubMedSearch : Cao_2013_Genome.Announc_1_E00200
PubMedID: 23682138
Gene_locus related to this paper: ecoli-d7xp23 , ecoli-ybff , ecoli-ycfp , ecoli-yiel , ecoli-yqia , ecoli-Z1930 , ecoli-YfhR

Title : Fully assembled genome sequence for Salmonella enterica subsp. enterica Serovar Javiana CFSAN001992 - Allard_2013_Genome.Announc_1_e0008113
Author(s) : Allard MW , Muruvanda T , Strain E , Timme R , Luo Y , Wang C , Keys CE , Payne J , Cooper T , Luong K , Song Y , Chin CS , Korlach J , Roberts RJ , Evans P , Musser SM , Brown EW
Ref : Genome Announc , 1 :e0008113 , 2013
Abstract : We report a closed genome of Salmonella enterica subsp. enterica serovar Javiana (S. Javiana). This serotype is a common food-borne pathogen and is often associated with fresh-cut produce. Complete (finished) genome assemblies will support pilot studies testing the utility of next-generation sequencing (NGS) technologies in public health laboratories.
ESTHER : Allard_2013_Genome.Announc_1_e0008113
PubMedSearch : Allard_2013_Genome.Announc_1_e0008113
PubMedID: 23516208

Title : Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases acetylcholinesterase activity of hippocampus in adult male mice - Luo_2013_Food.Chem.Toxicol_60C_177
Author(s) : Luo G , Wei R , Niu R , Wang C , Wang J
Ref : Food & Chemical Toxicology , 60C :177 , 2013
Abstract : The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which is involved in anxiety-like behavior. This study investigated behavioral phenotypes and AChE activity in male mice following BPA exposure during puberty. On postnatal day (PND) 35, male mice were exposed to 50mg BPA/kg diet per day for a period of 35days. On PND71, a behavioral assay was performed using the elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus. Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors.
ESTHER : Luo_2013_Food.Chem.Toxicol_60C_177
PubMedSearch : Luo_2013_Food.Chem.Toxicol_60C_177
PubMedID: 23871786

Title : Pyrene exposure influences the thyroid development of Sebastiscus marmoratus embryos - He_2012_Aquat.Toxicol_124-125_28
Author(s) : He C , Zuo Z , Shi X , Sun L , Wang C
Ref : Aquat Toxicol , 124-125 :28 , 2012
Abstract : Thyroid hormones play crucial roles in regulating development, morphogenesis, growth, and behavior in fishes. Some environmental pollutants have adverse effects on either development or function of the thyroid gland in fish. However, there are few reports on the effects of polycyclic aromatic hydrocarbons (PAHs) on fish thyroid. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to pyrene (Py) for 5 days at the concentrations of 0.5, 5, and 50 nmol/L. The results showed that Py exposure decreased the expression of thyroid primordium markers, Pax2.1 and Nk2.1a as detected by quantitative PCR and in situ hybridization, and reduced the concentration of T(3), but not T(4). Thyroid receptor genes (TRalpha and TRbeta) expression was down-regulated by Py. At the same time, Py exposure impaired the expression of thyroid development related genes, Fgfr2 and Hoxa3a expression, and altered the mRNA levels of thyroid function related genes, Deio1, Ttr, and Tg. In conclusion, the results demonstrated Py exposure inhibited thyroid development and influenced the function of thyroid system in rockfish embryos.
ESTHER : He_2012_Aquat.Toxicol_124-125_28
PubMedSearch : He_2012_Aquat.Toxicol_124-125_28