Liu K

References (39)

Title : Rhynchophylline relieves nonalcoholic fatty liver disease by activating lipase and increasing energy metabolism - Liu_2023_Int.Immunopharmacol_117_109948
Author(s) : Liu K , Liu S , Wu C , Wang Y , Zhang Y , Yu J , Li X , Qi X , Su S , Zhou L , Li Y
Ref : Int Immunopharmacol , 117 :109948 , 2023
Abstract : Hepatic fat metabolism may be altered in the context of overnutrition and obesity, often resulting in the accumulation of triglycerides in hepatocytes and leading to nonalcoholic fatty liver disease (NAFLD). Natural plant alkaloids have demonstrated great potential for the prevention and treatment of NAFLD. However, the role of rhynchophylline (RHY) in lipid metabolism is not clear. We explored the role of RHY in lipid metabolism in cells treated with oleic and palmitic acids to mimic high-fat diet (HFD) conditions. RHY attenuated oleic and palmitic acid-induced increases in triglyceride accumulation in HepG2, AML12, and LMH cells. RHY also increased energy metabolism and reduced oxidative stress. We further investigated the effect of RHY on hepatic lipid metabolism in mice fed an HFD including 40 mg/kg RHY. RHY alleviated hepatic steatosis, reduced fat deposition, promoted energy metabolism, and improved glucose metabolism. We investigated the mechanism responsible for this activity by docking with key proteins of lipid metabolism disorders using Discovery Studio software, which showed that RHY interacted well with lipases. Finally, we found that adding RHY promoted lipase activity and lipolysis. In conclusion, RHY ameliorated HFD-induced NAFLD and its complications by increasing lipase activity.
ESTHER : Liu_2023_Int.Immunopharmacol_117_109948
PubMedSearch : Liu_2023_Int.Immunopharmacol_117_109948
PubMedID: 37012893

Title : A Dual Fluorescence Assay Enables High-Throughput Screening for Poly(ethylene terephthalate) Hydrolases - Liu_2023_ChemSusChem_16_e202202019
Author(s) : Liu K , Xu Z , Zhao Z , Chen Y , Chai Y , Ma L , Li S
Ref : ChemSusChem , 16 :e202202019 , 2023
Abstract : The drastically increasing consumption of petroleum-derived plastics hasserious environmental impacts and raises public concerns. Poly(ethylene terephthalate) (PET) is amongst the most extensively produced synthetic polymers. Enzymatic hydrolysis of PET recently emerged as an enticing path for plastic degradation and recycling. In-lab directed evolution has revealed the great potential of PET hydrolases (PETases). However, the time-consuming and laborious PETase assays hinder the identification of effective variants in large mutant libraries. Herein, we devise and validate a dual fluorescence-based high-throughput screening (HTS) assay for a representative IsPETase. The two-round HTS of a pilot library consisting of 2850 IsPETase variants yields six mutant IsPETases with 1.3-4.9 folds improved activities. Compared to the currently used structure- or computational redesign-based PETase engineering, this HTS approach provides a new strategy for discovery of new beneficial mutation patterns of PETases.
ESTHER : Liu_2023_ChemSusChem_16_e202202019
PubMedSearch : Liu_2023_ChemSusChem_16_e202202019
PubMedID: 36511949

Title : OsLDDT1, encoding a transmembrane structural DUF726 family protein, is essential for tapetum degradation and pollen formation in rice - Sun_2023_Plant.Sci__111596
Author(s) : Sun Z , Liu K , Chen C , Chen D , Peng Z , Zhou R , Liu L , He D , Duan W , Chen H , Huang C , Ruan Z , Zhang Y , Cao L , Zhan X , Cheng S , Sun L
Ref : Plant Sci , :111596 , 2023
Abstract : Formation of the pollen wall, which is mainly composed of lipid substances secreted by tapetal cells, is important to ensure pollen development in rice. Although several regulatory factors related to lipid biosynthesis during pollen wall formation have been identified in rice, the molecular mechanisms controlling lipid biosynthesis are unclear. We isolated the male-sterile rice mutant oslddt1 (leaked and delayed degraded tapetum 1). oslddt1 plants show complete pollen abortion resulting from delayed degradation of the tapetum and blocked formation of Ubisch bodies and pollen walls. OsLDDT1 (LOC_Os03g02170) encodes a DUF726 containing protein of unknown functionwith highly conserved transmembrane and alpha/beta Hydrolase domains. OsLDDT1 localizes to the endoplasmic reticulum and the gene is highly expressed in rice panicles. Genes involved in regulating fatty acid synthesis and formation of sporopollenin and pollen exine during anther developmentshowed significantly different expression patterns in oslddt1 plants. Interestingly, the wax and cutin contents in mature oslddt1-1 anthers were decreased by 74.07% and 72.22% compared to WT, indicating that OsLDDT1 is involved in fatty acid synthesis and affects formation of the anther epidermis. Our results provide as deeper understanding of the role of OsLDDT1 in regulating male sterility and also provide materials for hybrid rice breeding.
ESTHER : Sun_2023_Plant.Sci__111596
PubMedSearch : Sun_2023_Plant.Sci__111596
PubMedID: 36657664
Gene_locus related to this paper: orysj-q10ss2

Title : Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer - Shen_2023_Appl.Microbiol.Biotechnol__
Author(s) : Shen K , Zhou X , Hu L , Xiao J , Cheng Q , Wang Y , Liu K , Fan H , Xu Z , Yang L
Ref : Applied Microbiology & Biotechnology , : , 2023
Abstract : Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16-1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. KEY POINTS: Rs15285 polymorphism is a risk factor for GC. Rs12585 TT genotype predicts a bad outcome in GC individuals. Rs15285 T allele enhances GC cells malignant biological behavior.
ESTHER : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedSearch : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedID: 37036527
Gene_locus related to this paper: human-LPL

Title : Role of cholinergic innervation in biliary remnants of patients with biliary atresia - Yang_2023_Front.Pediatr_11_1278978
Author(s) : Yang J , Chen X , Wang W , Su Y , Liu K , Abudusalamu A , Li D , He Y , Wang P , Xiong X , Feng J
Ref : Front Pediatr , 11 :1278978 , 2023
Abstract : OBJECTIVE: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. METHODS: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. RESULTS: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R(2 )= 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). CONCLUSIONS: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
ESTHER : Yang_2023_Front.Pediatr_11_1278978
PubMedSearch : Yang_2023_Front.Pediatr_11_1278978
PubMedID: 38259596

Title : Combined application of multiple biomarkers for early auxiliary diagnosis of silicosis - Liu_2023_Toxicol.Ind.Health__7482337231154636
Author(s) : Liu K , Sun L , Li S , Xu H
Ref : Toxicol Ind Health , :7482337231154636 , 2023
Abstract : Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84-0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.
ESTHER : Liu_2023_Toxicol.Ind.Health__7482337231154636
PubMedSearch : Liu_2023_Toxicol.Ind.Health__7482337231154636
PubMedID: 36734071

Title : Comparison of chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities between coffee flowers and leaves as potential novel foods - Shen_2023_Food.Sci.Nutr_11_917
Author(s) : Shen X , Nie F , Fang H , Liu K , Li Z , Li X , Chen Y , Chen R , Zheng T , Fan J
Ref : Food Sci Nutr , 11 :917 , 2023
Abstract : This study aimed to compare chemical compositions, antioxidant activities, and acetylcholinesterase inhibitory activities of coffee flowers (ACF) and coffee leaves (ACL) with green coffee beans (ACGB) of Coffea Arabica L. The chemical compositions were determined by employing high-performance liquid chromatography-mass spectroscopy (HPLC-MS) and gas chromatography-mass spectroscopy (GC-MS) techniques. Antioxidant effects of the components were evaluated using DPPH and ABTS radical scavenging assays, and the ferric reducing antioxidant power (FRAP) assay. Their acetylcholinesterase inhibitory activities were also evaluated. The coffee sample extracts contained a total of 214 components identified by HPLC-MS and belonged to 12 classes (such as nucleotides and amino acids and their derivatives, tannins, flavonoids, alkaloids, benzene, phenylpropanoids, and lipids.), where phenylpropanoids were the dominant component (>30%). The contents of flavonoids, alkaloids, saccharides, and carboxylic acid and its derivatives in ACF and ACL varied significantly (p < .05) compared to similar components in ACGB. Meanwhile, 30 differentially changed chemical compositions (variable importance in projection [VIP] > 1, p < .01 and fold change [FC] > 4, or <0.25), that determine the difference in characteristics, were confirmed in the three coffee samples. Furthermore, among 25 volatile chemical components identified by GC-MS, caffeine, n-hexadecanoic acid, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-phenol], and quinic acid were common in these samples with caffeine being the highest in percentage. In addition, ACL showed the significantly highest (p < .05) DPPH radical scavenging capacity with IC(50) value of 0.491 +/- 0.148 mg/ml, and acetylcholinesterase inhibitory activity with inhibition ratio 25.18 +/- 2.96%, whereas ACF showed the significantly highest (p < .05) ABTS radical scavenging activity with 36.413 +/- 1.523 mmol trolox/g Ex. The results suggested that ACL and ACF had potential values as novel foods in the future.
ESTHER : Shen_2023_Food.Sci.Nutr_11_917
PubMedSearch : Shen_2023_Food.Sci.Nutr_11_917
PubMedID: 36789063

Title : Soluble DPP4 can act as a diagnostic biomarker in Hashimoto's thyroiditis with thyroid papillary carcinoma - Zhang_2023_J.Cancer.Res.Ther_19_1048
Author(s) : Zhang Y , Zhang Q , Zheng Y , Chen J , Liu N , Liu K , Song W
Ref : J Cancer Research Ther , 19 :1048 , 2023
Abstract : BACKGROUND: Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. MATERIALS AND METHODS: Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. RESULTS: Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. CONCLUSIONS: The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC.
ESTHER : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedSearch : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedID: 37675735

Title : Nanozyme-based dual-signal sensing system for colorimetric and photothermal detection of AChE activity in the blood of liver-injured mice - He_2023_Anal.Bioanal.Chem__
Author(s) : He C , Ke Z , Liu K , Peng J , Yang Q , Wang L , Feng G , Fang J
Ref : Anal Bioanal Chem , : , 2023
Abstract : Acetylcholinesterase (AChE), a crucial enzyme related to liver function, is involved in numerous physiological processes such as neurotransmission and muscular contraction. The currently reported techniques for detecting AChE mainly rely on a single signal output, limiting their high-accuracy quantification. The few reported dual-signal assays are challenging to implement in dual-signal point-of-care testing (POCT) because of the need for large instruments, costly modifications, and trained operators. Herein, we report a colorimetric and photothermal dual-signal POCT sensing platform based on CeO(2)-TMB (3,3',5,5'-tetramethylbenzidine) for the visualization of AChE activity in liver-injured mice. The method compensates for the false positives of a single signal and realizes the rapid, low-cost portable detection of AChE. More importantly, the CeO(2)-TMB sensing platform enables the diagnosis of liver injury and provides an effective tool for studying liver disease in basic medicine and clinical applications. Rapid colorimetric and photothermal biosensor for sensitive detection of acetylcholinesterase (I) and acetylcholinesterase levels in mouse serum (II).
ESTHER : He_2023_Anal.Bioanal.Chem__
PubMedSearch : He_2023_Anal.Bioanal.Chem__
PubMedID: 36995409

Title : Two birds with one stone: An enzyme-regulated ratiometric fluorescent and photothermal dual-mode probe for organophosphorus pesticide detection - Jiang_2023_Biosens.Bioelectron_224_115074
Author(s) : Jiang W , Yang Z , Tong F , Zhang S , Zhu L , Wang L , Huang L , Liu K , Zheng M , Zhou Y , Hou R , Liu Y
Ref : Biosensors & Bioelectronics , 224 :115074 , 2023
Abstract : In this study, based on the oxidase activity and photothermal effect of manganese dioxide nanosheets (MnO(2) NSs), with thiamine (TH) as the fluorescence response signal and tris (2,2'-bipyridyl) ruthenium (II) hexahydrate as the reference signal, an enzyme-regulated ratiometric fluorescence and photothermal dual-mode probe was constructed for the quantitative detection of organophosphorus pesticide (OPs) residues. OPs reduced the production of the reductive product thiocholine by inhibiting the activity of acetylcholinesterase, thereby regulating the residual amount of MnO(2) NSs. With the increase of OPs concentration, the color of the probe solution gradually transitioned from red to blue, and the temperature gradually increased. Using dichlorvos and chlorpyrifos as pesticide models, the developed probes exhibited sensitive responses to OPs in a wide linear range of 0.1-8000sng/mL. The detection limits of dichlorvos and chlorpyrifos in fluorescence mode were 1.13sxs10(-3)sng/mL and 0.86sng/mL, respectively. The corresponding detection limits in photothermal mode were 1.01sng/mL and 1.02sng/mL, respectively. The proposed probe displayed excellent anti-interference and reliability in the analysis of OPs residues in real samples. The dual-mode probe with self-verification function is expected to provide more accurate and robust detection results than the single-mode probe, and has a wider application prospect.
ESTHER : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedSearch : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedID: 36638562

Title : Eucommia ulmoides Olive Male Flower Extracts Ameliorate Alzheimer's Disease-Like Pathology in Zebrafish via Regulating Autophagy, Acetylcholinesterase, and the Dopamine Transporter - Sun_2022_Front.Mol.Neurosci_15_901953
Author(s) : Sun C , Zhang S , Ba S , Dang J , Ren Q , Zhu Y , Liu K , Jin M
Ref : Front Mol Neurosci , 15 :901953 , 2022
Abstract : Alzheimer's disease (AD) is the most prevalent neural disorder. However, the therapeutic agents for AD are limited. Eucommia ulmoides Olive (EUO) is widely used as a traditional Chinese herb to treat various neurodegenerative disorders. Therefore, we investigated whether the extracts of EUO male flower (EUMF) have therapeutic effects against AD. We focused on the flavonoids of EUMF and identified the composition using a targeted HPLC-MS analysis. As a result, 125 flavonoids and flavanols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins were identified. Then, the anti-AD effects of the EUMF were tested by using zebrafish AD model. The behavioral changes were detected by automated video-tracking system. Abeta deposition was assayed by thioflavin S staining. Ache activity and cell apoptosis in zebrafish were tested by, Acetylcholine Assay Kit and TUNEL assay, respectively. The results showed that EUMF significantly rescued the dyskinesia of zebrafish and inhibited Abeta deposition, Ache activity, and occurrence of cell apoptosis in the head of zebrafish induced by AlCl(3). We also investigated the mechanism underlying anti-AD effects of EUMF by RT-qPCR and found that EUMF ameliorated AD-like symptoms possibly through inhibiting excessive autophagy and the abnormal expressions of ache and slc6a3 genes. In summary, our findings suggested EUMF can be a therapeutic candidate for AD treatment.
ESTHER : Sun_2022_Front.Mol.Neurosci_15_901953
PubMedSearch : Sun_2022_Front.Mol.Neurosci_15_901953
PubMedID: 35754707

Title : Preparation of 2-Arachidonoylglycerol by Enzymatic Alcoholysis: Effects of Solvent and Water Activity on Acyl Migration - Wang_2022_Foods_11_3213
Author(s) : Wang X , Liu K , Wang Y , Huang Z
Ref : Foods , 11 :3213 , 2022
Abstract : Enzymatic alcoholysis was performed in an organic medium to synthesize 2-monoacylglycerol (2-MAG) rich in arachidonic acid. The results showed that solvent type and water activity (a(w)) significantly affected the 2-MAG yield. Under the optimum conditions, 33.58% 2-MAG was produced in the crude product in t-butanol system. Highly pure 2-MAG was obtained after two-stage extraction using 85% ethanol aqueous solution and hexane at first stage and dichloromethane and water at second stage. Isolated 2-MAG was used as substrate to investigate the effect of solvent type and a(w) on 2-MAG acyl migration in a lipase-inactivated system. The results indicated that non-polar solvents accelerated the acyl migration of 2-MAG, whereas isomerization was inhibited in polar solvent systems. The a(w) exhibited the strongest inhibition effect on 2-MAG isomerization at 0.97, but also affected the hydrolysis of glycerides and lipase selectivity.
ESTHER : Wang_2022_Foods_11_3213
PubMedSearch : Wang_2022_Foods_11_3213
PubMedID: 37430962

Title : Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus - Sun_2022_Andrology__
Author(s) : Sun T , Xu W , Wang J , Wang T , Wang S , Liu K , Liu J
Ref : Andrology , : , 2022
Abstract : BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved.
ESTHER : Sun_2022_Andrology__
PubMedSearch : Sun_2022_Andrology__
PubMedID: 36113503

Title : Effects of Lipase and Xylanase Pretreatment on the Structure and Pulping Properties of Wheat Straw - Jia_2022_Polymers.(Basel)_14_
Author(s) : Jia Q , Chen J , Yang G , Liu K , Wang Y , Zhang K
Ref : Polymers (Basel) , 14 : , 2022
Abstract : Based on the reduction of environmental pollution, a biological enzyme assisted alkali-oxygen pulping method was explored to improve the delignification efficiency and fiber accessibility of wheat straw and improve the properties of wheat straw pulp. In this paper, lipase and xylanase were used to pretreat wheat straw and the effects of different enzyme types and enzyme dosage on the microstructure and pulp properties of wheat straw were investigated and experimented. The results showed that the lipase can remove fat and wax on the surface of wheat straw, while xylanase degraded the hemicellulose components, such as xylan, of wheat straw fiber, destroyed the structure of the lignin-carbohydrate complex, increasing lignin removal as a result and enhancing the impregnating, diffusion and penetration of alkali. Compared with wheat straw without enzyme pretreatment, the skeleton of wheat straw pretreated by enzyme became looser, the internal cavity appeared and the wall cavity became thin and transparent. The fines decreased obviously and the length of fibers increased. After combined pretreatment with lipase (15 U.g(-1)) and xylanase (15 U.g(-1)), the pulping performance of wheat straw was improved and the tensile index (97.37 N.m.g(-1)), brightness (40.9% ISO) and yield (58.10%) of the pulp increased by 12.9%, 19.9% and 9.9%, respectively. It can be seen that enzyme pretreatment is a green and effective approach to improving the alkali-oxygen pulping performance of wheat straw.
ESTHER : Jia_2022_Polymers.(Basel)_14_
PubMedSearch : Jia_2022_Polymers.(Basel)_14_
PubMedID: 36501524

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 : Hesperidin methyl chalcone ameliorates lipid metabolic disorders by activating lipase activity and increasing energy metabolism - Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
Author(s) : Liu S , Liu K , Wang Y , Wu C , Xiao Y , Yu J , Ma Z , Liang H , Li X , Li Y , Zhou L
Ref : Biochimica & Biophysica Acta Mol Basis Dis , :166620 , 2022
Abstract : Obesity has become an increasingly serious health issue with the continuous improvement in living standards. Its prevalence has become an economic burden on health care systems worldwide. Flavonoids have been shown to be beneficial in the prevention and treatment of obesity. Here, we evaluated the therapeutic potential of the flavonoid hesperidin methyl chalcone (HMC) on mice with high-fat diet (HFD)-induced hepatic steatosis in vivo and in vitro. Treatment with HMC reduced oleic and palmitic acid-induced increases in intracellular triglyceride accumulation in HepG2, AML12 and LMH cells. HMC also enhanced energy metabolism and lowered oxidative stress. We used Discovery studio to dock key proteins associated with lipid metabolism disorders to HMC, and found that HMC interacted with lipase. Furthermore, we demonstrated that HMC improved lipase activity and lipolysis. In addition, we found that HMC promoted glucose absorption, alleviated lipid metabolic disorders, improved HFD-induced liver injury, and regulated HFD-induced changes in energy metabolism. In conclusion, our study demonstrated that HMC ameliorated HFD-induced obesity and its complications by promoting lipase activity, and provides a novel approach for the prevention and treatment of obesity and related diseases.
ESTHER : Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
PubMedSearch : Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
PubMedID: 36494040

Title : Vincosamide Has a Function for Inhibiting Malignant Behaviors of Hepatocellular Carcinoma Cells - Zhu_2022_World.J.Oncol_13_272
Author(s) : Zhu MY , Gong ZS , Feng HP , Zhang QY , Liu K , Lin B , Zhang MN , Lin HF , Li MS
Ref : World J Oncol , 13 :272 , 2022
Abstract : BACKGROUND: Vincosamide (Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa, and Vinco has important anti-inflammatory effects and activity against cholinesterase, Vinco also has a trait to anti-tumor. However, whether Vinco can inhibit the malignant behaviors of hepatocellular carcinoma (HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells. METHODS: MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide), trypan blue exclusion assay, the Cell Counting Kit (CCK)-8 and flow cytometric analysis were applied to detect the proliferation and apoptosis of HCC cells; electron microscopy was performed to observe the change of cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; expression and localization of proteins were detected by laser confocal microscopy and Western blotting; the growth of the cancer cells in vivo was assessed in a mouse tumorous model. RESULTS: At a dose of 10 - 80 g/mL, Vinco inhibited the proliferation, migration, invasion and promoted apoptosis of HCC cells in a dose-dependent manner but had low cytotoxicity effect on normal liver cells. Additionally, 80 g/mL of Vinco could significantly disrupt the morphology of mitochondria, suppress the migration and invasion of HCC cells. The growth of HCC cells in the animal tumorous model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicated that Vinco (10 - 80 g/mL) played a role in activating caspase-3, promoting the expression of phosphate and tension homology deleted on chromosome 10 (PTEN), and inhibiting the phosphorylation of AKT (Ser473) and mTOR (Thr2448); Vinco also has a trait for suppressing the expression of CXCR4, Src, MMP9, EpCAM, Ras, Oct4 and cancer stem cell "stemness markers" CD133 and CD44 in HCC cells. CONCLUSIONS: Vinco has a role in inhibiting the malignant behaviors of HCC cells; the role molecular mechanism of Vinco may be involved in restraining expression of the growth-, metastasis-related factors, such as Src, Ras, MMP9, EpCAM, CXCR4; activating the activity of caspase-3 and blocking PI3K/AKT signaling pathway. Thus, Vinco should be considered as a new chemotherapy agent for HCC patients.
ESTHER : Zhu_2022_World.J.Oncol_13_272
PubMedSearch : Zhu_2022_World.J.Oncol_13_272
PubMedID: 36406198

Title : Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities - Zang_2021_Molecules_26_
Author(s) : Zang Y , Liu K , Wang W , Li C , Ma J , Yang J , Chen X , Wang X , Zhang D
Ref : Molecules , 26 : , 2021
Abstract : The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC(50)) 1.63-4.62 microM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
ESTHER : Zang_2021_Molecules_26_
PubMedSearch : Zang_2021_Molecules_26_
PubMedID: 33671020

Title : Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects - Issotina_2021_J.Hypertens__
Author(s) : Issotina Zibrila A , Wang Z , Ali MA , Osei JA , Sun Y , Zafar S , Liu K , Li C , Kang Y , Liu J
Ref : J Hypertens , : , 2021
Abstract : OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.
ESTHER : Issotina_2021_J.Hypertens__
PubMedSearch : Issotina_2021_J.Hypertens__
PubMedID: 34232157

Title : A Valuable Product of Microbial Cell Factories: Microbial Lipase - Yao_2021_Front.Microbiol_12_743377
Author(s) : Yao W , Liu K , Liu H , Jiang Y , Wang R , Wang W , Wang T
Ref : Front Microbiol , 12 :743377 , 2021
Abstract : As a powerful factory, microbial cells produce a variety of enzymes, such as lipase. Lipase has a wide range of actions and participates in multiple reactions, and they can catalyze the hydrolysis of triacylglycerol into its component free fatty acids and glycerol backbone. Lipase exists widely in nature, most prominently in plants, animals and microorganisms, among which microorganisms are the most important source of lipase. Microbial lipases have been adapted for numerous industrial applications due to their substrate specificity, heterogeneous patterns of expression and versatility (i.e., capacity to catalyze reactions at the extremes of pH and temperature as well as in the presence of metal ions and organic solvents). Now they have been introduced into applications involving the production and processing of food, pharmaceutics, paper making, detergents, biodiesel fuels, and so on. In this mini-review, we will focus on the most up-to-date research on microbial lipases and their commercial and industrial applications. We will also discuss and predict future applications of these important technologies.
ESTHER : Yao_2021_Front.Microbiol_12_743377
PubMedSearch : Yao_2021_Front.Microbiol_12_743377
PubMedID: 34616387

Title : A highly contiguous genome assembly of a polyphagous predatory mite Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae) - Yan_2021_Genome.Biol.Evol__
Author(s) : Yan Y , Zhang N , Liu C , Wu X , Liu K , Yin Z , Zhou X , Xie L
Ref : Genome Biol Evol , : , 2021
Abstract : As a polyphagous soil-dwelling predatory mite, Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae), formerly known as Stratiolaelaps miles (Berlese), is native to the Northern hemisphere and preys on soil invertebrates, including fungus gnats, springtails, thrips nymphs, nematodes, and other species of mites. Already mass-produced and commercialized in North America and Europe, S. scimitus is now introduced in China as a biocontrol agent for field crop. The introduction, however, can lead to unexpected genetic changes within populations of biological control agents, which might decrease the efficacy of pest management or increase the risks to local environments. To better understand the genetic basis of its biology and behavior, we sequenced and assembled the draft genome of S. scimitus using the PacBio Sequel platform II. We generated -150 x (64.81 Gb) PacBio long reads with an average read length of 12.60 kb. Reads longer than 5 kb were assembled into contigs, resulting in the final assembly of 158 contigs with a N50 length of 7.66 Mb, and captured 93.1% of the BUSCO gene set (n = 1,066). We identified 16.39% (69.91 Mb) repetitive elements, 1,686 non-coding RNAs, and 13,305 protein-coding genes, which represented 95.8% BUSCO completeness. Combining analyses of genome family evolution and function enrichment of gene ontology and pathway, a total of 135 families experienced significant expansions, which were mainly involved in digestion, detoxification, immunity and venom. Major expansions of the detoxification enzymes, i.e., P450s and carboxylesterases, suggest a possible genetic mechanism underlying polyphagy and ecological adaptions. Our high-quality genome assembly and annotation provide new insights on the evolutionary biology, soil ecology and biological control for predaceous mites.
ESTHER : Yan_2021_Genome.Biol.Evol__
PubMedSearch : Yan_2021_Genome.Biol.Evol__
PubMedID: 33528489

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 : Two carboxylesterase genes in Plutella xylostella associated with sex pheromones and plant volatiles degradation - Wang_2021_Pest.Manag.Sci__
Author(s) : Wang MM , Long GJ , Guo H , Liu XZ , Wang H , Dewer Y , Li ZQ , Liu K , Zhang QL , Ma YF , He P , He M
Ref : Pest Manag Sci , : , 2021
Abstract : BACKGROUND: Carboxyl/cholinesterases (CCEs) are thought to play a pivotal role in the degradation of sex pheromones and plant-derived odorants in insect, but their exact biochemistry and physiological functions remain unclear. RESULTS: In this study, two paralogous antennae-enriched CCEs from Plutella xylostella (PxylCCE16a and 16c) were identified and functionally characterized. High-purity protein preparations of active recombinant PxylCCE16a and 16c have been obtained from Sf9 insect cells by Ni(2+) affinity purification. Our results revealed that the purified recombinant PxylCCE016c is able to degrade two sex pheromone components Z9-14: Ac and Z11-16: Ac at 27.64 +/- 0.79% and 24.40 +/- 3.07% respectively, while PxylCCE016a presented relatively lower activity. Additionally, a similar difference in activity was measured in plant-derived odorants. Furthermore, both CCEs displayed obvious preferences for the two sex pheromone components, especially on Z11-16: Ac (K(m) values in the range of 7.82-45.06 microM) than plant odorants (K(m) values are in the range of 1290-4030 microM). Furthermore, the activity of the two newly identified CCEs is pH-dependent. The activity at pH 6.5 is obviously higher than at pH 5.0. Interestingly, only PxylCCE016c can be inhibited by a common esterase inhibitor triphenyl phosphate (TPP) with LC(50) of 1570 +/- 520 microM. CONCLUSION: PxylCCE16c played a more essential role on odorant degradation than PxylCCE16a. Moreover, the current study provides novel potential pesticide targets for the notorious moth Plutella xylostella. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Pest.Manag.Sci__
PubMedSearch : Wang_2021_Pest.Manag.Sci__
PubMedID: 33527628
Gene_locus related to this paper: pluxy-CCE016a , pluxy-CCE016c

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

Title : Drug-drug Interactions of Angiotensin Converting Enzyme Inhibitors Mediated by Metabolizing Enzymes and Transporters - Sun_2018_Curr.Drug.Metab_19_1119
Author(s) : Sun P , Liu K
Ref : Curr Drug Metab , 19 :1119 , 2018
Abstract : BACKGROUND: Patients with hypertension usually have to be treated with Angiotensin Converting Enzyme (ACE) inhibitors, and are therefore more exposed to drug-drug Interactions (DDIs) by various mechanisms, especially the mechanisms based on drug metabolizing enzymes and transporters. OBJECTIVE: This review article focuses on the pharmacokinetic interaction mechanisms with ACE inhibitors based on drug metabolizing enzymes and transporters, and the identification of these underlying mechanisms would help physicians and patients to predict, detect and prevent DDIs. METHOD: To identify the pharmacokinetic interaction mechanisms based on drug metabolizing enzymes and transporters of ACE inhibitors. An electronic search of PubMed, Medline, Science Direct, and Springer-Link database was conducted (from 1950 to December, 2017), using drug interactions, cytochrome P450, carboxylesterase, names of transporters, names of ACE inhibitors and pharmacokinetics as keywords. RESULTS AND CONCLUSION: Inhibition of metabolizing enzymes and transporter system can markedly alter the concentrations of ACE inhibitors. The genetic polymorphisms in the enzymes in some of the specific isoforms seem to explain the inter-individual differences in ACE inhibitors metabolism, and also the inter-individual variation in the pharmacokinetics of ACE inhibitors may be caused by changes in transporter function. Understanding the knowledge of how ACE inhibitors are metabolized and transported is important in predicting and managing DDIs. The data on the roles of drug metabolizing enzymes and transporters in the DDIs of ACE inhibitors should be studied and the selection of ACE inhibitors should be individualized to prevent DDIs in clinic.
ESTHER : Sun_2018_Curr.Drug.Metab_19_1119
PubMedSearch : Sun_2018_Curr.Drug.Metab_19_1119
PubMedID: 30062958

Title : Metabolism of KO143, an ABCG2 inhibitor - Liu_2017_Drug.Metab.Pharmacokinet_32_193
Author(s) : Liu K , Zhu J , Huang Y , Li C , Lu J , Sachar M , Li S , Ma X
Ref : Drug Metab Pharmacokinet , 32 :193 , 2017
Abstract : The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice. K1 is an analog of KO143 without the ester group. We found that the metabolic stability of K1 was significantly improved in HLM when compared to KO143. These data suggest that the ester group in KO143 is the major cause of the poor metabolic stability of KO143. The data from this study can be used to guide the development of KO143 analogs with better metabolic properties.
ESTHER : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedSearch : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedID: 28619281

Title : Molecular cloning and expression analysis on LPL of Coilia nasus - Wang_2016_Gene_583_147
Author(s) : Wang M , Xu D , Liu K , Yang J , Xu P
Ref : Gene , 583 :147 , 2016
Abstract : Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. At present, it has been on the "National Key Protective Species List" because of its severe resource damage. Lipid metabolism is very important during its long-distance migration. To make further research on lipid metabolism of C.nasus, we cloned lipoprotein lipase gene with homologous cloning method. A full-length cDNA of LPL of C.nasus was cloned from liver which covered 3537bp with a 1519bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5kDa and theoretical isoelectric point was 7.58. The deduced amino acids had high similarity with the reported LPL sequence of other species. It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C.nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with beta-actin as internal reference. LPL expressed in all the detected tissues. The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. The research on the cloning and differential expression of LPL of C.nasus will lay foundation for further research on lipid metabolism of C.nasus.
ESTHER : Wang_2016_Gene_583_147
PubMedSearch : Wang_2016_Gene_583_147
PubMedID: 26877109
Gene_locus related to this paper: 9tele-a0a140b115

Title : Fabrication of Propeller-Shaped Supra-amphiphile for Construction of Enzyme-Responsive Fluorescent Vesicles - Li_2016_ACS.Appl.Mater.Interfaces_8_27987
Author(s) : Li J , Liu K , Han Y , Tang BZ , Huang J , Yan Y
Ref : ACS Appl Mater Interfaces , 8 :27987 , 2016
Abstract : Propeller-shaped molecules have been recognized to display fantastic AIE (aggregation induced emission), but they can hardly self-assemble into nanostructures. Herein, we for the first time report that ionic complexation between a water-soluble tetrapheneyl derivative and an enzyme substrate in aqueous media produces a propeller-shaped supra-amphiphile that self-assembles into enzyme responsive fluorescent vesicles. The supra-amphiphile was fabricated upon complexation between a water-soluble propeller-shaped AIE luminogen TPE-BPA and myristoylcholine chloride (MChCl) in aqueous media. MChCl filled in the intramolecular voids of propeller-shaped TPE-BPA upon supra-amphiphile formation, which endows the supra-amphiphile superior self-assembling ability to the component molecules thus leading to the formation of fluorescent vesicles. Because MChCl is the substrate of cholinesterases, the vesicles dissemble in the presence of cholinesterases, and the fluorescent intensity can be correlated to the level of enzymes. The resulting fluorescent vesicles may be used to recognize the site of Alzheimer's disease, to encapsulate the enzyme inhibitor, and to release the inhibitor at the disease site.
ESTHER : Li_2016_ACS.Appl.Mater.Interfaces_8_27987
PubMedSearch : Li_2016_ACS.Appl.Mater.Interfaces_8_27987
PubMedID: 27668305

Title : Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution - Li_2015_Nat.Biotechnol_33_524
Author(s) : Li F , Fan G , Lu C , Xiao G , Zou C , Kohel RJ , Ma Z , Shang H , Ma X , Wu J , Liang X , Huang G , Percy RG , Liu K , Yang W , Chen W , Du X , Shi C , Yuan Y , Ye W , Liu X , Zhang X , Liu W , Wei H , Wei S , Zhu S , Zhang H , Sun F , Wang X , Liang J , Wang J , He Q , Huang L , Cui J , Song G , Wang K , Xu X , Yu JZ , Zhu Y , Yu S
Ref : Nat Biotechnol , 33 :524 , 2015
Abstract : Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
ESTHER : Li_2015_Nat.Biotechnol_33_524
PubMedSearch : Li_2015_Nat.Biotechnol_33_524
PubMedID: 25893780
Gene_locus related to this paper: gosra-a0a0d2rxs2 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , goshi-a0a1u8hr03 , gosra-a0a0d2vdc5 , goshi-a0a1u8ljh5 , gosra-a0a0d2vj24 , goshi-a0a1u8pxd3 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8mt09 , goshi-a0a1u8kis4 , goshi-a0a1u8ibk3 , goshi-a0a1u8ieg2 , goshi-a0a1u8iki6 , goshi-a0a1u8jvp4 , goshi-a0a1u8jw35 , gosra-a0a0d2pzd7 , goshi-a0a1u8ied7

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 : Evidences for B6C3-Tg (APPswe\/PSEN1dE9) Double-Transgenic Mice Between 3 and 10 Months as an Age-Related Alzheimer's Disease Model - Zhong_2014_J.Mol.Neurosci_53_370
Author(s) : Zhong Z , Yang L , Wu X , Huang W , Yan J , Liu S , Sun X , Liu K , Lin H , Kuang S , Tang X
Ref : Journal of Molecular Neuroscience , 53 :370 , 2014
Abstract : Transgenic mouse has shown great advantages in the study of Alzheimer's disease (AD) and drug screening as AD develops rapidly resent years, while more detail information of these transgenic mice and experience of application are needed. To obtain the basic background information of the B6C3-Tg (APPswe/PSEN1dE9) double-transgenic mouse, which was reported with early onset AD, three- to ten-month-old B6C3-Tg AD mice and normal C57BL/6 mice were selected randomly to test the ability of learning memory by Morris water maze, the brain acetylcholinesterase (AChE) activity by AChE kit, and beta amyloid protein level by immunohistochemistry staining. Compared with the control group, the escape latency time of B6C3-Tg AD mice at 9 and 10 months of age is significantly longer (P < 0.05) in Morris maze test, and the activity of brain AChE is higher. beta-Amyloid plaques were observed at 3 months of age and developed rapidly. Statistical analysis showed a positive correlation between the area of these plaques and the ages of B6C3-Tg AD mouse (y = 0.0355e(0.5557x), R = 0.9557). The model's behavior is conformed to simulate behaviors of human Alzheimer's disease at the early stage and may provide detail background information a new choice when transgenic mice are needed in the research of AD.
ESTHER : Zhong_2014_J.Mol.Neurosci_53_370
PubMedSearch : Zhong_2014_J.Mol.Neurosci_53_370
PubMedID: 24362678

Title : The genomes of four tapeworm species reveal adaptations to parasitism - Tsai_2013_Nature_496_57
Author(s) : Tsai IJ , Zarowiecki M , Holroyd N , Garciarrubio A , Sanchez-Flores A , Brooks KL , Tracey A , Bobes RJ , Fragoso G , Sciutto E , Aslett M , Beasley H , Bennett HM , Cai J , Camicia F , Clark R , Cucher M , De Silva N , Day TA , Deplazes P , Estrada K , Fernandez C , Holland PW , Hou J , Hu S , Huckvale T , Hung SS , Kamenetzky L , Keane JA , Kiss F , Koziol U , Lambert O , Liu K , Luo X , Luo Y , Macchiaroli N , Nichol S , Paps J , Parkinson J , Pouchkina-Stantcheva N , Riddiford N , Rosenzvit M , Salinas G , Wasmuth JD , Zamanian M , Zheng Y , Cai X , Soberon X , Olson PD , Laclette JP , Brehm K , Berriman M
Ref : Nature , 496 :57 , 2013
Abstract : Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.
ESTHER : Tsai_2013_Nature_496_57
PubMedSearch : Tsai_2013_Nature_496_57
PubMedID: 23485966
Gene_locus related to this paper: echgr-k4epc5 , hymmi-a0a068x9f5 , echmu-u6hbw4 , echgr-w6ugl0 , echmu-u6hr32 , echmu-a0a068y5f4 , hymmi-a0a068xag4 , hymmi-a0a068x810 , hymmi-a0a068xcc1 , echmu-a0a068yf54 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , hymmi-a0a068xge7 , hymmi-a0a068x8h9 , echmu-a0a068y747 , hymmi-a0a068xgj7 , echgr-a0a068wl60

Title : Draft Genome Sequence of Strain JLT2015T, Belonging to the Family Sphingomonadaceae of the Alphaproteobacteria - Tang_2013_Genome.Announc_1_e00226
Author(s) : Tang K , Liu K , Li S , Jiao N
Ref : Genome Announc , 1 : , 2013
Abstract : Strain JLT2015(T) was isolated from the southeastern Pacific, as a representative of a new genus of the family Sphingomonadaceae of the Alphaproteobacteria. Here, we present the draft genome sequence of strain JLT2015(T), which provides insight into the oligotrophic strategy of this organism.
ESTHER : Tang_2013_Genome.Announc_1_e00226
PubMedSearch : Tang_2013_Genome.Announc_1_e00226
PubMedID: 23661488
Gene_locus related to this paper: 9prot-m2u802 , 9prot-m2u3z8 , 9prot-m2u526

Title : Genome sequence of the date palm Phoenix dactylifera L - Al-Mssallem_2013_Nat.Commun_4_2274
Author(s) : Al-Mssallem IS , Hu S , Zhang X , Lin Q , Liu W , Tan J , Yu X , Liu J , Pan L , Zhang T , Yin Y , Xin C , Wu H , Zhang G , Ba Abdullah MM , Huang D , Fang Y , Alnakhli YO , Jia S , Yin A , Alhuzimi EM , Alsaihati BA , Al-Owayyed SA , Zhao D , Zhang S , Al-Otaibi NA , Sun G , Majrashi MA , Li F , Tala , Wang J , Yun Q , Alnassar NA , Wang L , Yang M , Al-Jelaify RF , Liu K , Gao S , Chen K , Alkhaldi SR , Liu G , Zhang M , Guo H , Yu J
Ref : Nat Commun , 4 :2274 , 2013
Abstract : Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants.
ESTHER : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedSearch : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedID: 23917264
Gene_locus related to this paper: phodc-a0a2h3y3d5 , phodc-a0a2h3z529 , phodc-a0a2h3y147 , phodc-a0a2h3xrz4 , phodc-a0a3q0ic37 , phodc-a0a2h3yxf0 , phodc-a0a2h3zh01 , phodc-a0a3q0hs32

Title : Draft genome sequence of Oceaniovalibus guishaninsula JLT2003T - Tang_2012_J.Bacteriol_194_6683
Author(s) : Tang K , Liu K , Jiao N
Ref : Journal of Bacteriology , 194 :6683 , 2012
Abstract : Oceaniovalibus guishaninsula, as a representative of a new genus within the family Rhodobacteraceae, was isolated from surface seawater that was sulfidic. Here, we present the draft genome sequence of the type strain, JLT2003(T).
ESTHER : Tang_2012_J.Bacteriol_194_6683
PubMedSearch : Tang_2012_J.Bacteriol_194_6683
PubMedID: 23144420
Gene_locus related to this paper: 9rhob-k2i8h8

Title : Click-based synthesis and proteomic profiling of lipstatin analogues - Ngai_2010_Chem.Commun.(Camb)_46_8335
Author(s) : Ngai MH , Yang PY , Liu K , Shen Y , Wenk MR , Yao SQ , Lear MJ
Ref : Chem Commun (Camb) , 46 :8335 , 2010
Abstract : Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death.
ESTHER : Ngai_2010_Chem.Commun.(Camb)_46_8335
PubMedSearch : Ngai_2010_Chem.Commun.(Camb)_46_8335
PubMedID: 20577697

Title : Isolation and biochemical characterization of two lipases from a metagenomic library of China Holstein cow rumen - Liu_2009_Biochem.Biophys.Res.Commun_385_605
Author(s) : Liu K , Wang J , Bu D , Zhao S , McSweeney C , Yu P , Li D
Ref : Biochemical & Biophysical Research Communications , 385 :605 , 2009
Abstract : Two novel lipase genes RlipE1 and RlipE2 which encoded 361- and 265-amino acid peptides, respectively, were recovered from a metagenomic library of the rumen microbiota of Chinese Holstein cows. A BLAST search revealed a high similarity (90%) between RlipE2 and a carboxylesterase from Thermosinus carboxydivorans Nor1, while there was a low similarity (below 50%) between RlipE1 and other lipases. Phylogenetic analysis indicated that RlipE2 clustered with the lipolytic enzymes from family V while RlipE1 clustered with six other putative bacterial lipases which might constitute a new subfamily. The recombinant lipases were thermally unstable and retained 60% activity over a pH range of 6.5-8.5. Substrate specificity assay indicated that both enzymes had higher hydrolytic activity toward laurate (C(12)), palmitate (C(16)) and stearate (C(18)). The novel phylogenetic affiliation and high specificity of both enzymes for long-chain fatty acid make them interesting targets for manipulation of rumen lipid metabolism.
ESTHER : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedSearch : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedID: 19486892
Gene_locus related to this paper: 9bact-c0k075 , 9bact-c0k085

Title : Prolonged effects of poly(lactic-co-glycolic acid) microsphere-containing huperzine A on mouse memory dysfunction induced by scopolamine - Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
Author(s) : Wang C , Zhang T , Ma H , Liu J , Fu F , Liu K
Ref : Basic Clin Pharmacol Toxicol , 100 :190 , 2007
Abstract : Huperzine A is an anticholinesterase and cognitive enhancer, which is able to alleviate the symptoms of memory dysfunction in the mouse. The fast metabolization rate and narrow therapeutic spectrum makes it unfit for clinical use. Poly(lactic-co-glycolic acid) microsphere as delivery system effectively maintains the blood concentration of huperzine A by a slow-release effect over a long time. In the present article, we investigated the prolonged protective effect of microsphere-containing huperzine A on memory dysfunction induced by scopolamine. Spectrophotometric assay was used to determine the activity of acetylcholinesterase (AChE) and passive avoidance tests to evaluate memory performance. The results show that a bolus dose of microsphere-containing huperzine A (at a dose of 300 microg/kg or 600 microg/kg) administered intramuscularly can effectively maintain drug activity and significantly decrease the activity of AChE from day 3 to 14, the strongest effect seen on day 3 and 7. Accompanying the reduction of the activity of AChE, microsphere-containing huperzine A (300 microg/kg or 600 microg/kg) remarkably increased transfer latency time and no transfer response on the second trial through mitigating the memory impairments induced by scopolamine as compared to the scopolamine model group. Microsphere-containing huperzine A showed cognitive enhancing properties and anticholinesterase activity and may thus be a candidate for treatment of memory impairment.
ESTHER : Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
PubMedSearch : Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
PubMedID: 17309523

Title : Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults (CARDIA) study - Fornage_2004_Circulation_109_335
Author(s) : Fornage M , Boerwinkle E , Doris PA , Jacobs D , Liu K , Wong ND
Ref : Circulation , 109 :335 , 2004
Abstract : BACKGROUND: Modulation of endogenous epoxide levels by soluble epoxide hydrolase (sEH) in the endothelium represents an important mechanism in the regulation of cardiovascular function. We examined the relationship between a common, functional polymorphism of the human sEH gene and coronary artery calcification (CAC) in young, largely asymptomatic African-American and non-Hispanic white subjects. METHODS AND
RESULTS: Multiple logistic regression and Tobit regression models were used to assess the relationship between the sEH Arg287Gln polymorphism and presence and quantity of CAC. Models adjusting for race (except in race-specific analyses), age, sex, smoking, body mass index, systolic blood pressure, LDL cholesterol, and HDL cholesterol were estimated. Allele and genotype frequency distributions were not significantly different between the 2 ethnic groups (P=0.22; P=0.17, respectively). The Arg287Gln polymorphism of the sEH gene was a significant predictor of CAC status in African-American participants, either alone or after adjusting for other risk factors. African-American subjects with at least 1 copy of the Gln287 allele had a 2-fold greater risk of having CAC compared with those not carrying this allele (95% CI, 1.1 to 2.9; P=0.02). There was no relationship between Arg287Gln polymorphism and the probability of having CAC in white participants (OR, 0.8; 95% CI, 0.5 to 1.3; P=0.49). Inferences from multivariable Tobit regression were similar to those obtained in the logistic regression models, indicating that the Arg287Gln polymorphism was a significant independent predictor of both presence and quantity of CAC in African-American but not white subjects.
CONCLUSIONS: These data suggest an intriguing and possibly novel role for sEH in the pathogenesis of atherosclerosis, which deserves additional investigation.
ESTHER : Fornage_2004_Circulation_109_335
PubMedSearch : Fornage_2004_Circulation_109_335
PubMedID: 14732757
Gene_locus related to this paper: human-EPHX2