Liu R

References (69)

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 : SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to beta-cypermethrin with stereoselectivity - Xu_2024_Bull.Entomol.Res__1
Author(s) : Xu L , Liu H , Li B , Li G , Liu R , Li D
Ref : Bull Entomol Res , :1 , 2024
Abstract : Carboxylesterases (CarEs) is an important detoxification enzyme system in phase participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to beta-cypermethrin showed stereoselectivity, with higher metabolic activity to -cypermethrin than the enantiomer alpha-cypermethrin. The metabolite of beta-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that beta-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of beta-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in beta-cypermethrin resistance in S. litura.
ESTHER : Xu_2024_Bull.Entomol.Res__1
PubMedSearch : Xu_2024_Bull.Entomol.Res__1
PubMedID: 38708572
Gene_locus related to this paper: spolt-SlCarE054

Title : Protective Effects of Myricetin and Morin on Neurological Damage in Abeta(1-42)\/Al(3+) -induced Alzheimer's Disease Model of Rats - Guo_2024_J.Chem.Neuroanat__102404
Author(s) : Guo L , Zhao Y , Kong Z , Liu R , Liu P
Ref : Journal of Chemical Neuroanatomy , :102404 , 2024
Abstract : Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Abeta(1-42) oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl(3).6H(2)O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Abeta, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Abeta(1-42)/Al(3+) through anti-oxidative stress and anti-apoptotic features.
ESTHER : Guo_2024_J.Chem.Neuroanat__102404
PubMedSearch : Guo_2024_J.Chem.Neuroanat__102404
PubMedID: 38423257

Title : Synthesis of EPA-enriched medium- and long-chain triacylglycerol by lipase-catalyzed transesterification: a novel strategy for clinical nutrition intervention - Wang_2023_J.Sci.Food.Agric__
Author(s) : Wang Y , Wei W , Liu R , Chang M , Jin Q , Wang X
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Eicosapentaenoic acid (EPA) has been recognized as a promising nutrient to improve the therapeutic efficacy of cancer patients. Nevertheless, there are certain limitations to the application of EPA due to its structural characteristics. To maximize the nutritive value of EPA, a type of medium- and long-chain triacylglycerol (MLCT) enriched with EPA was designed and synthesised via lipase-catalyzed transesterification of medium-chain triglyceride (MCT) and EPA-enriched fish oil (FO). RESULTS: The optimum synthesis conditions for EPA-enriched MLCT were Lipozyme RM as catalyst, substrate mass ratio (MCT/ EPA-enriched FO) 3:1, lipase loading 80 g kg(-1) , reaction temperature 60 degreesC, and reaction time 6 h. The content of MLCT was up to 80.79% after the transesterification reaction and the purification, and the content of MLCT containing EPA accounted for 70.21%. Furthermore, the distribution of EPA at the sn-2 position showed a significant increase in MLCT compared with original substrate, from 18.89% to 26.93%. Further, the in vitro digestion results demonstrated that MLCT had a significantly higher EPA bioaccessibility compared to the original substrate. CONCLUSION: The EPA-enriched MLCT has been developed, which may be a novel strategy for clinical nutrition intervention. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2023_J.Sci.Food.Agric__
PubMedSearch : Wang_2023_J.Sci.Food.Agric__
PubMedID: 36891643

Title : Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe - Chen_2023_Anal.Chem__
Author(s) : Chen Q , Liu J , Liu S , Zhang J , He L , Liu R , Jiang H , Han X , Zhang K
Ref : Analytical Chemistry , : , 2023
Abstract : Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 microM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 microM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.
ESTHER : Chen_2023_Anal.Chem__
PubMedSearch : Chen_2023_Anal.Chem__
PubMedID: 36802493

Title : Esterase-Responsive Polymeric Micelles Containing Tetraphenylethene and Poly(ethylene glycol) Moieties for Efficient Doxorubicin Delivery and Tumor Therapy - Xu_2023_Bioconjug.Chem__
Author(s) : Xu DZ , Sun XY , Liang YX , Huang HW , Liu R , Lu ZL , He L
Ref : Bioconjug Chem , : , 2023
Abstract : Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 microM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX.HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.
ESTHER : Xu_2023_Bioconjug.Chem__
PubMedSearch : Xu_2023_Bioconjug.Chem__
PubMedID: 36621834

Title : Latest advances in dual inhibitors of acetylcholinesterase and monoamine oxidase B against Alzheimer's disease - Zou_2023_J.Enzyme.Inhib.Med.Chem_38_2270781
Author(s) : Zou D , Liu R , Lv Y , Guo J , Zhang C , Xie Y
Ref : J Enzyme Inhib Med Chem , 38 :2270781 , 2023
Abstract : Alzheimer's disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered to contribute to pathologies of AD. Therefore, we reviewed the dual inhibitors of acetylcholinesterase (AChE) and MAO-B developed in the last five years. In this review, these dual-target inhibitors were classified into six groups according to the basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine and hydrazine, and other scaffolds. Their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B were analysed and discussed, giving valuable insights for the subsequent development of AChE and MAO-B dual inhibitors. Challenges in the development of balanced and potent AChE and MAO-B dual inhibitors were noted, and corresponding solutions were provided.
ESTHER : Zou_2023_J.Enzyme.Inhib.Med.Chem_38_2270781
PubMedSearch : Zou_2023_J.Enzyme.Inhib.Med.Chem_38_2270781
PubMedID: 37955252

Title : Mechanistic analysis of endothelial lipase G promotion of the occurrence and development of cervical carcinoma by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase\/protein kinase B\/mechanistic target of rapamycin kinase signalling pathway - Huang_2023_J.Obstet.Gynaecol_43_2151353
Author(s) : Huang J , Liu R , Zhang Y , Sheng X
Ref : J Obstet Gynaecol , 43 :2151353 , 2023
Abstract : Lipase G, endothelial type (LIPG) is expressed abundantly in tissues with a high metabolic rate and vascularisation. Research on LIPG has focussed on metabolic syndromes. However, the role of LIPG in providing lipid precursors suggests that it might function in the metabolism of carcinoma cells. Analysis in The Cancer Genome Atlas indicated that patients with cervical carcinoma with high LIPG expression had a lower survival prognosis compared with patients with low LIPG expression. The mechanism underlying the effects of LIPG in cervical carcinoma is unclear. The present study aimed to determine the role of LIPG in cervical carcinoma and its mechanism. The results showed that the LIPG expression level was higher in cervical cancer. Downregulation of LIPG expression inhibited cell migration, invasion, proliferation, and the formation of cell colonies, but increased the rate of apoptosis. The Human papillomavirus E6 protein might reduce the expression of miR-148a-3p, relieve the inhibitory effect of miR-148a-3p on LIPG expression, and promote the progression of cervical cancer through the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signalling pathway.IMPACT STATEMENTWhat is already known on this subject? LIPG provides lipid precursors, suggesting that it might function in the metabolism of carcinoma cellsWhat do the results of this study add? LIPG might be regulated by HPV16 E6/miR-148a-3p and promote cervical carcinoma progression via the PI3K/AKT/mTOR signalling pathway.What are the implications of these finding for clinical practice and/or further research? The results indicated that novel treatment and diagnosis strategies for cervical carcinoma could be developed related to LIPG. However, the detailed relationship between LIPG and cervical carcinoma remains to be fully determined.
ESTHER : Huang_2023_J.Obstet.Gynaecol_43_2151353
PubMedSearch : Huang_2023_J.Obstet.Gynaecol_43_2151353
PubMedID: 36606668
Gene_locus related to this paper: human-LIPG

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

Title : The Therapeutic Effects of Seven Lycophyte Compounds on Cell Models of Alzheimer's Disease - Guo_2022_J.Alzheimers.Dis__
Author(s) : Guo Q , Cai Q , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : J Alzheimers Dis , : , 2022
Abstract : BACKGROUND: As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. To search for new analogs or derivatives of Hup-A, we produced five Lycophyte alkaloids and two analogues by chemical synthesis: Lyconadins A-E, H-R-NOB, and 2JY-OBZ4. OBJECTIVE: To systematically evaluated the therapeutic effects of the seven compounds on AD cell models. METHODS: We assessed the effects of the seven compounds on cell viability via CCK-8 kit and used HEK293-hTau cells and N2a-hAPP cells as AD cell models to evaluate their potential therapeutic effects. We examined their effects on cholinesterase activity by employing the mice primary neuron. RESULTS: All compounds did not affect cell viability; in addition, Lyconadin A and 2JY-OBZ4 particularly increased cell viability. Lyconadin D and Lyconadin E restored tau phosphorylation at Thr231, and H-R-NOB and 2JY-OBZ4 restored tau phosphorylation at Thr231 and Ser396 in GSK-3beta-transfected HEK293-hTau cells. 2JY-OBZ4 decreased the level of PP2Ac-pY307 and increased the level of PP2Ac-mL309, supporting that 2JY-OBZ4 may activate PP2A. Lyconadin B, Lyconadin D, Lyconadin E, H-R-NOB, and 2JY-OBZ4 increased sAbetaPPalpha level in N2a-hAPP cells. 2JY-OBZ4 decreased the levels of BACE1 and sAbetaPPbeta, thereby reduced Abeta production. Seven compounds exhibited weaker AChE activity inhibition efficiency than Hup-A. Among them, 2JY-OBZ4 showed the strongest AChE inhibition activity with an inhibition rate of 17% at 10microM. CONCLUSION: Among the seven lycophyte compounds, 2JY-OBZ4 showed the most expected effects on promoting cell viability, downregulating tau hyperphosphorylation, and Abeta production and inhibiting AChE in AD.
ESTHER : Guo_2022_J.Alzheimers.Dis__
PubMedSearch : Guo_2022_J.Alzheimers.Dis__
PubMedID: 36189599

Title : Novel small molecular compound 2JY-OBZ4 alleviates AD pathology in cell models via regulating multiple targets - Guo_2022_Aging.(Albany.NY)_14_
Author(s) : Guo Q , Wu G , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : Aging (Albany NY) , 14 : , 2022
Abstract : Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, characterized by cognitive deficits and memory dysfunction, which is clinically incurable so far. Novel small molecular compound 2JY-OBZ4 is one of structural analogue of Huperzine A (Hup-A), an anti-AD drug in China. In our previous work, 2JY-OBZ4 exhibited potent effects on tau hyperphosphorylation, Abeta production and acetylcholinesterase (AChE) activity. However, 2JY-OBZ4's anti-AD effects and the underlying molecular mechanisms remain unclear. We here reported that 2JY-OBZ4 resisted tau hyperphosphorylation at Thr181 and Ser396 sites in HEK293-hTau cells transfected with GSK-3beta, decreased tau phosphorylation via upregulating the activity of PP2A in HEK293-hTau cells and reduced Abeta production through regulating protein levels of APP cleavage enzymes in N2a-hAPP cells. Meanwhile, we found that 2JY-OBZ4 had no adverse effects on cell viability of mice primary neuron even at high concentration, and ameliorated synaptic loss induced by human oligomeric Abeta42. 2JY-OBZ4 had moderate AChE inhibitory activity with the half maximal inhibitory concentration (IC50) to be 39.48 microg/ml in vitro, which is more than two times higher than Hup-A. Together, 2JY-OBZ4 showed promising therapeutic effects in AD cell models through regulating multiple targets. The research provides a new candidate for the therapeutic development of AD.
ESTHER : Guo_2022_Aging.(Albany.NY)_14_
PubMedSearch : Guo_2022_Aging.(Albany.NY)_14_
PubMedID: 36227154

Title : Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase - Li_2022_Molecules_27_6800
Author(s) : Li M , Dai X , Li A , Qi Q , Wang W , Cao J , Jiang Z , Liu R , Suo H , Xu L
Ref : Molecules , 27 :6800 , 2022
Abstract : Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe(3)O(4)@UiO-66-NH(2), was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe(3)O(4)@UiO-66-NH(2)) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) reached 74.4%, which was higher than that of PPL-Fe(3)O(4)@UiO-66-NH(2) (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe(3)O(4)@UiO-66-NH(2) had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe(3)O(4)@UiO-66-NH(2) modified by ionic liquids has great potential for immobilized enzymes.
ESTHER : Li_2022_Molecules_27_6800
PubMedSearch : Li_2022_Molecules_27_6800
PubMedID: 36296392

Title : Moringa Oleifera Alleviates Abeta Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP\/PS1 Mice - Mahaman_2022_Nutrients_14_
Author(s) : Mahaman YAR , Feng J , Huang F , Salissou MTM , Wang J , Liu R , Zhang B , Li H , Zhu F , Wang X
Ref : Nutrients , 14 : , 2022
Abstract : Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Abeta and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Abeta burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.
ESTHER : Mahaman_2022_Nutrients_14_
PubMedSearch : Mahaman_2022_Nutrients_14_
PubMedID: 36296969

Title : 5-Methyltetrahydrofolate Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Induced by D-Galactose and Aluminum Chloride - Zhang_2022_Int.J.Environ.Res.Public.Health_19_
Author(s) : Zhang Z , Wu H , Qi S , Tang Y , Qin C , Liu R , Zhang J , Cao Y , Gao X
Ref : Int J Environ Research Public Health , 19 : , 2022
Abstract : The effects of 5-methyltetrahydrofolate (5-MTHF) on a rat model of Alzheimer's disease (AD) induced by D-galactose (D-gal) and aluminum chloride (AlCl(3)) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl(3) to induce AD and three doses of 1 mg/kg, 5 mg/kg or 10 mg/kg 5-MTHF by oral gavage. A positive control group was treated with 1 mg/kg donepezil by gavage. Morris water maze performance showed that 5 and 10 mg/kg 5-MTHF significantly decreased escape latency and increased the number of platform crossings and time spent in the target quadrant for AD rats. The administration of 10 mg/kg 5-MTHF decreased the brain content of amyloid beta-protein 1-42 (Abeta(1-42)) and phosphorylated Tau protein (p-Tau) and decreased acetylcholinesterase and nitric oxide synthase activities. Superoxide dismutase activity, vascular endothelial growth factor level and glutamate concentration were increased, and malondialdehyde, endothelin-1, interleukin-6, tumor necrosis factor-alpha and nitric oxide decreased. The administration of 10 mg/kg 5-MTHF also increased the expression of disintegrin and metallopeptidase domain 10 mRNA and decreased the expression of beta-site amyloid precursor protein cleavage enzyme 1 mRNA. In summary, 5-MTHF alleviates memory impairment in a D-gal- and AlCl(3)-exposed rat model of AD. The inhibition of Abeta(1-42) and p-Tau release, reduced oxidative stress, the regulation of amyloid precursor protein processing and the release of excitatory amino acids and cytokines may be responsible.
ESTHER : Zhang_2022_Int.J.Environ.Res.Public.Health_19_
PubMedSearch : Zhang_2022_Int.J.Environ.Res.Public.Health_19_
PubMedID: 36554305

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

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

Title : Behavioral, histopathological, genetic, and organism-wide responses to phenanthrene-induced oxidative stress in Eisenia fetida earthworms in natural soil microcosms - He_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : He F , Yu H , Shi H , Li X , Chu S , Huo C , Liu R
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Phenanthrene (PHE) contamination not only changes the quality of soil environment but also threatens to the soil organisms. There is lack of focus on the eco-toxicity potential of this contaminant in real soil in the current investigation. Here, we assessed the toxic effects of PHE on earthworms (Eisenia fetida) in natural soil matrix. PHE exhibited a relatively high toxicity to E. fetida in natural soil, with the LC(50) determined to be 56.68 mg kg(-1) after a 14-day exposure. Excessive ROS induced by PHE, leading to oxidative damage to biomacromolecules in E. fetida, including lipid peroxidation, protein carbonylation, and DNA damage. The antioxidant defense system (total antioxidant capacity, glutathione S-transferase, peroxidase, catalase, carboxylesterase, and superoxide dismutase) in E. fetida responded quickly to scavenge excess ROS and free radicals. Exposure to PHE resulted in earthworm avoidance responses (2.5 mg kg(-1)) and habitat function loss (10 mg kg(-1)). Histological observations indicated that the intestine, body wall, and seminal vesicle in E. fetida were severely damaged after exposure to high-dose PHE. Moreover, earthworm growth (weight change) and reproduction (cocoon production and the number of juvenile) were also inhibited after exposure to this pollutant. Furthermore, the integrated toxicity of PHE toward E. fetida at different doses and exposure times was assessed by the integrated biomarker response (IBR), which confirmed that PHE is more toxic to earthworms in the high-dose and long-term exposure groups. Our results showed that PHE exposure induced oxidative stress, disturbed antioxidant defense system, and caused oxidative damage in E. fetida. These effects can trigger behavior changes and damage histological structure, finally cause growth inhibition, genotoxicity, and reproductive toxicity in earthworms. The strength of this study is the comprehensive toxicity evaluation of PHE to earthworms and highlights the need to investigate the eco-toxicity potential of exogenous environmental pollutants in a real soil environment.
ESTHER : He_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : He_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35113383

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 : Extraction and preparation of 5-lipoxygenase and acetylcholinesterase inhibitors from Astragalus membranaceus stems and leaves - Liu_2022_J.Sep.Sci__
Author(s) : Liu R , Zhang Y , Li S , Liu C , Zhuang S , Zhou X , Li Y , Liang J
Ref : J Sep Sci , : , 2022
Abstract : In this study, an efficient method that employs 5-lipoxygenase and acetylcholinesterase as biological target molecules in receptor-ligand affinity ultrafiltration-liquid chromatography was developed for the screening of enzyme inhibitors derived from the Astragalus membranaceus stems and leaves. The effects of the extraction time, number of extraction cycles, ethanol concentration, and liquid-solid ratio on the total yield of the target compounds were investigated using response surface methodology, and the bioactive components were isolated using a combination of semi-preparative high-performance liquid chromatography and high-speed countercurrent chromatography via a two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (1:6:2:6, v/v/v/v). Subsequently, ten naturally-occurring bioactive components in the Astragalus membranaceus stems and leaves, including wogonin, ononin, isoquercitrin, calycosin-7-glucoside, 3-hydroxy-9,10-dimethoxyptercarpan, hyperoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, baicalein, calycosin, and soyasaponin, were screened using affinity ultrafiltration to determine their potential effects against Alzheimer's disease. Consequently, all target compounds had purities higher than 95.0%, and the potential anti-Alzheimer's disease effect of the obtained bioactive compounds was verified using molecular docking analysis. Based on the results, the back-to-back screening of complex enzyme inhibitors and separation of the target bioactive compounds using complex chromatography could provide a new approach for the discovery and preparation of natural active ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2022_J.Sep.Sci__
PubMedSearch : Liu_2022_J.Sep.Sci__
PubMedID: 36502278

Title : Plasma exchange therapy for familial chylomicronemia syndrome in infant: A case report - Han_2022_Medicine.(Baltimore)_101_e29689
Author(s) : Han L , Qiang G , Yang L , Kou R , Li Q , Xin M , Liu R , Zhang Z
Ref : Medicine (Baltimore) , 101 :e29689 , 2022
Abstract : INTRODUCTION: Familial chylomicronemia syndrome (FCS) is a rare genetic disease. FCS usually manifests by the age of 10 years, and 25% of cases of FCS occur during infancy. Here we present a case of FCS in a male infant and summarize our experiences on the diagnosis and therapy of this case. PATIENT CONCERNS: A male infant aged 1 month and 8 days had recurrent hematochezia and hyperchylomicronemia. DIAGNOSIS: FCS based on symptoms and genetic test. INTERVENTIONS: Plasma exchange therapy. OUTCOMES: His development was normal with a good spirit and satisfactory weight gain, and no hematochezia occurred again. CONCLUSION: Genetic test is important for accurate diagnosis of FCS, and we identified a new mutation of lipoprotein lipase gene c.88C>A which conformed to autosomal recessive inheritance. Plasma exchange therapy can be applied to infants with FCS with low risk and good outcomes.
ESTHER : Han_2022_Medicine.(Baltimore)_101_e29689
PubMedSearch : Han_2022_Medicine.(Baltimore)_101_e29689
PubMedID: 35960041
Gene_locus related to this paper: human-LPL

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

Title : Enhancing bio-catalytic performance of lipase immobilized on ionic liquids modified magnetic polydopamine - Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
Author(s) : Suo H , Li M , Liu R , Xu L
Ref : Colloids Surf B Biointerfaces , 206 :111960 , 2021
Abstract : In this study, imidazolium-based ionic liquid with [tf(2)N](-) as the anion was successfully grafted to magnetic polydopamine nanoparticles (MPDA). The prepared materials were well characterized and used as supports for lipase immobilization. The immobilized lipase (PPL-ILs-MPDA) exhibited excellent activity and stability. The specific activity of PPL-ILs-MPDA was 2.15 and 1.49 folds higher than that of free PPL and PPL-MPDA. In addition, after 10 rounds of reuse, the residual activity of PPL-ILs-MPDA was 86.2 % higher than that of PPL-MPDA (75.4 %). Furthermore, the kinetic assay indicated that the affinity between PPL-ILs-MPDA and substrate had increased. Analysis of the secondary structure using circular dichroism was used to explain the mechanism underlying the improvement in the performance of PPL-ILs-MPDA. In addition, the immobilized lipase can be easily separated from the reaction system with a magnet. The observations regarding the development of new supports for lipase immobilization may provide new ideas regarding further studies in this field.
ESTHER : Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
PubMedSearch : Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
PubMedID: 34224932

Title : Nucleus basalis stimulation enhances working memory by stabilizing stimulus representations in primate prefrontal cortical activity - Qi_2021_Cell.Rep_36_109469
Author(s) : Qi XL , Liu R , Singh B , Bestue D , Compte A , Vazdarjanova AI , Blake DT , Constantinidis C
Ref : Cell Rep , 36 :109469 , 2021
Abstract : Acetylcholine plays a critical role in the neocortex. Cholinergic agonists and acetylcholinesterase inhibitors can enhance cognitive functioning, as does intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. Here we show in two male monkeys how NB stimulation affects working memory and alters its neural code. NB stimulation increases dorsolateral prefrontal activity during the delay period of spatial working memory tasks and broadens selectivity for stimuli but does not strengthen phasic responses to each neuron's optimal visual stimulus. Paradoxically, despite this decrease in neuronal selectivity, performance improves in many task conditions, likely indicating increased delay period stability. Performance under NB stimulation does decline if distractors similar to the target are presented, consistent with reduced prefrontal selectivity. Our results indicate that stimulation of the cholinergic forebrain increases prefrontal neural activity, and this neuromodulatory tone can improve cognitive performance, subject to a stability-accuracy tradeoff.
ESTHER : Qi_2021_Cell.Rep_36_109469
PubMedSearch : Qi_2021_Cell.Rep_36_109469
PubMedID: 34348147

Title : Association of TaD14-4D, a Gene Involved in Strigolactone Signaling, with Yield Contributing Traits in Wheat - Liu_2021_Int.J.Mol.Sci_22_
Author(s) : Liu R , Hou J , Li H , Xu P , Zhang Z , Zhang X
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Tillering is a crucial agronomic trait of wheat; it determines yield and plant architecture. Strigolactones (SLs) have been reported to inhibit plant branching. D14, a receptor of SLs, has been described to affect tillering in rice, yet it has seldomly been studied in wheat. In this study, three TaD14 homoeologous genes, TaD14-4A, TaD14-4B, and TaD14-4D, were identified. TaD14-4A, TaD14-4B, and TaD14-4D were constitutively expressed, and TaD14-4D had a higher expression level in most tissues. TaD14 proteins were localized in both cytoplasm and nucleus. An SNP and a 22 bp insertion/deletion (Indel) at the exon regions of TaD14-4D were detected, forming three haplotypes, namely 4D-HapI, 4D-HapII, and 4D-HapIII. Due to the frameshift mutation in the coding region of 4D-HapII, the interaction of 4D-HapII with TaMAX2 and TaD53 was blocked, which led to the blocking of SL signal transduction. Based on the two variation sites, two molecular markers, namely dCAPS-250 and Indel-747, were developed. Association analysis suggested that haplotypes of TaD14-4D were associated with effective tillering number (ETN) and thousand kernel weight (TKW) simultaneously in four environments. The favorable haplotype 4D-HapIII underwent positive selection in global wheat breeding. This study provides insights into understanding the function of natural variations of TaD14-4D and develops two useful molecular markers for wheat breeding.
ESTHER : Liu_2021_Int.J.Mol.Sci_22_
PubMedSearch : Liu_2021_Int.J.Mol.Sci_22_
PubMedID: 33916852

Title : Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer's disease - Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
Author(s) : Zhang J , Liu R , Zhang D , Zhang Z , Zhu J , Xu L , Guo Y
Ref : Colloids Surf B Biointerfaces , 200 :111584 , 2021
Abstract : Nanopeptide assembled from peptide-anchored nanoparticles possess an enormous research potential in the field of cellular medicine and disease treatment. The aim of this study was to explore the neuroprotective effects of maize tetrapeptide anchored gold nanoparticles against l-glutamic acid-induced PC12 cell apoptosis and a murine Alzheimer's disease model induced by aluminum chloride and d-galactose. The results revealed that the nanopeptide antioxidant inhibited intracellular ROS accumulation and promoted cell differentiation than that of maize bioactive tetrapeptide. Compared with untreated Alzheimer's disease model mice, nanopeptide administration shortened the escape latency time in a water maze test and improved the movements in the autonomic activity test. After 16 days of nanopeptide administration, the central cholinergic system function of acetylcholine and cholineacetyltransferase were enhanced, and the level of acetylcholinesterase was reduced. It also increased superoxide dismutase and glutathione peroxidase activity in sera and hypothalami. Moreover, nanopeptide treatment upregulated cerebral nuclear factor erythroid 2-related factor 2 and heme-oxygenase-1 and downregulated kelch-like ECH-associated protein 1 relative to untreated Alzheimer's disease model mice. Thus, the novel nanopeptide is expected to be used as the neuroprotective agent to prevent Alzheimer's disease.
ESTHER : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedSearch : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedID: 33508658

Title : Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome - He_2020_Ann.Palliat.Med_9_3436
Author(s) : He J , Yu Q , Wu C , Sun Z , Wu X , Liu R , Zhang H
Ref : Ann Palliat Med , 9 :3436 , 2020
Abstract : BACKGROUND: There are close relationships between the spleen and limb muscles and thoughts. The study aims to test the effects of ginsenoside Rg1 in combination with acupuncture of the Beishu acupoint on T cell subsets of rats with chronic fatigue syndrome (CFS). METHODS: The model was set up by combining forced cold-water swimming with chronic restraint. The rats were randomly divided into blank control, model, ginsenoside, acupuncture, and ginsenoside plus acupuncture groups (n=10). For the acupuncture group, the Beishu acupoint was acupunctured on the 2nd day after modeling. For the ginsenoside group, the ginsenoside Rg1 solution was injected into the tail vein on the 2nd day after modeling. For the combination group, both processes were conducted. These groups were compared regarding exhausted swimming time, number of struggles, resting time, serum levels of IgA, IgG, IgM, IFN-alpha, IFN-beta, and IFN-gamma, lymphocyte transformation rate, T cell subsets, and skeletal muscle activities of malondialdehyde (MDA), total antioxidative capacity (T-AOC) and acetylcholinesterase (Ache). RESULTS: The exhausted swimming time, number of struggles, and resting time of combination group surpassed those in the ginsenoside and acupuncture groups significantly (P<0.05). The serum levels of IgA, IgG, IgM, IFN-beta, IFN-gamma, T-AOC, and Ache, together with CD3+ and CD8+ T cell percentages of combination groups, were significantly higher than those of ginsenoside and acupuncture groups. However, the IFN-alpha level, MDA activity, and CD4+ T cell percentage were significantly lower (P<0.05). Compared with the model group, the CD4+/CD8+ T cell ratios of acupuncture, ginsenoside, and combination groups decreased significantly (P<0.05). Compared with the combination group, the ratio of the ginsenoside group increased significantly (P<0.05). CONCLUSIONS: Both acupuncture of the Beishu acupoint and intravenous injection of ginsenoside Rg1 have anti-fatigue effects, and their combination works synergistically. This study supplies an experimental basis for joint therapy using acupuncture and drugs to combat fatigue synergistically.
ESTHER : He_2020_Ann.Palliat.Med_9_3436
PubMedSearch : He_2020_Ann.Palliat.Med_9_3436
PubMedID: 33065794

Title : Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007 - Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
Author(s) : Liu R , Fang F , An Z , Huang R , Wang Y , Sun X , Fu S , Fu A , Deng Z , Liu T
Ref : J Ind Microbiol Biotechnol , 47 :275 , 2020
Abstract : Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of Actinomadura sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs in silico to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming Actinomadura sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.
ESTHER : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedSearch : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedID: 31853778
Gene_locus related to this paper: 9actn-a0a6i4pr03

Title : Ratiometric sensors with selective fluorescence enhancement effects based on photonic crystals for the determination of acetylcholinesterase and its inhibitor - Liu_2020_J.Mater.Chem.B_8_11001
Author(s) : Liu R , Bao L , Zhang S , Wu Z , Zhou J , Liu C , Yu R
Ref : J Mater Chem B , 8 :11001 , 2020
Abstract : Ratiometric fluorescent sensors are powerful tools for quantitative analyses. However, gold nano-clusters (AuNCs) as typical fluorophores in ratiometric sensors have some disadvantages, such as low luminous efficiency. In this study, a highly sensitive ratiometric fluorescence sensor was fabricated by the combination of AuNCs and fluorescein (FL), and the photonic crystals (PhCs) were used to selectively enhance the fluorescence intensity of AuNCs. This fluorescence sensor was used for the sensitive detection of acetylcholinesterase (AChE) and its inhibitor paraoxon. AChE can catalyze the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which can induce the fluorescence quenching of AuNCs while having no obvious influence on the fluorescence intensity of FL. AChE can be determined in the range from 0.1 to 25 mU mL-1 with a limit of detection (LOD) of 0.027 mU mL-1, and paraoxon can be determined in the range of 0.06 to 60 ng mL-1 with a LOD 0.025 ng mL-1. This method, as a new way to selectively improve the fluorescence signal of one of the fluorophores in the ratiometric sensor, would be a promising strategy for the sensitive determination of AChE and its inhibitor.
ESTHER : Liu_2020_J.Mater.Chem.B_8_11001
PubMedSearch : Liu_2020_J.Mater.Chem.B_8_11001
PubMedID: 33225325

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 : Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein - Liu_2020_Cell.Death.Differ__
Author(s) : Liu R , Wang X , Curtiss C , Sheikh MS , Huang Y
Ref : Cell Death Differ , : , 2020
Abstract : We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. We found that MGL directly interacted with XIAP and enhanced E3-ligase activity and proteasomal degradation of XIAP. MGL overexpression induced cell death that was coupled with caspase activation and reduced XIAP levels. N-terminus of MGL was found to mediate interactions with XIAP and induce cell death. MGL-deficient cells exhibited elevated XIAP levels and exhibited resistance to anticancer drugs. XIAP expression was significantly elevated in tissues of MGL-deficient animals as well as human lung cancers exhibiting reduced MGL expression. Thus, MGL appears to mediate its tumor-suppressive actions by inhibiting XIAP to induce cell death.
ESTHER : Liu_2020_Cell.Death.Differ__
PubMedSearch : Liu_2020_Cell.Death.Differ__
PubMedID: 32376875
Gene_locus related to this paper: human-MGLL

Title : First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant - Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
Author(s) : Zhang P , Wu B , Lu Y , Ni Q , Liu R , Zhou W , Wang H
Ref : Mol Genet Genomic Med , 8 :e1144 , 2020
Abstract : BACKGROUND: Congenital myasthenic syndrome 22 (CMS22) is a rare autosomal recessive disorder due to isolated PREPL deficiency and characterized by neonatal hypotonia, muscular weakness, and feeding difficulties. Eight such cases have already been reported, while maternal uniparental disomy with a PREPL pathogenic mutation has never been involved. METHODS: Trio whole-exome sequencing (WES), comparative genomic hybridization microarray (arry-CGH), and Sanger sequencing were performed on a 6-month-old girl with severe neonatal hypotonia and feeding difficulties. Also, the phenotype and genotype of reported CMS22 patients were reviewed. RESULTS: In this female infant, we identified a novel homozygous frameshift mutation in PREPL (c.1282_1285delTTTG, p.Phe428Argfs*18) by trio-WES. Sanger sequencing confirmed that her mother was heterozygous and her father was normal. Trio-WES data showed that 96.70% (1668/1725) variants on chromosome 2 were homozygous and maternally inherited, suggesting maternal uniparental disomy of chromosome 2 [UPD(2)mat]. Array-CGH did not show copy number variants (CNVs) but revealed complete UPD(2). CONCLUSION: To date, nine patients with CMS22 have been reported including our patient, and we report the youngest and the first UPD(2)mat with PREPL novel homozygous pathogenic mutation case, which expand the mutation spectrum of PREPL gene.
ESTHER : Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
PubMedSearch : Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
PubMedID: 31985178
Gene_locus related to this paper: human-PREPL

Title : The genome of broomcorn millet - Zou_2019_Nat.Commun_10_436
Author(s) : Zou C , Li L , Miki D , Li D , Tang Q , Xiao L , Rajput S , Deng P , Peng L , Jia W , Huang R , Zhang M , Sun Y , Hu J , Fu X , Schnable PS , Chang Y , Li F , Zhang H , Feng B , Zhu X , Liu R , Schnable JC , Zhu JK
Ref : Nat Commun , 10 :436 , 2019
Abstract : Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
ESTHER : Zou_2019_Nat.Commun_10_436
PubMedSearch : Zou_2019_Nat.Commun_10_436
PubMedID: 30683860
Gene_locus related to this paper: panmi-a0a3l6qvl9 , 9poal-a0a2s3hbt0 , panmi-a0a3l6sxg5 , 9poal-a0a2t7cdl4 , panmi-a0a3l6ta96 , panmi-a0a3l6qv47 , panmi-a0a3l6s688 , panmi-a0a3l6tph0

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

Title : A non-competitive surface plasmon resonance immunosensor for rapid detection of triazophos residue in environmental and agricultural samples - Guo_2018_Sci.Total.Environ_613-614_783
Author(s) : Guo Y , Liu R , Liu Y , Xiang D , Gui W , Li M , Zhu G
Ref : Sci Total Environ , 613-614 :783 , 2018
Abstract : The wide application of an organophosphate pesticide triazophos raises concern on the environmental pollution and the potential risk to human health. Thus, it is crucial to regularly monitor triazophos residue in the environment and agro-products. Herein we described a non-competitive immunoassay for trace detection of triazophos using a direct surface plasmon resonance (SPR) biosensor. Two anti-triazophos monoclonal antibodies (mAbs) were immobilized on the sensor chip and characterized by SPR-based kinetic analysis. The mAb with relatively slow dissociation rate was used for direct immunosensing of triazophos. The biosensor assay showed a high specificity and a low detection limit of 0.096ngmL-1 to triazophos, with the linear detection range of 0.98-8.29ngmL-1. Under the optimal condition, the sensor chip could be regenerated for 160cycles at least. Moreover, the sensitive method was applied to determine triazophos in the spiked environmental water and agricultural products, as well as in unknown real-life samples (including Chinese cabbage, cucumber, and apple). Desirable results demonstrated that the newly-developed immunosensor could be used as a rapid, convenient, and reliable tool to regularly monitor triazophos and meet the detection requirement of its maximum residue limits.
ESTHER : Guo_2018_Sci.Total.Environ_613-614_783
PubMedSearch : Guo_2018_Sci.Total.Environ_613-614_783
PubMedID: 28946376

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

Title : Exploring the binding interaction between copper ions and Candida rugosa lipase - Qu_2018_Toxicol.Res.(Camb)_7_1100
Author(s) : Qu W , Yuan D , Zhao L , Zong W , Liu R
Ref : Toxicol Res (Camb) , 7 :1100 , 2018
Abstract : The wide range of applications of copper have caused widespread concern about its toxicity. However, few studies have reported the mechanism of the binding interaction between copper ions and digestive enzymes, which play an important role in physiological health and industrial production. In this study, the effects of copper ions on the conformation and activity of Candida rugosa lipase (CRL) were evaluated by isothermal titration calorimetry (ITC), multiple spectral techniques, molecular simulation and enzyme activity assays. The results showed that copper ions can be combined with lipase, the binding affinity constant (K) was (2.91 +/- 0.619) x 10(-3) M(-1), the binding process was a spontaneous process, and the main force was the hydrophobic force. Rather than increasing the hydrophobicity of the amino acid microenvironment of CRL, the spectral methods demonstrated that copper can also make the protein peptide bond structure compact, changing its secondary structure. In addition, molecular simulation results showed that copper ions opened the "lid" of the CRL and entered the active center, which consequently changed the conformation of the CRL molecule. Structural changes may cause changes in enzyme activity. The increased activity of CRL with the addition of copper ions was verified by enzyme activity assay. In summary, copper showed an effect on CRL at the molecular level, which means its toxicity should receive more attention.
ESTHER : Qu_2018_Toxicol.Res.(Camb)_7_1100
PubMedSearch : Qu_2018_Toxicol.Res.(Camb)_7_1100
PubMedID: 30542604

Title : Intermittent stimulation in the nucleus basalis of meynert improves sustained attention in rhesus monkeys - Liu_2018_Neuropharmacol_137_202
Author(s) : Liu R , Crawford J , Callahan PM , Terry AV , Constantinidis C , Blake DT
Ref : Neuropharmacology , 137 :202 , 2018
Abstract : Sustained attention is essential in important behaviors in daily life. Many neuropsychiatric disorders are characterized by a compromised ability to sustain attention, making this cognitive domain an important therapeutic target. In this study, we tested a novel method of improving sustained attention. Monkeys were engaged in a continuous performance task (CPT) while the nucleus basalis of Meynert (NB), the main source of cholinergic innervation of the neocortex, was stimulated. Intermittent NB stimulation improved the animals' performance by increasing the hit rate and decreasing the false alarm rate. Administration of the cholinesterase inhibitor donepezil or the muscarinic antagonist scopolamine alone impaired performance, whereas the nicotinic antagonist mecamylamine alone improved performance. Applying NB stimulation while mecamylamine or donepezil were administered impaired CPT performance. Methylphenidate, a monoaminergic psychostimulant, was applied in conjunction with intermittent stimulation as a negative control, as it does not directly modulate cholinergic output. Methylphenidate also improved performance, and it produced further improvement when combined with NB stimulation. The additive effect of the combination suggested NB stimulation altered behavior independently from methylphenidate effects. We conclude that basal forebrain projections contribute to sustained attention, and that intermittent NB stimulation is an effective way of improving performance.
ESTHER : Liu_2018_Neuropharmacol_137_202
PubMedSearch : Liu_2018_Neuropharmacol_137_202
PubMedID: 29704983

Title : The binding interaction between cadmium-based, aqueous-phase quantum dots with Candida rugosa lipase - Zhao_2018_J.Mol.Recognit__e2712
Author(s) : Zhao L , Hu S , Meng Q , Xu M , Zhang H , Liu R
Ref : J Mol Recognit , :e2712 , 2018
Abstract : As a promising biolabeling biomaterials, quantum dots (QDs) present a great potential. However, the toxicity of QDs to organisms has attracted wide attention. In our research, we introduced an in vitro method to study the molecular mechanisms for the structure and activity alterations of Candida rugosa lipase (CRL) with the binding of 3-mercaptopropionic acid-capped CdTe QDs. Multiple spectroscopic methods, isothermal titration calorimetry, and enzyme activity measurements were used in this paper. QDs statically quenched the intrinsic fluorescence of CRL with the quenching constant decreases from 2.46 x 10(13) to 1.64 x 10(13) L mol(-1) second(-1) (298 to 310 K). It binds to CRL through hydrophobic force with 1 binding site, unfolding and loosening the skeleton and changed its secondary structure. Rather than aggregating on the surface, it enters the pocket of the CRL to interact with Ser-209 (2.43 A) and the residues surrounding Ser-209, making the catalytic triad more exposed. Furthermore, the activity of CRL was inhibited by approximately 15%. This work demonstrates that 3-mercaptopropionic acid-capped CdTe QDs may cause negative effects to CRL and obtains a molecular mechanism on QD-induced toxicity to proteins in vitro.
ESTHER : Zhao_2018_J.Mol.Recognit__e2712
PubMedSearch : Zhao_2018_J.Mol.Recognit__e2712
PubMedID: 29655217

Title : Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits - Zhang_2018_Cardiovasc.Diabetol_17_160
Author(s) : Zhang X , Zhang Z , Yang Y , Suo Y , Liu R , Qiu J , Zhao Y , Jiang N , Liu C , Tse G , Li G , Liu T
Ref : Cardiovasc Diabetol , 17 :160 , 2018
Abstract : BACKGROUND: There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. METHODS: A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-beta1, NF-kappaB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. RESULTS: DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1alpha/NRF1/Tfam signaling pathway. CONCLUSIONS: The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.
ESTHER : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedSearch : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedID: 30591063

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

Title : Glioblastoma recurrence correlates with NLGN3 levels - Liu_2018_Cancer.Med_7_2848
Author(s) : Liu R , Qin XP , Zhuang Y , Zhang Y , Liao HB , Tang JC , Pan MX , Zeng FF , Lei Y , Lei RX , Wang S , Liu AC , Chen J , Zhang ZF , Zhao D , Wu SL , Liu RZ , Wang ZF , Wan Q
Ref : Cancer Med , 7 :2848 , 2018
Abstract : Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum.
ESTHER : Liu_2018_Cancer.Med_7_2848
PubMedSearch : Liu_2018_Cancer.Med_7_2848
PubMedID: 29777576

Title : Acetylcholinesterase Inhibitory Alkaloids from the Whole Plants of Zephyranthes carinata - Zhan_2017_J.Nat.Prod_80_2462
Author(s) : Zhan G , Zhou J , Liu J , Huang J , Zhang H , Liu R , Yao G
Ref : Journal of Natural Products , 80 :2462 , 2017
Abstract : Eleven new alkaloids (1-11), classified as the 12-acetylplicamine (1), N-deformyl-seco-plicamine (2), plicamine (3-6), 4a-epi-plicamine (7), seco-plicamine (8), and lycorine (9-11) framework types, along with 15 known alkaloids (12-26) were isolated from the whole plants of Zephyranthes carinata. The structures of the new alkaloids 1-11 were established by extensive spectroscopic data interpretation. The absolute configurations of 9 and 10 were defined by single-crystal X-ray diffraction analysis. Zephycarinatines A (1), B (2), and G (7) represent the first examples of 12-acetylplicamine, N-deformyl-seco-plicamine, and 4a-epi-plicamine alkaloids, respectively. Alkaloids 6, 11, 17, and 20-23 exhibited AChE inhibitory activities with IC50 values ranging from 1.21 to 184.05 muM, and a preliminary structure-activity relationship is discussed.
ESTHER : Zhan_2017_J.Nat.Prod_80_2462
PubMedSearch : Zhan_2017_J.Nat.Prod_80_2462
PubMedID: 28898076

Title : Assessment of tissue-specific accumulation, elimination and toxic effects of dichlorodiphenyltrichloroethanes (DDTs) in carp through aquatic food web - Di_2017_Sci.Rep_7_2288
Author(s) : Di S , Liu R , Tian Z , Cheng C , Chen L , Zhang W , Zhou Z , Diao J
Ref : Sci Rep , 7 :2288 , 2017
Abstract : Microcosms containing DDT spiked-sediment, Tubifex tubifex and carp (Cyprinus carpio) were constructed to simulate a freshwater system. The accumulation, elimination and toxic effects of DDT (p,p'-DDT, o,p'-DDT), and its metabolites DDD (p,p'-DDD, o,p'-DDD) and DDE (p,p'-DDE, o,p'-DDE) were studied in T. tubifex and carp. Tissue/organ distributions of DDTs were also investigated in carp. The bioaccumulation and elimination of DDT differed in T. tubifex, carp and its tissues/organs. Unimodal or bimodal distributions were observed, and the concentrations of DDT metabolites (DDD and p,p'-DDE) increased over time. The carp organ with the highest concentrations of DDTs (DDT, DDD and DDE) was the gill. The largest mass distribution of DDTs was also in gill, followed by muscle and gastrointestinal tract. Maximum levels of DDTs in whole carp and carp muscle were 161 and 87 ng/g, respectively; therefore, the levels of DDTs observed in carp in this study were insufficient to constitute a health concern if present in fish for human consumption. Significant changes were observed in some biomarkers, including superoxide dismutase, catalase, glutathione-S-transferase, glutathione, and carboxylesterase, in T. tubifex and carp tissues during DDT exposure. Tissue-specific accumulation of DDTs in carp can be a key indicator of exposure to environmentally relevant concentrations.
ESTHER : Di_2017_Sci.Rep_7_2288
PubMedSearch : Di_2017_Sci.Rep_7_2288
PubMedID: 28536421

Title : Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer's disease - Blake_2017_Commun.Integr.Biol_10_e1389359
Author(s) : Blake DT , Terry AV , Plagenhoef M , Constantinidis C , Liu R
Ref : Commun Integr Biol , 10 :e1389359 , 2017
Abstract : The brain's cholinergic arousal pathways decline in parallel with the brain's executive functions in aging and Alzheimer's Disease. The frontline and currently most effective approach to treating Alzheimer's disease is the administration of cholinesterase inhibitors, which, in a dose dependent manner, improve the symptoms of cognitive decline over the first months of treatment before further decline occurs. We recently showed that intermittent deep brain stimulation of the nucleus basalis of Meynert improves working memory function in young adult monkeys, and that this improvement depended on cholinergic function. Within minutes, the monkeys' ability to remember stimuli over a delay period improved. Over months, the monkeys performed the working memory task better even in the absence of stimulation. Here, we show historical data from our monkey colony in which more than two dozen animals have performed the same behavioral task to asymptotic performance levels. Using a distribution based on our historical data, we estimate that the monkeys receiving intermittent stimulation leapt over the performance level of 32-44 percent of peer animals in the first several months after stimulation was initiated. Implications for a parallel increase in cognitive function for early Alzheimer's patients are discussed.
ESTHER : Blake_2017_Commun.Integr.Biol_10_e1389359
PubMedSearch : Blake_2017_Commun.Integr.Biol_10_e1389359
PubMedID: 29260798

Title : Interaction of a digestive protease, Candida rugosa lipase, with three surfactants investigated by spectroscopy, molecular docking and enzyme activity assay - Zhang_2017_Sci.Total.Environ_622-623_306
Author(s) : Zhang R , Liu Y , Huang X , Xu M , Liu R , Zong W
Ref : Sci Total Environ , 622-623 :306 , 2017
Abstract : The extensive use of surfactants in food, laundry products and agriculture has caused concern about their biosafety. However, few studies have been done on their potential effect on the lipase which has always been used with surfactants in food and laundry industry. Herein, we investigated the interaction of three surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), sodium lauryl sulfonate (SLS)) with Candida rugosa lipase (CRL), which is a popular biocatalyst used regularly with surfactants. The effect of the three surfactants on the conformation and activity of CRL was evaluated by using multiple spectral methods, enzyme activity assay and molecular docking modeling. The results demonstrated that CRL interacted with SDS, SDBS and SLS primarily through hydrophobic forces, H-bonding and electrostatic forces, respectively. The binding constants (KA) of SDBS with CRL varied with temperature: 1.99x10(3)mol/L at 298K and 4.13x10(3)mol/L at 318K. SDS and SDBS affected the secondary structure and skeleton of CRL, which changed the polarity of CRL and enhanced its activity. SLS also changed the secondary structure and activity of CRL moderately, but had little effect on its polarity and chromophore microenvironment. Accordingly, all three surfactants exhibited effect to CRL on the molecular level calling for more attention to pay on their biosafety. The work demonstrates that SDS, SDBS and SLS could cause negative effects to CRL from different angles and therefore are not bio-friendly detergents.
ESTHER : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedSearch : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedID: 29220758

Title : Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys - Liu_2017_Curr.Biol_27_2640
Author(s) : Liu R , Crawford J , Callahan PM , Terry AV, Jr. , Constantinidis C , Blake DT
Ref : Current Biology , 27 :2640 , 2017
Abstract : Acetylcholine in the neocortex is critical for executive function [1-3]. Degeneration of cholinergic neurons in aging and Alzheimer's dementia is commonly treated with cholinesterase inhibitors [4-7]; however, these are modestly effective and are associated with side effects that preclude effective dosing in many patients [8]. Electrical activation of the nucleus basalis (NB) of Meynert, the source of neocortical acetylcholine [9, 10], provides a potential method of improving cholinergic activation [11, 12]. Here we tested whether NB stimulation would improve performance of a working memory task in a nonhuman primate model. Unexpectedly, intermittent stimulation proved to be most beneficial (60 pulses per second, for 20 s every minute), whereas continuous stimulation often impaired performance. Pharmacological experiments confirmed that the effects depended on cholinergic activation. Donepezil, a cholinesterase inhibitor, restored performance in animals impaired by continuous stimulation but did not improve performance further during intermittent stimulation. Intermittent stimulation was rendered ineffective by either nicotinic or muscarinic receptor antagonists. In the months after stimulation began, performance also improved in sessions without stimulation. Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function in aging and Alzheimer's dementia.
ESTHER : Liu_2017_Curr.Biol_27_2640
PubMedSearch : Liu_2017_Curr.Biol_27_2640
PubMedID: 28823679

Title : MAPK cascade-mediated regulation of pathogenicity, conidiation and tolerance to abiotic stresses in the entomopathogenic fungus Metarhizium robertsii - Chen_2016_Environ.Microbiol_18_1048
Author(s) : Chen X , Xu C , Qian Y , Liu R , Zhang Q , Zeng G , Zhang X , Zhao H , Fang W
Ref : Environ Microbiol , 18 :1048 , 2016
Abstract : Metarhizium robertsii has been used as a model to study fungal pathogenesis in insects, and its pathogenicity has many parallels with plant and mammal pathogenic fungi. MAPK (Mitogen-activated protein kinase) cascades play pivotal roles in cellular regulation in fungi, but their functions have not been characterized in M. robertsii. In this study, we identified the full complement of MAPK cascade components in M. robertsii and dissected their regulatory roles in pathogenesis, conidiation and stress tolerance. The nine components of the Fus3, Hog1 and Slt2-MAPK cascades are all involved in conidiation. The Fus3- and Hog1-MAPK cascades are necessary for tolerance to hyperosmotic stress, and the Slt2- and Fus3-MAPK cascades both mediate cell wall integrity. The Hog1 and Slt2-MAPK cascades contribute to pathogenicity; the Fus3-MAPK cascade is indispensable for fungal pathogenesis. During its life cycle, M. robertsii experiences multiple microenvironments as it transverses the cuticle into the haemocoel. RNA-seq analysis revealed that MAPK cascades collectively play a major role in regulating the adaptation of M. robertsii to the microenvironmental change from the cuticle to the haemolymph. The three MAPKs each regulate their own distinctive subset of genes during penetration of the cuticle and haemocoel colonization, but they function redundantly to regulate adaptation to microenvironmental change.
ESTHER : Chen_2016_Environ.Microbiol_18_1048
PubMedSearch : Chen_2016_Environ.Microbiol_18_1048
PubMedID: 26714892
Gene_locus related to this paper: metra-pks2

Title : Effects of microbial lipases on hydrolyzed milk fat at different time intervals in flavour development and oxidative stability - Omar_2016_J.Food.Sci.Technol_53_1035
Author(s) : Omar KA , Gounga ME , Liu R , Mlyuka E , Wang X
Ref : J Food Sci Technol , 53 :1035 , 2016
Abstract : The interest in application of biocatalysis during natural milk fat flavours development has increased rapidly and lipases have become the most studied group in the development of bovine milk fat flavours. Lipozyme-435, Novozyme-435 and Thermomyces lanuginosus Immobilized (TL-IM) lipases were used to hydrolyze anhydrous milk fat (AMF) and anhydrous buffalo milk fat (ABF) and their volatile flavouring compounds were identified by solid-phase micro-extraction gas chromatography/mass spectrometry (SPME-GC/MS) and then compared at three hydrolysis intervals. Both AMF and ABF after lipolysis produced high amount of butanoic and hexanoic acids and other flavouring compounds; however, highest amount were produced by Lipozyme-435 and Novozyme-435 followed by TL-IM. The hydrolyzed products were assessed by Rancimat-743 for oxidative stability and found both that, for AMF and ABF treated butter oil, Lipozyme-435 and TL-IM were generally more stable compared to Novozyme-435. For both AMF and ABF treated butter oil, Lipozyme-435 was observed to cause no further oxidation consequences which indicates Lipozyme-435 was stable during hydrolysis at 55 degreeC for 24 h.
ESTHER : Omar_2016_J.Food.Sci.Technol_53_1035
PubMedSearch : Omar_2016_J.Food.Sci.Technol_53_1035
PubMedID: 27162383

Title : Surfactant-activated lipase hybrid nanoflowers with enhanced enzymatic performance - Cui_2016_Sci.Rep_6_27928
Author(s) : Cui J , Zhao Y , Liu R , Zhong C , Jia S
Ref : Sci Rep , 6 :27928 , 2016
Abstract : Increasing numbers of materials have been extensively used as platforms for enzyme immobilization to improve catalytic performance. However, activity of the most of the enzymes was declined after immobilization. Here, we develop a surfactant-activated lipase-inorganic flowerlike hybrid nanomaterials with rational design based on interfacial activation and self-assembly. The resulting surfactant-activated lipase-inorganic hybird nanoflower (activated hNF-lipase) exhibited 460% and 200% higher activity than native lipase and conventional lipase-inorganic hybird nanoflower (hNF-lipase). Furthermore, the activated hNF-lipase displayed good reusability due to its monodispersity and mechanical properties, and had excellent long-time stability. The superior catalytic performances were attributed to both the conformational modulation of surfactants and hierarchical structure of nanoflowers, which not only anchored lipases in an active form, but also decreased the enzyme-support negative interaction and mass-transfer limitations. This new biocatalytic system is promising to find widespread use in applications related to biomedicine, biosensor, and biodiesel.
ESTHER : Cui_2016_Sci.Rep_6_27928
PubMedSearch : Cui_2016_Sci.Rep_6_27928
PubMedID: 27297609

Title : Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities - Zhan_2016_J.Nat.Prod_79_760
Author(s) : Zhan G , Zhou J , Liu R , Liu T , Guo G , Wang J , Xiang M , Xue Y , Luo Z , Zhang Y , Yao G
Ref : Journal of Natural Products , 79 :760 , 2016
Abstract : Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 muM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 muM.
ESTHER : Zhan_2016_J.Nat.Prod_79_760
PubMedSearch : Zhan_2016_J.Nat.Prod_79_760
PubMedID: 26913788

Title : Discovery of Multitarget-Directed Ligands against Alzheimer's Disease through Systematic Prediction of Chemical-Protein Interactions - Fang_2015_J.Chem.Inf.Model_55_149
Author(s) : Fang J , Li Y , Liu R , Pang X , Li C , Yang R , He Y , Lian W , Liu AL , Du GH
Ref : J Chem Inf Model , 55 :149 , 2015
Abstract : To determine chemical-protein interactions (CPI) is costly, time-consuming, and labor-intensive. In silico prediction of CPI can facilitate the target identification and drug discovery. Although many in silico target prediction tools have been developed, few of them could predict active molecules against multitarget for a single disease. In this investigation, naive Bayesian (NB) and recursive partitioning (RP) algorithms were applied to construct classifiers for predicting the active molecules against 25 key targets toward Alzheimer's disease (AD) using the multitarget-quantitative structure-activity relationships (mt-QSAR) method. Each molecule was initially represented with two kinds of fingerprint descriptors (ECFP6 and MACCS). One hundred classifiers were constructed, and their performance was evaluated and verified with internally 5-fold cross-validation and external test set validation. The range of the area under the receiver operating characteristic curve (ROC) for the test sets was from 0.741 to 1.0, with an average of 0.965. In addition, the important fragments for multitarget against AD given by NB classifiers were also analyzed. Finally, the validated models were employed to systematically predict the potential targets for six approved anti-AD drugs and 19 known active compounds related to AD. The prediction results were confirmed by reported bioactivity data and our in vitro experimental validation, resulting in several multitarget-directed ligands (MTDLs) against AD, including seven acetylcholinesterase (AChE) inhibitors ranging from 0.442 to 72.26 muM and four histamine receptor 3 (H3R) antagonists ranging from 0.308 to 58.6 muM. To be exciting, the best MTDL DL0410 was identified as an dual cholinesterase inhibitor with IC50 values of 0.442 muM (AChE) and 3.57 muM (BCHE) as well as a H3R antagonist with an IC50 of 0.308 muM. This investigation is the first report using mt-QASR approach to predict chemical-protein interaction for a single disease and discovering highly potent MTDLs. This protocol may be useful for in silico multitarget prediction of other diseases.
ESTHER : Fang_2015_J.Chem.Inf.Model_55_149
PubMedSearch : Fang_2015_J.Chem.Inf.Model_55_149
PubMedID: 25531792

Title : Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects - Anderson_2015_Antivir.Ther_20_397
Author(s) : Anderson MS , Gilmartin J , Cilissen C , De Lepeleire I , Van Bortel L , Dockendorf MF , Tetteh E , Ancona JK , Liu R , Guo Y , Wagner JA , Butterton JR
Ref : Antivir Ther , 20 :397 , 2015
Abstract : BACKGROUND: Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes.
METHODS: The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects).
RESULTS: The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-infinity) and C24 h with no change in Cmax. Midazolam AUC0-infinity was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported.
CONCLUSIONS: Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.
ESTHER : Anderson_2015_Antivir.Ther_20_397
PubMedSearch : Anderson_2015_Antivir.Ther_20_397
PubMedID: 25470746

Title : Engineering Pseudomonas putida KT2440 for simultaneous degradation of organophosphates and pyrethroids and its application in bioremediation of soil - Zuo_2015_Biodegradation_26_223
Author(s) : Zuo Z , Gong T , Che Y , Liu R , Xu P , Jiang H , Qiao C , Song C , Yang C
Ref : Biodegradation , 26 :223 , 2015
Abstract : Agricultural soils are usually co-contaminated with organophosphate (OP) and pyrethroid pesticides. To develop a stable and marker-free Pseudomonas putida for co-expression of two pesticide-degrading enzymes, we constructed a suicide plasmid with expression cassettes containing a constitutive promoter J23119, an OP-degrading gene (mpd), a pyrethroid-hydrolyzing carboxylesterase gene (pytH) that utilizes the upp gene as a counter-selectable marker for upp-deficient P. putida. By introduction of suicide plasmid and two-step homologous recombination, both mpd and pytH genes were integrated into the chromosome of a robust soil bacterium P. putida KT2440 and no selection marker was left on chromosome. Functional expression of mpd and pytH in P. putida KT2440 was demonstrated by Western blot analysis and enzyme activity assays. Degradation experiments with liquid cultures showed that the mixed pesticides including methyl parathion, fenitrothion, chlorpyrifos, permethrin, fenpropathrin, and cypermethrin (0.2 mM each) were degraded completely within 48 h. The inoculation of engineered strain (10(6) cells/g) to soils treated with the above mixed pesticides resulted in a higher degradation rate than in noninoculated soils. All six pesticides could be degraded completely within 15 days in fumigated and nonfumigated soils with inoculation. Theses results highlight the potential of the engineered strain to be used for in situ bioremediation of soils co-contaminated with OP and pyrethroid pesticides.
ESTHER : Zuo_2015_Biodegradation_26_223
PubMedSearch : Zuo_2015_Biodegradation_26_223
PubMedID: 25917649

Title : Downregulation of N-myc downstream regulated gene 1 caused by the methylation of CpG islands of NDRG1 promoter promotes proliferation and invasion of prostate cancer cells - Li_2015_Int.J.Oncol_47_1001
Author(s) : Li Y , Pan P , Qiao P , Liu R
Ref : Int J Oncol , 47 :1001 , 2015
Abstract : Current studies tend to consider N-myc downstream regulated gene 1 (NDRG1) as a tumor suppressor gene, inhibiting cell proliferation and invasion. NDRG1 expression in cancer cells is generally low, but the molecular mechanism is unclear. Aberrant methylation of CpG islands (CGIs) in gene promoter was able to inactivate tumor suppressor genes and activate oncogenes, disordering cell proliferation and apoptosis, playing a promotion role in tumor occurrence and progression. The present study was performed to investigate the effect of epigenetic modification of NDRG1 on prostate cancer (PCa) cells. The protein expression in human specimens was measured by immunohistochemical staining. The expression level of NDRG1 was changed by plasmid vectors in PCa cells. These cells were used to study proliferation and invasiveness. NDRG1 expression in normal prostate cells was higher than that in PCa cells. Downregulation of NDRG1 expression enhanced cell proliferation and invasiveness. In contrast, its upregulation could reduce cell proliferation and invasiveness. In PCa cells, the methylation rate of CGIs in the promoter region of NDRG1 was higher than that in normal prostate cells. 5-Aza-CdR, a methylation inhibitor, was able to effectively reverse the aberrant methylation of NDRG1, enhancing its expression, inhibiting cell growth. NDRG1 can inhibit the cell proliferation and invasion of PCa, but its expression level is low. The aberrant methylation of NDRG1 promoter is an important mechanism for gene silencing, playing an important role in tumor occurrence and progression. Therefore, reversing the aberrant methylation of NDRG1 may be used for PCa treatment.
ESTHER : Li_2015_Int.J.Oncol_47_1001
PubMedSearch : Li_2015_Int.J.Oncol_47_1001
PubMedID: 26202882

Title : Lipozyme RM IM-catalyzed acidolysis of Cinnamomum camphora seed oil with oleic acid to produce human milk fat substitutes enriched in medium-chain fatty acids - Zou_2014_J.Agric.Food.Chem_62_10594
Author(s) : Zou XG , Hu JN , Zhao ML , Zhu XM , Li HY , Liu XR , Liu R , Deng ZY
Ref : Journal of Agricultural and Food Chemistry , 62 :10594 , 2014
Abstract : In the present study, a human milk fat substitute (HMFS) enriched in medium-chain fatty acids (MCFAs) was synthesized through acidolysis reaction from Cinnamomum camphora seed oil (CCSO) with oleic acid in a solvent-free system. A commercial immobilized lipase, Lipozyme RM IM, from Rhizomucor miehei, was facilitated as a biocatalyst. Effects of different reaction conditions, including substrate molar ratio, enzyme concentration, reaction temperature, and reaction time were investigated using response surface methodology (RSM) to obtain the optimal oleic acid incorporation. After optimization, results showed that the maximal incorporation of oleic acid into HMFS was 59.68%. Compared with CCSO, medium-chain fatty acids at the sn-2 position of HMFS accounted for >70%, whereas oleic acid was occupied predominantly at the sn-1,3 position (78.69%). Meanwhile, triacylglycerol (TAG) components of OCO (23.93%), CCO (14.94%), LaCO (13.58%), OLaO (12.66%), and OOO (11.13%) were determined as the major TAG species in HMFS. The final optimal reaction conditions were carried out as follows: substrate molar ratio (oleic acid/CCSO), 5:1; enzyme concentration, 12.5% (w/w total reactants); reaction temperature, 60 degreeC; and reaction time, 28 h. The reusability of Lipozyme RM IM in the acidolysis reaction was also evaluated, and it was found that it could be reused up to 9 times without significant loss of activities. Urea inclusion method was used to separate and purify the synthetic product. As the ratio of HMFS/urea increased to 1:2, the acid value lowered to the minimum. In a scale-up experiment, the contents of TAG and total tocopherols in HMFS (modified CCSO) were 77.28% and 12.27 mg/100 g, respectively. All of the physicochemical indices of purified product were within food standards. Therefore, such a MCFA-enriched HMFS produced by using the acidolysis method might have potential application in the infant formula industry.
ESTHER : Zou_2014_J.Agric.Food.Chem_62_10594
PubMedSearch : Zou_2014_J.Agric.Food.Chem_62_10594
PubMedID: 25298236
Gene_locus related to this paper: rhimi-lipas

Title : Acetylcholine modulates the immune response in Zhikong scallop Chlamys farreri - Shi_2014_Fish.Shellfish.Immunol_38_204
Author(s) : Shi X , Wang L , Zhou Z , Liu R , Li Y , Song L
Ref : Fish Shellfish Immunol , 38 :204 , 2014
Abstract : Acetylcholine (ACh) is an indispensable neurotransmitter and neuromodulator in the cholinergic nervous system and it is implicated in the dynamic modulation of immune response in vertebrates. Although ACh has also been identified in most invertebrates, the knowledge about its immunomodulation is still limited. In the present study, the immunoreactivities of ACh and acetylcholinesterase (AChE) were observed in all the tested tissues of scallop Chlamys farreri, including adductor muscle, mantle, gill, hepatopancreas, kidney and gonad. The ACh concentration in the supernate of scallop hemolymph increased from 11.59 +/- 0.27 to 14.36 +/- 0.17 muM L-1 at 6 h after LPS (0.5 mg ml-1) stimulation, and increased to 15.51 +/- 1.20 muM L-1 at 3 h after the stimulation of tumor necrosis factor alpha (TNF-alpha) (50 ng ml-1). After LPS stimulation, the mRNA expression levels of superoxide dismutase (CfSOD), catalase (CfCAT) and lysozyme (CfLYZ) in hemocytes increased significantly at 3 h (P < 0.05), 6 h (P < 0.05) and 12 h (P < 0.05), respectively. Compared with the LPS treatment, the induction of CfSOD, CfCAT and CfLYZ expression in hemocytes was repressed effectively (P < 0.05) by the co-stimulation of LPS and ACh (5 x 10-7 M) at 3 h (P < 0.05), 6 h (P < 0.05) and 12 h (P < 0.05), respectively. Furthermore, the expression level of CfCAT in hemocytes increased significantly after 12 h by the co-stimulation with LPS and ACh (P < 0.05). These results indicated collectively that the scallop cholinergic nervous system could be activated by immune stimulations, and it might play an essential role in immunomodulation of scallops.
ESTHER : Shi_2014_Fish.Shellfish.Immunol_38_204
PubMedSearch : Shi_2014_Fish.Shellfish.Immunol_38_204
PubMedID: 24680755

Title : Novel Multipotent AChEI-CCB Attenuates Hyperhomocysteinemia-Induced Memory Deficits and Neuropathologies in Rats - Xia_2014_J.Alzheimers.Dis_42_1029
Author(s) : Xia Y , Liu R , Chen R , Tian Q , Zeng K , Hu J , Liu X , Wang Q , Wang P , Wang XC , Wang JZ
Ref : J Alzheimers Dis , 42 :1029 , 2014
Abstract : Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3beta. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
ESTHER : Xia_2014_J.Alzheimers.Dis_42_1029
PubMedSearch : Xia_2014_J.Alzheimers.Dis_42_1029
PubMedID: 25024319

Title : A lifespan observation of a novel mouse model: in vivo evidence supports abeta oligomer hypothesis - Zhang_2014_PLoS.One_9_e85885
Author(s) : Zhang Y , Lu L , Jia J , Jia L , Geula C , Pei J , Xu Z , Qin W , Liu R , Li D , Pan N
Ref : PLoS ONE , 9 :e85885 , 2014
Abstract : Transgenic mouse models are powerful tools in exploring the mechanisms of AD. Most current transgenic models of AD mimic the memory impairment and the main pathologic features, among which the formation of beta-amyloid (Abeta) plaques is considered a dominant pathologic event. Recently, Abeta oligomers have been identified as more neurotoxic than Abeta plaques. However, no ideal transgenic mouse model directly support Abeta oligomers as a neurotoxic species due to the puzzling effects of amyloid plaques in the more widely-used models. Here, we constructed a single-mutant transgenic (Tg) model harboring the PS1V97L mutation and used Non-Tg littermates as a control group. Employing the Morris water maze, electrophysiology, immunohistochemistry, biochemistry, and electron microscopy, we investigated behavioral changes and pathology progression in our single-mutant transgenic model. We discovered the pathological alteration of intraneuronal accumulation of Abeta oligomers without Abeta plaques in the PS1V97L-Tg mouse model, which might be the result of PS1 gene mutation. Following Abeta oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for Abeta oligomers in the onset of AD and suggests that Abeta plaques may not be the only prerequisite. This model provides a useful tool for studying the role of Abeta oligomers in AD pathogenesis.
ESTHER : Zhang_2014_PLoS.One_9_e85885
PubMedSearch : Zhang_2014_PLoS.One_9_e85885
PubMedID: 24465766

Title : Hopeahainol A attenuates memory deficits by targeting beta-amyloid in APP\/PS1 transgenic mice - Zhu_2013_Aging.Cell_12_85
Author(s) : Zhu X , Ye L , Ge H , Chen L , Jiang N , Qian L , Li L , Liu R , Ji S , Zhang S , Jin J , Guan D , Fang W , Tan R , Xu Y
Ref : Aging Cell , 12 :85 , 2013
Abstract : Increasing evidence demonstrates that amyloid beta (Abeta) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Abeta is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2) O(2) -treated PC12 cells. In this study, we reported that HopA might bind to Abeta(1-42) directly and inhibit the Abeta(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Abeta(1-42) and Abeta-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.
ESTHER : Zhu_2013_Aging.Cell_12_85
PubMedSearch : Zhu_2013_Aging.Cell_12_85
PubMedID: 23107435

Title : Lipase-catalyzed preparation of diacylglycerol-enriched oil from high-acid rice bran oil in solvent-free system - Song_2012_Appl.Biochem.Biotechnol_168_364
Author(s) : Song Z , Liu Y , Jin Q , Li L , Wang X , Huang J , Liu R
Ref : Appl Biochem Biotechnol , 168 :364 , 2012
Abstract : The ability of immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) to catalyze the reaction of high-acid rice bran oil (RBO) and monoglyceride (MG) for diacylglycerol-enriched rice bran oil (RBO-DG) preparation was investigated. The effects of substrate ratio, reaction temperature, time, and enzyme load on the respective content of free fatty acid (FFA) and DG in the final RBO-DG products was investigated. Enzyme screening on the reaction was also investigated. Response surface methodology (RSM) was used to optimize the effects of the reaction temperature (50-70 degreeC), the enzyme load (2-6 %; relative to the weight of total substrates), and the reaction time (4-8 h) on the respective content of FFA and DG. Validation of the RSM model was verified by the good agreement between the experimental and the predicted values. The optimum preparation conditions were as follows: MG/RBO, 0.25; temperature, 56 degreeC; enzyme load, 4.77 %; and reaction time, 5.75 h. Under the suggested conditions, the respective content of FFA and DG was 0.28 and 27.98 %, respectively. Repeated reaction tests indicated that Lipozyme RM IM could be used nine times under the optimum conditions with 90 % of its original catalytic activity still retained.
ESTHER : Song_2012_Appl.Biochem.Biotechnol_168_364
PubMedSearch : Song_2012_Appl.Biochem.Biotechnol_168_364
PubMedID: 22948601

Title : The entomopathogenic bacterial endosymbionts Xenorhabdus and Photorhabdus: convergent lifestyles from divergent genomes - Chaston_2011_PLoS.One_6_e27909
Author(s) : Chaston JM , Suen G , Tucker SL , Andersen AW , Bhasin A , Bode E , Bode HB , Brachmann AO , Cowles CE , Cowles KN , Darby C , de Leon L , Drace K , Du Z , Givaudan A , Herbert Tran EE , Jewell KA , Knack JJ , Krasomil-Osterfeld KC , Kukor R , Lanois A , Latreille P , Leimgruber NK , Lipke CM , Liu R , Lu X , Martens EC , Marri PR , Medigue C , Menard ML , Miller NM , Morales-Soto N , Norton S , Ogier JC , Orchard SS , Park D , Park Y , Qurollo BA , Sugar DR , Richards GR , Rouy Z , Slominski B , Slominski K , Snyder H , Tjaden BC , van der Hoeven R , Welch RD , Wheeler C , Xiang B , Barbazuk B , Gaudriault S , Goodner B , Slater SC , Forst S , Goldman BS , Goodrich-Blair H
Ref : PLoS ONE , 6 :e27909 , 2011
Abstract : Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points.
ESTHER : Chaston_2011_PLoS.One_6_e27909
PubMedSearch : Chaston_2011_PLoS.One_6_e27909
PubMedID: 22125637
Gene_locus related to this paper: xenna-d3vdr8 , xenne-n1nl20 , xenbs-d3v2h2

Title : The effect of natural health products and traditional medicines on the activity of human hepatic microsomal-mediated metabolism of oseltamivir - Liu_2010_J.Pharm.Pharm.Sci_13_43
Author(s) : Liu R , Tam TW , Mao J , Saleem A , Krantis A , Arnason JT , Foster BC
Ref : J Pharm Pharm Sci , 13 :43 , 2010
Abstract : PURPOSE: Oseltamivir is a prodrug that requires metabolic activation but there is little information on whether natural health products interact to prevent the biotransformation by the carboxylesterase. METHODS: HPLC-DAD-ESI-MSD and fluorometric assays were used to determine if 50-pooled mixed gender human liver microsomes can mediate the formation of the active carboxylate metabolite and then if this reaction is affected by natural health products. RESULTS: Extracts from 6 traditional Cree botanicals, a commercially available Echinacea product, Goldenseal and a traditional Chinese medicine reduced the formation of the active drug. In addition to oseltamivir carboxylate we report the detection of two new metabolites which are derivatives of oseltamivir carboxylate, one of which is a metabonate formed as a result of methanol. CONCLUSIONS: In vitro studies would suggest that there is the potential for some natural health products used by patients in response to pandemic A/H1N1 to reduce drug efficacy. Further studies are required to determine if these potential interactions could be clinically significant.
ESTHER : Liu_2010_J.Pharm.Pharm.Sci_13_43
PubMedSearch : Liu_2010_J.Pharm.Pharm.Sci_13_43
PubMedID: 20456830

Title : Bicyclic cyanothiazolidines as novel dipeptidyl peptidase 4 inhibitors - Betancort_2009_Bioorg.Med.Chem.Lett_19_4437
Author(s) : Betancort JM , Winn DT , Liu R , Xu Q , Liu J , Liao W , Chen SH , Carney D , Hanway D , Schmeits J , Li X , Gordon E , Campbell DA
Ref : Bioorganic & Medicinal Chemistry Lett , 19 :4437 , 2009
Abstract : The synthesis and biochemical evaluation of novel cyanothiazolidine inhibitors of dipeptidyl peptidase 4 (DPP4) is described. Their main structural feature is a constrained bicyclic core that prevents the intramolecular formation of inactive cyclic species. The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution.
ESTHER : Betancort_2009_Bioorg.Med.Chem.Lett_19_4437
PubMedSearch : Betancort_2009_Bioorg.Med.Chem.Lett_19_4437
PubMedID: 19482472

Title : [The -384A >C polymorphism of endothelial lipase gene promoter region in Chinese healthy normolipidemic and endogenous hypertriglyceridemic subjects] - Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
Author(s) : Huang Y , Bai H , Fan P , Liu R , Liu Y , Liu BW
Ref : Zhonghua Yi Xue Yi Chuan Xue Za Zhi , 25 :443 , 2008
Abstract : OBJECTIVE: To investigate the effects of the -384A>C polymorphism in the promoter region of endothelial lipase (EL) gene on serum lipid and apolipoprotein levels in healthy normolipidemic (HTG) and endogenous hypertriglyceridemic (HTG) subjects.
METHODS: Two hundred and fourteen healthy normolipidemic and 103 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the radial immunadiffussion kits.
RESULTS: The frequency of the C allele at the -384A>C site in EL gene in the population (0.178) was higher than that of Japanese population (0.119) and Japanese Americans (0.115) (P < 0.01 and P < 0.01), respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers (A/C and C/C genotype carriers) had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA (5.23 +/- 0.74 mmol/L vs 4.93 +/- 0.74 mmol/L, P=0.025; 3.27 +/- 0.74 mmol/L vs 2.98 +/- 0.80 mmol/L, P=0.038; 3.81 +/- 0.73 mmol/L vs 3.49 +/- 0.85 mmol/L, P=0.031, respectively). Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group. CONCLUSION: These results suggest that the -384A>C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.
ESTHER : Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
PubMedSearch : Huang_2008_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_25_443
PubMedID: 18683147

Title : Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir - Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
Author(s) : Feng L , Wang W , Cheng J , Ren Y , Zhao G , Gao C , Tang Y , Liu X , Han W , Peng X , Liu R , Wang L
Ref : Proc Natl Acad Sci U S A , 104 :5602 , 2007
Abstract : The complete genome sequence of Geobacillus thermodenitrificans NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by in vivo and in vitro experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
ESTHER : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedSearch : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedID: 17372208
Gene_locus related to this paper: geotd-g3jwz2 , geoka-q5l1n0 , geotn-a4ijt0 , geotn-a4ilq0 , geotn-a4is13 , geotn-a4isp0 , geotn-a4isp3

Title : Double-stranded RNA injection produces null phenotypes in zebrafish - Li_2000_Dev.Biol_217_394
Author(s) : Li YX , Farrell MJ , Liu R , Mohanty N , Kirby ML
Ref : Developmental Biology , 217 :394 , 2000
Abstract : Zebrafish is a simple vertebrate that has many attributes that make it ideal for the study of developmental genetics. One feature that has been lacking in this model system is the ability to disable specifically targeted genes. Recently, double-stranded RNA has been used to silence gene expression in the nematode Caenorhabditis elegans. We have found that expression of the green fluorescent protein (GFP) from a microinjected plasmid vector can be suppressed in zebrafish embryos by the coinjection of a double-stranded RNA that is specifically targeted to GFP. To determine that double-stranded RNA can attenuate endogenous gene expression, single-cell zebrafish embryos were injected with double-stranded RNA specifically targeted to Zf-T and Pax6.1. We found that microinjection of double-stranded Zf-T RNA resulted in a high incidence of a phenotype similar to that of ntl. Furthermore, Zf-T gene expression could not be detected by in situ hybridization and the message was decreased by 75% by semiquantitative RT-PCR in 12-h embryos that had been injected with the double-stranded RNA. Expression of the zebrafish genes sonic hedgehog and floating head was altered in the embryos microinjected with the Zf-T double-stranded RNA in a manner that is remarkably similar to the zebrafish no-tail mutant. Microinjection of double-stranded RNA targeted to Pax6.1 was associated with depressed expression of Pax6. 1 and resulted in absent or greatly reduced eye and forebrain development, similar to the phenotype seen in mouse mutants. Simultaneous injection of Pax6.1 and Zf-T resulted in embryos lacking notochords, eyes, and brain structures.
ESTHER : Li_2000_Dev.Biol_217_394
PubMedSearch : Li_2000_Dev.Biol_217_394
PubMedID: 10625563

Title : Poster: Potent muscarinic analgesics derived from epibatidine: Role of the M4 receptor subtype -
Author(s) : Ellis JL , Harman D , Gonzalez J , Sepra ML , Liu R , Shen TY , Wypij DM , Zuo F
Ref : Life Sciences , 64 :556 , 1999

Title : Short-term effects of a high-sucrose diet on plasma lipid, lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats - Saku_1996_Artery_22_36
Author(s) : Saku K , Okamoto T , Takeda Y , Jimi S , Zhang B , Bai H , Liu R , Arakawa K
Ref : Artery , 22 :36 , 1996
Abstract : Short-term (2 weeks) effects of a high-sucrose diet on plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were investigated in rats. Three days of sucrose feeding significantly increased plasma TG (42 +/- 3 mg/dl vs. 56 +/- 2 mg/dl, p = 0.032), while TC increased significantly after 10 days of the diet (50 +/- 2 mg/dl vs. 62 +/- 2 mg/dl, p = 0.0001). HDL-C increased significantly after 3 days of sucrose feeding (36.2 +/- 0.9 mg/dl vs. 42.4 +/- 2.7 mg/dl, p = 0.011). Although LDL-C tended to decrease on days 3, 7 and 10, these changes were not significant. The plasma glucose level did not change during the study. Increased LPL activity in adipose tissue and decreased enzyme activities in skeletal and heart muscles were observed. Adipose tissue LPL returned to the baseline value after 14 days of the diet treatment, while LPL in skeletal and heart muscles remained at the decreased level. HTGL and HTGL/total liver lipase activities were significantly increased after 14 days of the diet. The different responses of lipase activities in various tissues may help to regulate serum lipid and lipoprotein levels in sucrose-fed rats.
ESTHER : Saku_1996_Artery_22_36
PubMedSearch : Saku_1996_Artery_22_36
PubMedID: 8781709

Title : Structurally different neuronal nicotinic acetylcholine receptor subtypes purified and characterized using monoclonal antibodies - Whiting_1987_J.Neurosci_7_4005
Author(s) : Whiting PJ , Liu R , Morley BJ , Lindstrom JM
Ref : Journal of Neuroscience , 7 :4005 , 1987
Abstract : Acetylcholine receptors that bind nicotine with high affinity but do not bind alpha-bungarotoxin have recently been immunoaffinity purified from brains of chickens and rats (Whiting and Lindstrom, 1986a, b; Whiting and Lindstrom, 1987a). Antisera to these receptors bind to the nicotinic receptors that regulate cation channel opening on chick ciliary ganglion neurons (Stollberg et al., 1986) and rat PC12 cells (Whiting et al., 1987c). Here we report the preparation and characterization of monoclonal antibodies to chicken brain acetylcholine receptors. These monoclonal antibodies are used to identify 2 nicotinic receptor subtypes in the chicken brain. The 2 subtypes have very similar affinities for nicotine and other cholinergic agonists and antagonists. However, they are structurally distinct, having very similar or identical alpha subunits (Mr 49,000), but different beta subunits (Mr 59,000, or for beta' subunit, Mr 75,000). Evidence is presented that suggests that the subunit stoichiometry of these neuronal nicotinic acetylcholine receptors is alpha n = 2 - 3 beta n = 2 - 3. Different levels of receptor subtype expression were detected in embryonic, compared to adult, chicken brain.
ESTHER : Whiting_1987_J.Neurosci_7_4005
PubMedSearch : Whiting_1987_J.Neurosci_7_4005
PubMedID: 3694260