Liu C

References (161)

Title : Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial - Guo_2024_Diabetes.Obes.Metab__
Author(s) : Guo L , Tian F , Liu L , Chen M , Jiang C , Li S , Liu C , Zhang Y , Qin J , Yu D , Zong Y , Dai W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
ESTHER : Guo_2024_Diabetes.Obes.Metab__
PubMedSearch : Guo_2024_Diabetes.Obes.Metab__
PubMedID: 38602409

Title : Identification and prognostic biomarkers among ZDHHC4\/12\/18\/24, and APT2 in lung adenocarcinoma - Bian_2024_Sci.Rep_14_522
Author(s) : Bian J , Xiong W , Yang Z , Li M , Song D , Zhang Y , Liu C
Ref : Sci Rep , 14 :522 , 2024
Abstract : S-palmitoylases and S-depalmitoylases are differentially expressed in various cancers and several malignant tumors and show a strong prognostic ability. Notwithstanding, the potential clinical impact of S-palmitoylases and S-depalmitoylases, particularly in the prognosis and progression of lung adenocarcinoma (LUAD), has not been clarified. Expression levels of S-palmitoylases and S-depalmitoylases in LUAD were investigated using TCGA. GEPIA was used to evaluate the mRNA levels of S-palmitoylases and S-depalmitoylases at different pathological stages. Metascape was used to investigate the biological significance of S-palmitoylases and S-depalmitoylases. The Kaplan-Meier plotter was used to analyze the prognostic value of S-palmitoylases and S-depalmitoylases. CBioportal was used to analyze gene alterations in S-palmitoylases and S-depalmitoylases. UALCAN was used to examine DNA promoter methylation levels of S-palmitoylases and S-depalmitoylases. Finally, we investigated the relationship between S-palmitoylases, S-depalmitoylases, and tumor-infiltrating immune cells using TIMER. Correlations with immune checkpoint-related genes were determined using the R packages reshape2, ggpubr, ggplot2, and corrplot. PCR was also performed to assess the degree of ZDHHC4/12/18/24 and APT2 transcript expression in lung adenocarcinoma and adjacent normal lung tissues. HPA was utilized to investigate protein levels of S-palmitoylases and S-depalmitoylases in LUAD and normal lung tissue. Our study found that ZDHHC2/3/4/5/6/7/9/12/13/16/18/20/21/23/24, APT1/2, PPT1, LYPLAL1, ABHD4/10/11/12/13 and ABHD17C mRNA expression was significantly upregulated in LUAD, whereas ZDHHC1/8/11/11B/14/15/17/19/22, ABHD6/16A and ABHD17A mRNA expression was significantly downregulated. The functions of the differentially expressed S-palmitoylases and S-depalmitoylases were mainly associated with protein-cysteine S-palmitoyltransferase and protein-cysteine S-acyltransferase activities. Patients with high expression of ZDHHC4/12/18/24, APT2, ABHD4, ABHD11 and ABHD12 had a shorter overall survival. Infiltration of six immune cells (B cells, CD8(+) T cells, CD4(+) T cells, macrophages, neutrophils, and dendritic cells) was closely associated with the expression of ZDHHC4/12/18/24 and APT2. ZDHHC4/12/18/24 and APT2 positively correlated with the immune checkpoint-related gene CD276. We assessed the mRNA levels of ZDHHC4/12/18/24 and APT2 using qRT-PCR and found increased expression of ZDHHC4/12/18/24 in LUAD compared with healty control lung tissues. ZDHHC4/12/18/24, and APT2 are potential prognostic biomarkers of LUAD. Their expression levels could be related to the tumor microenvironment in LUAD.
ESTHER : Bian_2024_Sci.Rep_14_522
PubMedSearch : Bian_2024_Sci.Rep_14_522
PubMedID: 38177255

Title : Sequence-based design and construction of synthetic nanobody library - Liu_2024_Biotechnol.Bioeng__
Author(s) : Liu C , Li Y , He Q , Fu J , Wei Q , Lin H , Luo Y , Tu Z
Ref : Biotechnol Bioeng , : , 2024
Abstract : Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time-consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S-Library), designed based on the systematic analysis of the next-generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01-IGHJ4*01) and complementary determining regions of constrained diversity. The S-Library containing 2.19 x 10(8) independent clones was constructed by the one-step assembly and rapid electro-transformation. The S-Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naive library (N-Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S-Library. Binders were isolated from both S-Library and N-Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S-Library to be built on conventional reagents and primers.
ESTHER : Liu_2024_Biotechnol.Bioeng__
PubMedSearch : Liu_2024_Biotechnol.Bioeng__
PubMedID: 38548653

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : A Versatile Thioesterase Involved in Dimerizationduring Cinnamoyl Lipid Biosynthesis - Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
Author(s) : Deng Z , Liu C , Wang F , Song N , Liu J , Li H , Liu S , Li T , Liu Z , Xiao F , Li W
Ref : Angew Chem Int Ed Engl , :e202402010 , 2024
Abstract : The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatic dimerization remains unknown. In this work, an unusual"gene-within-gene"thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with alpha/beta-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6Pi-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatic dimerization process, possibly via an unprecedent Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6Pi-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.
ESTHER : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedSearch : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedID: 38462490
Gene_locus related to this paper: 9actn-YsfF

Title : ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses - Xiong_2024_Cell.Insight_3_100145
Author(s) : Xiong Q , Ma C , Liu C , Tong F , Huang M , Yan H
Ref : Cell Insight , 3 :100145 , 2024
Abstract : Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from Sarbecovirus and Setracovirus subgenera, including three human coronaviruses: SARS-CoV, SARS-CoV-2, and NL63. We recently disclosed that NeoCoV and three other merbecoviruses (PDF-2180, MOW15-22, PnNL 2018B), which are MERS-CoV relatives found in African and European bats, also utilize ACE2 as their functional receptors through unique receptor binding mechanisms. This unexpected receptor usage assumes significance, particularly in light of the prior recognition of Dipeptidyl peptidase-4 (DPP4) as the only known protein receptor for merbecoviruses. In contrast to other ACE2-using coronaviruses, NeoCoV and PDF-2180 engage a distinct and relatively compact binding surface on ACE2, facilitated by protein-glycan interactions, which is demonstrated by the Cryo-EM structures of the receptor binding domains (RBDs) of these viruses in complex with a bat ACE2 orthologue. These findings further support the hypothesis that phylogenetically distant coronaviruses, characterized by distinct RBD structures, can independently evolve to acquire ACE2 affinity during inter-species transmission and adaptive evolution. To date, these viruses have exhibited limited efficiency in entering human cells, although single mutations like T510F in NeoCoV can overcome the incompatibility with human ACE2. In this review, we present a comprehensive overview of ACE2-using merbecoviruses, summarize our current knowledge regarding receptor usage and host tropism determination, and deliberate on potential strategies for prevention and intervention, with the goal of mitigating potential future outbreaks caused by spillover of these viruses.
ESTHER : Xiong_2024_Cell.Insight_3_100145
PubMedSearch : Xiong_2024_Cell.Insight_3_100145
PubMedID: 38476250

Title : Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio) - Zhu_2024_Chemosphere__142027
Author(s) : Zhu J , Huang M , Jiang P , Wang J , Zhu R , Liu C
Ref : Chemosphere , :142027 , 2024
Abstract : Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 hours post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.
ESTHER : Zhu_2024_Chemosphere__142027
PubMedSearch : Zhu_2024_Chemosphere__142027
PubMedID: 38621487

Title : Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections - Xiao_2024_J.Control.Release_369_39
Author(s) : Xiao J , Yin M , Yang M , Ren J , Liu C , Lian J , Lu X , Jiang Y , Yao Y , Luo J
Ref : J Control Release , 369 :39 , 2024
Abstract : The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.
ESTHER : Xiao_2024_J.Control.Release_369_39
PubMedSearch : Xiao_2024_J.Control.Release_369_39
PubMedID: 38508523

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

Title : Patterning amyloid-beta aggregation under the effect of acetylcholinesterase using a biological nanopore - an in vitro study - Subramanian_2023_Sens.Actuators.Rep_6_
Author(s) : Subramanian N , Watson B , Li CZ , Moss M , Liu C
Ref : Sens Actuators Rep , 6 : , 2023
Abstract : Aggregation of amyloid-beta peptide (Abeta) is hypothesized to be the primary cause of Alzheimer's disease (AD) progression. Abeta aggregation has been widely studied using conventional sensing tools like emission fluorescence, electron microscopy, mass spectroscopy, and circular dichroism. However, none of these techniques can provide cost-efficient, highly sensitive quantification of Abeta aggregation kinetics at the molecular level. Among the influences on Abeta aggregation of interest to disease progression is the acceleration of Abeta aggregation by acetylcholinesterase (AChE), which is present in the brain and inflicts the fast progression of disease due to its direct interaction with Abeta. In this work, we demonstrate the ability of a biological nanopore to map and quantify AChE accelerated aggregation of Abeta monomers to mixed oligomers and small soluble aggregates with single-molecule precision. This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated Abeta aggregation as well as disease prognosis.
ESTHER : Subramanian_2023_Sens.Actuators.Rep_6_
PubMedSearch : Subramanian_2023_Sens.Actuators.Rep_6_
PubMedID: 37663321

Title : Discovery of a new highly pathogenic toxin involved in insect sepsis - Zhang_2023_Microbiol.Spectr__e0142223
Author(s) : Zhang Y , Li H , Wang F , Liu C , Reddy GVP , Li Z , Sun Y , Zhao Z
Ref : Microbiol Spectr , :e0142223 , 2023
Abstract : Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25 degreesC while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
ESTHER : Zhang_2023_Microbiol.Spectr__e0142223
PubMedSearch : Zhang_2023_Microbiol.Spectr__e0142223
PubMedID: 37787562

Title : Whole-genome analysis of Comamonas sp. USTBZA1 for biodegrading diethyl phthalate - Zhao_2023_3.Biotech_13_329
Author(s) : Zhao Z , Liu Y , Liu C , Xu Q , Song M , Yan H
Ref : 3 Biotech , 13 :329 , 2023
Abstract : Extensive use of phthalic acid esters (PAEs) as plasticizer causes diffusion into the environment, which posed a great threat to mankind. It was reported that Comamonas sp. was a potentially robust aromatic biodegrader. Although the biodegradation of several PAEs by Comamonas sp. was studies, the comprehensive genomic analysis of Comamonas sp. was few reported. In the present study, one promising bacterial strain for biodegrading diethyl phthalate (DEP) was successfully isolated from activated sludge and characterized as Comamonas sp. USTBZA1 based on the 16S rRNA sequence analysis. The results showed that pH 7.5, 30 degreesC and inoculum volume ratio of 6% were optimal for biodegradation. Initial DEP of 50 mg/L could be completely biodegrade by strain USTBZA1 within 24 h which conformed to the Gompertz model. Based on the Q-TOF LC/MS analysis, monoethyl phthalate (MEP) and phthalic acid (PA) were identified as the metabolic products of DEP biodegradation by USTBZA1. Furthermore, the whole genome of Comamonas sp. USTBZA1 was analyzed to clarify the molecular mechanism for PAEs biodegradation by USTBZA1. There were 3 and 41 genes encoding esterase/arylesterase and hydrolase, respectively, and two genes regions (pht34512 and pht4253) were responsible for the conversion of PA to protocatechuate (PCA), and two genes regions (ligCBAIKJ) were involved in PCA metabolism in USTBZA1. These results substantiated that Comamonas sp. USTBZA1 has potential application in the DEP bioremediation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03736-3.
ESTHER : Zhao_2023_3.Biotech_13_329
PubMedSearch : Zhao_2023_3.Biotech_13_329
PubMedID: 37670801

Title : Improving pesticide residue detection: Immobilized enzyme microreactor embedded in microfluidic paper-based analytical devices - Zhang_2023_Food.Chem_439_138179
Author(s) : Zhang J , Li Y , Zhang T , Zheng Z , Jing H , Liu C
Ref : Food Chem , 439 :138179 , 2023
Abstract : Orientationally immobilized enzyme microreactors (OIMERs), embedded in microfluidic paper-based analytical devices (microPADs) were developed for improved detection of pesticide residues in food. Acetylcholinesterase (AChE) was orientationally immobilized on the reusable Part I of the microPADs, using the specific affinity binding of concanavalin A (Con A) to a glycosyl group on AChE. Using the disposable Part II, facile colorimetric quantification was performed with a smartphone and software, or qualitative detection by a naked-eye visual test. The AChE immobilized in OIMERs not only had improved activity and stability, but also high sensitivity, with a limit of detection as low as (0.007 +/- 0.003) microg/mL. The method was used to detect pesticides residues in real vegetable samples; the recovery (88.6-102.7%) showed high reliability for pesticide residues detection in foods. A molecular docking study and an enzyme kinetic analysis were conducted to characterize the mechanism of action of the OIMERs.
ESTHER : Zhang_2023_Food.Chem_439_138179
PubMedSearch : Zhang_2023_Food.Chem_439_138179
PubMedID: 38091789

Title : Efficient Combination of Complex Chromatography, Molecular Docking and Enzyme Kinetics for Exploration of Acetylcholinesterase Inhibitors from Poria cocos - Wu_2023_Molecules_28_1228
Author(s) : Wu T , Hou W , Liu C , Li S , Zhang Y
Ref : Molecules , 28 :1228 , 2023
Abstract : Poria cocos (P. cocos) is a traditional Chinese medicinal product with the same origin as medicine and food. It has diuretic, anti-inflammatory and liver protection properties, and has been widely used in a Chinese medicine in the treatment of Alzheimer's disease (AD). This study was conducted to explore the activity screening, isolation of acetylcholinesterase inhibitors (AChEIs), and in vitro inhibiting effect of P. cocos. The aim was to develop a new extraction process optimization method based on the Matlab genetic algorithm combined with a traditional orthogonal experiment. Moreover, bio-affinity ultrafiltration combined with molecular docking was used to screen and evaluate the activity of the AChEIs, which were subsequently isolated and purified using high-speed counter-current chromatography (HSCCC) and semi-preparative high-performance liquid chromatography (semi-preparative HPLC). The change in acetylcholinesterase (AChE) activity was tested using an enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on AChE and explore its mechanism of action. Five potential AChEIs were screened via bio-affinity ultrafiltration. Molecular docking results showed that they had good binding affinity for the active site of AChE. Meanwhile, the five active compounds had reversible inhibitory effects on AChE: Polyporenic acid C and Tumulosic acid were non-competitive inhibitors; 3-Epidehydrotumulosic acid was a mixed inhibitor; and Pachymic acid and Dehydrotrametenolic acid were competitive inhibitors. This study provided a basis for the comprehensive utilization of P. cocos and drug development for the treatment of AD.
ESTHER : Wu_2023_Molecules_28_1228
PubMedSearch : Wu_2023_Molecules_28_1228
PubMedID: 36770895

Title : In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices - Du_2023_Chem.Sci_14_506
Author(s) : Du Z , Liu C , Liu Z , Song H , Scott P , Du X , Ren J , Qu X
Ref : Chem Sci , 14 :506 , 2023
Abstract : The pathogenesis of Alzheimer's disease (AD) is closely related to several contributing factors, especially amyloid-beta (Abeta) aggregation. Bioorthogonal reactions provide a general, facile, and robust route for the localization and derivatization of Abeta-targeted agents. Herein, a pair of chiral alkyne-containing metallohelices (A and deltaA) were demonstrated to enantioselectively target and modulate Abeta aggregation, which has been monitored in triple-transgenic AD model mice and proved to improve cognitive function. Compared with its enantiomer deltaA, A performed better in blocking Abeta fibrillation, relieving Abeta-triggered toxicity, and recovering memory deficits in vivo. Moreover, clickable A could act as a functional module for subsequent visualization and versatile modification of amyloid via bioorthogonal reaction. As a proof-of-concept, thioflavin T, tacrine, and magnetic nanoparticles were conjugated with A to realize Abeta photo-oxygenation, acetylcholinesterase inhibition, and Abeta clearance, respectively. This proof-of-principle work provided new insights into the biolabeling and bioconjugation of multifunctional metallosupramolecules through click reactions for AD therapy.
ESTHER : Du_2023_Chem.Sci_14_506
PubMedSearch : Du_2023_Chem.Sci_14_506
PubMedID: 36741518

Title : Systems pharmacology-based mechanism exploration of Acanthopanax senticosusin for Alzheimer's disease using UPLC-Q-TOF-MS, network analysis, and experimental validation - Zhuo_2023_Eur.J.Pharmacol__175895
Author(s) : Zhuo Y , Fu X , Jiang Q , Lai Y , Gu Y , Fang S , Chen H , Liu C , Pan H , Wu Q , Fang J
Ref : European Journal of Pharmacology , :175895 , 2023
Abstract : BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. PURPOSE: This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. METHODS: In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We next performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining, were conducted to verify our systems pharmacology-based analysis. RESULTS: 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine. CONCLUSION: Overall, this study applied systems pharmacology approach, via UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD.
ESTHER : Zhuo_2023_Eur.J.Pharmacol__175895
PubMedSearch : Zhuo_2023_Eur.J.Pharmacol__175895
PubMedID: 37422122

Title : Eco-friendly and efficient extraction of polyphenols from Ligustrum robustum by deep eutectic solvent assisted ultrasound - Qin_2023_Food.Chem_429_136828
Author(s) : Qin G , Zhang F , Ren M , Chen X , Liu C , Li G , Gao Q , Qiao L , Jiang Y , Zhu L , Guo Y , Wang G
Ref : Food Chem , 429 :136828 , 2023
Abstract : An eco-friendly and efficient extraction method using deep eutectic solvents assisted ultrasound extraction (DESs-UAE) for the polyphenols from Ligustrum robustum was developed. Among the 34 kinds of DESs prepared, tetraethyl ammonium bromide: 1,2,4-butanol (Teab: 1,2,4-But) was proved to be a suitable extraction solvent based on the extraction efficiency. The extraction parameters including temperature, water content, liquid-solid ratio were optimized with response surface methodology (RSM). Under the optimal conditions, the total phenolic content (TPC) and total flavonoid content (TFC) were 101.46 +/- 2.96 mg GAE/g DW and 264.17 +/- 5.39 mg RE/g DW, respectively. Furthermore, the extraction mechanism of DESs-UAE was investigated by extraction kinetics, molecular dynamic simulation and theory calculations of interaction. In particular, 9 kinds of polyphenols compounds from Ligustrum robustum were firstly identified by UPLC-Q-TOF-MS. Moreover, the recovered polyphenols exhibited significant antioxidant, alpha-glucosidase inhibition, acetylcholinesterase inhibition and anticancer activity.
ESTHER : Qin_2023_Food.Chem_429_136828
PubMedSearch : Qin_2023_Food.Chem_429_136828
PubMedID: 37478601

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

Title : Curcumin protects against fenvalerate-induced neurotoxicity in zebrafish (Danio rerio) larvae through inhibition of oxidative stress - Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
Author(s) : Zhu J , Huang M , Liu C , Wang J , Zou L , Yang F , Zhu R
Ref : Ecotoxicology & Environmental Safety , 264 :115484 , 2023
Abstract : Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 microg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.
ESTHER : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedSearch : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedID: 37716069

Title : Biodegradation mechanism of chlorpyrifos by Bacillus sp. H27: Degradation enzymes, products, pathways and whole genome sequencing analysis - Liu_2023_Environ.Res__117315
Author(s) : Liu C , Zhao C , Wang L , Du X , Zhu L , Wang J , Mo Kim Y
Ref : Environ Research , :117315 , 2023
Abstract : Chlorpyrifos (CP) is a pesticide widely used in agricultural production. However, excessive use of CP is risky for human health and the ecological environment. Microbial remediation has become a research hotspot of environmental pollution control. In this study, the effective CP-degrading strain H27 (Bacillus cereus) was screened from farmland soil, and the degradation ratio was more than 80%. Then, the degradation mechanism was discussed in terms of enzymes, pathways, products and genes, and the mechanism was improved in terms of cell motility, secretory transport system and biofilm formation. The key CP-degrading enzymes were mainly intracellular enzymes (IE), and the degradation ratio reached 49.6% within 30 min. The optimal pH for IE was 7.0, and the optimal temperature was 25 degreesC. Using DFT and HPLC-MS analysis, it was found that degradation mainly involved oxidation, hydrolysis and other reactions, and 3 degradation pathways and 14 products were identified, among which TCP (3,5,6-trichloro-2-pyridinol) was the main primary degradation product in addition to small molecules such as CO(2) and H(2)O. Finally, the whole genome of strain H27 was sequenced, and the related degrading genes and enzymes were investigated to improve the metabolic pathways. Strain H27 had perfect genes related to flagellar assembly and chemotaxis and tended to tolerate CP. Moreover, it can secrete esterase, phosphatase and other substances, which can form biofilms and degrade CP in the environment. In addition, CP enters the cell under the action of permeases or transporters, and it is metabolized by IE. The degradation mechanism of CP by strain H27 is speculated in this study, which provided a theoretical basis for enriching CP-degrading bacteria resources, improving degradation metabolic pathways and mechanisms, and applying strain H27 to environmental pollution remediation.
ESTHER : Liu_2023_Environ.Res__117315
PubMedSearch : Liu_2023_Environ.Res__117315
PubMedID: 37805180

Title : Screening of Acetylcholinesterase Inhibitors by Capillary Electrophoresis with Oriented-Immobilized Enzyme Microreactors Based on Gold Nanoparticles - Zhang_2023_Molecules_29_
Author(s) : Zhang J , Li Y , Chen L , Zheng Z , Liu C
Ref : Molecules , 29 : , 2023
Abstract : A facial and efficient method for the screening of acetylcholinesterase (AChE) inhibitors by capillary electrophoresis was developed. Based on the specific affinity of concanavalin A (Con A) for binding to the glycosyl group of AChE, enzyme molecules were oriented-immobilized on the surface of gold nanoparticles (AuNPs@Con A@AChE). Then, these modified nanoparticles were bounded to the capillary inlet (about 1.0 cm) by electrostatic self-assembly to obtain the oriented-immobilized enzyme microreactor (OIMER). Compared to an IMER with a free enzyme, the peak area of the product obtained by the OIMER increased by 52.6%. The Michaelis-Menten constant (K(m)) was as low as (0.061 +/- 0.003) mmol/L. The method exhibits good repeatability with a relative standard deviation (RSD) of 1.3% for 100 consecutive runs. The system was successfully applied to detect the IC(50) values of donepezil and four components from Chinese medicinal plants. This work demonstrates the potential of this method as a low cost, simple, and accurate screening method for other enzyme inhibitors.
ESTHER : Zhang_2023_Molecules_29_
PubMedSearch : Zhang_2023_Molecules_29_
PubMedID: 38202701

Title : Identification and Functions of JHE 6 Specifically Expressed in Bombyx mori Silk Gland - Zhang_2023_Insects_14_
Author(s) : Zhang X , Zhang J , Wu K , Yang H , Cheng T , Liu C
Ref : Insects , 14 : , 2023
Abstract : Juvenile hormone esterase (JHE) is the specific enzyme that degrades juvenile hormone (JH) and regulates the JH titer in insects. JH also regulates the development of the silk gland and the synthesis and secretion of silk proteins in Bombyx mori. Here, we identified nine possible JHE family members, Bmjhe1-9. Notably, Bmjhe6 is specifically expressed in the silk gland. Using semi-quantitative, quantitative real-time RT-PCR and Western blot, it was confirmed that Bmjhe6 was specifically expressed in the middle silk gland (MSG) with high levels in the anterior region of the MSG (A-MSG). The immunofluorescence localization analysis revealed that Bmjhe6 is produced within cells, secreted into the gland lumen, and co-transported with silk proteins into the anterior silk gland (ASG). In vitro hormone induction experiments demonstrated that Bmjhe6 responds to a JH analog, increasing its expression after 12-24 h, whereas 20-hydroxyecdysone inhibited it. In addition, Bmjhe6 knockdown using dsBmjhe6 injections accelerated larval development, resulting in increased larval body and silk gland weight. This induced disordered sericin genes (Ser2, Ser3) expression, and key genes in the JH synthesis pathway (BmKr-h1 and BmMet1) were significantly upregulated along with the transcription factors (SGF-1 and Sage). These results indicate that Bmjhe6 plays an important role in silk gland growth and silk protein synthesis by modulating JH signal.
ESTHER : Zhang_2023_Insects_14_
PubMedSearch : Zhang_2023_Insects_14_
PubMedID: 38132582

Title : Development of a Nomogram for Predicting Mortality Risk in Sepsis Patients During Hospitalization: A Retrospective Study - Lu_2023_Infect.Drug.Resist_16_2311
Author(s) : Lu B , Pan X , Wang B , Jin C , Liu C , Wang M , Shi Y
Ref : Infect Drug Resist , 16 :2311 , 2023
Abstract : PURPOSE: We attempted to establish a model for predicting the mortality risk of sepsis patients during hospitalization. PATIENTS AND METHODS: Data on patients with sepsis were collected from a clinical record mining database, who were hospitalized at the Affiliated Dongyang Hospital of Wenzhou Medical University between January 2013 and August 2022. These included patients were divided into modeling and validation groups. In the modeling group, the independent risk factors of death during hospitalization were determined using univariate and multi-variate regression analyses. After stepwise regression analysis (both directions), a nomogram was drawn. The discrimination ability of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the GiViTI calibration chart assessed the model calibration. The Decline Curve Analysis (DCA) was performed to evaluate the clinical effectiveness of the prediction model. Among the validation group, the logistic regression model was compared to the models established by the SOFA scoring system, random forest method, and stacking method. RESULTS: A total of 1740 subjects were included in this study, 1218 in the modeling population and 522 in the validation population. The results revealed that serum cholinesterase, total bilirubin, respiratory failure, lactic acid, creatinine, and pro-brain natriuretic peptide were the independent risk factors of death. The AUC values in the modeling group and validation group were 0.847 and 0.826. The P values of calibration charts in the two population sets were 0.838 and 0.771. The DCA curves were above the two extreme curves. Moreover, the AUC values of the models established by the SOFA scoring system, random forest method, and stacking method in the validation group were 0.777, 0.827, and 0.832, respectively. CONCLUSION: The nomogram model established by combining multiple risk factors could effectively predict the mortality risk of sepsis patients during hospitalization.
ESTHER : Lu_2023_Infect.Drug.Resist_16_2311
PubMedSearch : Lu_2023_Infect.Drug.Resist_16_2311
PubMedID: 37155474

Title : Multiomics Analyses Identify Proline Endopeptidase-Like Protein As a Key Regulator of Protein Trafficking, a Pathway Underlying Alzheimer's Disease Pathogenesis - Duarte_2023_Mol.Pharmacol_104_1
Author(s) : Duarte ML , Wang M , Gomes I , Liu C , Sharma A , Fakira AK , Gupta A , Mack SM , Zhang B , Devi LA
Ref : Molecular Pharmacology , 104 :1 , 2023
Abstract : Current treatments for Alzheimer's disease (AD) help reduce symptoms for a limited time but do not treat the underlying pathology. To identify potential therapeutic targets for AD, an integrative network analysis was previously carried out using 364 human postmortem control, mild cognitive impairment, and AD brains. This analysis identified proline endopeptidase-like protein (PREPL), an understudied protein, as a downregulated protein in late-onset AD patients. In this study we investigate the role of PREPL. Analyses of data from human postmortem samples and PREPL knockdown (KD) cells suggest that PREPL expression modulates pathways associated with protein trafficking, synaptic activities, and lipid metabolism. Furthermore, PREPL KD impairs cell proliferation and modulates the structure of vesicles, levels of neuropeptide-processing enzymes, and secretion of neuropeptides. In addition, decrease in PREPL levels leads to changes in the levels of a number of synaptic proteins as well as changes in the levels of secreted amyloid beta (Abeta) 42 peptide and Tau phosphorylation. Finally, we report that local decrease in PREPL levels in mouse hippocampus attenuates long-term potentiation, suggesting a role in synaptic plasticity. Together, our results indicate that PREPL affects neuronal function by modulating protein trafficking and synaptic function, an important mechanism of AD pathogenesis. SIGNIFICANCE STATEMENT: Integrative network analysis reveals proline endopeptidase-like protein (PREPL) to be downregulated in human sporadic late-onset Alzheimer's disease brains. Down regulation of PREPL leads to increases in amyloid beta secretion, Tau phosphorylation, and decreases in protein trafficking and long-term potentiation.
ESTHER : Duarte_2023_Mol.Pharmacol_104_1
PubMedSearch : Duarte_2023_Mol.Pharmacol_104_1
PubMedID: 37147110
Gene_locus related to this paper: human-PREPL

Title : Integrated transcriptomic and biochemical characterization of the mechanisms governing stress responses in soil-dwelling invertebrate (Folsomia candida) upon exposure to dibutyl phthalate - Zheng_2023_J.Hazard.Mater_462_132644
Author(s) : Zheng Y , Liu C , Chen J , Tang J , Luo J , Zou D , Tang Z , He J , Bai J
Ref : J Hazard Mater , 462 :132644 , 2023
Abstract : Dibutyl phthalate (DBP) is one of the most commonly utilized plasticizers and a frequently detected phthalic acid ester (PAE) compound in soil samples. However, the toxicological effects of DBP on soil-dwelling organisms remain poorly understood. This study employed a multi-biomarker approach to investigate the impact of DBP exposure on Folsomia candida's survival, reproduction, enzyme activity levels, and transcriptional profiles. Analyses of antioxidant biomarkers, including catalase (CAT) and glutathione S-transferase (GST), as well as detoxifying enzymes such as acetylcholinesterase (AChE), Cytochrome P450 (CYP450), and lipid peroxidation (LPO), revealed significant increases in CAT activity, GST levels, and CYP450 expression following treatment with various doses of DBP for 2, 4, 7, or 14 days. Additionally, LPO induction was observed along with significant AChE inhibition. In total, 3175 differentially expressed genes (DEGs) were identified following DBP treatment that were enriched in six Gene Ontology (GO) terms and 144 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including 85 upregulated and 59 downregulated primarily associated with lipid metabolism, signal transduction, DNA repair, and cell growth and death. Overall these results provide foundational insights for further research into the molecular mechanisms underlying responses of soil invertebrates to DBP exposure.
ESTHER : Zheng_2023_J.Hazard.Mater_462_132644
PubMedSearch : Zheng_2023_J.Hazard.Mater_462_132644
PubMedID: 37820532

Title : Genome-wide identification and analysis of the SUPPRESSOR of MAX2 1-LIKE gene family and its interaction with DWARF14 in poplar - Sun_2023_BMC.Plant.Biol_23_105
Author(s) : Sun M , Wang D , Liu C , Liu Y , Niu M , Wang J , Li J
Ref : BMC Plant Biol , 23 :105 , 2023
Abstract : BACKGROUND: Strigolactones (SLs) are important phytohormones that can regulate branch development in plants. Although SUPPRESSOR of MAX2 1-LIKE proteins (SMXLs) play a crucial role in SL signaling transduction, the SMXL gene family has not been well characterized in poplar. RESULTS: In this study, 12 members of the poplar SMXL gene family were identified and phylogenetically classified into four clades. Motif and 3D structural analyses revealed that PtSMXL proteins are structurally very conserved; however, the P-loop NTPase domain at the C-terminal was found to vary substantially among clades. A genomic collinearity analysis indicated that PtSMXL gene family members have expanded during recent genome doubling events in poplar, with all gene pairs subsequently undergoing purifying selection. According to a Cis-element analysis, PtSMXL promoters contain many light-responsive elements. In an expression pattern analysis, all 12 PtSMXL genes displayed tissue-specific expression, especially PtSMXL8a. PtSMXL7b expression was significantly downregulated after axillary bud growth begins. In addition, the expressions of PtSMXL7b and PtSMXL8a were highly induced by 2 microM GR24, a synthetic SL analog, thus suggesting that these genes are involved in SL-regulated axillary bud growth. In a yeast two-hybrid assay, only PtSMXL7b in clade II was able to interact with the SL receptor PtD14a in an SL dependent manner, which indicates that PtSMXL7b may be the functional homolog of D53/SMXL6/7/8 in poplar. Finally, we established its ability to affect axillary bud growth by constructing poplar overexpressing the PtSMXL7b gene. CONCLUSIONS: Our findings may inform future research on the functions of SMXLs in poplar, especially with respect to branch development.
ESTHER : Sun_2023_BMC.Plant.Biol_23_105
PubMedSearch : Sun_2023_BMC.Plant.Biol_23_105
PubMedID: 36814183

Title : COX-2\/sEH-mediated macrophage activation is a target for pulmonary protection in mouse models of chronic obstructive pulmonary disease - Duan_2023_Lab.Invest__100319
Author(s) : Duan JX , Guan XX , Cheng W , Deng DD , Chen P , Liu C , Zhou Y , Hammock BD , Yang HH
Ref : Lab Invest , :100319 , 2023
Abstract : Effective inhibition of macrophage activation is critical for resolving inflammation and restoring pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Here, we identified the dual enhanced cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) as a novel regulator of macrophage activation in COPD. Both COX-2 and sEH were found to be increased in patients and mice with COPD, as well as in macrophages exposed to cigarette smoke extract (CSE). Pharmacological reduction of the COX-2 and sEH by PTUPB effectively prevented macrophage activation, down-regulated inflammation-related genes, and reduced lung injury, thereby improving respiratory function in a mouse model of COPD induced by cigarette smoke and lipopolysaccharide. Mechanistically, enhanced COX-2/sEH triggered the activation of the NLRP3 inflammasome, leading to the cleavage of pro-IL-1beta into its active form in macrophages and amplifying inflammatory responses. These findings demonstrate that targeting COX-2/sEH-mediated macrophage activation may be a promising therapeutic strategy for COPD. Importantly, our data support the potential use of the dual COX-2 and sEH inhibitor PTUPB as a therapeutic drug for the treatment of COPD.
ESTHER : Duan_2023_Lab.Invest__100319
PubMedSearch : Duan_2023_Lab.Invest__100319
PubMedID: 38158123

Title : The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling - Luo_2023_J.Transl.Med_21_71
Author(s) : Luo A , Wu Z , Li S , McReynolds CB , Wang D , Liu H , Huang C , He T , Zhang X , Wang Y , Liu C , Hammock BD , Hashimoto K , Yang C
Ref : J Transl Med , 21 :71 , 2023
Abstract : BACKGROUND: Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown. METHODS: According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling. RESULTS: In anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1beta (IL-1beta) and the tumor necrosis factor alpha (TNF-alpha), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU. CONCLUSIONS: sEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling.
ESTHER : Luo_2023_J.Transl.Med_21_71
PubMedSearch : Luo_2023_J.Transl.Med_21_71
PubMedID: 36732752

Title : Identification and characterization of novel carboxyl ester lipase gene variants in patients with different subtypes of diabetes - Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
Author(s) : Wu H , Shu M , Liu C , Zhao W , Li Q , Song Y , Zhang T , Chen X , Shi Y , Shi P , Fang L , Wang R , Xu C
Ref : BMJ Open Diabetes Res Care , 11 : , 2023
Abstract : INTRODUCTION: Mutations of CEL gene were first reported to cause a new type of maturity-onset diabetes of the young (MODY) denoted as MODY8 and then were also found in patients with type 1 (T1D) and type 2 diabetes (T2D). However, its genotype-phenotype relationship has not been fully determined and how carboxyl ester lipase (CEL) variants result in diabetes remains unclear. The aim of our study was to identify pathogenic variants of CEL in patients with diabetes and confirm their pathogenicity. RESEARCH DESIGN AND METHODS: All five patients enrolled in our study were admitted to Shandong Provincial Hospital and diagnosed with diabetes in the past year. Whole-exome sequencing was performed to identify pathogenic variants in three patients with MODY-like diabetes, one newborn baby with T1D and one patient with atypical T2D, as well as their immediate family members. Then the consequences of the identified variants were predicted by bioinformatic analysis. Furthermore, pathogenic effects of two novel CEL variants were evaluated in HEK293 cells transfected with wild-type and mutant plasmids. Finally, we summarized all CEL gene variants recorded in Human Gene Mutation Database and analyzed the mutation distribution of CEL. RESULTS: Five novel heterozygous variants were identified in CEL gene and they were predicted to be pathogenic by bioinformatic analysis. Moreover, in vitro studies indicated that the expression of CEL(R540C) was remarkably increased, while p.G729_T739del variant did not significantly affect the expression of CEL. Both novel variants obviously abrogated the secretion of CEL. Furthermore, we summarized all reported CEL variants and found that 74.3% of missense mutations were located in exons 1, 3, 4, 10 and 11 and most missense variants clustered near catalytic triad, Arg-83 and Arg-443. CONCLUSION: Our study identified five novel CEL variants in patients with different subtypes of diabetes, expanding the gene mutation spectrum of CEL and confirmed the pathogenicity of several novel variants.
ESTHER : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedSearch : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedID: 36634979
Gene_locus related to this paper: human-CEL

Title : Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities - Puopolo_2022_Med.Cannabis.Cannabinoids_5_85
Author(s) : Puopolo T , Liu C , Ma H , Seeram NP
Ref : Med Cannabis Cannabinoids , 5 :85 , 2022
Abstract : INTRODUCTION: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate and choline at the neuromuscular junction. Abnormal hyperactivity of AChE and BChE can lead to cholinergic deficiency, which is associated with several neurological disorders including cognitive decline and memory impairments. Preclinical studies support that some cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC) may exert pharmacological effects on the cholinergic system, but it remains unclear whether cannabinoids can inhibit AChE and BChE activities. Herein, we aimed to evaluate the inhibitory effects of a panel of cannabinoids including CBD, delta8-THC, cannabigerol (CBG), cannabigerolic acid (CBGA), cannabicitran (CBT), cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) on AChE and BChE activities. METHODS: The inhibitory effects of cannabinoids on the activities of AChE and BChE enzymes were evaluated with the Ellman method using acetyl- and butyryl-thiocholines as substrates. The inhibition mechanism of cannabinoids on AChE and BChE was studied with enzyme kinetic assays including the Lineweaver-Burk and Michaelis-Menten analyses. In addition, computational-based molecular docking experiments were performed to explore the interactions between the cannabinoids and the enzyme proteins. RESULTS: Cannabinoids including CBD, delta8-THC, CBG, CBGA, CBT, CBDV, CBC, and CBN (at 200 microM) inhibited the activities of AChE and BChE by 70.8, 83.7, 92.9, 76.7, 66.0, 79.3, 13.7, and 30.5%, and by 86.8, 80.8, 93.2, 87.1, 77.0, 78.5, 27.9, and 22.0%, respectively. The inhibitory effects of these cannabinoids (with IC(50) values ranging from 85.2 to >200 microM for AChE and 107.1 to >200 microM for BChE) were less potent as compared to the positive control galantamine (IC(50) 1.21 and 6.86 microM for AChE and BChE, respectively). In addition, CBD, as a representative cannabinoid, displayed a competitive type of inhibition on both AChE and BChE. Data from the molecular docking studies suggested that cannabinoids interacted with several amino acid residues on the enzyme proteins, which supported their overall inhibitory effects on AChE and BChE. CONCLUSION: Cannabinoids showed moderate inhibitory effects on the activities of AChE and BChE enzymes, which may contribute to their modulatory effects on the cholinergic system. Further studies using cell-based and in vivo models are warranted to evaluate whether cannabinoids' neuroprotective effects are associated with their anti-cholinesterase activities.
ESTHER : Puopolo_2022_Med.Cannabis.Cannabinoids_5_85
PubMedSearch : Puopolo_2022_Med.Cannabis.Cannabinoids_5_85
PubMedID: 35702400

Title : Catalytic Features and Thermal Adaptation Mechanisms of a Deep Sea Bacterial Cutinase-Type Poly(Ethylene Terephthalate) Hydrolase - Liu_2022_Front.Bioeng.Biotechnol_10_865787
Author(s) : Liu Y , Liu C , Liu H , Zeng Q , Tian X , Long L , Yang J
Ref : Front Bioeng Biotechnol , 10 :865787 , 2022
Abstract : Poly (ethylene terephthalate) (PET) plastic is chemically inert and persistent. Massive quantities of PET waste end up in landfill sites and oceans, posing major global pollution concerns. PET degrading enzymes with high efficiency provide plastic recycling and bioremediation possibilities. Here, we report a novel cutinase, MtCut with distinct catalytic behaviors, derived from the deep sea Nocardiopsaceae family strain. Biochemical analyses showed MtCut efficiently hydrolyzed PET at ambient temperatures and in an exo-type manner. The activity and stability of MtCut were enhanced by the addition of calcium ions. Notably, no hydrolysis products inhibition was observed during PET depolymerization, suggesting MtCut is a better biocatalyst when compared to other PET hydrolases. In addition, structural components associated with thermal adaptation were investigated using molecular dynamic (MD) simulations, and key regions regulating MtCut thermostability were identified. Our biochemical and structural analyses of MtCut deepen the understanding of PET hydrolysis by cutinases, and provide invaluable insights on improvement and performance engineering strategies for PET-degrading biocatalysts.
ESTHER : Liu_2022_Front.Bioeng.Biotechnol_10_865787
PubMedSearch : Liu_2022_Front.Bioeng.Biotechnol_10_865787
PubMedID: 35557867
Gene_locus related to this paper: 9actn-a0a1t4kk94

Title : Effects of larval exposure to the insecticide flumethrin on the development of honeybee (Apis mellifera) workers - Liu_2022_Front.Physiol_13_1054769
Author(s) : Liu C , Wu X , Yang H , Yu L , Zhang Y
Ref : Front Physiol , 13 :1054769 , 2022
Abstract : Flumethrin is a widely used acaricide, but its improper use often leads to residue accumulation in honeybee colonies, thus threatening the health of honeybees, especially at the larval stage. Therefore, this study aimed to describe the direct toxicity of flumethrin on honeybee (Apis mellifera) larvae by conducting bioassays for immune and detoxification-related enzymes and transcriptome sequencing to determine the potential effects on newly emerged adults who were exposed to flumethrin during the larval stage. Results showed that the higher the concentration of flumethrin the honeybee larvae were exposed to, the greater the damage to the physiology of honeybee larvae and the newly emerged worker bees. When honeybee larvae were exposed to flumethrin concentrations higher than 0.01smg/L, the activities of glutathione sulfur transferase and carboxylesterase were affected, and the metabolism-related genes in the head of newly emerged honeybees exposed to flumethrin during the larval stage were down-regulated. Flumethrin concentration higher than 0.1smg/L significantly increased mixed-functional oxidase content in honeybee larvae, reduced the larval survival rate, and down-regulated the expression levels of olfactory-related and antioxidant-related genes in newly emerged honeybees. Furthermore, a flumethrin concentration of 1smg/L significantly down-regulated the expression levels of immune and detoxification-related genes in newly emerged honeybees. These findings provide a comprehensive understanding of the response of honeybee larvae to sublethal flumethrin toxicity and could be used to further investigate the complex molecular mechanisms in honeybees under pesticide stress.
ESTHER : Liu_2022_Front.Physiol_13_1054769
PubMedSearch : Liu_2022_Front.Physiol_13_1054769
PubMedID: 36589443

Title : Rapid screening for acetylcholinesterase inhibitors in Selaginella doederleinii Hieron by using functionalized magnetic Fe(3)O(4) nanoparticles - Zhang_2022_Talanta_243_123284
Author(s) : Zhang F , Li S , Liu C , Fang K , Jiang Y , Zhang J , Lan J , Zhu L , Pang H , Wang G
Ref : Talanta , 243 :123284 , 2022
Abstract : Insufficient acetylcholine (ACh) can cause cognitive and memory dysfunction, clinically known as, Alzheimer's disease (AD). Acetylcholinesterase (AChE) can hydrolyze ACh into acetic acid and inactivate choline. Therefore, inhibiting the activity of AChE would help to improve the effectiveness of AD treatment. Currently, the methods for rapid screening of AChE inhibitors are limited. This study reports the application of AChE-immobilized magnetic nanoparticles as a drug screening tool to screen AChE inhibitors for natural products. First, AChE was immobilized on a surface of amino-modified magnetic nanoparticles using covalent binding and the AChE concentration, and the pH as well as time was optimized to obtain the maximum enzyme immobilization yield (61.4 microg/mg), and the kinetic model indicated that AChE-immobilized magnetic nanoparticles and the substrate had the high affinity and specificity. Then, a ligand fishing experiment was carried out using a mixed model of tacrine (an inhibitor of AChE) and caffeic acid (a non-inhibitor of AChE) to verify the specificity of the immobilized AChE, and the conditions for ligand fishing were further optimized. Finally, the optimized immobilized AChE was combined with UPLC-MS to screen for AChE inhibitors in Selaginella doederleinii Hieron extracts. Four compounds were confirmed to be potent AChE inhibitors. Among the four compounds, amentoflavone had a stronger AChE inhibitory effect than tacrine (positive control) with an IC(50) of 0.73 +/- 0.009 micromol/L. The results showed that AChE-functionalized magnetic nanoparticles can be used in the discovery of target drugs from complex matrices.
ESTHER : Zhang_2022_Talanta_243_123284
PubMedSearch : Zhang_2022_Talanta_243_123284
PubMedID: 35255433

Title : Potato (Solanum tuberosum L.) Leaf Extract Concentration Affects Performance and Oxidative Stress in Green Peach Aphids (Myzus persicae (Sulzer) - Quandahor_2022_Plants.(Basel)_11_
Author(s) : Quandahor P , Gou Y , Lin C , Liu C
Ref : Plants (Basel) , 11 : , 2022
Abstract : This study was conducted to determine the aphicidal effect of a leaf extract of the Atlantic potato cultivar on the performance of green peach aphids. Three concentrations of the leaf extract (100, 75, and 50% potato extract), synthetic pesticide (Beta cypermethrin 4.5%), and distilled water (control) treatments were applied in a greenhouse experiment. The results showed that the synthetic pesticide, which was used as a standard check, caused the maximum aphid mortality, followed by the 100% potato leaf extract. Compared with the other botanical treatments, the 100% extract produced low mean rates of survival, aphids' average daily reproduction, the number of nymphs per plant, and the number of nymphs per adult. This treatment also increased the accumulation of hydrogen Peroxide (H(2)O(2)) and malondialdehyde (MDA), glutathione-s-transferase, mixed-function oxidase, and carboxylesterase content in the green peach aphid. Moreover, the 100% extract also protected the host plants against green peach aphid attacks by demonstrating higher chlorophyll content, net photosynthesis, above-ground fresh weight, and above-ground dry weight of the host plant. This study demonstrates that the highest concentration of potato (Atlantic cultivar) leaf extract (100% extract) could be used as the appropriate dosage for the control of green peach aphids on potatoes, which could greatly reduce the use of synthetic insecticides and promote ecosystem sustainability.
ESTHER : Quandahor_2022_Plants.(Basel)_11_
PubMedSearch : Quandahor_2022_Plants.(Basel)_11_
PubMedID: 36297780

Title : Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain - Yan_2022_Environ.Sci.Ecotechnol_12_100198
Author(s) : Yan Z , Feng C , Jin X , Wang F , Liu C , Li N , Qiao Y , Bai Y , Wu F , Giesy JP
Ref : Environ Sci Ecotechnol , 12 :100198 , 2022
Abstract : Organophosphate esters (OPEs) are widespread in various environmental media, and can disrupt thyroid endocrine signaling pathways. Mechanisms by which OPEs disrupt thyroid hormone (TH) signal transduction are not fully understood. Here, we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways. OPEs can bind to transthyretin (TTR) and thyroxine-binding globulin, thereby affecting the transport of TH in the blood, and to the brain by TTR through the blood-brain barrier. When GH3 cells were exposed to OPEs, cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH. Cresyl diphenyl phosphate was shown to be an effective antagonist of TH. Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis. Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, signaling pathways related to thyroid endocrine functions, such as receptor-ligand binding and regulation of hormone levels, were identified as being affected by exposure to OPEs. Effects were also associated with the biosynthesis and metabolism of lipids, and neuroactive ligand-receptor interactions. These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.
ESTHER : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedSearch : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedID: 36157343

Title : A Novel Multifunctional 5,6-Dimethoxy-Indanone-Chalcone-Carbamate Hybrids Alleviates Cognitive Decline in Alzheimer's Disease by Dual Inhibition of Acetylcholinesterase and Inflammation - Liu_2022_Front.Aging.Neurosci_14_922650
Author(s) : Liu C , Sang Z , Pan H , Wu Q , Qiu Y , Shi J
Ref : Front Aging Neurosci , 14 :922650 , 2022
Abstract : BACKGROUNDS: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. The treatment of AD through multiple pathological targets may generate therapeutic efficacy better. The multifunctional molecules that simultaneously hit several pathological targets have been of great interest in the intervention of AD. METHODS: Here, we combined the chalcone scaffold with carbamate moiety and 5,6-dimethoxy-indanone moiety to generate a novel multi-target-directed ligand (MTDL) molecule (E)-3-((5,6-dimethoxy-1-oxo-1,3-dihydro-2H-inden-2-ylidene)-methyl)phenylethyl(methyl) carbamate (named AP5). In silico approaches were used to virtually predict the binding interaction of AP5 with AChE, the drug-likeness, and BBB penetrance, and later validated by evaluation of pharmacokinetics (PK) in vivo by LC-MS/MS. Moreover, studies were conducted to examine the potential of AP5 for inhibiting AChE and AChE-induced amyloid-beta (Abeta) aggregation, attenuating neuroinflammation, and providing neuroprotection in the APP/PS1 model of AD. RESULTS: We found that AP5 can simultaneously bind to the peripheral and catalytic sites of AChE by molecular docking. AP5 exhibited desirable pharmacokinetic (PK) characteristics including oral bioavailability (67.2%), >10% brain penetrance, and favorable drug-likeness. AP5 inhibited AChE activity and AChE-induced Abeta aggregation in vivo and in vitro. Further, AP5 lowered Abeta plaque deposition and insoluble Abeta levels in APP/PS1 mice. Moreover, AP5 exerted anti-inflammatory responses by switching microglia to a disease-associated microglia (DAM) phenotype and preventing A1 astrocytes formation. The phagocytic activity of microglial cells to Abeta was recovered upon AP5 treatment. Importantly, chronic AP5 treatment significantly prevented neuronal and synaptic damage and memory deficits in AD mice. CONCLUSION: Together, our work demonstrated that AP5 inhibited the AChE activity, decreased Abeta plaque deposition by interfering Abeta aggregation and promoting microglial Abeta phagocytosis, and suppressed inflammation, thereby rescuing neuronal and synaptic damage and relieving cognitive decline. Thus, AP5 can be a new promising candidate for the treatment of AD.
ESTHER : Liu_2022_Front.Aging.Neurosci_14_922650
PubMedSearch : Liu_2022_Front.Aging.Neurosci_14_922650
PubMedID: 35860673

Title : Sensitivity Differences and Biochemical Characteristics of Laodelphax striatellus (Falln) to Seven Insecticides in Different Areas of Shandong, China - Xue_2022_Insects_13_
Author(s) : Xue Y , Liu C , Liu D , Ding W , Li Z , Cao J , Xia X
Ref : Insects , 13 : , 2022
Abstract : Laodelphax striatellus Fallen is one of the main pests that can severely harm rice, corn, and wheat. Insecticides acting on the nicotinic acetylcholine receptor (nAChR) are the main type of pesticides used for the control of L. striatellus in Shandong Province, a major grain-producing region in China. In this study, the rice seedling dipping method was used to determine the sensitivities of six field L. striatellus populations in Shandong to seven insecticides acting on nAChR. The results showed that all the field populations were sensitive to clothianidin, nitenpyram, and triflumezopyrim, and the Jiaxiang population exhibited the lowest resistance ratio (RR) to imidacloprid, dinotefuran, sulfoxaflor, and thiamethoxam. The Donggang population showed a medium-level resistance to imidacloprid, with the highest RR of 17.48-fold. The Yutai population showed low-level resistance to imidacloprid and thiamethoxam, with RRs of 7.23- and 7.02-fold, respectively. The contents of cytochrome P450 monooxygenase (P450s), carboxylesterase (CarE), and glutathione S-transferase (GST) were the highest in the Donggang population and the lowest in the Jiaxiang population. The P450 gene CYP314A1 and the CarE gene LsCarE12 were highly up-regulated in all populations. No mutations of V62I, R81T, and K265E in the nAChR beta1 subunit were found in any of the populations. These results provide valuable information for the strategies of resistance management of L. striatellus in the field.
ESTHER : Xue_2022_Insects_13_
PubMedSearch : Xue_2022_Insects_13_
PubMedID: 36135481

Title : Impacts of di-(2-ethylhexyl) phthalate on Folsomia candida (Collembola) assessed with a multi-biomarker approach - Zheng_2022_Ecotoxicol.Environ.Saf_232_113251
Author(s) : Zheng Y , Zhou K , Tang J , Liu C , Bai J
Ref : Ecotoxicology & Environmental Safety , 232 :113251 , 2022
Abstract : Di-(2-ethylhexyl) phthalate (DEHP) is extensively used as an additive to produce plastics, but it may damage non-target organisms in soil. In this study, the effects of DEHP on Folsomia candida in terms of survival, reproduction, enzyme activities, and DNA damage were investigated in spiked artificial soil using a multi-biomarker strategy. The 7-day LC(50) (median lethal concentration) and 28-day EC(50) (median effect concentration) values of DEHP were 1256.25 and 19.72 mg a.i. (active ingredient) kg(-1) dry soil, respectively. Biomarkers involved in antioxidant defense including catalase (CAT-catalase), glutathione S-transferases (GST), detoxifying enzymes including acetylcholinesterase (AChE), Cytochrome P450 (CYP450), and peroxidative damage (LPO-lipid peroxide) were also measured (EC(10), EC(20), and EC(50)) after exposure for 2, 4, 7, and 14 days. The Comet assay was also applied to assess the level of genetic damage. The activity of CAT and LPO was drastically enhanced by the highest dose (EC(50)) of DEHP on day two. The activities of GST and AChE in DEHP treatment groups were found to be blocked. In contrast, the activity of CYP450 was significantly enhanced compared to the respective control groups during the first four days of incubation. The Comet assay in F.candida demonstrated that DEHP (EC(50)) could induce DNA damage. The obtained multi-biomarker data were analyzed using an integrated biomarker response (IBR) index, indicating that limited-time exposure triggered higher stress than long-term exposure at low concentrations of DEHP. These results demonstrate that DEHP may cause biochemical and genetic toxicity to F. candida, which illustrated the potential risks of DEHP in the soil environment and might affect soil ecosystem processes. Further studies are necessary to elucidate the toxic mechanisms of DEHP on other non-target organisms in soil.
ESTHER : Zheng_2022_Ecotoxicol.Environ.Saf_232_113251
PubMedSearch : Zheng_2022_Ecotoxicol.Environ.Saf_232_113251
PubMedID: 35121260

Title : Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism - Wang_2022_Mol.Psychiatry__
Author(s) : Wang L , Mirabella VR , Dai R , Su X , Xu R , Jadali A , Bernabucci M , Singh I , Chen Y , Tian J , Jiang P , Kwan KY , Pak C , Liu C , Comoletti D , Hart RP , Chen C , Sudhof TC , Pang ZP
Ref : Mol Psychiatry , : , 2022
Abstract : Mutations in many synaptic genes are associated with autism spectrum disorders (ASD), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C mutation on human neurons has not been investigated. Here, we generated human knockin neurons with the NLGN3 R451C and NLGN3 null mutations. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses; meanwhile NLGN3 knockout neurons showed reduction in excitatory synaptic strengths. Moreover, overexpression of NLGN3 R451C recapitulated the synaptic enhancement in human neurons. Notably, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons corresponding to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASD.
ESTHER : Wang_2022_Mol.Psychiatry__
PubMedSearch : Wang_2022_Mol.Psychiatry__
PubMedID: 36280753

Title : An efficient strategy based on two-stage chromatography and in vitro evaluation for rapid screening and isolation of acetylcholinesterase inhibitors from Scutellaria baicalensis Georgi - Hou_2022_J.Sep.Sci__
Author(s) : Hou W , Liu C , Li S , Zhang Y , Jin Y , Li X , Liu Z , Niu H , Xia J
Ref : J Sep Sci , : , 2022
Abstract : The extraction of Scutellaria baicalensis Georgi was investigated using the response surface methodology-genetic algorithm mathematical regression model, and the extraction variables were optimized to maximize the flavonoid yield. Furthermore, a simple and efficient ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods was developed for the rapid screening and identification of acetylcholinesterase inhibitors present in Scutellaria baicalensis Georgi. Subsequently, four major chemical constituents, namely baicalein, norwogonin, wogonin, and oroxylin A, were identified as potent acetylcholinesterase inhibitors. This novel approach, involving the use of ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods combined with stepwise flow rate counter-current chromatography and semi-preparative high-performance liquid chromatography, could potentially provide a powerful tool for the screening and extraction of acetylcholinesterase inhibitors from complex matrices and be a useful platform for the production of bioactive and nutraceutical ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Hou_2022_J.Sep.Sci__
PubMedSearch : Hou_2022_J.Sep.Sci__
PubMedID: 34990521

Title : Resistance selection of triflumezopyrim in Laodelphax striatellus (falln): Resistance risk, cross-resistance and metabolic mechanism - Wen_2022_Front.Physiol_13_1048208
Author(s) : Wen S , Liu C , Wang X , Wang Y , Wang J , Xia X
Ref : Front Physiol , 13 :1048208 , 2022
Abstract : The risk assessment and resistance mechanisms of insecticide resistance are critical for resistance management strategy before a new insecticide is widely used. Triflumezopyrim (TFM) is the first commercialized mesoionic insecticide, which can inhibit nicotinic acetylcholine receptor with high-performance against the small brown planthopper (SBPH), Laodelphax striatellus (Fallen). In our study, the resistance of SBPH to TFM increased 26.29-fold, and the actual heritability of resistance was 0.09 after 21 generations of continuous selection by TFM. After five generations of constant feeding under insecticide-free conditions from F(16) generation, the resistance level decreased 2.05-fold, and the average resistance decline rate per generation was 0.01, but there were no statistical decline. The TFM resistant strains had no cross-resistance to imidacloprid, nitenpyram, thiamethoxam, dinotefuran, flonicamid, pymetrozine, and chlorfenapyr. The third and fifth nymphal stage duration, pre-adult stage, adult preoviposition period, longevity, emergence rate, and hatchability of the resistant strain were significantly lower than those of the susceptible strain, while the female-male ratio was considerably increased. The fitness cost was 0.89. Further, cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) activities were markedly increased, but only the enzyme inhibitor piperonyl butoxide (PBO) had a significant synergistic effect on the resistant strain. The expression of CYP303A1, CYP4CE2, and CYP419A1v2 of P450 genes was significantly increased. SBPH has a certain risk of resistance to TFM with continuous application. The TFM resistance may be due to the increased activity of P450 enzyme regulated by the overexpression of P450 genes.
ESTHER : Wen_2022_Front.Physiol_13_1048208
PubMedSearch : Wen_2022_Front.Physiol_13_1048208
PubMedID: 36523557

Title : Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1\/2-CREB-BDNF signaling pathways in PC12 cells - Chen_2022_Metab.Brain.Dis__
Author(s) : Chen C , Bu L , Liu H , Rang Y , Huang H , Xiao X , Ou G , Liu C
Ref : Metabolic Brain Disease , : , 2022
Abstract : 1,4-butanediol (1,4-BD) is a known gamma-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-alpha) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.
ESTHER : Chen_2022_Metab.Brain.Dis__
PubMedSearch : Chen_2022_Metab.Brain.Dis__
PubMedID: 35348994

Title : A multifunctional anti-AD approach: Design, synthesis, X-ray crystal structure, biological evaluation and molecular docking of chrysin derivatives - Yang_2022_Eur.J.Med.Chem_233_114216
Author(s) : Yang A , Liu C , Zhang H , Wu J , Shen R , Kou X
Ref : Eur Journal of Medicinal Chemistry , 233 :114216 , 2022
Abstract : With the aging of the population intensifying, finding a cure or reasonable treatment for Alzheimer' disease (AD) has become an urgent priority. To target the multi-facets of AD, a class of chrysin derivatives (1-4) were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, which were characterized by (1)H NMR, (13)C NMR, MS and elemental analysis. 1-4 showed inhibitory activities on reactive oxygen species, Abeta(1-42) aggregation (self-, Cu(2+)-induced, AChE-induced). They were also potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with selectivity toward BuChE. Compound 1 as the most promising candidate exhibited the highest selective BuChE inhibition (SI = 15). Furthermore, the kinetic study suggested compound 1 to be a mixed type inhibitor. The results of docking study were consistent with the in vitro results. In addition, compound 1-4 showed favorable blood-brain barrier (BBB) penetration and drug-like property in silico prediction. The corresponding copper complexes of 1-4 have also been synthesized. 1-4 selectively chelated Cu(2+), Fe(2+), Zn(2+) and Al(3+) ions, while had no chelating ability to other biometals. The copper complexes also showed good AChE, BuChE and reactive oxygen species inhibitory activities. Notably, the single crystals of 1-Cu(II) complex [Cu(C(19)H(18)NO(4))(2)] were prepared for the first time and characterized by X-ray single crystal diffraction. X-ray crystallography analysis of 1-Cu(II) complex provided a reliable structure-activity insight at the molecular level about the antioxidative and Abeta(1-42) disaggregation activities. Compound 1 might be a good lead compound to develop promising candidate analogs as AD therapeutics.
ESTHER : Yang_2022_Eur.J.Med.Chem_233_114216
PubMedSearch : Yang_2022_Eur.J.Med.Chem_233_114216
PubMedID: 35227980

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

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 : Insight into the Inhibitory Mechanism of Aryl Formyl Piperidine Derivatives on Monoacylglycerol Lipase through Molecular Dynamics Simulations - Liu_2022_Molecules_27_7512
Author(s) : Liu C , Guan S , E J , Yang Z , Zhang X , Ju J , Wang S , Zhang H
Ref : Molecules , 27 :7512 , 2022
Abstract : Monoacylglycerol lipase (MAGL) can regulate the endocannabinoid system and thus becomes a target of antidepressant drugs. In this paper, molecular docking and molecular dynamics simulations, combined with binding free energy calculation, were employed to investigate the inhibitory mechanism and binding modes of four aryl formyl piperidine derivative inhibitors with different 1-substituents to MAGL. The results showed that in the four systems, the main four regions where the enzyme bound to the inhibitor included around the head aromatic ring, the head carbonyl oxygen, the tail amide bond, and the tail benzene ring. The significant conformational changes in the more flexible lid domain of the enzyme were caused by 1-substituted group differences of inhibitors and resulted in different degrees of flipping in the tail of the inhibitor. The flipping led to a different direction of the tail amide bond and made a greater variation in its interaction with some of the charged residues in the enzyme, which further contributed to a different swing of the tail benzene ring. If the swing is large enough, it can weaken the binding strength of the head carbonyl oxygen to its nearby residues, and even the whole inhibitor with the enzyme so that the inhibition decreases.
ESTHER : Liu_2022_Molecules_27_7512
PubMedSearch : Liu_2022_Molecules_27_7512
PubMedID: 36364337

Title : 2, 5-dichloro-1, 4-benuinone exposure to zebrafish embryos\/larvae causes neurodevelopmental toxicity - Chen_2022_Ecotoxicol.Environ.Saf_243_114007
Author(s) : Chen Y , Xiao L , Gao G , He L , Zhao K , Shang X , Liu C
Ref : Ecotoxicology & Environmental Safety , 243 :114007 , 2022
Abstract : 2, 5-dichloro-1, 4-benuinone (2, 5-DCBQ) is an emerging disinfection by-product belonging to the class of halobenzoquinones (HBQs). However, there is limited evidence regarding the neurotoxic effects of 2, 5-DCBQ. To better understand the toxicological mechanisms of aquatic organisms, zebrafish embryos were exposed to 0.2 mg/L, 0.4 mg/L, and 0.6 mg/L of 2, 5-DCBQ from 4 h post-fertilization (hpf) to 120 hpf. Developmental defects, such as reduced body length, decreased heart rate, decreased pigmentation, and abnormal motor axon structure was observed. In particular, the locomotor activity of zebrafish larvae reduced with exposure to increasing 2, 5-DCBQ concentrations, and this effect was more pronounced under dark stimulation. The results indicated that the genes associated with neuronal development (gfap, mbp, syn2a, elavl3, ache, and a1-tubulin) were significantly downregulated after treatment with 2, 5-DCBQ. Furthermore, the KEGG result showed the neuroactive ligand-receptor interaction and apoptosis pathways were visibly disrupted, and we found acetylcholinesterase activity was also affected. In summary, the disinfection by-product, 2, 5-DCBQ, exhibits neurodevelopmental toxicity in zebrafish embryos, providing novel evidence for comprehensive analyses of its toxicity.
ESTHER : Chen_2022_Ecotoxicol.Environ.Saf_243_114007
PubMedSearch : Chen_2022_Ecotoxicol.Environ.Saf_243_114007
PubMedID: 36030688

Title : Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-kB\/miR-155-5p\/eNOS\/NO\/IkB Cycle in Hypertensive Rats - Wang_2022_Antioxidants.(Basel)_11_
Author(s) : Wang X , Han W , Zhang Y , Zong Y , Tan N , Li L , Liu C , Liu L
Ref : Antioxidants (Basel) , 11 : , 2022
Abstract : Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-kappaB/miR-155-5p/eNOS/NO/IkappaB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy.
ESTHER : Wang_2022_Antioxidants.(Basel)_11_
PubMedSearch : Wang_2022_Antioxidants.(Basel)_11_
PubMedID: 35883863

Title : Subchronic toxicity of oral deltamethrin in laying chickens - Liu_2022_Front.Vet.Sci_9_1079580
Author(s) : Liu Y , Han M , Liu C , Tang Y , Jia M , Chen X , Liang H , Gao Y , Gu X
Ref : Front Vet Sci , 9 :1079580 , 2022
Abstract : Pyrethroid pesticides, with low toxicity to birds and mammals and short persistence in the environment, are widely used now. With the development of intensive poultry farming, pesticide application leads to residues in poultry products and pollution in ecological environment. The aim of the present study was to examine deltamethrin subchronic toxicity in laying chickens. One hundred and twelve laying chickens were randomly assigned to 14 groups including 13 groups medicated with deltamethrin (n = 8) and one unmedicated group used as control (n = 8). Tissue samples were collected during and after administration for weighing and histopathological analysis. A single dose of deltamethrin (20 was administered orally to laying chickens for 14 days. The results showed that deltamethrin has no significant effect on the relative organ weight of laying chickens (p > 0.05). The activities of aspartate aminotransferase and cholinesterase in the plasma gradually decreased over time in the medicated group (p < 0.05). Plasma concentrations of urea nitrogen, uric acid, cholesterol, triglycerides, and creatinine significantly increased during treatment (p < 0.05), and significant liver damage and loss of intestinal villous epithelium were observed. The intestinal wall thickness, villus height, and crypt depth of laying chickens were altered by deltamethrin treatment. During treatment was withdrawn, the intestinal repair was more extensive than the liver repair.
ESTHER : Liu_2022_Front.Vet.Sci_9_1079580
PubMedSearch : Liu_2022_Front.Vet.Sci_9_1079580
PubMedID: 36570503

Title : Characteristics of a recombinant Fusarium verticillioides cutinase and its effects on enzymatic hydrolysis of rice straw - Gu_2021_Int.J.Biol.Macromol_171_382
Author(s) : Gu S , Liu C , Zhang W , Qu M , Li Y , Zang Y , Xiong X , Pan K , Zhao X
Ref : Int J Biol Macromol , 171 :382 , 2021
Abstract : The current study heterologously expressed a cutinase from Fusarium verticillioides by Pichia pastoris and investigated its properties and effects on the hydrolysis of rice straw. The optimal pH and temperature for F. verticillioides cutinase were 8.0 and 50 degreesC, respectively. F. verticillioides cutinase had poor thermal stability and could be inhibited by some metal ions, inhibitors, and detergents (5 mM), including Ni(2+), Zn(2+), Cu(2+), Ca(2+), Mn(2+), sodium dodecyl sulfate, EDTA, and Tween-20. F. verticillioides cutinase could tolerate 15% methanol and dimethyl sulfoxide but was significantly repressed by 15% ethanol and acetone with 48% and 63% residual activity, respectively. F. verticillioides cutinase could degrade the cuticle of rice straw with palmitic acid and stearic acid as the main products. However, the dissolving sugars released from the rice straw treated with F. verticillioides cutinase were significantly reduced by 29.2 microg/mL compared with the control (107.9 microg/mL). Similarly, the reducing sugars produced from the cellulase hydrolysis of rice straw pretreated with F. verticillioides cutinase were reduced by 63.5 microg/mL relative to the control (253.6 microg/mL). Scanning electron microscopy results showed that numerous tuberculate or warty protrusions were present nearly everywhere on the surface of rice straw treated with F. verticillioides cutinase, and some protrusions even covered and blocked the stomata of the rice straw surface. Current limited data indicate that F. verticillioides cutinase might not be an appropriate choice for improving the utilization of agricultural straws.
ESTHER : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedSearch : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedID: 33434547
Gene_locus related to this paper: gibm7-w7lbp5

Title : Cu(2+)-Regulated reversible coordination interaction of GQD@Tb\/GMP ICP nanoparticles: towards directly monitoring cerebrospinal acetylcholinesterase as a biomarker for cholinic brain dysfunction - Liu_2021_Analyst_145_7849
Author(s) : Liu C , Huang C , Ma R , Zhai W , Deng J , Zhou T
Ref : Analyst , 145 :7849 , 2021
Abstract : This work demonstrates a new strategy for sensing cerebrospinal acetylcholinesterase (AChE) as a cholinergic biomarker for brain dysfunction based on graphene quantum dot (GQD)-functionalized lanthanide infinite coordination polymer (Ln-ICP) nanoparticles. The ICPs used in this work were comprised of two components, i.e. a supramolecular Ln-ICP host formed by the coordination between the GMP ligand and central metal ion Tb3+, and guest GQDs with abundant functional groups, which were utilized as antenna ligands to further sensitize the fluorescence of Tb/GMP. Upon excitation at 300 nm, the obtained GQD@Tb/GMP ICP nanoparticles exhibited enhanced green fluorescence from Tb/GMP. With the addition of Cu2+, the competitive coordination between Cu2+ and GQDs weakened the antenna effect, leading to a decrease in the fluorescence of GQD@Tb/GMP ICPs. However, in the presence of thiocholine (TCh), a thiol-containing compound hydrolyzed from acetylthiocholine (ATCh) by AChE, a stronger coordination interaction between Cu2+ and TCh occurred, resulting in the restoration of the fluorescence of GQD@Tb/GMP ICPs. Using the method established herein, the cerebrospinal AChE fluctuation of rats with acute organophosphorus pesticide (OP) poisoning or chronic Alzheimer's disease (AD) could be monitored. This study essentially provides a novel approach to realize the direct monitoring of a biomarker for brain dysfunction by regulating the competitive coordination interaction reversibly, which is critical in the early diagnosis and therapy of brain diseases.
ESTHER : Liu_2021_Analyst_145_7849
PubMedSearch : Liu_2021_Analyst_145_7849
PubMedID: 33410430

Title : Red-to-blue paper-based colorimetric sensor integrated with smartphone for point-of-use analysis of cerebral AChE upon Cd(2+) exposure - Liu_2021_Nanoscale__
Author(s) : Liu C , Luo Y , Wen H , Qi Y , Shi G , Deng J , Zhou T
Ref : Nanoscale , : , 2021
Abstract : Herein, combined with a pervasive smartphone installed with a color recognition app, dual-responsive CDs@Eu/GMP ICPs were designed as a red-to-blue paper-based colorimetric sensor for the point-of-use analysis of cerebral acetylcholinesterase (AChE) upon Cd2+ exposure. Blue-emitting CDs with multi-functional groups as guests were encapsulated into the network of Eu/GMP ICPs to obtain CDs@Eu/GMP ICPs with the sensitized red fluorescence of Eu3+. With the presence of thiocholine (TCh), derived from acetylthiocholine (ATCh) hydrolyzed by AChE, the coordination environment of the CDs@Eu/GMP ICPs was interrupted, leading to the collapse of the CDs@Eu/GMP ICP network and the corresponding release of guest CDs into the surrounding environment. Consequently, the sensitized red fluorescence of Eu3+ decreased and the blue fluorescence of the CDs increased. This obvious red-to-blue fluorescent color changes of CDs@Eu/GMP ICPs on test paper could then be integrated with the smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure, which not only offers a new analytical platform for a better understanding of the environmental risk of Alzheimer's Dementia (AD), but also holds great potential in the early diagnosis of AD even at the asymptomatic stage with the decrease in CSF AChE as an early biomarker.
ESTHER : Liu_2021_Nanoscale__
PubMedSearch : Liu_2021_Nanoscale__
PubMedID: 33406172

Title : A preliminary study on the neurotoxic mechanism of harmine in Caenorhabditis elegans - Sun_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109038
Author(s) : Sun Q , Liu C , Jiang K , Fang Y , Kong C , Fu J , Liu Y
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109038 , 2021
Abstract : Harmine is a beta-carboline and harmala alkaloid with extensive bioactivities. However, its toxicity, especially in neural system, is not systematically assessed and the toxic mechanism is not yet clear. Using Caenorhabditis elegans (C. elegans) as a model system, we found that harmine exhibited dosage dependent (0, 5, 10, 20, 40, 80, 160, and 320 micromol/L) toxic effect, such as growth inhibition, egg laying defects, shortened life span and increased mortality. Although harmine did not result in obvious structural alterations in neurite or death of neurons, it did show direct acetylcholinesterase inhibition activity. Further, we found that harmine treatment decreased worm pharyngeal pump rate and lowered the content of nitric oxide (NO) in worm body, implying foraging disorders, which is an indicator of acetylcholinergic neuron activity inhibition. Besides, network pharmacology and molecular docking reveals that acetylcholinesterase is one of the major neural toxicity targets as well. Above all, harmine can directly inhibit the activity of acetylcholinesterase, leading to excessive accumulation of acetylcholine, which may be one of the harmine neurotoxicity mechanisms.
ESTHER : Sun_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109038
PubMedSearch : Sun_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109038
PubMedID: 33794375

Title : Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity - Huang_2021_J.Inflamm.Res_14_6735
Author(s) : Huang Y , Liu C , Song X , An M , Liu M , Yao L , Famurewa AC , Olatunji OJ
Ref : J Inflamm Res , 14 :6735 , 2021
Abstract : BACKGROUND: Cisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats. MATERIALS AND METHODS: CDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration. RESULTS: CCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-alpha, IL-6 and IL-1beta and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology. CONCLUSION: The findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.
ESTHER : Huang_2021_J.Inflamm.Res_14_6735
PubMedSearch : Huang_2021_J.Inflamm.Res_14_6735
PubMedID: 34916822

Title : One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase - Liu_2021_J.Org.Chem__
Author(s) : Liu C , Wang Y , Liu J , Chen A , Xu J , Zhang R , Wang F , Nie K , Deng L
Ref : J Org Chem , : , 2021
Abstract : 4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.
ESTHER : Liu_2021_J.Org.Chem__
PubMedSearch : Liu_2021_J.Org.Chem__
PubMedID: 34085515

Title : On-line coupling pressurised liquid extraction with two-dimensional counter current chromatography for isolation of natural acetylcholinesterase inhibitors from Astragalus membranaceus - Li_2021_Phytochem.Anal_32_640
Author(s) : Li S , Liu C , Zhang Y , Tsao R
Ref : Phytochem Anal , 32 :640 , 2021
Abstract : INTRODUCTION: Radix Astragali, the dried root of Astragalus membranaceus (Fish.) Bge. (family Fabaceae), which is known as Huangqi in China, has been proven to be an immunostimulant, diuretic, antidiabetic, analgesic, and it has also been used as a health food supplement in some Asian populations and also serves as a lead herb in many traditional Chinese medicine formulations as well as in Chinese ethnic tonifying soups. OBJECTIVE: Screening and purification of bioactive compounds from natural products is challenging work due to their complexity. We present the first report on the use of pressurised liquid extraction and on-line two-dimensional counter current chromatography as an efficient medium for scaled-up extraction and separation of six bioactive compounds from Astragalus membranaceus. METHOD: We applied the established method with ultrafiltration-liquid chromatography to screen acetylcholinesterase inhibitors, which were then evaluated and confirmed for anti-Alzheimer activity using PC12 cell model. RESULTS: Six major compounds, namely, calycosin-7-O-beta-d-glucoside, pratensein-7-O-beta-d-glucoside, formononetin-7-O-beta-d-glucoside, calycosin, genistein, and formononetin, with acetylcholinesterase binding affinities were identified and isolated from the raw plant materials via two sets of n-hexane/ethyl acetate/0.2% acetic acid (first-stage counter current chromatography) and n-hexane/ethyl acetate/methanol/water (second-stage counter current chromatography) solvent systems: 1.87:1.0:1.33 and 5.62:1.0:2.42:5.25, v/v/v/v, which were optimised by a mathematical model. CONCLUSION: Therefore, a useful platform for the large-scale production of bioactive and nutraceutical ingredients was developed herein. With the on-line system developed here, we present a feasible, selective, and effective strategy for rapid screening and identification of enzyme inhibitors from complex mixtures.
ESTHER : Li_2021_Phytochem.Anal_32_640
PubMedSearch : Li_2021_Phytochem.Anal_32_640
PubMedID: 33238329

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

Title : Novel chrysin derivatives as hidden multifunctional agents for anti-Alzheimer's disease: design, synthesis and in vitro evaluation - Liu_2021_Eur.J.Pharm.Sci__105976
Author(s) : Liu C , Kou X , Wang X , Wu J , Yang A , Shen R
Ref : Eur J Pharm Sci , :105976 , 2021
Abstract : Alzheimer's disease (AD) is the most common type of dementia, the exact etiology of the disease has not been known yet. The use of single-target drugs limits the efficacy of drugs and has certain side effects. In this study, the 'hidden' multi-target strategy was used in combination with chrysin's metal chelating site and rivastigmine's anti-cholinesterase pharmacophore to form an ester, which improves the hydrophobicity and protects the phenolic hydroxyl group at the same time. Four derivatives (1-4) were synthesized as the hidden multifunctional agents for AD therapy. Most of the compounds displayed good activities of anti-cholinesterase, antioxidant, appropriate blood brain barrier (BBB) penetration and certain inhibitory activity of beta-amyloid (Abeta) aggregation. Compound 3 was demonstrated as the highest selective butyrylcholinesterase (BuChE) inhibitor and targeted both the catalytic active site (CAS) and the peripheral anion site (PAS). And it could be hydrolyzed by BuChE to release chrysin with good ability to chelate Cu(2+) and Fe(2+). At the same time, phenol fragment can exert its good antioxidant effect. Overall, these findings demonstrated that compound 3 might be considered as a potential hidden multifunctional candidate in the therapy of AD.
ESTHER : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedSearch : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedID: 34419572

Title : In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis - Liu_2021_Parasit.Vectors_14_450
Author(s) : Liu C , Fan H , Ma J , Ma L , Ge RL
Ref : Parasit Vectors , 14 :450 , 2021
Abstract : BACKGROUND: Alveolar echinococcosis (AE) is a chronic zoonosis caused by the larval form of Echinococcus multilocularis (E. multilocularis). Current chemotherapy against AE has relied on albendazole and mebendazole, which only exhibit parasitostatic and not parasiticidal efficacy. Therefore, novel compounds for the treatment of this disease are needed. METHODS: Phosphoglucose isomerase (PGI) assays were used for compound screening of seven neonicotinoids. The anti-parasitic effects of thiacloprid were then evaluated on E. multilocularis metacestode vesicles, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFF) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. Glucose consumption in E. multilocularis protoscoleces and germinal cells was assessed by measuring uptake of 2-deoxyglucose (2-DG). Molecular docking was used to evaluate the potential binding sites of thiacloprid to acetylcholine receptors. In vivo efficacy of thiacloprid was evaluated in mice by secondary infection with E. multilocularis. In addition, ELISA and flow cytometry were used to evaluate the effects of cytokines and T lymphocyte subsets after thiacloprid treatment. Furthermore, collagen deposition and degradation in the host lesion microenvironment were evaluated. RESULTS: We found that thiacloprid is the most promising compound, with an IC(50) of 4.54 +/- 1.10 microM and 2.89 +/- 0.34 microM, respectively, against in vitro-cultured E. multilocularis metacestodes and germinal cells. Thiacloprid was less toxic for HFF and RH mammalian cell lines than for metacestodes. In addition, thiacloprid inhibited the acetylcholinesterase activity in protoscoleces, metacestodes and germinal cells. Thiacloprid inhibited glucose consumption by protoscoleces and germinal cells. Subsequently, transmission electron microscopy revealed that treatment with thiacloprid damaged the germinal layer. In vivo, metacestode weight was significantly reduced following oral administration of thiacloprid at 15 and 30 mg/kg. The level of CD4(+) T lymphocytes in metacestodes and spleen increased after thiacloprid treatment. Anti-echinococcosis-related cytokines (IL-2, IL-4, IL-10) were significantly increased. Furthermore, thiacloprid inhibited the expression of matrix metalloproteinases (MMPs 1, 3, 9, 13) and promoted collagen deposition in the host lesion microenvironment. CONCLUSIONS: The results demonstrated that thiacloprid had parasiticidal activity against E. multilocularis in vitro and in vivo, and could be used as a novel lead compound for the treatment of AE.
ESTHER : Liu_2021_Parasit.Vectors_14_450
PubMedSearch : Liu_2021_Parasit.Vectors_14_450
PubMedID: 34488852

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

Title : The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis - Li_2021_Chemosphere_263_128238
Author(s) : Li Y , Fang R , Liu Z , Jiang L , Zhang J , Li H , Liu C , Li F
Ref : Chemosphere , 263 :128238 , 2021
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.
ESTHER : Li_2021_Chemosphere_263_128238
PubMedSearch : Li_2021_Chemosphere_263_128238
PubMedID: 33297185

Title : Characterization and genomic analysis of an efficient dibutyl phthalate degrading bacterium Microbacterium sp. USTB-Y - Zhao_2021_World.J.Microbiol.Biotechnol_37_212
Author(s) : Zhao Z , Liu C , Xu Q , Ahmad S , Zhang H , Pang Y , Aikemu A , Liu Y , Yan H
Ref : World J Microbiol Biotechnol , 37 :212 , 2021
Abstract : A promising bacterial strain for biodegrading dibutyl phthalate (DBP) was successfully isolated from activated sludge and characterized as a potential novel Microbacterium sp. USTB-Y based on 16S rRNA sequence analysis and whole genome average nucleotide identity (ANI). Initial DBP of 50 mg/L could be completely biodegraded by USTB-Y both in mineral salt medium and in DBP artificially contaminated soil within 12 h at the optimal culture conditions of pH 7.5 and 30 degC, which indicates that USTB-Y has a strong ability in DBP biodegradation. Phthalic acid (PA) was identified as the end-product of DBP biodegraded by USTB-Y using GC/MS. The draft genome of USTB-Y was sequenced by Illumina NovaSeq and 29 and 188 genes encoding for putative esterase/carboxylesterase and hydrolase/alpha/beta hydrolase were annotated based on NR (non redundant protein sequence database) analysis, respectively. Gene3781 and gene3780 from strain USTB-Y showed 100% identity with dpeH and mpeH from Microbacterium sp. PAE-1. But no phthalate catabolic gene (pht) cluster was found in the genome of strain USTB-Y. The results in the present study are valuable for obtaining a more holistic understanding on diverse genetic mechanisms of PAEs biodegrading Microbacterium sp. strains.
ESTHER : Zhao_2021_World.J.Microbiol.Biotechnol_37_212
PubMedSearch : Zhao_2021_World.J.Microbiol.Biotechnol_37_212
PubMedID: 34738191
Gene_locus related to this paper: 9mico-DpeH , 9mico-MpeH

Title : Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE\/GSK3beta inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine - Jiang_2021_Eur.J.Med.Chem_223_113663
Author(s) : Jiang X , Liu C , Zou M , Xie H , Lin T , Lyu W , Xu J , Li Y , Feng F , Sun H , Liu W
Ref : Eur Journal of Medicinal Chemistry , 223 :113663 , 2021
Abstract : Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3beta (Glycogen synthase kinase 3beta) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3beta inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD.
ESTHER : Jiang_2021_Eur.J.Med.Chem_223_113663
PubMedSearch : Jiang_2021_Eur.J.Med.Chem_223_113663
PubMedID: 34198150

Title : Discovery of potent glycogen synthase kinase 3\/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer's disease - Jiang_2021_Bioorg.Med.Chem_30_115940
Author(s) : Jiang X , Wang Y , Liu C , Xing C , Lyu W , Wang S , Li Q , Chen T , Chen Y , Feng F , Liu W , Sun H
Ref : Bioorganic & Medicinal Chemistry , 30 :115940 , 2021
Abstract : In the present work, a novel series of pyridinethiazole bearing benzylpiperidine hybrids were designed and synthesized as dual-target inhibitors of GSK-3beta/AChE. Among them, GD29 was the most promising candidate, with an IC(50) value of 0.3 M for hAChE and an IC(50) value of 0.003 M for hGSK-3beta, respectively. The compounds exhibited good drug-like properties with optimal inhibitory enzyme activities. Moreover, GD29 showed anti-inflammatory properties at micromolar concentrations and displayed interesting neuroprotective profiles in an in vitro model of oxidative stress-induced neuronal death. Notably, the compounds also exhibited good permeability across the blood-brain-barrier (BBB) both in vitro. Central cholinomimetic activity was confirmed using a scopolamine-induced cognition impairment model in Institute of Cancer Research (ICR) mice upon oral administration. The current work identified optimized compounds and explored the therapeutic potential of glycogen synthase kinase 3/cholinesterase inhibition for the treatment of AD.
ESTHER : Jiang_2021_Bioorg.Med.Chem_30_115940
PubMedSearch : Jiang_2021_Bioorg.Med.Chem_30_115940
PubMedID: 33340937

Title : A review on alpha-mangostin as a potential multi-target-directed ligand for Alzheimer's disease - Yang_2021_Eur.J.Pharmacol__173950
Author(s) : Yang A , Liu C , Wu J , Kou X , Shen R
Ref : European Journal of Pharmacology , :173950 , 2021
Abstract : Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive memory loss, declining language skills and other cognitive disorders. AD has brought great mental and economic burden to patients, families and society. However due to the complexity of AD's pathology, drugs developed for the treatment of AD often fail in clinical or experimental trials. The main problems of current anti-AD drugs are low efficacy due to mono-target method or side effects, especially high hepatotoxicity. To tackle these two main problems, multi-target-directed ligand (MTDL) based on "one molecule, multiple targets" has been studied. MTDLs can regulate multiple biological targets at the same time, so it has shown higher efficacy, better safety. As a natural active small molecule, alpha-mangostin (alpha-M) has shown potential multi-factor anti-AD activities in a series of studies, furthermore it also has a certain hepatoprotective effect. The good availability of alpha-M also provides support for its application in clinical research. In this work, multiple activities of alpha-M related to AD therapy were reviewed, which included anti-cholinesterase, anti-amyloid-cascade, anti-inflammation, anti-oxidative stress, low toxicity, hepatoprotective effects and drug formulation. It shows that alpha-M is a promising candidate for the treatment of AD.
ESTHER : Yang_2021_Eur.J.Pharmacol__173950
PubMedSearch : Yang_2021_Eur.J.Pharmacol__173950
PubMedID: 33607107

Title : Analysis of Differentially Expressed Transcripts in Apolygus lucorum (Meyer-Dur) Exposed to Different Temperature Coefficient Insecticides - An_2020_Int.J.Mol.Sci_21_658
Author(s) : An J , Liu C , Dou Y , Gao Z , Dang Z , Yan X , Pan W , Li Y
Ref : Int J Mol Sci , 21 :658 , 2020
Abstract : The existence of a temperature effect of insecticides frustrated the control of the green plant bug Apolygus lucorum (Meyer-Dur). Previous studies mostly focused on the application of insecticides, but the underlying mechanism remains incompletely understood. Here, we report a transcriptome profiling of A. lucorum treated by three kinds of temperature coefficient insecticides (TCIs) (positive TCI: imidacloprid, negative TCI: b-cypermethrin and non-effect TCI: phoxim) at 15 degrees C, 25 degrees C and 35 degrees C by using next- and third-generation RNA-Seq methods. A total of 34,739 transcripts were annotated from 277.74 Gb of clean data. There were more up-regulated transcripts than down-regulated transcripts in all three kinds of TCI treatments. Further Venn diagrams indicate the regulatory transcripts and regulatory modes were different at the three temperatures. The responses to imidacloprid involved more detox and stress response transcripts such as cytochrome P450 (CYP450), carboxylesterase (CarE) and catalase (CAT) at 35 degrees C, which was the case for beta-cypermethrin at 15 degrees C. UDP-glucuronyltransferase (UGT) and heat shock protein (HSP) transcripts were heavily involved, and thus deserve particular note in the temperature effect of insecticides. This high-confidence transcriptome atlas provides improved gene information for further study on the insecticide temperature effect related physiological and biochemical processes of A. lucorum.
ESTHER : An_2020_Int.J.Mol.Sci_21_658
PubMedSearch : An_2020_Int.J.Mol.Sci_21_658
PubMedID: 31963875

Title : Enantioconvergent hydrolysis of m-nitrostyrene oxide at an elevated concentration by Phaseolus vulgaris epoxide hydrolase in the organic\/aqueous two-phase system - Wen_2020_Lett.Appl.Microbiol_70_181
Author(s) : Wen Z , Zhao J , Liu YY , Zhou JJ , Liu C , Li C , Wu MC
Ref : Lett Appl Microbiol , 70 :181 , 2020
Abstract : (R)-m-Nitrophenyl-1,2-ethanediol (m-NPED) is a versatile and highly value-added chiral building block for the synthesis of some bioactive compounds, such as (R)-Nifenalol. To efficiently produce (R)-m-NPED through the enantioconvergent hydrolysis of racemic (rac-) m-nitrostyrene oxide (m-NSO) using the whole resting cells of Escherichia coli/pCold-pveh2 intracellularly expressing PvEH2, an epoxide hydrolase from Phaseolus vulgaris, two reaction systems were investigated. In the Na2 HPO4 -NaH2 PO4 buffer (50 mmol l(-1) , pH 7.0) system, merely 15 mmol l(-1) rac-m-NSO was successfully subjected to enantioconvergent hydrolysis, producing (R)-m-NPED with 86.0% enantiomeric excess (eep ) and 177.6 mg l(-1) h(-1) space-time yield (STY). The experimental result indicated that there is inhibitory effect of rac-m-NSO at high concentration on PvEH2. To efficiently increase the concentration of rac-m-NSO and the STY of (R)-m-NPED, petroleum ether was first selected to construct an organic/aqueous two-phase system. Then, both the volume ratio (vo /vb ) of petroleum ether to phosphate buffer and the weight ratio (wc /ws ) of E. coli/pCold-pveh2 dry cells to rac-m-NSO were optimized as 2 : 8 and 5 : 1, respectively. In the optimized petroleum ether/phosphate buffer two-phase system, the enantioconvergent hydrolysis of rac-m-NSO at 40 mmol l(-1) (6.6 mg ml(-1) ) was carried out at 25 degrees C for 12 h using 33.0 mg ml(-1) vacuum freeze-dried cells of E. coli/pCold-pveh2, producing (R)-m-NPED with 87.4% eep , 82.3% yield and 502.4 mg l(-1) h(-1) STY. SIGNIFICANCE AND IMPACT OF THE STUDY: Epoxide hydrolases play a crucial role in producing enantiopure epoxides and/or vicinal diols. However, numerous biocatalytic reactions of organic compounds, such as epoxides, in aqueous phase suffered various restrictions. Herein, the enantioconvergent hydrolysis of rac-m-NSO in two reaction systems was investigated using the whole cells of Escherichia coli/pCold-pveh2. As a result, the concentration of rac-m-NSO and the space-time yield of (R)-m-NPED in organic/aqueous two-phase system were significantly increased, when compared with those in aqueous phase. To our knowledge, this is the first report about the production of (R)-m-NPED from rac-m-NSO at an elevated concentration by PvEH2 in the two-phase system.
ESTHER : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedSearch : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedID: 31784998

Title : [Determination of gastrodin activity inhibition on acetylcholinesterase by capillary electrophoresis] - Zhang_2020_Se.Pu_38_1102
Author(s) : Zhang J , Zhang B , He M , Han L , Gao D , Liu C
Ref : Se Pu , 38 :1102 , 2020
Abstract : Alzheimer's disease (AD) is the most common cause of dementia in elderly individuals. Currently, acetylcholinesterase inhibitors (AChEI) are the most effective clinical treatment for AD. AChEIs in natural products may have therapeutic potential and should be screened for use in AD treatment. The authors describe a simple and reliable method for AChEI screening by capillary electrophoresis (CE). A hexadimethrine bromide (HDB) solution was pushed into a capillary (0.015 MPax10 s) and incubated for 5 min. The capillary was flushed with deionized water for 5 min to remove free HDB, followed by plugging with an acetylcholinesterase (AChE) solution. After a 5 min incubation, the AChE was immobilized on the positively charged coating by ion binding, and the micro-reactor was created. The substrate solution, acetylthiocholine iodide (AThC), was injected into the capillary and incubated in the micro-reactor for 1 min. The unreacted substrate and the enzymolysis product were separated by CE. Gastrodin, an important component of Gastrodia elata, can inhibit AChE activity. After a certain amount of gastrodin was spiked into the substance solution, the peak area of the product decreased. Greater peak area reduction indicated stronger inhibition of AChEI. We observed good reproducibility of the product peak, with relative standard deviation (RSD) values less than 5.3%. The micro-reactor can be reused up to 300 times, which greatly improves efficiency. When the concentration of gastrodin was 5.24 micromol/L, the inhibition rate of AChE reached 64.8%. The IC(50) of gastrodin was (2.26+/-0.14) micromol/L (R(2)=0.9983), which was consistent with the result of traditional UV method (2.09+/-0.18 micromol/L). If the function of the micro-reactor deteriorates, it can be conveniently renewed by flushing the column to remove the enzyme and repeating the AChE immobilization protocol. The proposed method is simple, efficient, and low cost, and can be used to screen AChEI from natural products, thus contributing to the improvement of AD treatment.
ESTHER : Zhang_2020_Se.Pu_38_1102
PubMedSearch : Zhang_2020_Se.Pu_38_1102
PubMedID: 34213277

Title : Application of accelerated solvent extraction coupled with online two-dimensional countercurrent chromatography for continuous extraction and separation of bioactive compounds from Citrus limon peel - Li_2020_J.Sep.Sci_43_3793
Author(s) : Li S , Liu C , Zhang Y , Shi D , Tsao R
Ref : J Sep Sci , 43 :3793 , 2020
Abstract : Drug discovery from complex mixtures, like Chinese herbs, is challenging and extensive false positives make it difficult to obtain compounds with anti-Alzheimer's activity. In this study, a continuous method comprised of accelerated solvent extraction coupled with online two-dimensional countercurrent chromatography was developed for the efficient, scaled-up extraction and separation of six bioactive compounds from Citrus limon peels: neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin, and limonin. These active compounds were isolated and purified from the raw plant materials by two-dimensional countercurrent chromatography separation via two sets of an n-hexane/n-butanol/methanol/water solvent system: 0.23:1.00:0.25:1.13 and 0.47:1.00:0.38:1.46, v/v/v/v. The compounds were collected in yields of 0.22, 0.25, 0.10, 0.31, 0.29, and 0.28 mg/g, respectively, with purities of 95.79, 96.47, 97.69, 97.22, 98.11, and 98.82%, respectively. Subsequently, a simple and efficient in vitro method was developed for rapidly evaluating the acetylcholinesterase inhibitory activities of six bioactive components. Furthermore, the PC12 cell model and the in vitro metabolism of cytochromes P450 were employed to verify the monomers obtained from the continuous method. The results demonstrated that these six bioactive extracts from the C. limon peels were strong acetylcholinesterase inhibitors.
ESTHER : Li_2020_J.Sep.Sci_43_3793
PubMedSearch : Li_2020_J.Sep.Sci_43_3793
PubMedID: 32745365

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 : Double-enzymes-mediated Fe(2+)\/Fe(3+) conversion as magnetic relaxation switch for pesticide residues sensing - Wu_2020_J.Hazard.Mater_403_123619
Author(s) : Wu L , Zhou M , Liu C , Chen X , Chen Y
Ref : J Hazard Mater , 403 :123619 , 2020
Abstract : It is a great challenge to develop a newly rapid and accurate detection method for pesticide residues. In this work, based on acetylcholinesterase (AChE) and choline oxidase (CHO), a double-enzymes-mediated Fe(2+)/Fe(3+) conversion as magnetic relaxation switch was explored for the measurement of acetamiprid residue. In the double-enzymes reactions, acetylcholine chloride (ACh) can be catalyzed to produce choline by AChE, which is successively hydrolyzed to betaine and hydrogen peroxide (H(2)O(2)) by CHO. According to the enzyme inhibition principle, AChE activity will be inactivated in the presence of acetamiprid, thus leading to the less production of H(2)O(2). Wherein, Fe(2+), ACh, AChE and CHO were optimized as the reaction substrates. In the reaction system, acetamiprid can be reflected by the transverse relaxation time (T(2)) that related with H(2)O(2) mediated Fe(2+) variations, which was further developed as an enzyme cascade amplification method. The detection linear range is 0.01~1000 mug mL(-1) (R(2) = 0.99), and the limit of detection (LOD) is 2.66 ng mL(-1) (S/N = 3, n = 3), behaving a 335-fold improvement in LOD than that of traditional enzyme inhibition method (0.89 mug mL(-1)). This method can realize "one-step mixing" detection of acetamiprid, which makes it a promising analytical tool for monitoring pesticide residue in complicated samples.
ESTHER : Wu_2020_J.Hazard.Mater_403_123619
PubMedSearch : Wu_2020_J.Hazard.Mater_403_123619
PubMedID: 32827859

Title : Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip\/knee replacement: a prospective cohort study - Lin_2020_BMC.Anesthesiol_20_246
Author(s) : Lin X , Tang J , Liu C , Li X , Cao X , Wang B , Dong R , Xu W , Yu X , Wang M , Bi Y
Ref : BMC Anesthesiol , 20 :246 , 2020
Abstract : BACKGROUND: Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. METHODS: Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. RESULTS: POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-alpha and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-alpha were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. CONCLUSION: The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. TRIAL REGISTRATION: This study was registered at (NO. ChiCTR1900023729 ) June 9th, 2019. (Retrospectively registered).
ESTHER : Lin_2020_BMC.Anesthesiol_20_246
PubMedSearch : Lin_2020_BMC.Anesthesiol_20_246
PubMedID: 32988381

Title : Stimulus Response of GQD-Sensitized Tb\/GMP ICP Nanoparticles with Dual-Responsive Ratiometric Fluorescence: Toward Point-of-Use Analysis of Acetylcholinesterase and Organophosphorus Pesticide Poisoning with Acetylcholinesterase as a Biomarker - Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
Author(s) : Ma R , Xu M , Liu C , Shi G , Deng J , Zhou T
Ref : ACS Appl Mater Interfaces , 12 :42119 , 2020
Abstract : In this study, by rationally designing the stimulus response of graphene quantum dot (GQD)-sensitized terbium/guanine monophosphate (Tb/GMP) infinite coordination polymer (ICP) nanoparticles, we have constructed a smartphone-based colorimetric assay with ratiometric fluorescence, which could be applied for the detection of acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) directly. First, GQDs with abundant functional groups were chosen as the guest, which not only could be used as one of the signal readouts but also served as the antenna ligand to further sensitize the fluorescence of the host Tb/GMP. Upon being excited at 330 nm, the green fluorescence of the Tb/GMP host is highly enhanced, while the blue fluorescence of GQDs is suppressed due to the confinement of the ICP host. With the presence of thiocholine (TCh), an enzymatic product hydrolyzed from acetylthiocholine (ATCh) by AChE, the competitive coordination of Tb(3+) between GMP and TCh results in the collapse of the ICP network and thereby the release of GQDs into the solution; thus, the fluorescence of Tb/GMP turns off and the fluorescence of GQDs turns on. The dual-responsive ratiometric fluorescent intensity change leads to the corresponding green-to-blue fluorescent color change obviously, which constitutes a novel mechanism for the colorimetric analysis of AChE. Moreover, when OPs are subsequently introduced, the activity of AChE is blocked, thus preventing the stimulus response of GQD@Tb/GMP ICP nanoparticles, leading to the fluorescent color change from greenish-blue to green, which could also be employed for OP detection. Benefitting from the high sensitivity, good reliability, and the obvious color changes, the method demonstrated here is a promising candidate to realize smartphone-based point-of-use applications, which is of great importance for timely clinical diagnosis and treatment of OPs related to health issues with AChE as an exposure biomarker in less industrialized countries, in remote settings, or even in home care services.
ESTHER : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedSearch : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedID: 32805836

Title : Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer's disease - Jiang_2020_Eur.J.Med.Chem_207_112751
Author(s) : Jiang X , Zhou J , Wang Y , Chen L , Duan Y , Huang J , Liu C , Chen Y , Liu W , Sun H , Feng F , Qu W
Ref : Eur Journal of Medicinal Chemistry , 207 :112751 , 2020
Abstract : A key factor in the success of the MTDLs drug discovery approach is the selection of suitable target proteins. Based on the results of our previous research regarding dual-target inhibitors of AChE/GSK-3beta and analysis of target proteins, in the current study, 28 hybrids were designed and synthesized. Docking studies allowed us to rationalize the binding mode of the synthesized compounds in both targets. In vitro enzyme inhibition studies identified compound GT15 as a lead molecule with preferential AChE/GSK-3beta inhibition (hAChE IC(50) = 1.2 +/- 0.1 nM; hGSK-3beta IC(50) = 22.2 +/- 1.4 nM). In addition, GT15 showed high kinase selectivity for GSK-3, except for DYRK1, with inhibition rate of 83.69% and 67.94% against DYRK1alpha and DYRK1beta at a concentration of 20 muM. The compound also exhibited good permeability across the blood-brain-barrier and ability to inhibit the phosphorylation of tau protein. Upon oral administration, GT15 exhibited promising cognitive improvement in the scopolamine-induced cognitive deficit mice in the Morris water maze model. These results suggest that AChE and GSK-3 based multitargeted approach have therapeutic potential for Alzheimer's disease.
ESTHER : Jiang_2020_Eur.J.Med.Chem_207_112751
PubMedSearch : Jiang_2020_Eur.J.Med.Chem_207_112751
PubMedID: 32950908

Title : Gamete binning: chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes - Campoy_2020_Genome.Biol_21_306
Author(s) : Campoy JA , Sun H , Goel M , Jiao WB , Folz-Donahue K , Wang N , Rubio M , Liu C , Kukat C , Ruiz D , Huettel B , Schneeberger K
Ref : Genome Biol , 21 :306 , 2020
Abstract : Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes enabling separation of the whole-genome sequencing reads into haplotype-specific reads sets. After assembling the reads of each haplotype, the contigs are scaffolded to chromosome level using a genetic map derived from the gametes. We assemble the two genomes of a diploid apricot tree based on whole-genome sequencing of 445 individual pollen grains. The two haplotype assemblies (N50: 25.5 and 25.8 Mb) feature a haplotyping precision of greater than 99% and are accurately scaffolded to chromosome-level.
ESTHER : Campoy_2020_Genome.Biol_21_306
PubMedSearch : Campoy_2020_Genome.Biol_21_306
PubMedID: 33372615
Gene_locus related to this paper: pruar-a0a6j5xc26 , pruar-a0a6j5xjr9

Title : Extraction and Isolation of Acetylcholinesterase Inhibitors from Citrus limon Peel Using an in vitro Method - Liu_2020_J.Sep.Sci__
Author(s) : Liu C , Hou W , Li S , Tsao R
Ref : J Sep Sci , : , 2020
Abstract : A simple and efficient ultrafiltration-liquid chromatography-mass spectrometry-based method was developed for the rapid screening and identification of ligands from Citrus limon peel, which are suitable acetylcholinesterase inhibitors. Subsequently, the anti-Alzheimer's activity of these compounds was assessed using a PC12 cell model. Six major compounds, viz. neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin, and limonin, were identified as potent acetylcholinesterase inhibitors. A continuous and efficient online method, which involved the use of a microwave-assisted extraction device, solvent concentration tank, and centrifugal partition chromatography column, was developed for the scale-up of these compounds, and the obtained compounds presented high purity. Next, their bioactivity was evaluated using a PC12 cell model. This novel approach, which was based on ultrafiltration-liquid chromatography-mass spectrometry, microwave-assisted extraction online coupled with solvent concentration tank, and centrifugal partition chromatography along with in vitro evaluation, could represent a powerful tool for the screening and extraction of acetylcholinesterase inhibitors from complex matrices, and could be a useful platform for the large-scale production of bioactive and nutraceutical ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2020_J.Sep.Sci__
PubMedSearch : Liu_2020_J.Sep.Sci__
PubMedID: 31999045

Title : Clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning - Jiang_2019_Saudi.J.Biol.Sci_26_2018
Author(s) : Jiang SZ , Ma BE , Liu C , Wang R
Ref : Saudi J Biol Sci , 26 :2018 , 2019
Abstract : Objective: To observe the clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning patients, and investigate the potential mechanism. Methods: In this study, we enrolled 136 organophosphorus poisoning patients who received treatment in this hospital between January 2009 and December 2017, and they were divided into three groups according to the clinical treatment methods, i.e. Group A (comprehensive treatment with HP, n=47), Group B (continuous intravenous infusion of atropine with micropump, n=43) and Group C (regular intravenous infusion of atropine, n=46). In addition to the close monitoring of vital signs, we recorded the atropinization time (min), cholinesterase reactivation time (h), total dose of atropine, recurrence, incidence rate of atropine poisoning (%), hospitalization time (d) and cure rate (%). Results: In comparison with Group C, patients in Group A and B manifested more stable vital signs with lower total dose of atropine and incidence rate of atropine poisoning and shorter cholinesterase reactivation time, while the cure rate was remarkably increased (p<0.05), and no significant differences were observed in atropinization time among three groups (p>0.05). Compared to Group B and C, total dose of atropine in Group A was significantly decreased with obvious excellence in hospitalization time, reduction of complications and increases in cure rates (p<0.05). Moreover, patients in Group A had the lowest mortality rate among three groups. Conclusion: In treatment of organophosphorus poisoning patients, HP and continuous intravenous infusion of atropine using micropump can elevate the survival rate, reduce the incidence of adverse reaction, shorten the reactivation time of cholinesterase and decrease the incidence rate of complications, which are superior to the traditional treatment method.
ESTHER : Jiang_2019_Saudi.J.Biol.Sci_26_2018
PubMedSearch : Jiang_2019_Saudi.J.Biol.Sci_26_2018
PubMedID: 31889787

Title : Compartmentalized biosynthesis of mycophenolic acid - Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
Author(s) : Zhang W , Du L , Qu Z , Zhang X , Li F , Li Z , Qi F , Wang X , Jiang Y , Men P , Sun J , Cao S , Geng C , Wan X , Liu C , Li S
Ref : Proc Natl Acad Sci U S A , 116 :13305 , 2019
Abstract : Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.
ESTHER : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedSearch : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedID: 31209052
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats - Wang_2019_Front.Pharmacol_10_1003
Author(s) : Wang K , Chen Q , Wu N , Li Y , Zhang R , Wang J , Gong D , Zou X , Liu C , Chen J
Ref : Front Pharmacol , 10 :1003 , 2019
Abstract : Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.
ESTHER : Wang_2019_Front.Pharmacol_10_1003
PubMedSearch : Wang_2019_Front.Pharmacol_10_1003
PubMedID: 31551793

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

Title : Highly Selective Synthesis of Monolaurin via Enzymatic Transesterification under Batch and Continuous Flow Conditions - Chen_2019_J.Oleo.Sci_68_1125
Author(s) : Chen F , Zhang G , Liu C , Zhang J , Zhao F , Xu B
Ref : J Oleo Sci , 68 :1125 , 2019
Abstract : This study aimed to investigate the highly selective production of monolaurin via enzymatic transesterification of methyl laurate and glycerol. It was determined that a binary solvent system (tert-butanol/iso-propanol, 20:80, wt./wt.) was suitable for the enzymatic production of monolaurin, especially in the continuous process. The highest mass fraction of monolaurin in the product mixture (80.8 wt.%) was achieved in a batch mode under the following conditions: a methyl laurate-to-glycerol molar ratio of 1:6, a substrate concentration (methyl laurate in the binary solvent) of 15 wt.%, an enzyme dosage of 6 wt.% of the amount of methyl laurate, and a reaction time of 1.5 h at 50 degC. Compared with the results under the batch conditions, a slightly higher yield of monolaurin (82.5 +/- 2.5 wt.%) was obtained in a continuous flow system at a flow rate of 0.1 mL/min, while the mass fraction of dilaurin in the product mixture was only 0.7 +/- 0.6 wt.%. In addition, the yield of monolaurin remained almost unchanged during the 18 tested days of the continuous experiment.
ESTHER : Chen_2019_J.Oleo.Sci_68_1125
PubMedSearch : Chen_2019_J.Oleo.Sci_68_1125
PubMedID: 31611516

Title : Structural and functional characterization of polyethylene terephthalate hydrolase from Ideonella sakaiensis - Liu_2019_Biochem.Biophys.Res.Commun_508_289
Author(s) : Liu C , Shi C , Zhu S , Wei R , Yin CC
Ref : Biochemical & Biophysical Research Communications , 508 :289 , 2019
Abstract : Polyethylene terephthalate (PET) hydrolase from Ideonella sakaiensis (IsPETase) can be used to degrade PET. In order to use IsPETase in industry, we studied the enzymatic activity of IsPETase in different conditions containing environmental and physicochemical factors commonly found in nature. We observed that salts and glycerol enhanced the enzymatic activity, while detergents and organic solvents reduced the enzymatic activity. IsPETase hydrolyzed p-nitrophenyl (p-NP) esters instead of naphthyl esters. To make IsPETase an enzyme capable of hydrolyzing naphthyl esters, site-directed mutagenesis was carried out based on the structural information provided by the crystal structure. We found that the IsPETase(S93M), IsPETase(W159F), and IsPETase(N241F) mutants can hydrolyze naphthyl esters. IsPETase engineering can direct researchers to use this alpha/beta-hydrolase protein scaffold to design enzymes that can hydrolyze a variety of polyesters.
ESTHER : Liu_2019_Biochem.Biophys.Res.Commun_508_289
PubMedSearch : Liu_2019_Biochem.Biophys.Res.Commun_508_289
PubMedID: 30502092
Gene_locus related to this paper: idesa-peth

Title : Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway - Luo_2019_Front.Pharmacol_10_395
Author(s) : Luo H , Xiang Y , Qu X , Liu H , Liu C , Li G , Han L , Qin X
Ref : Front Pharmacol , 10 :395 , 2019
Abstract : Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by impairments of cognitive function as a result of synaptic deficits and neuronal loss, is associated with inflammation. Apelin-13, a predominant neuropeptide with inhibiting effect on inflammation, has beneficial effects on cognition memory and neuronal damage. However, whether apelin-13 can protect neurons to ameliorate cognitive deficits in AD by inhibiting the inflammatory response remains largely unknown. To test this hypothesis, rats were intracerebroventricularly (ICV) injected with streptozotocin (3 mg/kg) alone or in combination with apelin-13 (2 mug). And tyrosine receptor kinase B (TrkB) blocker K252a (200 nM) was administrated 10 min before apelin injection. Furthermore, cognitive performance was assessed by new object recognition (NOR) and Y-maze tests. Protein expression of apelin, APJ, microglial marker (IBA1), astroglia marker (GFAP), interleukin 1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB) in the hippocampus were examined by western blotting or immunohistochemistry. And the gene expression of IBA1, GFAP, IL-1beta, TNF-alpha, and SYP were detected by real-time quantitative polymerase chain reaction (PCR). Inflammatory disorder in the hippocampus was tested by hematoxylin and eosin (H&E) staining. The enzyme-linked immunosorbent assay (ELISA) was used to study the expression level of acetylcholine. And the activity of acetylcholinesterase was detected by Acetylcholinesterase Assay Kit. We observed that apelin/APJ signaling was downregulated in the hippocampus of rats administrated with STZ. Apelin-13 was found to significantly ameliorate STZ-induced AD-like phenotypes including congnitive deficit, cholinergic disfunction and the damage of neuron and synaptic plasticity. Moreover, apelin-13 inhibited microglia and astrocyte activation, reduced IL-1beta and TNF-alpha expression and hippocampal BDNF/TrkB expression deficit in AD rats. Finally, apelin-13-mediated effects were blocked by TrkB receptor antagonist K252a. These results suggest that apelin-13 upregulates BDNF/TrkB pathway against cognitive deficit in a STZ-induced rat model of sporadic AD by attenuating inflammation.
ESTHER : Luo_2019_Front.Pharmacol_10_395
PubMedSearch : Luo_2019_Front.Pharmacol_10_395
PubMedID: 31040784

Title : Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process - Wang_2019_Virol.Sin_34_59
Author(s) : Wang J , Wu F , Liu C , Dai W , Teng Y , Su W , Kong W , Gao F , Cai L , Hou A , Jiang C
Ref : Virol Sin , 34 :59 , 2019
Abstract : Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated. In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.
ESTHER : Wang_2019_Virol.Sin_34_59
PubMedSearch : Wang_2019_Virol.Sin_34_59
PubMedID: 30725320

Title : Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection - Zhang_2019_Antiviral.Res__104693
Author(s) : Zhang H , Liu J , Zhu X , Li X , Jin W , Chen H , Wu M , Li C , Liu C , JunqiNiu , Ding Y
Ref : Antiviral Res , :104693 , 2019
Abstract : BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224.
ESTHER : Zhang_2019_Antiviral.Res__104693
PubMedSearch : Zhang_2019_Antiviral.Res__104693
PubMedID: 31838002

Title : Should we pay attention to the aberrant nerve communication between the lingual and mylohyoid nerves? - Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
Author(s) : Zhan C , Yuan Z , Qu R , Zou L , He S , Li Z , Liu C , Xiao Z , Ouyang J , Dai J
Ref : Br J Oral Maxillofac Surg , 57 :317 , 2019
Abstract : An unusual communication between the lingual and mylohyoid nerves has been identified as one reason for incomplete mandibular anaesthesia, and for neuropathy. However, its anatomical features and function are poorly understood and its relations with neighbouring structures, which are valuable in reducing the side effects of surgical operations, have not been sufficiently described. The aim of this study, therefore, was to describe the communication between the nerves and to assess the implications for oral and maxillofacial surgery. We explored the communication between the mylohyoid nerves of 62 embalmed, and 16 fresh, hemifaces. The diameter, length of the communication, and other variables were measured, and the junctions with the two nerves microdissected. The nervous communications of fresh specimens and relative nerves were stained histochemically for acetylcholinesterase. Of the 62 embalmed specimens, 19 had a communication that pierced the mylohyoid muscle, and staining showed that this was a sensory nerve. Our results suggest that the sensory communication between the lingual and mylohyoid nerves pierces the mylohyoid muscle and connects these otherwise unrelated nerves, thereby contributing to the likelihood of operative side effects.
ESTHER : Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
PubMedSearch : Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
PubMedID: 30940405

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route - Jiang_2019_Int.J.Nanomedicine_14_9217
Author(s) : Jiang Y , Liu C , Zhai W , Zhuang N , Han T , Ding Z
Ref : Int J Nanomedicine , 14 :9217 , 2019
Abstract : Background: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer's disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems. Purpose: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration. Methods: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency. Results: Optimized HupA-NE had a particle size of 15.24+/-0.67 nm, polydispersity index (PDI) of 0.128+/-0.025, and zeta potential of -4.48+/-0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2+/-0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE. Conclusion: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.
ESTHER : Jiang_2019_Int.J.Nanomedicine_14_9217
PubMedSearch : Jiang_2019_Int.J.Nanomedicine_14_9217
PubMedID: 31819426

Title : Laboratory and field evaluation of the aphidicidal activity of moso bamboo (Phyllostachys pubescens) leaf extract and identification of the active components - Gao_2019_Pest.Manag.Sci_75_3167
Author(s) : Gao Q , Shi Y , Liao M , Xiao J , Li X , Zhou L , Liu C , Liu P , Cao H
Ref : Pest Manag Sci , 75 :3167 , 2019
Abstract : BACKGROUND: Botanical pesticides increasingly play important roles in the control of agricultural pests. In this study, the aphidicidal effect of moso bamboo (Phyllostachys pubescens) extract against mustard aphid was confirmed, the main active compounds identified, and aphidicidal mechanism of the most active compound established. RESULTS: When the treatment concentration was 10.0 g L(-1) , the corrected mortality of bamboo leaf extract (BE) was 53.22 +/- 5.20% and the petroleum ether component of bamboo leaf extract (PE) reached 82.76 +/- 4.50%, which also showed a synergistic effect with imidacloprid. Four flavonoids were identified as the main active components in the BE via activity tracking and phytochemical method. Isoorientin had an LC50 of 313.22 mg L(-1) , and affected the activities of acetylcholinesterase and peroxidase significantly, revealing the possible aphidicidal mechanism. When the treatment of 11.1% PE.imidacloprid was 200 mL, the control effect was 99.07%, which was better than that observed with 10% of imidacloprid or 0.5% of matrine. CONCLUSIONS: These data provide a better understanding of the aphidicidal activity and aphidicidal mechanism of moso bamboo leaf extract and the most active compound, isoorientin. This will help in developing a more effective botanical aphicide. (c) 2019 Society of Chemical Industry.
ESTHER : Gao_2019_Pest.Manag.Sci_75_3167
PubMedSearch : Gao_2019_Pest.Manag.Sci_75_3167
PubMedID: 30941856

Title : Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos - Guo_2018_Environ.Pollut_241_1018
Author(s) : Guo X , Zhang S , Lu S , Zheng B , Xie P , Chen J , Li G , Liu C , Wu Q , Cheng H , Sang N
Ref : Environ Pollut , 241 :1018 , 2018
Abstract : Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6mg/L PFDoA for 120h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system.
ESTHER : Guo_2018_Environ.Pollut_241_1018
PubMedSearch : Guo_2018_Environ.Pollut_241_1018
PubMedID: 30029309

Title : Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply - Liu_2018_Nat.Commun_9_1310
Author(s) : Liu C , Han T , Stachura DL , Wang H , Vaisman BL , Kim J , Klemke RL , Remaley AT , Rana TM , Traver D , Miller YI
Ref : Nat Commun , 9 :1310 , 2018
Abstract : Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis.
ESTHER : Liu_2018_Nat.Commun_9_1310
PubMedSearch : Liu_2018_Nat.Commun_9_1310
PubMedID: 29615667

Title : The Rosa genome provides new insights into the domestication of modern roses - Raymond_2018_Nat.Genet_50_772
Author(s) : Raymond O , Gouzy J , Just J , Badouin H , Verdenaud M , Lemainque A , Vergne P , Moja S , Choisne N , Pont C , Carrere S , Caissard JC , Couloux A , Cottret L , Aury JM , Szecsi J , Latrasse D , Madoui MA , Francois L , Fu X , Yang SH , Dubois A , Piola F , Larrieu A , Perez M , Labadie K , Perrier L , Govetto B , Labrousse Y , Villand P , Bardoux C , Boltz V , Lopez-Roques C , Heitzler P , Vernoux T , Vandenbussche M , Quesneville H , Boualem A , Bendahmane A , Liu C , Le Bris M , Salse J , Baudino S , Benhamed M , Wincker P , Bendahmane M
Ref : Nat Genet , 50 :772 , 2018
Abstract : Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species. Genomic segments of Chinese ancestry identified new candidate genes for recurrent blooming. Reconstructing regulatory and secondary metabolism pathways allowed us to propose a model of interconnected regulation of scent and flower color. This genome provides a foundation for understanding the mechanisms governing rose traits and should accelerate improvement in roses, Rosaceae and ornamentals.
ESTHER : Raymond_2018_Nat.Genet_50_772
PubMedSearch : Raymond_2018_Nat.Genet_50_772
PubMedID: 29713014
Gene_locus related to this paper: rosch-a0a2p6p237 , rosch-a0a2p6r1h5 , rosch-a0a2p6saq0 , rosch-a0a2p6sap4 , rosch-a0a2p6san0 , rosch-a0a2p6san7 , rosch-a0a2p6rkg2 , rosch-a0a2p6pxu1 , rosch-a0a2p6s382 , rosch-a0a2p6s367 , rosch-a0a2p6q0b7 , rosch-a0a2p6pi87 , rosch-a0a2p6p278 , rosch-a0a2p6s545 , rosch-a0a2p6r6x5 , rosch-a0a2p6rqc2

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Neuroprotective effects of cordycepin inhibit Abeta-induced apoptosis in hippocampal neurons - Song_2018_Neurotoxicol_68_73
Author(s) : Song H , Huang LP , Li Y , Liu C , Wang S , Meng W , Wei S , Liu XP , Gong Y , Yao LH
Ref : Neurotoxicology , 68 :73 , 2018
Abstract : In Alzheimer's disease (AD), beta-amyloid (Abeta) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Abeta-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Abeta-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Abeta25-35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Abeta25-35-induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis. Cordycepin inhibits ROS production, elevated levels of Ca(2+) induced by Abeta25-35, and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis. In addition, it decreases the increased p-Tau expression that plays a key role in the initiation of the AD. Results showed that the anti-apoptotic effects of cordycepin are partially dependent on the activation of adenosine A1 receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders, such as AD.
ESTHER : Song_2018_Neurotoxicol_68_73
PubMedSearch : Song_2018_Neurotoxicol_68_73
PubMedID: 30031108

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 : Genome Sequencing of Streptomyces atratus SCSIOZH16 and Activation Production of Nocardamine via Metabolic Engineering - Li_2018_Front.Microbiol_9_1269
Author(s) : Li Y , Zhang C , Liu C , Ju J , Ma J
Ref : Front Microbiol , 9 :1269 , 2018
Abstract : The Actinomycetes are metabolically flexible microorganisms capable of producing a wide range of interesting compounds, including but by no means limited to, siderophores which have high affinity for ferric iron. In this study, we report the complete genome sequence of marine-derived Streptomyces atratus ZH16 and the activation of an embedded siderophore gene cluster via the application of metabolic engineering methods. The S. atratus ZH16 genome reveals that this strain has the potential to produce 26 categories of natural products (NPs) barring the ilamycins. Our activation studies revealed S. atratus SCSIO ZH16 to be a promising source of the production of nocardamine-type (desferrioxamine) compounds which are important in treating acute iron intoxication and performing ecological remediation. We conclude that metabolic engineering provides a highly effective strategy by which to discover drug-like compounds and new NPs in the genomic era.
ESTHER : Li_2018_Front.Microbiol_9_1269
PubMedSearch : Li_2018_Front.Microbiol_9_1269
PubMedID: 29963027
Gene_locus related to this paper: strar-a0a2z5jcs5

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

Title : Biopanning of allergens from wasp sting patients - Chai_2018_Biosci.Rep_38_
Author(s) : Chai L , Yang X , Liu M , Liu C , Han L , Guo H , Li C , Sun Y , Li X , Xiao M , Fang Z
Ref : Bioscience Reports , 38 : , 2018
Abstract : OBJECTIVE: Wasp venom is a potentially important natural drug, but it can cause hypersensitivity reactions. The purpose of the present study was to systematically study the epitopes of wasp venom. METHODS: Using a random 12-peptide phage library, we performed antibody-binding epitope panning on ten serum samples from wasp sting victims at 3 h and 4 days after the sting. The panning epitopes were identified by high-throughput sequencing and matched with wasp venom proteins by BLAST. The panned antibody-binding epitopes were verified by ELISA. RESULTS: A total of 35 specific potential wasp venom epitopes in 4 days were identified. Amongst them, twelve peptide epitopes were matched with nine wasp venom proteins, namely, vitellogenin precursor, hexamerin 70b precursor, venom carboxylesterase-6 precursor, MRJP5, major royal jelly protein 8 precursor, venom acid phosphatase Acph-1 precursor, phospholipase A2, venom serine protease 34 precursor, and major royal jelly protein 9 precursor. The changes in serum IgM antibodies induced by wasp venom were confirmed by ELISA based on the 12 peptide epitopes. CONCLUSION: The nine wasp venom proteins are potential allergens, which should be excluded or modified in the potential biomedical applications of wasp venom.
ESTHER : Chai_2018_Biosci.Rep_38_
PubMedSearch : Chai_2018_Biosci.Rep_38_
PubMedID: 30249752

Title : A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study - Zhou_2018_Eur.J.Hum.Genet_26_838
Author(s) : Zhou D , Zhang D , Sun X , Li Z , Ni Y , Shan Z , Li H , Liu C , Zhang S , Liu Y , Zheng R , Pan F , Zhu Y , Shi Y , Lai M
Ref : Eur J Hum Genet , 26 :838 , 2018
Abstract : Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (Pcombined = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.
ESTHER : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedSearch : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedID: 29476167

Title : Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development - You_2018_Int.J.Mol.Sci_19_
Author(s) : You H , Liu C , Du X , Nawaratna S , Rivera V , Harvie M , Jones M , McManus DP
Ref : Int J Mol Sci , 19 : , 2018
Abstract : To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNgamma in splenic CD4(+) T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.
ESTHER : You_2018_Int.J.Mol.Sci_19_
PubMedSearch : You_2018_Int.J.Mol.Sci_19_
PubMedID: 30115897

Title : Prunella vulgaris L., an Edible and Medicinal Plant, Attenuates Scopolamine-Induced Memory Impairment in Rats - Qu_2017_J.Agric.Food.Chem_65_291
Author(s) : Qu Z , Zhang J , Yang H , Gao J , Chen H , Liu C , Gao W
Ref : Journal of Agricultural and Food Chemistry , 65 :291 , 2017
Abstract : Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-kappaB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.
ESTHER : Qu_2017_J.Agric.Food.Chem_65_291
PubMedSearch : Qu_2017_J.Agric.Food.Chem_65_291
PubMedID: 28001065

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

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

Title : Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells - Yang_2017_Mol.Neurobiol_54_788
Author(s) : Yang H , Liu C , Chen B , An J , Zhang R , Zhang Q , Zhao J , He B , Hao DJ
Ref : Molecular Neurobiology , 54 :788 , 2017
Abstract : Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings.
ESTHER : Yang_2017_Mol.Neurobiol_54_788
PubMedSearch : Yang_2017_Mol.Neurobiol_54_788
PubMedID: 27566610

Title : Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest - Cheng_2017_Nat.Ecol.Evol_1_1747
Author(s) : Cheng T , Wu J , Wu Y , Chilukuri RV , Huang L , Yamamoto K , Feng L , Li W , Chen Z , Guo H , Liu J , Li S , Wang X , Peng L , Liu D , Guo Y , Fu B , Li Z , Liu C , Chen Y , Tomar A , Hilliou F , Montagne N , Jacquin-Joly E , d'Alencon E , Seth RK , Bhatnagar RK , Jouraku A , Shiotsuki T , Kadono-Okuda K , Promboon A , Smagghe G , Arunkumar KP , Kishino H , Goldsmith MR , Feng Q , Xia Q , Mita K
Ref : Nat Ecol Evol , 1 :1747 , 2017
Abstract : The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
ESTHER : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedSearch : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedID: 28963452

Title : A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism - Liu_2017_Int.J.Oncol_50_1792
Author(s) : Liu W , Zhang B , Hu Q , Qin Y , Xu W , Shi S , Liang C , Meng Q , Xiang J , Liang D , Ji S , Liu J , Hu P , Liu L , Liu C , Long J , Ni Q , Yu X , Xu J
Ref : Int J Oncol , 50 :1792 , 2017
Abstract : N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1alpha level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1alpha, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.
ESTHER : Liu_2017_Int.J.Oncol_50_1792
PubMedSearch : Liu_2017_Int.J.Oncol_50_1792
PubMedID: 28350132

Title : Hormone-sensitive lipase deficiency alters gene expression and cholesterol content of mouse testis - Wang_2017_Reproduction_153_175
Author(s) : Wang F , Chen Z , Ren X , Tian Y , Liu C , Jin P , Li Z , Zhang F , Zhu B
Ref : Reproduction , 153 :175 , 2017
Abstract : Hormone-sensitive lipase-knockout (HSL-/-) mice exhibit azoospermia for unclear reasons. To explore the basis of sterility, we performed the following three experiments. First, HSL protein distribution in the testis was determined. Next, transcriptome analyses were performed on the testes of three experimental groups. Finally, the fatty acid and cholesterol levels in the testes with three different genotypes studied were determined. We found that the HSL protein was present from spermatocyte cells to mature sperm acrosomes in wild-type (HSL+/+) testes. Spermiogenesis ceased at the elongation phase of HSL-/- testes. Transcriptome analysis indicated that genes involved in lipid metabolism, cell membrane, reproduction and inflammation-related processes were disordered in HSL-/- testes. The cholesterol content was significantly higher in HSL-/- than that in HSL+/+ testis. Therefore, gene expression and cholesterol ester content differed in HSL-/- testes compared to other testes, which may explain the sterility of male HSL-/- mice.
ESTHER : Wang_2017_Reproduction_153_175
PubMedSearch : Wang_2017_Reproduction_153_175
PubMedID: 27920259

Title : Extraction and in vitro screening of potential acetylcholinesterase inhibitors from the leaves of Panax japonicus - Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
Author(s) : Li S , Liu C , Zhang Y
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1061-1062 :139 , 2017
Abstract : Ultrafiltration liquid chromatography-mass spectrometry (UFLC-MS) is an efficient method that can be applied to rapidly screen and identify ligands for acetylcholinesterase (AChE) from the leaves of Panax japonicus. Using this method, we identified 5 major compounds, chikusetsusaponins V, Ib, IV, IVa, and IVa ethyl ester, as potent AChE inhibitors, which were assessed for anti-Alzheimer disease activity using the PC12 cell model. A continuous online method, which consisted of microwave-assisted extraction, a solvent concentration tank, and centrifugal partition chromatography (MAE-SCT-CPC), was newly developed for scaled up production of these compounds with high purity and efficiency. The bioactivities of the compounds separated were assessed by the PC12 cell model. This novel approach of using UFLC-MS coupled with MAE-SCT-CPC and a PC12 cell model could be applied to efficiently screen, extract, and separate AChE inhibitors from complex samples, and could serve as an important platform for the large-scale production of functional food and nutraceutical ingredients.
ESTHER : Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
PubMedSearch : Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
PubMedID: 28734162

Title : Acetylcholinesterase and Nicotinic Acetylcholine Receptors in Schistosomes and Other Parasitic Helminths - You_2017_Molecules_22_
Author(s) : You H , Liu C , Du X , McManus DP
Ref : Molecules , 22 : , 2017
Abstract : Schistosomiasis, which is caused by helminth trematode blood flukes of the genus Schistosoma, is a serious health and economic problem in tropical areas, and the second most prevalent parasitic disease after malaria. Currently, there is no effective vaccine available and treatment is entirely dependent on a single drug, praziquantel (PZQ), raising a significant potential public health threat due to the emergence of PZQ drug resistance. It is thus urgent and necessary to explore novel therapeutic targets for the treatment of schistosomiasis. Previous studies demonstrated that acetylcholinesterase (AChE) and nicotinic acetylcholine receptors (nAChRs) play important roles in the schistosome nervous system and ion channels, both of which are targeted by a number of currently approved and marketed anthelminthic drugs. To improve understanding of the functions of the cholinergic system in schistosomes, this article reviews previous studies on AChE and nAChRs in schistosomes and other helminths and discusses their potential as suitable targets for vaccine development and drug design against schistosomiasis.
ESTHER : You_2017_Molecules_22_
PubMedSearch : You_2017_Molecules_22_
PubMedID: 28906438

Title : Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients - Liu_2017_PLoS.One_12_e0169939
Author(s) : Liu C , Gaudet D , Miller YI
Ref : PLoS ONE , 12 :e0169939 , 2017
Abstract : Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Apolipoprotein C-II (APOC2) is an obligatory cofactor for lipoprotein lipase (LPL), the major enzyme catalyzing plasma triglyceride hydrolysis. We have created an apoc2 knockout zebrafish model, which mimics the familial chylomicronemia syndrome (FCS) in human patients with a defect in the APOC2 or LPL gene. In this study, we measured plasma levels of free cholesterol (FC) and cholesterol esters (CE) and found that apoc2 mutant zebrafish have a significantly higher FC to CE ratio (FC/CE), when compared to the wild type. Feeding apoc2 mutant zebrafish a low-fat diet reduced triglyceride levels but not the FC/CE ratio. In situ hybridization and qPCR results demonstrated that the hepatic expression of lecithin-cholesterol acyltransferase (lcat), the enzyme responsible for esterifying plasma FC to CE, and of apolipoprotein A-I, a major protein component of HDL, were dramatically decreased in apoc2 mutants. Furthermore, the FC/CE ratio was significantly increased in the whole plasma and in a chylomicron-depleted fraction of human FCS patients. The FCS plasma LCAT activity was significantly lower than that of healthy controls. In summary, this study, using a zebrafish model and human patient samples, reports for the first time the defect in plasma cholesterol esterification associated with LPL deficiency.
ESTHER : Liu_2017_PLoS.One_12_e0169939
PubMedSearch : Liu_2017_PLoS.One_12_e0169939
PubMedID: 28107429
Gene_locus related to this paper: danre-q6nyh6

Title : Unexpected extrapyramidal symptoms and pulmonary aspergillosis in exertional heatstroke with fulminant liver failure: a case report - Jiao_2017_J.Med.Case.Rep_11_37
Author(s) : Jiao J , Zhou F , Kang H , Liu C , Yang M , Hu J
Ref : J Med Case Rep , 11 :37 , 2017
Abstract : BACKGROUND: Exertional heatstroke is a life-threatening condition with high mortality because of the rapid progress of multiple organ dysfunction syndrome even if aggressive treatments are initiated rapidly. Mild to moderate hepatic injury is common in exertional heatstroke, while fulminant liver failure is rare. Extrapyramidal symptoms and pulmonary aspergillosis secondary to liver failure induced by exertional heatstroke have never been reported in prior cases. CASE PRESENTATION: A 25-year-old Han Chinese man presented with exertional heatstroke with fulminant liver failure, subsequent pulmonary aspergillosis, and extrapyramidal symptoms. Moreover, he also presented with coma, rhabdomyolysis, acute kidney injury, and disseminated intravascular coagulation. He recovered under conservative treatment including therapeutic plasma exchange plus continuous veno-venous hemofiltration, fluid resuscitation, antibiotics, and other support therapy.
CONCLUSIONS: Therapeutic plasma exchange plus continuous veno-venous hemofiltration could be effective for patients with heatstroke who suffer liver failure and other organ failure. Patients with liver failure are at high risk for pulmonary aspergillosis. Movement disorder in these patients might be extrapyramidal symptoms induced by consistent low level of cholinesterase resulted from hepatic injury besides brain injury.
ESTHER : Jiao_2017_J.Med.Case.Rep_11_37
PubMedSearch : Jiao_2017_J.Med.Case.Rep_11_37
PubMedID: 28183359

Title : A microfluidic paper-based device to assess acetylcholinesterase activity - Liu_2017_Electrophoresis_38_1002
Author(s) : Liu C , Gomez FA
Ref : Electrophoresis , 38 :1002 , 2017
Abstract : Neurotransmitters play key roles in cell-to-cell communication. These chemical messengers are involved in many functional processes, including growth, reproduction, memory, and behavior. In this communication, we describe a novel microfluidic paper-based analytical device (muPAD) to detect acetylcholinesterase (AChE) activity and inhibitor screening through a colorimetric analysis. The muPAD is easily fabricated via a wax printing process whereby wax is deposited onto the surface of chromatographic paper, and heated to create a hydrophobic barrier. Separate solutions of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and samples containing AChE and acetylthiocholine iodide (ATC) (or cysteine, Cys), respectively, are directly spotted onto the muPAD. DTNB and AChE/ATC (or Cys) flow towards each other where a reaction occurs to form the yellow colored 2-nitro-5-thiobenzoic acid anion (TNB2- ). The device is dried, scanned, and analyzed yielding a linear range of average inverse yellow intensities versus substrate concentration. An IC50 value (0.045 nM) with a known inhibitor, neostigmine bromide (NB), is obtained on the device. muPADs are low cost and easy to fabricate and have great potential to quantify neurotransmitter activity.
ESTHER : Liu_2017_Electrophoresis_38_1002
PubMedSearch : Liu_2017_Electrophoresis_38_1002
PubMedID: 28008633

Title : Parental transfer of microcystin-LR induced transgenerational effects of developmental neurotoxicity in zebrafish offspring - Wu_2017_Environ.Pollut_231_471
Author(s) : Wu Q , Yan W , Cheng H , Liu C , Hung TC , Guo X , Li G
Ref : Environ Pollut , 231 :471 , 2017
Abstract : Microcystin-LR (MCLR) has been reported to cause developmental neurotoxicity in zebrafish, but there are few studies on the mechanisms of MCLR-induced transgenerational effects of developmental neurotoxicity. In this study, zebrafish were exposed to 0, 1, 5, and 25 mug/L MCLR for 60 days. The F1 zebrafish embryos from the above-mentioned parents were collected and incubated in clean water for 120 h for hatching. After examining the parental zebrafish and F1 embryos, MCLR was detected in the gonad of adults and F1 embryos, indicating MCLR could potentially be transferred from parents to offspring. The larvae also showed a serious hypoactivity. The contents of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were further detected, but only the first three neurotransmitters showed significant reduction in the 5 and 25 mug/L MCLR parental exposure groups. In addition, the acetylcholinesterase (AChE) activity was remarkably decreased in MCLR parental exposure groups, while the expression levels of manf, bdnf, ache, htr1ab, htr1b, htr2a, htr1aa, htr5a, DAT, TH1 and TH2 genes coincided with the decreased content of neurotransmitters (dopamine, DOPAC and serotonin) and the activity of AChE. Neuronal development related genes, alpha1-tubulin, syn2a, mbp, gfap, elavl3, shha and gap43 were also measured, but gap43 was the gene only up-regulated. Our results demonstrated MCLR could be transferred to offspring, and subsequently induce developmental neurotoxicity in F1 zebrafish larvae by disturbing the neurotransmitter systems and neuronal development.
ESTHER : Wu_2017_Environ.Pollut_231_471
PubMedSearch : Wu_2017_Environ.Pollut_231_471
PubMedID: 28837927

Title : Tris(1,3-dichloro-2-propyl) phosphate disrupts axonal growth, cholinergic system and motor behavior in early life zebrafish - Cheng_2017_Aquat.Toxicol_192_7
Author(s) : Cheng R , Jia Y , Dai L , Liu C , Wang J , Li G , Yu L
Ref : Aquat Toxicol , 192 :7 , 2017
Abstract : Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) could have neurotoxic effects and alter motor behaviors in zebrafish (Danio rerio) larvae, however, the underlying mechanisms are still unknown. In this study, zebrafish embryos were subjected to waterborne exposure of TDCIPP at 100, 300, 600, 900mug/L from 2 to 120-h post-fertilization (hpf). Behavioral measurements indicate that TDCIPP exposure significantly elevated spontaneous movement, and altered swimming behavior response of larvae to both light and dark stimulation. Interestingly, in accordance with these motor effects, TDCIPP significantly decreased expression of the neuron-specific GFP in transgenic (HuC-GFP) zebrafish larvae as well as decreased expression of the neural marker genes elavl3 and ngn1, inhibited the axonal growth of the secondary motoneurons and altered the expressions of axon-related genes (alpha1-tubulin, shha and netrin2) in zebrafish larvae. Furthermore, TDCIPP exposure at 900mug/L significantly increased the activity of acetylcholinesterase (AChE) enzyme, and decreased the total acetylcholine (ACh) concentration. Our data indicate that the alteration in motor neuron and inhibition of cholinergic system could together lead to the TDCIPP induced motor behavior alterations in zebrafish larvae.
ESTHER : Cheng_2017_Aquat.Toxicol_192_7
PubMedSearch : Cheng_2017_Aquat.Toxicol_192_7
PubMedID: 28898785

Title : Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice - Liu_2016_Brain.Res_1631_137
Author(s) : Liu C , Wu Y , Zha S , Liu M , Wang Y , Yang G , Ma K , Fei Y , Zhang Y , Hu X , Yang W , Qian Y
Ref : Brain Research , 1631 :137 , 2016
Abstract : Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by beta-amyloid protein (Abeta) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan IIA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus. Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD.
ESTHER : Liu_2016_Brain.Res_1631_137
PubMedSearch : Liu_2016_Brain.Res_1631_137
PubMedID: 26656068

Title : Clinical, biochemical and molecular analysis of two infants with familial chylomicronemia syndrome - Zhang_2016_Lipids.Health.Dis_15_88
Author(s) : Zhang Y , Zhou J , Zheng W , Lan Z , Huang Z , Yang Q , Liu C , Gao R
Ref : Lipids Health Dis , 15 :88 , 2016
Abstract : Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. It usually happens in late childhood and adolescence, which can have serious consequences if misdiagnosed or untreated. In the present study, we investigated two Chinese male babies (A and B), 30d and 48d in age, respectively, who have milky plasma. Clinical, biochemical, and radiological assessments were performed, while samples from the patients were referred for molecular diagnosis, including genetic testing and subsequent analysis of related genes. The fasting serum lipids of the two patients showed extreme lipid abnormalities. Through a low-lipid formula diet including skimmed milk and dietary advice, their plasma lipid levels were significantly lower and more stable at the time of hospital discharge. The genetic testing revealed compound heterozygote mutations in the lipoprotein lipase (LPL) gene for patient A and two known compound heterozygote LPL gene mutations for the patient B. FCS is the most dramatic example of severe hypertriglyceridemia. Early diagnosis and timely dietary intervention is very important for affected children.
ESTHER : Zhang_2016_Lipids.Health.Dis_15_88
PubMedSearch : Zhang_2016_Lipids.Health.Dis_15_88
PubMedID: 27153815
Gene_locus related to this paper: human-LPL

Title : Hypocholesterolaemic mechanism of bitter melon aqueous extracts via inhibition of pancreatic cholesterol esterase and reduction of cholesterol micellar solubility - Su_2016_Int.J.Food.Sci.Nutr_67_20
Author(s) : Su J , Wang H , Ma C , Liu C , Gao C , Nie R , Tanver Rahman MR
Ref : Int J Food Sci Nutr , 67 :20 , 2016
Abstract : This study investigated the hypocholesterolaemic effects of bitter melon aqueous extracts (BMAE) in vitro, the inhibitory effects of BMAE on pancreatic cholesterol esterase (CEase) and incorporation of cholesterol into micelles were investigated. BMAE decreased the in vitro micellar solubility of cholesterol in a dose-dependent manner. The conformation of CEase was investigated by means of circular dichroism (CD) and fluorescence. The result revealed the decrease of alpha-helix contents, increase of beta-sheet and exposure of aromatic amino acid residuals. The incorporation of cholesterol into micelles was inhibited by BMAE. A complex was observed by transmission electron microscopy (TEM), which indicated interaction between cholesterol and BMAE. The result revealed that BMAE can play a role in decreased intestinal cholesterol absorption via inhibition of CEase, and of micelle formation.
ESTHER : Su_2016_Int.J.Food.Sci.Nutr_67_20
PubMedSearch : Su_2016_Int.J.Food.Sci.Nutr_67_20
PubMedID: 26653879

Title : Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits - Jing_2016_Vet.Parasitol_223_165
Author(s) : Jing J , Liu C , Zhu SX , Jiang YM , Wu LC , Song HY , Shao YX
Ref : Vet Parasitol , 223 :165 , 2016
Abstract : To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000+/-20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits.
ESTHER : Jing_2016_Vet.Parasitol_223_165
PubMedSearch : Jing_2016_Vet.Parasitol_223_165
PubMedID: 27198796

Title : Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARx03B3\; Signaling - Yang_2016_Cell.Physiol.Biochem_38_696
Author(s) : Yang D , Chen H , Zeng X , Xie P , Wang X , Liu C
Ref : Cell Physiol Biochem , 38 :696 , 2016
Abstract : BACKGROUND/AIMS: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages.
METHODS: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined.
RESULTS: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARx03B3; expression and activity, respectively. Most importantly, the PPARx03B3;-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARx03B3; in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARx03B3; promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARx03B3; signaling in macrophages. CONCLUSION: These results demonstrate that macrophage CGI-58 enhances PPARx03B3; signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.
ESTHER : Yang_2016_Cell.Physiol.Biochem_38_696
PubMedSearch : Yang_2016_Cell.Physiol.Biochem_38_696
PubMedID: 26872126

Title : Functionalized photonic crystal for the sensing of Sarin agents - Yan_2016_Talanta_159_412
Author(s) : Yan C , Qi F , Li S , Xu J , Liu C , Meng Z , Qiu L , Xue M , Lu W , Yan Z
Ref : Talanta , 159 :412 , 2016
Abstract : The indiscriminate use of nerve agents by terrorist groups has attracted attention of the scientific communities toward the development of novel sensor technique for these deadly chemicals. A photonic crystal (PhC) hydrogel immobilized with butyrylcholinesterase (BuChE) was firstly prepared for the sensing of Sarin agents. Periodic polystyrene colloidal (240nm) array was embedded inside an acrylamide hydrogel, and then BuChE was immobilized inside the hydrogel matrix via condensation with 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3h)-one (DEPBT). It indicated that a total of 3.7 units of BuChE were immobilized onto the PhC hydrogel. The functionalized hydrogel recognized the Sarin agent and then shrunk, thus the diffraction of PhC hydrogel blue shifted significantly, and a limit of detection (LOD) of 10(-15)molL(-1) was achieved.
ESTHER : Yan_2016_Talanta_159_412
PubMedSearch : Yan_2016_Talanta_159_412
PubMedID: 27474325

Title : Lysinibacillus endophyticus sp. nov., an indole-3-acetic acid producing endophytic bacterium isolated from corn root (Zea mays cv. Xinken-5) - Yu_2016_Antonie.Van.Leeuwenhoek_109_1337
Author(s) : Yu J , Guan X , Liu C , Xiang W , Yu Z , Liu X , Wang G
Ref : Antonie Van Leeuwenhoek , 109 :1337 , 2016
Abstract : A Gram-positive, aerobic, motile, rod-shaped bacterium, designated strain C9(T), was isolated from surface sterilised corn roots (Zea mays cv. Xinken-5) and found to be able to produce indole-3-acetic acid. A polyphasic taxonomic study was carried out to determine the status of strain C9(T). The major cellular fatty acids were found to contain iso-C15:0, anteiso-C15:0 and anteiso-C17:0, and the only menaquinone was identified as MK-7. The polar lipid profile was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and an unidentified lipid. The cell wall peptidoglycan was found to be of the A4alpha L-Lys-D-Asp type and the whole cell sugar was found to be glucose. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain C9(T) belongs to the genus Lysinibacillus and is closely related to Lysinibacillus chungkukjangi NBRC 108948(T) (98.1 % similarity) and Lysinibacillus sinduriensis DSM 27595(T) (98.0 %). However, the low levels of DNA-DNA relatedness and some differential phenotypic characteristics allowed the strain to be distinguished from its close relatives. Therefore, it is concluded that strain C9(T) represents a novel species of the genus Lysinibacillus, for which the name Lysinibacillus endophyticus sp. nov. is proposed. The type strain is C9(T) (=DSM 100506(T) = CGMCC 1.15291(T)).
ESTHER : Yu_2016_Antonie.Van.Leeuwenhoek_109_1337
PubMedSearch : Yu_2016_Antonie.Van.Leeuwenhoek_109_1337
PubMedID: 27401830
Gene_locus related to this paper: 9baci-a0a494yt46

Title : Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice - Zhao_2016_Metab.Brain.Dis_31_1455
Author(s) : Zhao X , Liu C , Qi Y , Fang L , Luo J , Bi K , Jia Y
Ref : Metabolic Brain Disease , 31 :1455 , 2016
Abstract : Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer's disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.
ESTHER : Zhao_2016_Metab.Brain.Dis_31_1455
PubMedSearch : Zhao_2016_Metab.Brain.Dis_31_1455
PubMedID: 27444169

Title : Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo - Wu_2016_Environ.Pollut_213_793
Author(s) : Wu Q , Yan W , Liu C , Li L , Yu L , Zhao S , Li G
Ref : Environ Pollut , 213 :793 , 2016
Abstract : Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnalpha7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. a1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons.
ESTHER : Wu_2016_Environ.Pollut_213_793
PubMedSearch : Wu_2016_Environ.Pollut_213_793
PubMedID: 27038211

Title : Expression and characterization of a lipase-related protein in the malpighian tubules of the Chinese oak silkworm, Antheraea pernyi - Wang_2016_Bull.Entomol.Res_106_615
Author(s) : Wang L , Li J , Zhao X , Qian C , Wei G , Zhu B , Liu C
Ref : Bull Entomol Res , 106 :615 , 2016
Abstract : Lipases are ubiquitous enzymes in nature, which play a crucial role in fat metabolism by catalyzing the hydrolysis of triacylglycerol to free fatty acids and glycerol. However, reports concerning insect lipase are rare. In this study, we studied the expression and activity of a lipase-related protein from Antheraea pernyi (ApLRP). Recombinant ApLRP was expressed in Escherichia coli cells and used to raise rabbit anti-ApLRP polyclonal antibodies. ApLRP mRNA and protein expression were abundant in the midgut and malpighian tubules, respectively. After challenge with four different microorganisms (E. coli, Beauveria bassiana, Micrococcus luteus and nuclear polyhedrosis virus), the expression levels of ApLRP mRNA in midgut were inducted significantly compared with the control. The different pathogens induced different ApLRP gene expression patterns. The optimum temperature and pH for the enzyme's activity were 35 degrees C and 7.0, respectively. ApLRP activity was stimulated in the presence of Mg2+, Na+, Ca2+ and b-mercaptoethanol; while Zn2+, Cu2+ and Fe3+ inhibited its activity. Detergents such as SDS, glycerol and Tween-20 increased the lipase activity by 20-30%. Our results indicated that ApLRP might play an important role in the innate immunity of insects.
ESTHER : Wang_2016_Bull.Entomol.Res_106_615
PubMedSearch : Wang_2016_Bull.Entomol.Res_106_615
PubMedID: 27297450
Gene_locus related to this paper: antpe-a0a191xqw7

Title : Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases - London_2015_Biochemistry_54_528
Author(s) : London N , Farelli JD , Brown SD , Liu C , Huang H , Korczynska M , Al-Obaidi NF , Babbitt PC , Almo SC , Allen KN , Shoichet BK
Ref : Biochemistry , 54 :528 , 2015
Abstract : Enzyme function prediction remains an important open problem. Though structure-based modeling, such as metabolite docking, can identify substrates of some enzymes, it is ill-suited to reactions that progress through a covalent intermediate. Here we investigated the ability of covalent docking to identify substrates that pass through such a covalent intermediate, focusing particularly on the haloalkanoate dehalogenase superfamily. In retrospective assessments, covalent docking recapitulated substrate binding modes of known cocrystal structures and identified experimental substrates from a set of putative phosphorylated metabolites. In comparison, noncovalent docking of high-energy intermediates yielded nonproductive poses. In prospective predictions against seven enzymes, a substrate was identified for five. For one of those cases, a covalent docking prediction, confirmed by empirical screening, and combined with genomic context analysis, suggested the identity of the enzyme that catalyzes the orphan phosphatase reaction in the riboflavin biosynthetic pathway of Bacteroides.
ESTHER : London_2015_Biochemistry_54_528
PubMedSearch : London_2015_Biochemistry_54_528
PubMedID: 25513739

Title : Functional characterization of MpaG', the O-methyltransferase involved in the biosynthesis of mycophenolic acid - Zhang_2015_Chembiochem_16_565
Author(s) : Zhang W , Cao S , Qiu L , Qi F , Li Z , Yang Y , Huang S , Bai F , Liu C , Wan X , Li S
Ref : Chembiochem , 16 :565 , 2015
Abstract : Mycophenolic acid (MPA, 1) is a clinically important immunosuppressant. In this report, a gene cluster mpa' responsible for the biosynthesis of 1 was identified from Penicillium brevicompactum NRRL 864. The S-adenosyl-L-methionine-dependent (SAM-dependent) O-methyltransferase encoded by the mpaG' gene was functionally and kinetically characterized in vitro. MpaG' catalyzes the methylation of demethylmycophenolic acid (DMMPA, 6) to form 1. It also showed significant substrate flexibility by methylating two structural derivatives of 6 prepared by organic synthesis.
ESTHER : Zhang_2015_Chembiochem_16_565
PubMedSearch : Zhang_2015_Chembiochem_16_565
PubMedID: 25630520
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Neuroprotective Effect of Biatractylenolide Against Memory Impairment in D-Galactose-induced Aging Mice - Ji_2015_J.Mol.Neurosci_55_678
Author(s) : Ji ZH , Liu C , Zhao H , Yu XY
Ref : Journal of Molecular Neuroscience , 55 :678 , 2015
Abstract : Biatractylenolide, a sesquiterpene lactone, which exerted the neuroprotective effect against glutamate-induced excitotoxicity, was isolated from Atractylodis macrocephala in our previous study. In this study, we evaluated the neuroprotective effect of biatractylenolide against D-galactose-induced memory impairment and explored the potential mechanism of its action. The results showed that administration of biatractylenolide could significantly improve behavioral performance of D-galactose-treated mice in passive avoidance test and spatial learning-memory test. Administration of biatractylenolide could significantly decrease the formation of reactive oxygen species (ROS), decrease the activity of acetylcholinesterase (AChE), and increase the expression of synapsin I and protein kinase C (PKC) in D-galactose-treated mice. Our findings provide first evidence for the neuroprotective effect of biatractylenolide against D-galactose-induced memory impairment. The potential mechanisms underlying the neuroprotective effect of biatractylenolide in D-galactose-treated mice might be (i) attenuating oxidative damage via decreasing ROS formation, (ii) restoring cholinergic neurotransmission via decreasing AChE activity, and (iii) increasing the expression of memory-related proteins (synapsin I and PKC). Biatractylenolide may have therapeutic potential in aging-related memory impairment.
ESTHER : Ji_2015_J.Mol.Neurosci_55_678
PubMedSearch : Ji_2015_J.Mol.Neurosci_55_678
PubMedID: 25173400

Title : Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus - Yang_2015_J.Virol_89_9119
Author(s) : Yang Y , Liu C , Du L , Jiang S , Shi Z , Baric RS , Li F
Ref : J Virol , 89 :9119 , 2015
Abstract : To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts.
ESTHER : Yang_2015_J.Virol_89_9119
PubMedSearch : Yang_2015_J.Virol_89_9119
PubMedID: 26063432

Title : Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo - Zhang_2015_Neurosci_305_169
Author(s) : Zhang Q , Li J , Liu C , Song C , Li P , Yin F , Xiao Y , Jiang W , Zong A , Zhang X , Wang F
Ref : Neuroscience , 305 :169 , 2015
Abstract : In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Abeta)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Abeta25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Abeta1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Abeta peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease.
ESTHER : Zhang_2015_Neurosci_305_169
PubMedSearch : Zhang_2015_Neurosci_305_169
PubMedID: 26254241

Title : Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats - Wang_2015_Mol.Med.Rep_11_775
Author(s) : Wang F , Zeng X , Zhu Y , Ning D , Liu J , Liu C , Jia X , Zhu D
Ref : Mol Med Rep , 11 :775 , 2015
Abstract : A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a signi fi cant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2015_Mol.Med.Rep_11_775
PubMedSearch : Wang_2015_Mol.Med.Rep_11_775
PubMedID: 25371181

Title : Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice - Liu_2015_Evid.Based.Complement.Alternat.Med_2015_873243
Author(s) : Liu ZH , Chen HG , Wu PF , Yao Q , Cheng HK , Yu W , Liu C
Ref : Evid Based Complement Alternat Med , 2015 :873243 , 2015
Abstract : Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.
ESTHER : Liu_2015_Evid.Based.Complement.Alternat.Med_2015_873243
PubMedSearch : Liu_2015_Evid.Based.Complement.Alternat.Med_2015_873243
PubMedID: 26060502

Title : Molecular Basis of the General Base Catalysis of an alpha\/beta-Hydrolase Catalytic Triad - Sun_2014_J.Biol.Chem_289_15867
Author(s) : Sun Y , Yin S , Feng Y , Li J , Zhou J , Liu C , Zhu G , Guo Z
Ref : Journal of Biological Chemistry , 289 :15867 , 2014
Abstract : The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis.
ESTHER : Sun_2014_J.Biol.Chem_289_15867
PubMedSearch : Sun_2014_J.Biol.Chem_289_15867
PubMedID: 24737327
Gene_locus related to this paper: ecoli-YFBB

Title : Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women - Anderson_2014_J.Clin.Endocrinol.Metab_99_552
Author(s) : Anderson MS , Gendrano IN , Liu C , Jeffers S , Mahon C , Mehta A , Mostoller K , Zajic S , Morris D , Lee J , Stoch SA
Ref : J Clinical Endocrinology Metab , 99 :552 , 2014
Abstract : BACKGROUND: Odanacatib is a cathepsin K inhibitor in development for the treatment of osteoporosis. Evaluation of therapies to ensure that treatment effects are relevant regardless of sex is clinically important.
METHODS: In this double-blind, randomized controlled trial, older men (aged 50-75 years) and postmenopausal women (aged 45-75 years) were given odanacatib 50 mg once weekly or placebo for 4 weeks. Pharmacodynamic (PD) evaluation measured weighted average inhibition (WAI) of urine amino-terminal cross-linked telopeptide of type I collagen/creatinine (uNTx/Cr) after odanacatib administration. Pharmacokinetic (PK) parameter data were collected, and an analysis of sex as a factor in the PK/PD relationship was conducted. Adverse events were monitored. The hypotheses were that WAI of uNTx/Cr would be >40% (including >40% for the lower limit of the 90% confidence intervals [CIs]) for older men and postmenopausal women, that there would be no important differences in area under the curve from 0 to 168 hours (AUC0-168 h) between men and women, and that odanacatib would be safe and well tolerated.
RESULTS: A total of 44 subjects (32 men and 12 women) were randomized. The least squares mean WAI (uNTx/Cr) at week 4 was 42.8% (90% CI, 35.5%-49.3%) for men and 42.7% (90% CI, 30.3%-52.9%) for women; mean values were >40%, but lower bounds were <40% as prespecified in the primary hypothesis. The differences among men and women in PD parameters were not meaningful (0.1; 90% CI, -14.7 to 14.9). PK parameters for both groups were comparable (geometric mean ratio of AUC0-168 h, 0.90; 90% CI, 0.75-1.07). A PK/PD analysis found that the EC50 and maximum fractional inhibition were similar in male and female subjects. There were no notable or serious adverse events in this study.
CONCLUSIONS: Although the primary hypothesis was not met, there were no clinically meaningful differences in PD, PK, or PK/PD parameters between older men and postmenopausal women, supporting further research on odanacatib (50 mg once weekly) as a treatment for male osteoporosis. Odanacatib was generally well tolerated.
ESTHER : Anderson_2014_J.Clin.Endocrinol.Metab_99_552
PubMedSearch : Anderson_2014_J.Clin.Endocrinol.Metab_99_552
PubMedID: 24276460

Title : Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe - Liu_2014_Anal.Biochem_465C_172
Author(s) : Liu C , Shen Y , Yin P , Li L , Liu M , Zhang Y , Li H , Yao S
Ref : Analytical Biochemistry , 465C :172 , 2014
Abstract : A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl-1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity.
ESTHER : Liu_2014_Anal.Biochem_465C_172
PubMedSearch : Liu_2014_Anal.Biochem_465C_172
PubMedID: 25132563

Title : Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus - Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
Author(s) : Yang Y , Du L , Liu C , Wang L , Ma C , Tang J , Baric RS , Jiang S , Li F
Ref : Proc Natl Acad Sci U S A , 111 :12516 , 2014
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes approximately 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.
ESTHER : Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
PubMedSearch : Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
PubMedID: 25114257

Title : Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice - Miao_2014_Cell.Rep_7_223
Author(s) : Miao H , Ou J , Ma Y , Guo F , Yang Z , Wiggins M , Liu C , Song W , Han X , Wang M , Cao Q , Chung BH , Yang D , Liang H , Xue B , Shi H , Gan L , Yu L
Ref : Cell Rep , 7 :223 , 2014
Abstract : Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)gamma signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages.
ESTHER : Miao_2014_Cell.Rep_7_223
PubMedSearch : Miao_2014_Cell.Rep_7_223
PubMedID: 24703845

Title : A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides - Yi_2013_Anal.Chem_85_11464
Author(s) : Yi Y , Zhu G , Liu C , Huang Y , Zhang Y , Li H , Zhao J , Yao S
Ref : Analytical Chemistry , 85 :11464 , 2013
Abstract : Sensitive, rapid, and simple detection methods for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents are in urgent demand. A novel label-free silicon quantum dots (SiQDs)-based sensor was designed for ultrasensitive detection of pesticides. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce betaine and H2O2 which can quench the photoluminescence (PL) of SiQDs. Upon the addition of pesticides, the activity of AChE is inhibited, leading to the decrease of the generated H2O2, and hence the PL of SiQDs increases. By measuring the increase in SiQDs PL, the inhibition efficiency of pesticide to AChE activity was evaluated. It was found that the inhibition efficiency was linearly dependent on the logarithm of the pesticides concentration. Consequently, pesticides, such as carbaryl, parathion, diazinon, and phorate, were determined with the SiQDs PL sensing method. The lowest detectable concentrations for carbaryl, parathion, diazinon, and phorate reached 7.25 x 10(-9), 3.25 x 10(-8), 6.76 x 10(-8), and 1.9 x 10(-7) g/L, respectively, which were much lower than those previously reported. The detecting results of pesticide residues in food samples via this method agree well with those from high-performance liquid chromatography. The simple strategy reported here should be suitable for on-site pesticides detection, especially in combination with other portable platforms.
ESTHER : Yi_2013_Anal.Chem_85_11464
PubMedSearch : Yi_2013_Anal.Chem_85_11464
PubMedID: 24160846

Title : Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus - Chen_2013_J.Virol_87_10777
Author(s) : Chen Y , Rajashankar KR , Yang Y , Agnihothram SS , Liu C , Lin YL , Baric RS , Li F
Ref : J Virol , 87 :10777 , 2013
Abstract : The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans.
ESTHER : Chen_2013_J.Virol_87_10777
PubMedSearch : Chen_2013_J.Virol_87_10777
PubMedID: 23903833

Title : Baroreflex deficiency hampers angiogenesis after myocardial infarction via acetylcholine-alpha7-nicotinic ACh receptor in rats - Yu_2013_Eur.Heart.J_34_2412
Author(s) : Yu JG , Song SW , Shu H , Fan SJ , Liu AJ , Liu C , Guo W , Guo JM , Miao CY , Su DF
Ref : Eur Heart J , 34 :2412 , 2013
Abstract : AIMS: Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats. METHODS AND
RESULTS: Baroreflex sensitivity (BRS) was determined in conscious rats at 1 month after occlusion of the left anterior descending coronary artery. The survival time was significantly shorter in Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS >/=0.60 ms/mmHg. Sinoaortic denervation destroyed ABR, and decreased capillary density, regional blood flow and vascular endothelial growth factor (VEGF) concentration after MI. Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density, regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression of vesicular acetylcholine (ACh) transporter and alpha7-nicotinic ACh receptor (alpha7-nAChR). Angiogenesis after MI was significantly attenuated in alpha7-nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In cultured cardiac microvascular endothelial cells, ACh stimulated the expression of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner dependent upon alpha7-nAChR. CONCLUSION: Our results demonstrated that ABR deficiency could attenuate angiogenesis in ischaemic myocardium. These findings provide further mechanistic basis for enhancing baroreflex function in the treatment of MI.
ESTHER : Yu_2013_Eur.Heart.J_34_2412
PubMedSearch : Yu_2013_Eur.Heart.J_34_2412
PubMedID: 21849351

Title : [Progress in the structure and function of human carboxylesterase 1] - Tong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_1414
Author(s) : Tong J , Yi Y , Cao P , Liu C , Wang L , Lu Y
Ref : Sheng Wu Gong Cheng Xue Bao , 28 :1414 , 2012
Abstract : Human carboxylesterase 1 (HCE1), belonging to a multigene serine hydrolase family, is a major liver carboxylesterase responsible for the hydrolysis and metabolism of various xenobiotics. It also plays an important role in the transportation and metabolism of endogenous cholesterol ester and free fatty acid, and is closely associated with the pathogenesis of hepatocellular carcinoma. This review describes current developments in the molecular structure, the roles in drug, toxins and lipid metabolism, and the early diagnosis for hepatocellular carcinoma of human carboxylesterase 1.
ESTHER : Tong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_1414
PubMedSearch : Tong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_1414
PubMedID: 23593865

Title : Formation of cyclic structure at amino-terminus of glucagon-like peptide-1 exhibited a prolonged half-life in vivo - Cao_2012_Diabetes.Res.Clin.Pract_96_362
Author(s) : Cao Z , Li Y , Tang L , Xu W , Liu C , Zhang J , Gong M
Ref : Diabetes Res Clin Pract , 96 :362 , 2012
Abstract : The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the therapy of type 2 diabetes. However, the biological half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The stabilization of GLP-1 is critical for its utility in drug development. In this study, several GLP-1 mutants containing an N-terminal cyclic conformation were prepared in that the existence of cyclic conformation is predicted to increase the stabilization of GLP-1 in vivo. In this study, the binding capacities of the mutants were determined, the stabilities of the mutants were investigated and the physiological functions of the mutants were compared with those of wild-type GLP-1 in animals. The results indicated that the mutant (GLP1N8) remarkably raised the half-life in vivo; it also showed better glucose tolerance and higher HbA(1c) reduction than GLP-1 and exendin-4 in rodents. These results suggest that the GLP-1 analog (GLP1N8) which contains an N-terminal cyclic structure might be utilized as possible potent anti-diabetic drugs in the treatment of type 2 diabetes mellitus.
ESTHER : Cao_2012_Diabetes.Res.Clin.Pract_96_362
PubMedSearch : Cao_2012_Diabetes.Res.Clin.Pract_96_362
PubMedID: 22284602

Title : Molecular Cloning and Heterologous Expression of a True Lipase in Pichia pastoris Isolated via a Metagenomic Approach - Zheng_2012_J.Mol.Microbiol.Biotechnol_22_300
Author(s) : Zheng J , Liu L , Liu C , Jin Q
Ref : J Molecular Microbiology Biotechnol , 22 :300 , 2012
Abstract : Lipases are important enzymes for various biotechnological applications. By using functional expression screening, lipZ03, a novel lipase gene, was isolated from a soil-derived metagenomic library. The gene was supposed to encode a protein of 617 amino acids with a C-terminal targeting signal region and four potential N-linked glycosylation sites. The protein sequence shared a conserved GXSXG motif (X represents any amino acid residue) with other microbial lipases. Gene lipZ03 was expressed in Pichia pastoris and the molecular weight was estimated to be approximately 65 kDa by electrophoresis. The optimum reaction temperature and pH value for LipZ03 was 50C and 9.0, respectively. The enzyme was highly stable in the temperature range of 40-60C and under alkaline conditions (pH 8-10). Lipolytic activity was significantly enhanced by Ca(2+) and Mg(2+) ions, but dramatically inhibited by Cu(2+), Ni(2+) and Hg(2+) ions and EDTA. The purified enzyme preferentially hydrolyzed relatively long-chain triacylglycerols and was a true lipase rather than an esterase. Using a multi-stepwise methanol supply, the purified LipZ03 achieved a conversion yield of biodiesel production up to 74% after 36 h. Some interesting characteristics described here showed that the recombinant lipase may have potential to be a useful enzyme in industrial applications.
ESTHER : Zheng_2012_J.Mol.Microbiol.Biotechnol_22_300
PubMedSearch : Zheng_2012_J.Mol.Microbiol.Biotechnol_22_300
PubMedID: 23128414

Title : Switch of substrate specificity of hyperthermophilic acylaminoacyl peptidase by combination of protein and solvent engineering - Liu_2011_Protein.Cell_2_497
Author(s) : Liu C , Yang G , Wu L , Tian G , Zhang Z , Feng Y
Ref : Protein Cell , 2 :497 , 2011
Abstract : The inherent evolvability of promiscuous enzymes endows them with great potential to be artificially evolved for novel functions. Previously, we succeeded in transforming a promiscuous acylaminoacyl peptidase (apAAP) from the hyperthermophilic archaeon Aeropyrum pernix K1 into a specific carboxylesterase by making a single mutation. In order to fulfill the urgent requirement of thermostable lipolytic enzymes, in this paper we describe how the substrate preference of apAAP can be further changed from p-nitrophenyl caprylate (pNP-C8) to p-nitrophenyl laurate (pNP-C12) by protein and solvent engineering. After one round of directed evolution and subsequent saturation mutagenesis at selected residues in the active site, three variants with enhanced activity towards pNP-C12 were identified. Additionally, a combined mutant W474V/F488G/R526V/T560W was generated, which had the highest catalytic efficiency (k (cat)/K (m)) for pNP-C12, about 71-fold higher than the wild type. Its activity was further increased by solvent engineering, resulting in an activity enhancement of 280-fold compared with the wild type in the presence of 30% DMSO. The structural basis for the improved activity was studied by substrate docking and molecular dynamics simulation. It was revealed that W474V and F488G mutations caused a significant change in the geometry of the active center, which may facilitate binding and subsequent hydrolysis of bulky substrates. In conclusion, the combination of protein and solvent engineering may be an effective approach to improve the activities of promiscuous enzymes and could be used to create naturally rare hyperthermophilic enzymes.
ESTHER : Liu_2011_Protein.Cell_2_497
PubMedSearch : Liu_2011_Protein.Cell_2_497
PubMedID: 21748600

Title : Genome analyses of Icelandic strains of Sulfolobus islandicus, model organisms for genetic and virus-host interaction studies - Guo_2011_J.Bacteriol_193_1672
Author(s) : Guo L , Brugger K , Liu C , Shah SA , Zheng H , Zhu Y , Wang S , Lillestol RK , Chen L , Frank J , Prangishvili D , Paulin L , She Q , Huang L , Garrett RA
Ref : Journal of Bacteriology , 193 :1672 , 2011
Abstract : The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad host range for exceptional crenarchaeal viruses and conjugative plasmids and was selected for studying their life cycles and host interactions. The genomes of strains REY15A and HVE10/4 are 2.5 and 2.7 Mb, respectively, and each genome carries a variable region of 0.5 to 0.7 Mb where major differences in gene content and gene order occur. These include gene clusters involved in specific metabolic pathways, multiple copies of VapBC antitoxin-toxin gene pairs, and in strain HVE10/4, a 50-kb region rich in glycosyl transferase genes. The variable region also contains most of the insertion sequence (IS) elements and high proportions of the orphan orfB elements and SMN1 miniature inverted-repeat transposable elements (MITEs), as well as the clustered regular interspaced short palindromic repeat (CRISPR)-based immune systems, which are complex and diverse in both strains, consistent with them having been mobilized both intra- and intercellularly. In contrast, the remainder of the genomes are highly conserved in their protein and RNA gene syntenies, closely resembling those of other S. islandicus and Sulfolobus solfataricus strains, and they exhibit only minor remnants of a few genetic elements, mainly conjugative plasmids, which have integrated at a few tRNA genes lacking introns. This provides a possible rationale for the presence of the introns.
ESTHER : Guo_2011_J.Bacteriol_193_1672
PubMedSearch : Guo_2011_J.Bacteriol_193_1672
PubMedID: 21278296
Gene_locus related to this paper: sulir-f0nbu1 , sulso-APEH1 , sulso-APEH3 , sulso-dlhh , sulir-f0ndq1

Title : Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice - Duan_2010_Biomaterials_31_894
Author(s) : Duan Y , Liu J , Ma L , Li N , Liu H , Wang J , Zheng L , Liu C , Wang X , Zhao X , Yan J , Wang S , Wang H , Zhang X , Hong F
Ref : Biomaterials , 31 :894 , 2010
Abstract : In an effort to examine liver injury, immune response, and other physiological effects in mice caused by intragastric administration of nanoparticulate anatase titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte counts, hematological indices, biochemical parameters of liver functions, and histopathological changes in nanoparticulate titanium dioxide -treated mice. Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed a reduction in body weight, an increase in coefficients of the liver and histopathological changes in the liver. Specifically, in these nanoparticulate titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased, whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red (cell) distribution width, platelets, hematocrit, mean platelet volume of mice were increased. Furthermore, liver functions were also disrupted, as evidenced by the enhanced activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase of the total protein, and the reduction of ratio of albumin to globulin, the total bilirubin, triglycerides, and the total cholesterol levels. These results suggested that the liver function damage observed in mice treated with higher dose nanoparticulate titanium dioxide is likely associated with the damage of haemostasis blood system and immune response. However, low dose nanoparticulate anatase TiO(2) has little influences on haemostasis blood system and immune response in mice.
ESTHER : Duan_2010_Biomaterials_31_894
PubMedSearch : Duan_2010_Biomaterials_31_894
PubMedID: 19857890

Title : Complete genome sequence of Bifidobacterium longum JDM301 - Wei_2010_J.Bacteriol_192_4076
Author(s) : Wei YX , Zhang ZY , Liu C , Zhu YZ , Zhu YQ , Zheng H , Zhao GP , Wang S , Guo XK
Ref : Journal of Bacteriology , 192 :4076 , 2010
Abstract : Bifidobacteria, known as probiotic bacteria, are high-G+C Gram-positive bacteria which naturally inhabit the human gastrointestinal tract and vagina. Recently, we completely sequenced Bifidobacterium longum JDM301, which is a widely used Chinese commercial strain with several probiotic properties.
ESTHER : Wei_2010_J.Bacteriol_192_4076
PubMedSearch : Wei_2010_J.Bacteriol_192_4076
PubMedID: 20525832
Gene_locus related to this paper: biflj-d6zvy3 , biflo-BL0073 , biflo-BL0336 , biflo-BL0581 , biflo-BL0582 , biflo-BL1109 , biflo-BL1514 , biflo-PTRB , bifln-c2gtr2

Title : Complete genome sequence of Lactobacillus plantarum JDM1 - Zhang_2009_J.Bacteriol_191_5020
Author(s) : Zhang ZY , Liu C , Zhu YZ , Zhong Y , Zhu YQ , Zheng HJ , Zhao GP , Wang SY , Guo XK
Ref : Journal of Bacteriology , 191 :5020 , 2009
Abstract : Lactobacillus plantarum is a lactic acid bacterium (LAB) species commonly used as a probiotic. We have sequenced the genome of Lactobacillus plantarum JDM1, which is a Chinese commercial LAB with several probiotic functions, using a GS 20 system. We recommend that each commercial probiotic strain should undergo complete genome sequencing to ensure safety and stability.
ESTHER : Zhang_2009_J.Bacteriol_191_5020
PubMedSearch : Zhang_2009_J.Bacteriol_191_5020
PubMedID: 19465650
Gene_locus related to this paper: lacpl-EST1 , lacpl-EST2 , lacpl-HPO , lacpl-LP.0796 , lacpl-LP.0973 , lacpl-LP.1002 , lacpl-LP.1156 , lacpl-LP.1165 , lacpl-LP.1935 , lacpl-LP.2586 , lacpl-LP.2737 , lacpl-LP.2923 , lacpl-LP.3205 , lacpl-LP.3561 , lacpl-PEPI , lacpl-PEPR1 , lacpl-PEPR2 , lacpl-pepx , lacpl-tanL

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : An evolutionarily conserved presynaptic protein is required for isoflurane sensitivity in Caenorhabditis elegans - Metz_2007_Anesthesiology_107_971
Author(s) : Metz LB , Dasgupta N , Liu C , Hunt SJ , Crowder CM
Ref : Anesthesiology , 107 :971 , 2007
Abstract : BACKGROUND: Volatile general anesthetics inhibit neurotransmitter release by an unknown mechanism. A mutation in the presynaptic soluble NSF attachment protein receptor (SNARE) protein syntaxin 1A was previously shown to antagonize the anesthetic isoflurane in Caenorhabditis elegans. The mechanism underlying this antagonism may identify presynaptic anesthetic targets relevant to human anesthesia.
METHODS: Sensitivity to isoflurane concentrations in the human clinical range was measured in locomotion assays on adult C. elegans. Sensitivity to the acetylcholinesterase inhibitor aldicarb was used as an assay for the global level of C. elegans neurotransmitter release. Comparisons of isoflurane sensitivity (measured by the EC50) were made by simultaneous curve fitting and F test as described by Waud.
RESULTS: Expression of a truncated syntaxin fragment (residues 1-106) antagonized isoflurane sensitivity in C. elegans. This portion of syntaxin interacts with the presynaptic protein UNC-13, suggesting the hypothesis that truncated syntaxin binds to UNC-13 and antagonizes an inhibitory effect of isoflurane on UNC-13 function. Consistent with this hypothesis, overexpression of UNC-13 suppressed the isoflurane resistance of the truncated syntaxins, and unc-13 loss-of-function mutants were highly isoflurane resistant. Normal anesthetic sensitivity was restored by full-length UNC-13, by a shortened form of UNC-13 lacking a C2 domain, but not by a membrane-targeted UNC-13 that might bypass isoflurane inhibition of membrane translocation of UNC-13. Isoflurane was found to inhibit synaptic localization of UNC-13.
CONCLUSIONS: These data show that UNC-13, an evolutionarily conserved protein that promotes neurotransmitter release, is necessary for isoflurane sensitivity in C. elegans and suggest that its vertebrate homologs may be a component of the general anesthetic mechanism.
ESTHER : Metz_2007_Anesthesiology_107_971
PubMedSearch : Metz_2007_Anesthesiology_107_971
PubMedID: 18043066

Title : Simultaneous determination of ZT-1 and its metabolite Huperzine A in plasma by high-performance liquid chromatography with ultraviolet detection - Wei_2006_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_830_120
Author(s) : Wei G , Xiao S , Lu R , Liu C
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 830 :120 , 2006
Abstract : ZT-1 is a novel acetylcholinesterase (AChE) inhibitor. It is rapidly transformed to Huperzine A (Hup A) in vitro. A simple and rapid HPLC-UV method for the simultaneous determination of ZT-1 and its metabolite Hup A in plasma is described. The chromatographic separations were achieved on a C(18) ODS column (250 mm x 4.6 mm ID) using methanol-1 mmol/L ammonium acetate (70:30,v/v) as mobile phase. The flow rate was 0.7 mL/min, the detection wavelength was 313 nm and the column temperature was kept at 35 degrees C. Plasma samples were prepared as rapidly as possible and extracted immediately with 5 mL of chloroform:iso-propyl alcohol mixture (v/v, 9:1). The retention times of ZT-1 and Huperzine A (Hup A) were 18.7 and 14.4 min, respectively. The mean absolute recoveries of two analytes were >90%. Quantification limits were all 0.02 nmol/mL for ZT-1 and Hup A. This analytical method was reliable and convenient procedure that meets the criteria for the pharmacokinetic evaluation of ZT-1 on experimental animals.
ESTHER : Wei_2006_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_830_120
PubMedSearch : Wei_2006_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_830_120
PubMedID: 16288904

Title : Muscarinic M2 antagonists: anthranilamide derivatives with exceptional selectivity and in vivo activity - Clader_2004_Bioorg.Med.Chem_12_319
Author(s) : Clader JW , Billard W , Binch H, 3rd , Chen LY , Crosby G, Jr. , Duffy RA , Ford J , Kozlowski JA , Lachowicz JE , Li S , Liu C , McCombie SW , Vice S , Zhou G , Greenlee WJ
Ref : Bioorganic & Medicinal Chemistry , 12 :319 , 2004
Abstract : Anthranilamide analogues such as 23 are potent and highly selective muscarinic M2 antagonists that also show good oral bioavailability and in vivo activity.
ESTHER : Clader_2004_Bioorg.Med.Chem_12_319
PubMedSearch : Clader_2004_Bioorg.Med.Chem_12_319
PubMedID: 14723952

Title : Complete genome sequence of the apicomplexan, Cryptosporidium parvum - Abrahamsen_2004_Science_304_441
Author(s) : Abrahamsen MS , Templeton TJ , Enomoto S , Abrahante JE , Zhu G , Lancto CA , Deng M , Liu C , Widmer G , Tzipori S , Buck GA , Xu P , Bankier AT , Dear PH , Konfortov BA , Spriggs HF , Iyer L , Anantharaman V , Aravind L , Kapur V
Ref : Science , 304 :441 , 2004
Abstract : The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.
ESTHER : Abrahamsen_2004_Science_304_441
PubMedSearch : Abrahamsen_2004_Science_304_441
PubMedID: 15044751
Gene_locus related to this paper: crypv-q5cph4 , crypv-q5cpw0 , crypv-q5cpw1 , crypv-q5cq27 , crypv-q5cq66 , crypv-q5cq99 , crypv-q5cqb9 , crypv-q5cql0 , crypv-q5cqw5 , crypv-q5cr67 , crypv-q5cre8 , crypv-q5cs42 , crypv-q5cs81 , crypv-q5csw2 , crypv-q5cv08 , crypv-q5cv20

Title : [The profiles of free organophosphorus poisons in the bile of rabbits poisoned with different organophosphates] - Hou_2002_Zhonghua.Nei.Ke.Za.Zhi_41_795
Author(s) : Hou Y , Fu F , Liu S , Liu C , Sun Y , Qiu S
Ref : Zhonghua Nei Ke Za Zhi , 41 :795 , 2002
Abstract : OBJECTIVE: To study the process and significance of the distribution of free organophosphorus poisons (FOPs) in the blood and bile of rabbits poisoned with organophosphates. METHODS: Seventy two livid blue rabbits, male, 2 - 2.5 kg in weight, were divided into 3 groups: trichlorfon (556.0 mg/kg), monocrotophos (11.12 mg/kg) and methyl parathion (37.05 mg/kg). Each group consisted of 24 rabbits. All organophosphates were administered by subcutaneous route. Blood and bile were collected at time intervals of 1, 6, 24, 96 hours after administration. Blood cells and plasma were separated. Acetylcholinesterase (AChE) activity was measured with dithiobisnitrobenzoic acid (DTNB) enzyme kinetic method. The levels of FOPs in plasma and bile were determined with enzyme inhibited method. RESULTS: From 1 h to 96 h after administration negative correlation was found between time and FOP concentration in plasma (trichlorfon, r = -0.74, P < 0.01; monocrotophos, r = -0.55, P < 0.01; methyl parathion, r = -0.69, P < 0.01), and it was also found in bile between time and FOP concentration of trichlorfon (r = -0.97, P < 0.01) and monocrotophos (r = -0.71, P < 0.01). There is no linear correlation between time and concentration of methyl parathion in bile (r = -0.14, P > 0.05). When FOPs in plasma were not detectable at 96 h after administration, high levels of FOPs could still be detected in bile [trichlorfon (300.3 +/- 174.44) IU/L; monocrotophos (362.8 +/- 136.62) IU/L; methyl parathion (101.0 +/- 75.85) IU/L]. CONCLUSION: The bile is the most important store for FOPs in animal. FOPs can exist in bile over 96 h. The process of poisoning is a changing process of absorption, distribution and redistribution and it is different owing to various physical and chemical properties of organophosphates.
ESTHER : Hou_2002_Zhonghua.Nei.Ke.Za.Zhi_41_795
PubMedSearch : Hou_2002_Zhonghua.Nei.Ke.Za.Zhi_41_795
PubMedID: 12654229

Title : Muscarinic agonists and antagonists in the treatment of Alzheimer's disease - Greenlee_2001_Farmaco_56_247
Author(s) : Greenlee W , Clader J , Asberom T , McCombie S , Ford J , Guzik H , Kozlowski J , Li S , Liu C , Lowe D , Vice S , Zhao H , Zhou G , Billard W , Binch H , Crosby R , Duffy R , Lachowicz J , Coffin V , Watkins R , Ruperto V , Strader C , Taylor L , Cox K
Ref : Farmaco , 56 :247 , 2001
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.
ESTHER : Greenlee_2001_Farmaco_56_247
PubMedSearch : Greenlee_2001_Farmaco_56_247
PubMedID: 11421251

Title : Role of the M1 receptor in regulating circadian rhythms - Gillette_2001_Life.Sci_68(22-23)_2467
Author(s) : Gillette MU , Buchanan GF , Artinian L , Hamilton SE , Nathanson NM , Liu C
Ref : Life Sciences , 68 :2467 , 2001
Abstract : Cholinergic stimuli are potent regulators of the circadian clock in the hypothalamic suprachiasmatic nucleus (SCN). Using a brain slice model, we have found that the SCN clock is subject to muscarinic regulation, a sensitivity expressed only during the night of the clock's 24-h cycle. Pharmacological and signal transduction characteristics are compatible with a response mediated by an M1-like receptor. Molecular manipulation of muscarinic receptors will provide important insights as to the receptor subtype(s) regulating circadian rhythms.
ESTHER : Gillette_2001_Life.Sci_68(22-23)_2467
PubMedSearch : Gillette_2001_Life.Sci_68(22-23)_2467
PubMedID: 11392614

Title : [Effect of acupuncture on enzymology of motor neuron of anterior horn of experimental spinal cord injury in rats] - Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
Author(s) : Wu Y , Liu C , Chen Q
Ref : Zhongguo Zhong Xi Yi Jie He Za Zhi , 19 :740 , 1999
Abstract : OBJECTIVE To study the effect of acupuncture on enzymology of the motor neuron of anterior horn of injured spinal cord in rats METHODS Chemical staining method was used to quantitatively analyze the acetylcholinesterase ACHE succinate dehydrogenase SDH acid phosphatase ACP changes in motor neuron of anterior horn of spinal cord simultaneously and auto-analysis photogram apparatus was used to quantitatively analyze RESULTS After spinal cord was injured the AchE and SDH reduced ACP raised in the acupuncture group ACHE and SDH were increased and ACP was lowered after acupuncture P 0.05 P 0.01 CONCLUSION Acupuncture could regulate enzymology of the motor neuron of anterior horn of injured spinal cord Acupuncture could inhibit or delay the deterioration of neuron and also could promote the recovery
ESTHER : Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
PubMedSearch : Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
PubMedID: 11783148

Title : Nicotine exposure during a critical period of development leads to persistent changes in nicotinic acetylcholine receptors of adult rat brain - Miao_1998_J.Neurochem_70_752
Author(s) : Miao H , Liu C , Bishop K , Gong ZH , Nordberg A , Zhang X
Ref : Journal of Neurochemistry , 70 :752 , 1998
Abstract : Effects of neonatal nicotine exposure on the development of nicotinic acetylcholine receptor (nAChR) alpha2, alpha3, alpha4, alpha7, and beta2 subunit mRNAs and the number of nAChR isoforms in rat brain were studied. The mRNA levels for nAChR subunits were measured by ribonuclease protection assay, and the number of nAChR isoforms was measured with (-)-[3H]nicotine, [3H]epibatidine, and alpha-[3H]bungarotoxin ([3H]alpha-Bgt). Pups were divided into two groups: One group received (-)-nicotine treatment (0.1 mg/kg s.c. free base twice per day) during postnatal day (P)1 to P21 and the other during P8 to P16. The period from P8 to P16 was chosen due to persistent changes that occur in brain nAChRs and in the behavior of adult mice that received (-)-nicotine treatment during P10 to P16. (-)-Nicotine exposure from P1 to P21 significantly up-regulated the number of [3H]epibatidine and high-affinity (-)-[3H]nicotine binding sites in most of the brain regions studied but did not influence the number of [3H]alpha-Bgt binding sites. This effect was a transient one: The up-regulated binding sites returned to control level 1 week after withdrawal from nicotine. (-)-Nicotine exposure during P8 to P16 resulted in a significant and long-lasting increase in the number of nAChR isoforms labeled by (-)-[3H]nicotine, but not by [3H]epibatidine, in the cortex, hippocampus, and striatum of adult rat. This treatment converted the low-affinity binding sites of (-)-nicotine into a high-affinity state revealed by the competition studies of (-)-[3H]nicotine/(-)-nicotine. No changes in the mRNA levels of the subunits studied were observed following nicotine treatment during these two periods. These results suggest that the second postnatal week is a critical period during which nicotine treatment can induce permanent effects on the nAChRs in rat brain. The underlying mechanisms involved in the up-regulation of the number of nAChRs observed in this study are posttranscriptional.
ESTHER : Miao_1998_J.Neurochem_70_752
PubMedSearch : Miao_1998_J.Neurochem_70_752
PubMedID: 9453571

Title : Postnatal changes of nicotinic acetylcholine receptor alpha 2, alpha 3, alpha 4, alpha 7 and beta 2 subunits genes expression in rat brain - Zhang_1998_Int.J.Dev.Neurosci_16_507
Author(s) : Zhang X , Liu C , Miao H , Gong ZH , Nordberg A
Ref : Int J Developmental Neuroscience , 16 :507 , 1998
Abstract : Postnatal changes of nicotinic acetylcholine receptor (nAChR) alpha 2, alpha 3, alpha 4, alpha 7 and beta 2 subunits mRNAs were investigated in rat brain using ribonuclease protection assay. Multiple developmental patterns were observed: (1) transient expression during the first few postnatal weeks; alpha 2 in the hippocampus and brain stem, alpha 3 in the striatum, cerebellum and cortex, alpha 4 in the hippocampus, striatum and cerebellum, alpha 7 in the cerebellum and beta 2 in the striatum. (2) Constant expression across development; alpha 2 and alpha 3 in the thalamus, alpha 4 in the cortex, thalamus and brain stem, alpha 7 in the thalamus and brain stem and beta 2 in all brain regions except striatum. (3) Non-detection across development; alpha 2 in the cortex, striatum and cerebellum. (4) Increase with age; alpha 7 in the cortex and hippocampus. (5) Bell-shaped development; alpha 7 in the striatum. Postnatal changes of nAChR isoforms in different brain regions of rat were investigated by receptor binding assays. The developmental patterns of [3H]epibatidine and (-)-[3H]nicotine binding sites were similar to each other in each brain region, but different from that of [3H] alpha-bungarotoxin binding sites. No obvious correlation was observed between the developmental patterns of [3H] alpha-bungarotoxin, [3H]epibatidine and (-)-[3H]nicotine binding sites and corresponding subunits mRNAs. These results indicate that multiple mechanisms are involved in changes of gene expression of nAChRs subunits in the brain of developing rats.
ESTHER : Zhang_1998_Int.J.Dev.Neurosci_16_507
PubMedSearch : Zhang_1998_Int.J.Dev.Neurosci_16_507
PubMedID: 9881299

Title : Coupling of muscarinic cholinergic receptors and cGMP in nocturnal regulation of the suprachiasmatic circadian clock - Liu_1997_J.Neurosci_17_659
Author(s) : Liu C , Ding JM , Faiman LE , Gillette MU
Ref : Journal of Neuroscience , 17 :659 , 1997
Abstract : Acetylcholine has long been implicated in nocturnal phase adjustment of circadian rhythms, yet the subject remains controversial. Although the suprachiasmatic nucleus (SCN), site of the circadian clock, contains no intrinsic cholinergic somata, it receives choline acetyltransferase-immunopositive projections from basal forebrain and mesopontine tegmental nuclei that contribute to sleep and wakefulness. We have demonstrated that the SCN of inbred rats in a hypothalamic brain slice is sensitive to cholinergic phase adjustment via muscarinic receptors (mAChRs) only at night. We used this paradigm to probe the muscarinic signal transduction mechanism and the site(s) gating nocturnal responsiveness. The cholinergic agonist carbachol altered the circadian rhythm of SCN neuronal activity in a pattern closely resembling that for analogs of cGMP; nocturnal gating of clock sensitivity of each is preserved in vitro. Specific inhibitors of guanylyl cyclase (GC) and cGMP-dependent protein kinase (PKG), key elements in the cGMP signal transduction cascade, blocked phase shifts induced by carbachol. Further, carbachol administration to the SCN at night increased cGMP production and PKG activity. The carbachol-induced increase in cGMP was blocked both by atropine, an mAChR antagonist, and by LY83583, a GC inhibitor. We conclude that (1) mAChR regulation of the SCN is mediated via GC-->cGMP-->PKG, (2) nocturnal gating of this pathway is controlled by the circadian clock, and (3) a gating site is positioned downstream from cGMP. This study is among the first to identify a functional context for mAChR-cGMP coupling in the CNS.
ESTHER : Liu_1997_J.Neurosci_17_659
PubMedSearch : Liu_1997_J.Neurosci_17_659
PubMedID: 8987788

Title : Cholinergic regulation of the suprachiasmatic nucleus circadian rhythm via a muscarinic mechanism at night - Liu_1996_J.Neurosci_16_744
Author(s) : Liu C , Gillette MU
Ref : Journal of Neuroscience , 16 :744 , 1996
Abstract : In mammals, the suprachiasmatic nucleus (SCN) is responsible for the generation of most circadian rhythms and for their entrainment to environmental cues. Carbachol, an agonist of acetylcholine (ACh), has been shown to shift the phase of circadian rhythms in rodents when injected intracerebroventricularly. However, the site and receptor type mediating this action have been unknown. In the present experiments, we used the hypothalamic brain-slice technique to study the regulation of the SCN circadian rhythm of neuronal firing rate by cholinergic agonists and to identify the receptor subtypes involved. We found that the phase of the oscillation in SCN neuronal activity was reset by a 5 min treatment with a carbachol microdrop (1 microliter, 100 microM), but only when applied during the subjective night, with the largest phase shift (+ 6 hr) elicited during the middle of the subjective night. This effect also was produced by ACh and two muscarinic receptor (mAChR) agonists, muscarine and McN-A-343 (M1-selective), but not by nicotine. Furthermore, the effect of carbachol was blocked by the mAChR antagonist atropine (0.1 microM), not by two nicotinic antagonists, dihydro-beta-erythroidine (10 microM) and d-tubocurarine (10 microM). The M1-selective mAChR antagonist pirenzepine completely blocked the carbachol effect at 1 microM, whereas an M3-selective antagonist, 4,2-(4,4'-diacetoxydiphenylmethyl)pyridine, partially blocked the effect at the same concentration. These results demonstrate that carbachol acts directly on the SCN to reset the phase of its firing rhythm during the subjective night via an M1-like mAChR.
ESTHER : Liu_1996_J.Neurosci_16_744
PubMedSearch : Liu_1996_J.Neurosci_16_744
PubMedID: 8551357

Title : Differential co-expression of nicotinic acetylcholine receptor alpha 4 and beta 2 subunit genes in various regions of rat brain - Liu_1996_Neuroreport_7_1645
Author(s) : Liu C , Nordberg A , Zhang X
Ref : Neuroreport , 7 :1645 , 1996
Abstract : The predominant nicotinic acetylcholine receptor (nAChR) subtype in brain binds nicotine with high affinity and has an alpha 4:beta 2 subunit stoichiometry of 2:3. In this study, the mRNA levels of nAChR alpha 4 and beta 2 subunits were simultaneously quantitated by ribonuclease protection assay and compared with the number of alpha 4 beta 2 receptor subtype, measured by (-)-[3H]nicotine binding in the cerebellum, brain stem, hippocampus, cortex, thalamus and striatum of rat brain. The rank order of abundance of alpha 4 and beta 2 mRNA was different from that of alpha 4 beta 2 receptor subtype levels in the six brain regions studied. The ratio of alpha 4:beta 2 transcripts varied from 2:2.6 to 2:33 in these brain regions. These results reveal a differential co-expression of alpha 4 and beta 2 subunit genes in various regions of rat brain.
ESTHER : Liu_1996_Neuroreport_7_1645
PubMedSearch : Liu_1996_Neuroreport_7_1645
PubMedID: 8904774