Jin Y


Full name : Jin Yishi

First name : Yishi

Mail : Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, San Diego, CA

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Country : USA

Email : yjin1@me.com

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References (63)

Title : A rare case of anti-DPPX encephalitis combined with neuroleptospirosis - Jin_2024_BMC.Neurol_24_34
Author(s) : Jin Y , Lan W , Chen X , Liu W , Luo W , Chen S
Ref : BMC Neurol , 24 :34 , 2024
Abstract : BACKGROUND: Neuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF). CASE PRESENTATION: A previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy. CONCLUSION: We highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.
ESTHER : Jin_2024_BMC.Neurol_24_34
PubMedSearch : Jin_2024_BMC.Neurol_24_34
PubMedID: 38243162
Gene_locus related to this paper: human-DPP6

Title : ABHD6 suppresses colorectal cancer progression via AKT signaling pathway - Xiong_2024_Mol.Carcinog__
Author(s) : Xiong X , Yang C , Jin Y , Zhang R , Wang S , Gan L , Hou S , Bao Y , Zeng Z , Ye Y , Gao Z
Ref : Mol Carcinog , : , 2024
Abstract : Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.
ESTHER : Xiong_2024_Mol.Carcinog__
PubMedSearch : Xiong_2024_Mol.Carcinog__
PubMedID: 38197491
Gene_locus related to this paper: human-ABHD6

Title : Synaptogenesis: unmasking molecular mechanisms using Caenorhabditis elegans - Mizumoto_2023_Genetics__
Author(s) : Mizumoto K , Jin Y , Bessereau JL
Ref : Genetics , : , 2023
Abstract : The nematode Caenorhabditis elegans is a research model organism particularly suited to the mechanistic understanding of synapse genesis in the nervous system. Armed with powerful genetics, knowledge of complete connectomics, and modern genomics, studies using C. elegans have unveiled multiple key regulators in the formation of a functional synapse. Importantly, many signaling networks display remarkable conservation throughout animals, underscoring the contributions of C. elegans research to advance the understanding of our brain. In this chapter, we will review up-to-date information of the contribution of C. elegans to the understanding of chemical synapses, from structure to molecules and to synaptic remodeling.
ESTHER : Mizumoto_2023_Genetics__
PubMedSearch : Mizumoto_2023_Genetics__
PubMedID: 36630525

Title : Dual functional antioxidant and butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of novel melatonin-alkylbenzylamine hybrids - Liu_2023_Bioorg.Med.Chem_78_117146
Author(s) : Liu P , Cheng M , Guo J , Cao D , Luo J , Wan Y , Fang Y , Jin Y , Xie SS , Liu J
Ref : Bioorganic & Medicinal Chemistry , 78 :117146 , 2023
Abstract : Here, we have designed and synthesized a series of melatonin-alkylbenzylamine hybrids as multitarget agents for the treatment of Alzheimer's disease (AD). Most of them exhibited a potent multifunctional profile involving cholinesterase inhibition and antioxidant effects. Among these compounds, compound 5 was most the potent antioxidant (ORAC =5.13) and also an excellent selective inhibitor of BuChE (huBuChE IC(50)=1.20 microM, huAChE IC(50) = 177.49 microM, SIs= 147.91). Moreover, kinetic study indicated compound 5 was a mixed-type inhibitor for huBuChE. Furthermore, it could induce expression of the Nrf2 as well as its downstream markers at the protein level in cells. More importantly, compound 5 display no acute toxicity in mice at doses up to 2500 mg/kg. And we found compound 5 could improve memory function of scopolamine-induced amnesia mice. These results highlighted compound 5 as a possible hit molecule for further investigation of new anti-AD drugs.
ESTHER : Liu_2023_Bioorg.Med.Chem_78_117146
PubMedSearch : Liu_2023_Bioorg.Med.Chem_78_117146
PubMedID: 36580744

Title : Co-exposure to sodium hypochlorite and cadmium induced locomotor behavior disorder by influencing neurotransmitter secretion and cardiac function in larval zebrafish - Ma_2023_Environ.Pollut_342_123070
Author(s) : Ma L , Yang H , Xiao X , Chen Q , Lv W , Xu T , Jin Y , Wang W , Xiao Y
Ref : Environ Pollut , 342 :123070 , 2023
Abstract : Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 microg/L), 1/100 Cd group (48 microg/L), 1/30 Cd group (160 microg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.
ESTHER : Ma_2023_Environ.Pollut_342_123070
PubMedSearch : Ma_2023_Environ.Pollut_342_123070
PubMedID: 38056588

Title : Application of Marine Natural Products against Alzheimer's Disease: Past, Present and Future - Hu_2023_Mar.Drugs_21_
Author(s) : Hu D , Jin Y , Hou X , Zhu Y , Chen D , Tai J , Chen Q , Shi C , Ye J , Wu M , Zhang H , Lu Y
Ref : Mar Drugs , 21 : , 2023
Abstract : Alzheimer's disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer's disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD.
ESTHER : Hu_2023_Mar.Drugs_21_
PubMedSearch : Hu_2023_Mar.Drugs_21_
PubMedID: 36662216

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 : A multi-target directed ligands strategy for the treatment of Alzheimer's disease: Dimethyl fumarate plus Tranilast modified Dithiocarbate as AChE inhibitor and Nrf2 activator - Guo_2022_Eur.J.Med.Chem_242_114630
Author(s) : Guo J , Cheng M , Liu P , Cao D , Luo J , Wan Y , Fang Y , Jin Y , Xie SS , Liu J
Ref : Eur Journal of Medicinal Chemistry , 242 :114630 , 2022
Abstract : Alzheimer's disease (AD) possessed intricate pathogenesis. Currently, multi-targeted drugs were considered to have the potential to against AD by simultaneously triggering molecules in functionally complementary pathways. Hence, a series of molecules based on the pharmacophoric features of Dimethyl fumarate, Tranilast, and Dithiocarbate were designed and synthesized. These compounds showed significant AChE inhibitory activity in vitro. Among them, compound 4c(2) displayed the mighty inhibitory activity to hAChE (IC(50) = 0.053 microM) and held the ability to cross the BBB. Kinetic study and molecular docking pointed out that 4c(2) bound well into the active sites of hAChE, forming steady and sturdy interactions with key residues in hAChE. Additionally, 4c(2) as an Nrf2 activator could promote the nuclear translocation of Nrf2 protein and induce the expressions of Nrf2-dependent enzymes HO-1, NQO1, and GPX4. Moreover, 4c(2) rescued BV-2 cells from H(2)O(2)-induced injury and inhibited ROS accumulation. For the anti-neuroinflammatory potential of 4c(2), we observed that 4c(2) could lower the levels of pro-inflammatory cytokines (NO, IL-6 and TNF-alpha) and suppressed the expressions of iNOS and COX-2. In particular, 4c(2) was well tolerated in mice (2500 mg/kg, p.o.) and efficaciously recovered the memory impairment in a Scopolamine-induced mouse model. Overall, these results highlighted that 4c(2) was a promising multi-targeted agent for treating AD.
ESTHER : Guo_2022_Eur.J.Med.Chem_242_114630
PubMedSearch : Guo_2022_Eur.J.Med.Chem_242_114630
PubMedID: 35987018

Title : Combined effects of chlorpyrifos and cyfluthrin on neurobehavior and neurotransmitter levels in larval zebrafish - Zhang_2022_J.Appl.Toxicol__
Author(s) : Zhang W , Fan R , Luo S , Liu Y , Jin Y , Li Y , Xiong M , Chen Y , Jia L , Yuan X
Ref : J Appl Toxicol , : , 2022
Abstract : Chlorpyrifos and cyfluthrin are insecticides commonly used in agriculture. The mixed residues of chlorpyrifos and cyfluthrin in the aquatic environment may have combined effects on non-target species. Therefore, studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to environmental risk assessment. To evaluate the risk of combined exposure, we examined the effects of both compounds, separately and together, on motor activity, acetylcholinesterase (AChE) activity, and neurotransmitter levels in larval zebrafish. Chlorpyrifos exposure significantly reduced functional motor capacity (swim distance and velocity) and enhanced meandering, while cyfluthrin exposure alone had no significant effects on swim parameters. However, combined exposure significantly reduced total swimming distance and mean velocity, and increased meandering. Both compounds alone and the combination significantly reduced AChE activity, and the combined effect was antagonistic. Combined exposure also significantly altered the concentrations of serotonin, serotonin precursors, and dopamine precursors, as well as concentrations of the amino acid neurotransmitters glycine, alanine, and aspartic acid. Combined exposure to chlorpyrifos and cyfluthrin exhibited distinct joint action modes in terms of neurobehavior, AChE activity, and neurotransmitter levels, thereby providing an experimental basis for assessing the combined exposure to chlorpyrifos and cyfluthrin's environmental risk.
ESTHER : Zhang_2022_J.Appl.Toxicol__
PubMedSearch : Zhang_2022_J.Appl.Toxicol__
PubMedID: 35470462

Title : Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer - Xu_2022_Ann.Transl.Med_10_169
Author(s) : Xu Y , Wang X , Chu Y , Li J , Wang W , Hu X , Zhou F , Zhang H , Zhou L , Kuai R , Jin Y , Yang D , Peng H
Ref : Ann Transl Med , 10 :169 , 2022
Abstract : BACKGROUND: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. METHODS: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). RESULTS: A total of 237 significantly differentially expressed genes (P(adj)<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. CONCLUSIONS: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
ESTHER : Xu_2022_Ann.Transl.Med_10_169
PubMedSearch : Xu_2022_Ann.Transl.Med_10_169
PubMedID: 35280417

Title : Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1H)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease - Guo_2022_Drug.Des.Devel.Ther_16_1495
Author(s) : Guo J , Xu A , Cheng M , Wan Y , Wang R , Fang Y , Jin Y , Xie SS , Liu J
Ref : Drug Des Devel Ther , 16 :1495 , 2022
Abstract : BACKGROUND: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports. PURPOSE: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate. METHODS: All compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo. RESULTS: Most compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC(50)=0.28 microM to eeAChE; IC(50)=0.34 microM to hAChE; IC(50)=2.81 microM to hMAO-B; IC(50)=0.91 microM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 microM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.). CONCLUSION: This work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.
ESTHER : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedSearch : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedID: 35611357

Title : Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway - Liu_2021_J.Pharm.Sci__
Author(s) : Liu H , Jin Y , Menon R , Laskowich E , Bareford L , de Vilmorin P , Kolwyck D , Yeung B , Yi L
Ref : J Pharm Sci , : , 2021
Abstract : A liquid chromatography-mass spectrometry (LC-MS) method was developed to provide a fingerprint of polysorbate 80 (PS80) subspecies that enables identification of PS80 degradation pathway. The developed method demonstrates unique monoester peak profile of PS80 from different vendors, attributed by differences in relative abundance of the fatty acid monoesters. The LC-MS method was also applied to examine the susceptibility of PS80, at different grades, to auto-oxidation and hydrolysis. PS80 oxidative degradation induced by iron or occurred in open bottle without nitrogen overlay was found to follow the same pathway, but at a much faster rate in the former scenario. The oxidation preferentially occurs at the double bond of fatty acid chains, thus providing explanation on the faster degradation observed in PS80 at Chinese Pharmacopia (ChP) grade than at multi-compendial (MC) grade. In contrast, the difference in susceptibility of MC and ChP grade PS80 against esterase-induced hydrolysis in placebo was not pronounced. The method was also able to provide a fingerprint to identify both PS80 hydrolysis and oxidation in mAb drug product stability samples, but it requires a solid phase extraction step to remove protein prior to the analysis.
ESTHER : Liu_2021_J.Pharm.Sci__
PubMedSearch : Liu_2021_J.Pharm.Sci__
PubMedID: 34416271

Title : Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhang_2021_Eur.J.Med.Chem_213_113154
Author(s) : Zhang Z , Guo J , Cheng M , Zhou W , Wan Y , Wang R , Fang Y , Jin Y , Liu J , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 213 :113154 , 2021
Abstract : In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC(50) values 0.85 microM and 0.59 microM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu(2+) and Al(3+) at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedSearch : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedID: 33476932

Title : Nutritional Status and Body Composition in Wilson Disease: A Cross-Sectional Study From China - Geng_2021_Front.Nutr_8_790520
Author(s) : Geng H , Wang S , Jin Y , Cheng N , Song B , Shu S , Li B , Han Y , Gao L , Ding Z , Xu Y , Wang X , Ma Z , Sun Y
Ref : Front Nutr , 8 :790520 , 2021
Abstract : Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes. Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally. Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P<0.01); while there were no significant differences in muscle and skeletal muscle between these two subtypes. The overall prevalence of abnormal nutritional status in WD patients was 43.41% (56/129). The prevalence of high-nutritional risk and overweight in WD patients was 17.83% (23 of 129) and 25.58% (33 of 129), respectively. Compare with patients with high nutritional risk, macro platelet ratio, alkaline phosphatase, the basal metabolic rate (p < 0.05), creatinine, trunk fat rate (p < 0.01) and appendicular skeletal muscle mass (p < 0.001) were significantly higher in patients without nutritional risk (p < 0.001). Patients with a high nutritional risk tend to have a lower cholinesterase concentration (x (2) = 4.227, p < 0.05). Conclusion: Both patients with H-subtype and N-subtype are prone to have an abnormal nutritional status. Longitudinal studies are required to investigate if nutritional status and body composition could reflect prognosis in WD patients, and which of these body composition indexes contribute to malnutrition and worse prognosis.
ESTHER : Geng_2021_Front.Nutr_8_790520
PubMedSearch : Geng_2021_Front.Nutr_8_790520
PubMedID: 35036410

Title : Clinical significance of EPHX2 deregulation in prostate cancer - Liu_2021_Asian.J.Androl_23_109
Author(s) : Liu MS , Zhao H , Xu CX , Xie PB , Wang W , Yang YY , Lee WH , Jin Y , Zhou HQ
Ref : Asian J Androl , 23 :109 , 2021
Abstract : The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.
ESTHER : Liu_2021_Asian.J.Androl_23_109
PubMedSearch : Liu_2021_Asian.J.Androl_23_109
PubMedID: 32687069

Title : Perspective on prenatal polychlorinated biphenyl exposure and the development of the progeny nervous system (Review) - Wang_2021_Int.J.Mol.Med_48_
Author(s) : Wang Y , Hu C , Fang T , Jin Y , Wu R
Ref : Int J Mol Med , 48 : , 2021
Abstract : The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's longterm susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxinlike (DLPCBs) and nondioxinlike PCBs (NDLPCBs), are synthetic persistent environmental endocrinedisrupting chemicals. The toxicological mechanisms of DLPCBs have been associated with the activation of the aryl hydrocarbon receptor and NDLPCBs have been associated with ryanodine receptormediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.
ESTHER : Wang_2021_Int.J.Mol.Med_48_
PubMedSearch : Wang_2021_Int.J.Mol.Med_48_
PubMedID: 34132363

Title : Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh-activated ion channels - Treinin_2021_J.Neurochem_158_1274
Author(s) : Treinin M , Jin Y
Ref : Journal of Neurochemistry , 158 :1274 , 2021
Abstract : Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground-breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine-mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine-activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in-depth current knowledge on acetylcholine-activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.
ESTHER : Treinin_2021_J.Neurochem_158_1274
PubMedSearch : Treinin_2021_J.Neurochem_158_1274
PubMedID: 32869293

Title : In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease - Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
Author(s) : Song X , Wang T , Guo L , Jin Y , Wang J , Yin G , Jiang K , Wang L , Huang H , Zeng L
Ref : Evid Based Complement Alternat Med , 2020 :2804849 , 2020
Abstract : Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.
ESTHER : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedSearch : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedID: 32148536

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

Title : Detoxification enzymes associated with butene-fipronil resistance in Epacromius coerulipes - Jin_2020_Pest.Manag.Sci_76_227
Author(s) : Jin Y , Gao Y , Zhang H , Wang L , Yang K , Dong H
Ref : Pest Manag Sci , 76 :227 , 2020
Abstract : BACKGROUND: Epacromius coerulipes is a widely distributed locust pest species. Chemical control is the main method used to kill locusts; however, this can result in the selection of locusts with resistance to chemical pesticides. Therefore, the study of resistance is of great significance for the sustainable management of locusts. RESULTS: In this study, to investigate the relationship between detoxification enzymes and butene-fipronil resistance in E. coerulipes, resistant strains of the locust were compared with sensitive strains. The synergism of synergistic agents was significantly enhanced, and the activities of multifunctional oxidase, carboxylesterase, and glutathione sulfur transferase were significantly increased. Transcriptome sequencing revealed 226 detoxification enzyme genes and 23 upregulated genes. Neighbor-joining was used to construct a phylogenetic tree of related gene families, which included 59 P450 genes, 52 carboxylesterases (CarE) genes, and 25 glutathione S-transferase (GST) genes. Reverse transcription polymerase chain reaction (RT-PCR) analysis results of overexpressed genes in the resistant population combined with a phylogenetic tree showed that four P450 genes belonged to the CYP6, CYP4, CYP18 and CYP302 families, two CarE genes belonged to Clade A families, and one GST gene belonged to the Sigma family. These family members were annotated as detoxification enzyme genes of metabolic insecticide in the transcriptome databases. CONCLUSIONS: This study showed that P450, CarE and GST together resulted in moderate resistance to butene-fipronil in locusts. The analysis revealed several overexpressed detoxification enzyme genes that will be the focus of future studies on the mechanism of resistance to butene-fipronil. (c) 2019 Society of Chemical Industry.
ESTHER : Jin_2020_Pest.Manag.Sci_76_227
PubMedSearch : Jin_2020_Pest.Manag.Sci_76_227
PubMedID: 31150148

Title : Reassembly of native components with donepezil to execute dual-missions in Alzheimer's disease therapy - Zhang_2019_J.Control.Release_296_14
Author(s) : Zhang H , Zhao Y , Yu M , Zhao Z , Liu P , Cheng H , Ji Y , Jin Y , Sun B , Zhou J , Ding Y
Ref : J Control Release , 296 :14 , 2019
Abstract : Alzheimer's disease (AD) is a multifaceted and progressive neurodegenerative disease characterized by accumulation of amyloid-beta (Abeta) and deficits of acetylcholine. Accordingly, the intra-/extra-cerebral level of high density lipoprotein (HDL) is crucial on the pathogenesis of AD; and most of all, various HDL-protein subtypes play a double-edged role in AD pathology, of which apolipoprotein A-I (apoA-I) gives protective outcomes. Inspired from "HDL bionics", we proposed biologically reassembled nanodrugs, donepezil-loaded apolipoprotein A-I-reconstituted HDL (rHDL/Do) that concurrently executed dual-missions of Abeta-targeting clearance and acetylcholinesterase (AChE) inhibition in AD therapy. Once prepared, rHDL/Do nanodrug achieved high drug encapsulation efficiency of 90.47%, and mimicked the configurations and properties of natural lipoproteins aiming to significantly enhance BBB penetration and modulate Abeta-induced neuronal damage both in vitro and in vivo. Surface plasmon resonance (SPR) analysis confirmed that rHDL/Do facilitated microglial-mediated Abeta intake and degradation, demonstrating low KD value with Abeta affinity (2.45x10(-8) of Abeta monomer and 2.78x10(-8) of Abeta oligomer). In AD animal models, daily treatment of rHDL/Do efficiently inhibited AChE activity, ameliorated neurologic variation, promoted Abeta clearance, and rescued memory loss at a safe level. The collective findings indicated that the biological nanodrug was provided with the capacities of BBB penetration, Abeta capture and degradation via microglial cells, and cholinergic dysfunction amelioration after controlled donepezil release. In summary, rHDL/Do nanodrugs could offer a promising strategy to synergize both symptom control and disease modification in AD therapy.
ESTHER : Zhang_2019_J.Control.Release_296_14
PubMedSearch : Zhang_2019_J.Control.Release_296_14
PubMedID: 30639387

Title : Maternal Ribosomes Are Sufficient for Tissue Diversification during Embryonic Development in C. elegans - Cenik_2019_Dev.Cell_48_811
Author(s) : Cenik ES , Meng X , Tang NH , Hall RN , Arribere JA , Cenik C , Jin Y , Fire A
Ref : Dev Cell , 48 :811 , 2019
Abstract : Caenorhabditis elegans provides an amenable system to explore whether newly composed ribosomes are required to progress through development. Despite the complex pattern of tissues that are formed during embryonic development, we found that null homozygotes lacking any of the five different ribosomal proteins (RPs) can produce fully functional first-stage larvae, with similar developmental competence seen upon complete deletion of the multi-copy ribosomal RNA locus. These animals, relying on maternal but not zygotic contribution of ribosomal components, are capable of completing embryogenesis. In the absence of new ribosomal components, the resulting animals are arrested before progression from the first larval stage and fail in two assays for postembryonic plasticity of neuronal structure. Mosaic analyses of larvae that are a mixture of ribosome-competent and non-competent cells suggest a global regulatory mechanism in which ribosomal insufficiency in a subset of cells triggers organism-wide growth arrest.
ESTHER : Cenik_2019_Dev.Cell_48_811
PubMedSearch : Cenik_2019_Dev.Cell_48_811
PubMedID: 30799226

Title : DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in mature neurons - Noblett_2019_J.Cell.Biol_218_125
Author(s) : Noblett N , Wu Z , Ding ZH , Park S , Roenspies T , Flibotte S , Chisholm AD , Jin Y , Colavita A
Ref : Journal of Cell Biology , 218 :125 , 2019
Abstract : Neuronal morphology and circuitry established during early development must often be maintained over the entirety of animal lifespans. Compared with neuronal development, the mechanisms that maintain mature neuronal structures and architecture are little understood. The conserved disco-interacting protein 2 (DIP2) consists of a DMAP1-binding domain and two adenylate-forming domains (AFDs). We show that the Caenorhabditis elegans DIP-2 maintains morphology of mature neurons. dip-2 loss-of-function mutants display a progressive increase in ectopic neurite sprouting and branching during late larval and adult life. In adults, dip-2 also inhibits initial stages of axon regeneration cell autonomously and acts in parallel to DLK-1 MAP kinase and EFA-6 pathways. The function of DIP-2 in maintenance of neuron morphology and in axon regrowth requires its AFD domains and is independent of its DMAP1-binding domain. Our findings reveal a new conserved regulator of neuronal morphology maintenance and axon regrowth after injury.
ESTHER : Noblett_2019_J.Cell.Biol_218_125
PubMedSearch : Noblett_2019_J.Cell.Biol_218_125
PubMedID: 30396999

Title : Association between EPHX1 polymorphism rs1051740 and the risk of ovarian cancer: a meta-analysis - Jin_2019_Artif.Cells.Nanomed.Biotechnol_47_2338
Author(s) : Jin Y
Ref : Artif Cells Nanomed Biotechnol , 47 :2338 , 2019
Abstract : Objective: We carried out a meta-analysis of case-control studies to determine whether epoxide hydrolase 1 (EPHX1) gene polymorphism rs1051740 was related to the risk of ovarian cancer. Methods: Electronic databases were searched for relevant articles published in English or Chinese language. We calculated crude odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the relationship of EPHX1 polymorphism rs1051740 with ovarian cancer risk. In addition, subgroup analyses were also conducted based on ethnicity and control source. Between-study heterogeneity was inspected with Q test and I(2) statistic. Results: Five eligible studies with a total of 1919 ovarian cancer patients and 1829 controls were ultimately included in the present meta-analysis. Overall results demonstrated that the association between EPHX1 polymorphism rs1051740 and ovarian cancer risk had no statistical significance either in total analysis or in subgroup analyses by ethnicity and source of control. Conclusion: EPHX1 polymorphism rs1051740 may have no independent effect on ovarian cancer susceptibility.
ESTHER : Jin_2019_Artif.Cells.Nanomed.Biotechnol_47_2338
PubMedSearch : Jin_2019_Artif.Cells.Nanomed.Biotechnol_47_2338
PubMedID: 31174441

Title : Building stereotypic connectivity: mechanistic insights into structural plasticity from C. elegans - Jin_2018_Curr.Opin.Neurobiol_48_97
Author(s) : Jin Y , Qi YB
Ref : Current Opinion in Neurobiology , 48 :97 , 2018
Abstract : The ability of neurons to modify or remodel their synaptic connectivity is critical for the function of neural circuitry throughout the life of an animal. Understanding the mechanisms underlying neuronal structural changes is central to our knowledge of how the nervous system is shaped for complex behaviors and how it further adapts to developmental and environmental demands. Caenorhabditis elegans provides a powerful model for examining developmental processes and for discovering mechanisms controlling neural plasticity. Recent findings have identified conserved themes underlying neural plasticity in development and under environmental stress.
ESTHER : Jin_2018_Curr.Opin.Neurobiol_48_97
PubMedSearch : Jin_2018_Curr.Opin.Neurobiol_48_97
PubMedID: 29182952

Title : A Neuronal piRNA Pathway Inhibits Axon Regeneration in C. elegans - Kim_2018_Neuron_97_511
Author(s) : Kim KW , Tang NH , Andrusiak MG , Wu Z , Chisholm AD , Jin Y
Ref : Neuron , 97 :511 , 2018
Abstract : The PIWI-interacting RNA (piRNA) pathway has long been thought to function solely in the germline, but evidence for its functions in somatic cells is emerging. Here we report an unexpected role for the piRNA pathway in Caenorhabditis elegans sensory axon regeneration after injury. Loss of function in a subset of components of the piRNA pathway results in enhanced axon regrowth. Two essential piRNA factors, PRDE-1 and PRG-1/PIWI, inhibit axon regeneration in a gonad-independent and cell-autonomous manner. By smFISH analysis we find that prde-1 transcripts are present in neurons, as well as germ cells. The piRNA pathway inhibits axon regrowth independent of nuclear transcriptional silencing but dependent on the slicer domain of PRG-1/PIWI, suggesting that post-transcriptional gene silencing is involved. Our results reveal the neuronal piRNA pathway as a novel intrinsic repressor of axon regeneration.
ESTHER : Kim_2018_Neuron_97_511
PubMedSearch : Kim_2018_Neuron_97_511
PubMedID: 29395906

Title : Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD(+) in axon regeneration - Kim_2018_Elife_7_
Author(s) : Kim KW , Tang NH , Piggott CA , Andrusiak MG , Park S , Zhu M , Kurup N , Cherra SJ, 3rd , Wu Z , Chisholm AD , Jin Y
Ref : Elife , 7 : , 2018
Abstract : The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD(+)) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms. NMAT-2 enzymatic activity is required to repress regrowth. Further, we find differential requirements for proteins in membrane contact site, components and regulators of the extracellular matrix, membrane trafficking, microtubule and actin cytoskeleton, the conserved Kelch-domain protein IVNS-1, and the orphan transporter MFSD-6 in axon regrowth. Identification of these new pathways expands our understanding of the molecular basis of axonal injury response and regeneration.
ESTHER : Kim_2018_Elife_7_
PubMedSearch : Kim_2018_Elife_7_
PubMedID: 30461420

Title : Intermediate filament accumulation can stabilize microtubules in Caenorhabditis elegans motor neurons - Kurup_2018_Proc.Natl.Acad.Sci.U.S.A_115_3114
Author(s) : Kurup N , Li Y , Goncharov A , Jin Y
Ref : Proc Natl Acad Sci U S A , 115 :3114 , 2018
Abstract : Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of Caenorhabditis elegans, synapses of motor neurons are stereotypically rewired through a process facilitated by dynamic microtubules (MTs). Through a genetic suppressor screen on mutant animals that fail to rewire synapses, and in combination with live imaging and ultrastructural studies, we find that intermediate filaments (IFs) stabilize MTs to prevent synapse rewiring. Genetic ablation of IFs or pharmacological disruption of IF networks restores MT growth and rescues synapse rewiring defects in the mutant animals, indicating that IF accumulation directly alters MT stability. Our work sheds light on the impact of IFs on MT dynamics and axonal transport, which is relevant to the mechanistic understanding of several human motor neuron diseases characterized by IF accumulation in axonal swellings.
ESTHER : Kurup_2018_Proc.Natl.Acad.Sci.U.S.A_115_3114
PubMedSearch : Kurup_2018_Proc.Natl.Acad.Sci.U.S.A_115_3114
PubMedID: 29511101

Title : Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans - Yang_2018_Arch.Toxicol_92_2779
Author(s) : Yang S , Zhang H , Zhang J , Li Y , Jin Y , Zhang S , De Saeger S , Zhou J , Sun F , De Boevre M
Ref : Archives of Toxicology , 92 :2779 , 2018
Abstract : Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry. Additionally, in vivo metabolism of ZEN-14G was conducted in model animals, rats, by oral administration. As a result, 29 phase I metabolites and 6 phase II metabolites were identified and significant inter-species metabolic differences were observed as well. What is more, ZEN-14G could be considerably deglucosidated into its free form of ZEN after the incubation with animals and human liver microsomes in the absence of NADPH, which was mainly metabolized by human carboxylesterase CES-I and II. Furthermore, results showed that the major metabolic pathways of ZEN-14G were deglucosylation, hydroxylation, hydrogenation and glucuronidation. Although interspecies differences in the biotransformation of ZEN-14G were observed, ZEN, alpha-ZEL-14G, beta-ZEL-14G, alpha-ZEL, ZEN-14G-16GlcA and ZEN-14GlcA were the major metabolites of ZEN-14G. Additionally, a larger yield of 6-OH-ZEN-14G and 8-OH-ZEN-14G was also observed in human liver microsomes. The obtained data would be of great importance for the safety assessment of modified mycotoxin, ZEN-14G, and provide another perspective for risk assessment of mycotoxin.
ESTHER : Yang_2018_Arch.Toxicol_92_2779
PubMedSearch : Yang_2018_Arch.Toxicol_92_2779
PubMedID: 30019167

Title : Pharming for Genes in Neurotransmission: Combining Chemical and Genetic Approaches in Caenorhabditis elegans - Blazie_2018_ACS.Chem.Neurosci_9_1963
Author(s) : Blazie SM , Jin Y
Ref : ACS Chem Neurosci , 9 :1963 , 2018
Abstract : Synaptic transmission is central to nervous system function. Chemical and genetic screens are valuable approaches to probe synaptic mechanisms in living animals. The nematode Caenorhabditis elegans is a prime system to apply these methods to discover genes and dissect the cellular pathways underlying neurotransmission. Here, we review key approaches to understand neurotransmission and the action of psychiatric drugs in C. elegans. We start with early studies on cholinergic excitatory signaling at the neuromuscular junction, and move into mechanisms mediated by biogenic amines. Finally, we discuss emerging work toward understanding the mechanisms driving synaptic plasticity with a focus on regulation of protein translation.
ESTHER : Blazie_2018_ACS.Chem.Neurosci_9_1963
PubMedSearch : Blazie_2018_ACS.Chem.Neurosci_9_1963
PubMedID: 29432681

Title : Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation - He_2018_Bioorg.Chem_81_512
Author(s) : He Q , Liu J , Lan JS , Ding J , Sun Y , Fang Y , Jiang N , Yang Z , Sun L , Jin Y , Xie SS
Ref : Bioorg Chem , 81 :512 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
ESTHER : He_2018_Bioorg.Chem_81_512
PubMedSearch : He_2018_Bioorg.Chem_81_512
PubMedID: 30245233

Title : Genistein, a Phytoestrogen in Soybean, Induces the Expression of Acetylcholinesterase via G Protein-Coupled Receptor 30 in PC12 Cells - Liu_2018_Front.Mol.Neurosci_11_59
Author(s) : Liu EYL , Xu ML , Jin Y , Wu KQY , Dong TTX , Tsim KWK
Ref : Front Mol Neurosci , 11 :59 , 2018
Abstract : Genistein, 4',5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs), markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA)-linked acetyl-cholinesterase (G4 AChE), a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA. The genistein-induced AChE expression was fully blocked by the pre-treatment of H89 (an inhibitor of protein kinase A, PKA) and G15 (a selective G protein-coupled receptor 30 (GPR30) antagonist), which suggested a direct involvement of a membrane-bound estrogen receptor (ER), named as GPR30 in the cultures. In parallel, the estrogen-induced activation of GPR30 induced AChE expression in a dose-dependent manner. The genistein/estrogen-induced AChE expression was triggered by a cyclic AMP responding element (CRE) located on the ACHE gene promoter. The binding of this CRE site by cAMP response element-binding protein (CREB) induced ACHE gene transcription. In parallel, increased expression levels of miR132 and miR212 were found when cultured PC12 cells were treated with genistein or G1. Thus, a balance between production and destruction of AChE by the activation of GPR30 was reported here. We have shown for the first time that the activation of GPR30 could be one way for estrogen or flavonoids, possessing estrogenic properties, to enhance cholinergic functions in the brain, which could be a good candidate for possible treatment of neurodegenerative diseases.
ESTHER : Liu_2018_Front.Mol.Neurosci_11_59
PubMedSearch : Liu_2018_Front.Mol.Neurosci_11_59
PubMedID: 29535608

Title : Excitatory motor neurons are local oscillators for backward locomotion - Gao_2018_Elife_7_
Author(s) : Gao S , Guan SA , Fouad AD , Meng J , Kawano T , Huang YC , Li Y , Alcaire S , Hung W , Lu Y , Qi YB , Jin Y , Alkema M , Fang-Yen C , Zhen M
Ref : Elife , 7 : , 2018
Abstract : Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron's oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron's intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network.
ESTHER : Gao_2018_Elife_7_
PubMedSearch : Gao_2018_Elife_7_
PubMedID: 29360035

Title : Rapid Integration of Multi-copy Transgenes Using Optogenetic Mutagenesis in Caenorhabditis elegans - Noma_2018_G3.(Bethesda)_8_2091
Author(s) : Noma K , Jin Y
Ref : G3 (Bethesda) , 8 :2091 , 2018
Abstract : Stably transmitted transgenes are indispensable for labeling cellular components and manipulating cellular functions. In Caenorhabditis elegans, transgenes are generally generated as inheritable multi-copy extrachromosomal arrays, which can be stabilized in the genome through a mutagenesis-mediated integration process. Standard methods to integrate extrachromosomal arrays primarily use protocols involving ultraviolet light plus trimethylpsoralen or gamma- or X-ray irradiation, which are laborious and time-consuming. Here, we describe a one-step integration method, following germline-mutagenesis induced by mini Singlet Oxygen Generator (miniSOG). Upon blue light treatment, miniSOG tagged to histone (Histone-miniSOG) generates reactive oxygen species (ROS) and induces heritable mutations, including DNA double-stranded breaks. We demonstrate that we can bypass the need to first establish extrachromosomal transgenic lines by coupling microinjection of desired plasmids with blue light illumination on Histone-miniSOG worms to obtain integrants in the F3 progeny. We consistently obtained more than one integrant from 12 injected animals in two weeks. This optogenetic approach significantly reduces the amount of time and labor for transgene integration. Moreover, it enables to generate stably expressed transgenes that cause toxicity in animal growth.
ESTHER : Noma_2018_G3.(Bethesda)_8_2091
PubMedSearch : Noma_2018_G3.(Bethesda)_8_2091
PubMedID: 29691291

Title : Molecular cloning and expression analysis of a prawn (Macrobrachium rosenbergii) juvenile hormone esterase-like carboxylesterase following immune challenge - Zhu_2018_Fish.Shellfish.Immunol_80_10
Author(s) : Zhu XJ , Xiong Y , He W , Jin Y , Qian YQ , Liu J , Dai ZM
Ref : Fish Shellfish Immunol , 80 :10 , 2018
Abstract : Methyl farnesoate (MF), the crustacean juvenile hormone (JH), plays critical roles in various physiological processes in crustaceans. The titer of MF is precisely regulated by specific carboxylesterase. Here, we report for the first time that the cloning and expression analysis of a JH esterase-like carboxylesterase from the prawn Macrobrachium rosenbergii (named as MrCXE). MrCXE contained a 1935-bp open reading frame (ORF) conceptually translated into a 644-amino acids protein. MrCXE protein shared the highest identity (36%) with JH esterase-like carboxylesterase from the swimming crab, Portunus trituberculatus and exhibited the typical motifs of JH esterase-like carboxylesterases. MrCXE was most abundantly expressed in hepatopancreas, the major tissue for MF metabolism. MrCXE was expressed at a low level in gut and was not detected in other tissues. Additionally, MrCXE expression was upregulated in hepatopancreas by eyestalk ablation to increase MF level. Furthermore, the mRNA level of MrCXE was significantly increased in the hepatopancreas when challenged by the bacterial pathogens Aeromonas hydrophila and Vibrio parahaemolyticus. To our knowledge, this is the first report that the JH esterase-like carboxylesterase is involved in the innate immune response of the crustaceans.
ESTHER : Zhu_2018_Fish.Shellfish.Immunol_80_10
PubMedSearch : Zhu_2018_Fish.Shellfish.Immunol_80_10
PubMedID: 29803663

Title : Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System - Jin_2017_Neurochem.Res_42_1299
Author(s) : Jin Y , Peng J , Wang X , Zhang D , Wang T
Ref : Neurochem Res , 42 :1299 , 2017
Abstract : Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 mug/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests. Furthermore, ginsenoside Rg1 treatment prevented LPS-induced decrease of acetylcholine (ACh) levels and increase of acetylcholinesterase (AChE) activity. Ginsenoside Rg1 treatment also reverted the decrease of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) protein expression in the prefrontal cortex (PFC) and hippocampus of LPS-treated rats. These findings suggest that ginsenoside Rg1 has protective effect against LPS-induced cognitive deficit and that prevention of LPS-induced changes in cholinergic system is crucial to this ameliorating effect.
ESTHER : Jin_2017_Neurochem.Res_42_1299
PubMedSearch : Jin_2017_Neurochem.Res_42_1299
PubMedID: 28078612

Title : Distinct cis elements in the 3' UTR of the C. elegans cebp-1 mRNA mediate its regulation in neuronal development - Sharifnia_2017_Dev.Biol_429_240
Author(s) : Sharifnia P , Kim KW , Wu Z , Jin Y
Ref : Developmental Biology , 429 :240 , 2017
Abstract : The 3' untranslated regions (3' UTRs) of mRNAs mediate post-transcriptional regulation of genes in many biological processes. Cis elements in 3' UTRs can interact with RNA-binding factors in sequence-specific or structure-dependent manners, enabling regulation of mRNA stability, translation, and localization. Caenorhabditis elegans CEBP-1 is a conserved transcription factor of the C/EBP family, and functions in diverse contexts, from neuronal development and axon regeneration to organismal growth. Previous studies revealed that the levels of cebp-1 mRNA in neurons depend on its 3' UTR and are also negatively regulated by the E3 ubiquitin ligase RPM-1. Here, by systematically dissecting cebp-1's 3' UTR, we test the roles of specific cis elements in cebp-1 expression and function in neurons. We present evidence for a putative stem-loop in the cebp-1 3' UTR that contributes to basal expression levels of mRNA and to negative regulation by rpm-1. Mutant animals lacking the endogenous cebp-1 3' UTR showed a noticeable increased expression of cebp-1 mRNA and enhanced the neuronal developmental phenotypes of rpm-1 mutants. Our data reveal multiple cis elements within cebp-1's 3' UTR that help to optimize CEBP-1 expression levels in neuronal development.
ESTHER : Sharifnia_2017_Dev.Biol_429_240
PubMedSearch : Sharifnia_2017_Dev.Biol_429_240
PubMedID: 28673818

Title : A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans - Knowlton_2017_Front.Neurosci_11_263
Author(s) : Knowlton WM , Hubert T , Wu Z , Chisholm AD , Jin Y
Ref : Front Neurosci , 11 :263 , 2017
Abstract : The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo, we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1. Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7, and isp-1, and the putative oxidoreductase rad-8. In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1. Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury.
ESTHER : Knowlton_2017_Front.Neurosci_11_263
PubMedSearch : Knowlton_2017_Front.Neurosci_11_263
PubMedID: 28539870

Title : Differential regulation of polarized synaptic vesicle trafficking and synapse stability in neural circuit rewiring in Caenorhabditis elegans - Kurup_2017_PLoS.Genet_13_e1006844
Author(s) : Kurup N , Yan D , Kono K , Jin Y
Ref : PLoS Genet , 13 :e1006844 , 2017
Abstract : Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement.
ESTHER : Kurup_2017_PLoS.Genet_13_e1006844
PubMedSearch : Kurup_2017_PLoS.Genet_13_e1006844
PubMedID: 28636662

Title : Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca(2+) Sensor Protein - Zhou_2017_Cell.Rep_19_1117
Author(s) : Zhou K , Cherra SJ, 3rd , Goncharov A , Jin Y
Ref : Cell Rep , 19 :1117 , 2017
Abstract : Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca(2+) binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance.
ESTHER : Zhou_2017_Cell.Rep_19_1117
PubMedSearch : Zhou_2017_Cell.Rep_19_1117
PubMedID: 28494862

Title : Novel Mutations in Synaptic Transmission Genes Suppress Neuronal Hyperexcitation in Caenorhabditis elegans - McCulloch_2017_G3.(Bethesda)_7_2055
Author(s) : McCulloch KA , Qi YB , Takayanagi-Kiya S , Jin Y , Cherra SJ, 3rd
Ref : G3 (Bethesda) , 7 :2055 , 2017
Abstract : Acetylcholine (ACh) receptors (AChR) regulate neural circuit activity in multiple contexts. In humans, mutations in ionotropic acetylcholine receptor (iAChR) genes can cause neurological disorders, including myasthenia gravis and epilepsy. In Caenorhabditis elegans, iAChRs play multiple roles in the locomotor circuit. The cholinergic motor neurons express an ACR-2-containing pentameric AChR (ACR-2R) comprised of ACR-2, ACR-3, ACR-12, UNC-38, and UNC-63 subunits. A gain-of-function mutation in the non-alpha subunit gene acr-2 [acr-2(gf)] causes defective locomotion as well as spontaneous convulsions. Previous studies of genetic suppressors of acr-2(gf) have provided insights into ACR-2R composition and assembly. Here, to further understand how the ACR-2R regulates neuronal activity, we expanded the suppressor screen for acr-2(gf)-induced convulsions. The majority of these suppressor mutations affect genes that play critical roles in synaptic transmission, including two novel mutations in the vesicular ACh transporter unc-17 In addition, we identified a role for a conserved major facilitator superfamily domain (MFSD) protein, mfsd-6, in regulating neural circuit activity. We further defined a role for the sphingosine (SPH) kinase (Sphk) sphk-1 in cholinergic neuron activity, independent of previously known signaling pathways. Overall, the genes identified in our study suggest that optimal modulation of synaptic activity is balanced by the differential activities of multiple pathways, and the novel alleles provide valuable reagents to further dissect neuronal mechanisms regulating the locomotor circuit.
ESTHER : McCulloch_2017_G3.(Bethesda)_7_2055
PubMedSearch : McCulloch_2017_G3.(Bethesda)_7_2055
PubMedID: 28468816

Title : Tissue-specific regulation of alternative polyadenylation represses expression of a neuronal ankyrin isoform in C. elegans epidermal development - Chen_2017_Development_144_698
Author(s) : Chen F , Chisholm AD , Jin Y
Ref : Development , 144 :698 , 2017
Abstract : Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In C. elegans, several ankyrin isoforms are produced from the unc-44 locus through alternative polyadenylation. Here, we identify a key role for an intronic polyadenylation site (PAS) in temporal- and tissue-specific regulation of UNC-44/ankyrin isoforms. Removing an intronic PAS results in ectopic expression of the neuronal ankyrin isoform in non-neural tissues. This mis-expression underlies epidermal developmental defects in mutants of the conserved tumor suppressor death-associated protein kinase dapk-1 We have previously reported that the use of this intronic PAS depends on the nuclear polyadenylation factor SYDN-1, which inhibits the RNA polymerase II CTD phosphatase SSUP-72. Consistent with this, loss of sydn-1 blocks ectopic expression of neuronal ankyrin and suppresses epidermal morphology defects of dapk-1 These effects of sydn-1 are mediated by ssup-72 autonomously in the epidermis. We also show that a peptidyl-prolyl isomerase PINN-1 antagonizes SYDN-1 in the spatiotemporal control of neuronal ankyrin isoform. Moreover, the nuclear localization of PINN-1 is altered in dapk-1 mutants. Our data reveal that tissue and stage-specific expression of ankyrin isoforms relies on differential activity of positive and negative regulators of alternative polyadenylation.
ESTHER : Chen_2017_Development_144_698
PubMedSearch : Chen_2017_Development_144_698
PubMedID: 28087624

Title : Microtubule-dependent ribosome localization in C. elegans neurons - Noma_2017_Elife_6_
Author(s) : Noma K , Goncharov A , Ellisman MH , Jin Y
Ref : Elife , 6 : , 2017
Abstract : Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level. We found that axonal ribosomes change localization during neuronal development and after axonal injury. By examining mutants affecting axonal trafficking and performing a forward genetic screen, we showed that the microtubule cytoskeleton and the JIP3 protein UNC-16 exert distinct effects on localization of axonal and somatic ribosomes. Our data demonstrate the utility of tissue-specific visualization of ribosomes in vivo, and provide insight into the mechanisms of active regulation of ribosome localization in neurons.
ESTHER : Noma_2017_Elife_6_
PubMedSearch : Noma_2017_Elife_6_
PubMedID: 28767038

Title : Atrazine and its main metabolites alter the locomotor activity of larval zebrafish (Danio rerio) - Liu_2016_Chemosphere_148_163
Author(s) : Liu Z , Wang Y , Zhu Z , Yang E , Feng X , Fu Z , Jin Y
Ref : Chemosphere , 148 :163 , 2016
Abstract : Atrazine (ATZ) and its main chlorometabolites, i.e., diaminochlorotriazine (DACT), deisopropylatrazine (DIP), and deethylatrazine (DE), have been widely detected in aquatic systems near agricultural fields. However, their possible effects on aquatic animals are still not fully understood. In this study, it was observed that several developmental endpoints such as the heart beat, hatchability, and morphological abnormalities were influenced by ATZ and its metabolites in different developmental stages. In addition, after 5 days of exposure to 30, 100, 300 mug L-1 ATZ and its main chlorometabolites, the swimming behaviors of larval zebrafish were significantly disturbed, and the acetylcholinesterase (AChE) activities were consistently inhibited. Our results also demonstrate that ATZ and its main chlorometabolites are neuroendocrine disruptors that impact the expression of neurotoxicity-related genes such as Ache, Gap43, Gfap, Syn2a, Shha, Mbp, Elavl3, Nestin and Ngn1 in early developmental stages of zebrafish. According to our results, it is possible that not only ATZ but also its metabolites (DACT, DIP and DE) have the same or even more toxic effects on different endpoints of the early developmental stages of zebrafish.
ESTHER : Liu_2016_Chemosphere_148_163
PubMedSearch : Liu_2016_Chemosphere_148_163
PubMedID: 26803580

Title : Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes) - Sun_2016_Environ.Toxicol.Chem_35_2931
Author(s) : Sun L , Tan H , Peng T , Wang S , Xu W , Qian H , Jin Y , Fu Z
Ref : Environ Toxicol Chem , 35 :2931 , 2016
Abstract : Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. (c) 2016 SETAC.
ESTHER : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedSearch : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedID: 27146889

Title : The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish - Jin_2016_Chemosphere_153_455
Author(s) : Jin Y , Zhu Z , Wang Y , Yang E , Feng X , Fu Z
Ref : Chemosphere , 153 :455 , 2016
Abstract : The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 mug L-1 or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 mug L-1 IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development.
ESTHER : Jin_2016_Chemosphere_153_455
PubMedSearch : Jin_2016_Chemosphere_153_455
PubMedID: 27035382

Title : Genome-wide identification, classification and expression analysis in fungal-plant interactions of cutinase gene family and functional analysis of a putative ClCUT7 in Curvularia lunata - Liu_2016_Mol.Genet.Genomics_291_1105
Author(s) : Liu T , Hou J , Wang Y , Jin Y , Borth W , Zhao F , Liu Z , Hu J , Zuo Y
Ref : Mol Genet Genomics , 291 :1105 , 2016
Abstract : Cutinase is described as playing various roles in fungal-plant pathogen interactions, such as eliciting host-derived signals, fungal spore attachment and carbon acquisition during saprophytic growth. However, the characteristics of the cutinase genes, their expression in compatible interactions and their roles in pathogenesis have not been reported in Curvularia lunata, an important leaf spot pathogen of maize in China. Therefore, a cutinase gene family analysis could have profound significance. In this study, we identified 13 cutinase genes (ClCUT1 to ClCUT13) in the C. lunata genome. Multiple sequence alignment showed that most fungal cutinase proteins had one highly conserved GYSQG motif and a similar DxVCxG[ST]-[LIVMF](3)-x(3)H motif. Gene structure analyses of the cutinases revealed a complex intron-exon pattern with differences in the position and number of introns and exons. Based on phylogenetic relationship analysis, C. lunata cutinases and 78 known cutinase proteins from other fungi were classified into four groups with subgroups, but the C. lunata cutinases clustered in only three of the four groups. Motif analyses showed that each group of cutinases from C. lunata had a common motif. Real-time PCR indicated that transcript levels of the cutinase genes in a compatible interaction between pathogen and host had varied expression patterns. Interestingly, the transcript levels of ClCUT7 gradually increased during early pathogenesis with the most significant up-regulation at 3 h post-inoculation. When ClCUT7 was deleted, pathogenicity of the mutant decreased on unwounded maize (Zea mays) leaves. On wounded maize leaves, however, the mutant caused symptoms similar to the wild-type strain. Moreover, the ClCUT7 mutant had an approximately 10 % reduction in growth rate when cutin was the sole carbon source. In conclusion, we identified and characterized the cutinase family genes of C. lunata, analyzed their expression patterns in a compatible host-pathogen interaction, and explored the role of ClCUT7 in pathogenicity. This work will increase our understanding of cutinase genes in other fungal-plant pathogens.
ESTHER : Liu_2016_Mol.Genet.Genomics_291_1105
PubMedSearch : Liu_2016_Mol.Genet.Genomics_291_1105
PubMedID: 26767524

Title : The toxicity of chlorpyrifos on the early life stage of zebrafish: A survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity - Jin_2015_Fish.Shellfish.Immunol_43_405
Author(s) : Jin Y , Liu Z , Peng T , Fu Z
Ref : Fish Shellfish Immunol , 43 :405 , 2015
Abstract : Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 mug/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor alpha (Tnfalpha), interferon (Ifn), interleukin-1 beta (Il-1beta), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 mug/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish.
ESTHER : Jin_2015_Fish.Shellfish.Immunol_43_405
PubMedSearch : Jin_2015_Fish.Shellfish.Immunol_43_405
PubMedID: 25634256

Title : Lipoprotein lipase deficiency leads to alpha-synuclein aggregation and ubiquitin C-terminal hydrolase L1 reduction - Yang_2015_Neurosci_290_1
Author(s) : Yang H , Zhou T , Wang H , Liu T , Ueda K , Zhan R , Zhao L , Tong Y , Tian X , Zhang T , Jin Y , Han X , Li Z , Zhao Y , Guo X , Xiao W , Fan D , Liu G , Chui D
Ref : Neuroscience , 290 :1 , 2015
Abstract : We have previously reported that presynaptic dysfunction and cognitive decline have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism remains to be elucidated. Accumulating evidence supported that alpha-synuclein (alpha-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal synaptic and cognitive function. In this study, we found that alpha-syn aggregated and the expression of UCHL1 decreased in the brain of LPL deficient mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5-methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination of alpha-syn. These results indicated that aggregation of alpha-syn and reduction of UCHL1 expression in LPL-deficient mice may affect synaptic function.
ESTHER : Yang_2015_Neurosci_290_1
PubMedSearch : Yang_2015_Neurosci_290_1
PubMedID: 25595992

Title : Potential mechanisms of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose VOCs - Wang_2014_Inhal.Toxicol_26_250
Author(s) : Wang F , Li C , Liu W , Jin Y
Ref : Inhal Toxicol , 26 :250 , 2014
Abstract : Abstract To investigate effects of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose volatile organic compounds (VOCs) and the possible mechanism for these effects, 60 male Kunming mice were exposed in 5 similar static chambers, 0 (control) and 4 different doses of VOCs mixture (G1-4) for consecutively 90 d at 2 h/d. The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.05 + 0.05 + 0.10 + 0.10 mg/m(3), 0.10 + 0.11 + 0.20 + 0.20 mg/m(3), 0.50 + 0.55 + 1.00 + 1.00 mg/m(3), 1.00 +1.10 + 2.00 + 2.00 mg/m(3), respectively, which corresponded to 1/2, 1, 5, and 10 times of indoor air quality standard in China. Morris water maze (MWM) and Grip strength (GS) test were performed in the last 7 weeks. One day following VOCs exposure, oxidative stress markers, neurotransmitters, and cholinergic system enzymes in brain were examined. In addition, the expressions of N-methyl-d-aspartate (NMDA) receptor in hippocampus were determined. VOCs exposure induced behavioral impairment of mice in MWM and GS test. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutamic acid (Glu) were significantly increased, while the acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and acetylcholine (ACh) levels, and the expression of NMDA receptor were significantly decreased in VOCs exposed groups. Results showed that sub-chronic exposure to low-dose VOCs induced damage on physique and motor function, as well as impairment on learning and memory capacity of mice. Oxidative damage, abnormal metabolism of neurotransmitters and cholinergic system enzymes, and the alternation of NMDA receptor expression may be the possible mechanism for VOCs-induced neurotoxicity.
ESTHER : Wang_2014_Inhal.Toxicol_26_250
PubMedSearch : Wang_2014_Inhal.Toxicol_26_250
PubMedID: 24568580

Title : Complete genome sequence of Bacillus amyloliquefaciens LL3, which exhibits glutamic acid-independent production of poly-gamma-glutamic acid - Geng_2011_J.Bacteriol_193_3393
Author(s) : Geng W , Cao M , Song C , Xie H , Liu L , Yang C , Feng J , Zhang W , Jin Y , Du Y , Wang S
Ref : Journal of Bacteriology , 193 :3393 , 2011
Abstract : Bacillus amyloliquefaciens is one of most prevalent Gram-positive aerobic spore-forming bacteria with the ability to synthesize polysaccharides and polypeptides. Here, we report the complete genome sequence of B. amyloliquefaciens LL3, which was isolated from fermented food and presents the glutamic acid-independent production of poly-gamma-glutamic acid.
ESTHER : Geng_2011_J.Bacteriol_193_3393
PubMedSearch : Geng_2011_J.Bacteriol_193_3393
PubMedID: 21551302
Gene_locus related to this paper: baca2-a7z811

Title : Exposure of nicotine to ventral tegmental area slices induces glutamatergic synaptic plasticity on dopamine neurons - Jin_2011_Synapse_65_332
Author(s) : Jin Y , Yang K , Wang H , Wu J
Ref : Synapse , 65 :332 , 2011
Abstract : Nicotine promotes glutamatergic synaptic plasticity in dopaminergic (DA) neurons in the ventral tegmental area (VTA), which is thought to be an important mechanism underlying nicotine reward. However, it is unclear whether exposure of nicotine alone to VTA slice is sufficient to increase glutamatergic synaptic strength on DA neurons and which nicotinic acetylcholine receptor (nAChR) subtype mediates this effect. Here, we report that the incubation of rat VTA slices with 500 nM nicotine induces glutamatergic synaptic plasticity in DA neurons. We measure the ratio of AMPA and NMDA receptor-mediated currents (AMPA/NMDA) and compare these ratios between nicotine-treated and -untreated slices. Our results demonstrate that the incubation of VTA slices with 500 nM nicotine for 1 h (but not for 10 min) significantly increases the AMPA/NMDA ratio when compared with controls. Preincubation with 10 nM of the alpha7-nAChR antagonist, methyllycaconitine (MLA) but not 1 muM alpha4-containing nAChR antagonist, dihydro-beta-erythroidine (DHbetaE) prevents nicotinic effect, suggesting that alpha7-nAChRs are mainly mediated this nicotinic effect. This finding is further supported by the disappearance of this nicotinic effect in nAChR alpha7 knockout (KO) mice. Furthermore, nicotine reduced paired-pulse ratio (PPR) of evoked excitatory postsynaptic potential (eEPSP) in the VTA slices prepared from wild-type (WT) mice but not alpha7 KO mice. Collectively, these findings suggest that exposure of smoking-relevant concentrations of nicotine to VTA slices is sufficient to increase glutamatergic synaptic strength on DA neurons and that alpha7-nAChRs likely mediate this nicotinic effect through increasing presynaptic release of glutamate.
ESTHER : Jin_2011_Synapse_65_332
PubMedSearch : Jin_2011_Synapse_65_332
PubMedID: 20730803

Title : Prenatal and early life arsenic exposure induced oxidative damage and altered activities and mRNA expressions of neurotransmitter metabolic enzymes in offspring rat brain - Xi_2010_J.Biochem.Mol.Toxicol_24_368
Author(s) : Xi S , Guo L , Qi R , Sun W , Jin Y , Sun G
Ref : J Biochem Mol Toxicol , 24 :368 , 2010
Abstract : To better understand the effect of arsenic on central nervous system by prenatal and early life exposure, the oxidative stress and neurotransmitter metabolic enzymes were determined in offspring rats' brain cortex and hippocampus. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic (As)-containing water as the dams. The level of malondialdehyde in 100 mg/L As-exposed pup's brain on PND 0 and cortex on PND 28 and 42 were significantly higher than in the control group (p < 0.05). Reduced glutathione (GSH) levels showed a clear decreasing trend in pup's cortex and hippocampus on PND 42. Activity of acetylcholinesterase was significantly higher in 100 mg/L As-exposed pup's hippocampus than in control group on PND 28 and 42. mRNA expression of glutamate decarboxylase (GAD(65) and GAD(67)) in 100 mg/L As-exposed pup's cortex or hippocampus on PND 28 and 42 were significantly higher than in control (p < 0.05). These alterations in the neurotransmitters and reduced antioxidant defence may lead to neurobehavioral and learning and memory changes in offspring rats.
ESTHER : Xi_2010_J.Biochem.Mol.Toxicol_24_368
PubMedSearch : Xi_2010_J.Biochem.Mol.Toxicol_24_368
PubMedID: 20376865

Title : Mechanisms involved in systemic nicotine-induced glutamatergic synaptic plasticity on dopamine neurons in the ventral tegmental area - Gao_2010_J.Neurosci_30_13814
Author(s) : Gao M , Jin Y , Yang K , Zhang D , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 30 :13814 , 2010
Abstract : Systemic exposure to nicotine induces glutamatergic synaptic plasticity on dopamine (DA) neurons in the ventral tegmental area (VTA), but mechanisms are largely unknown. Here, we report that single, systemic exposure in rats to nicotine (0.17 mg/kg free base) increases the ratio of DA neuronal currents mediated by AMPA relative to NMDA receptors (AMPA/NMDA ratio) assessed 24 h later, based on slice-patch recording. The AMPA/NMDA ratio increase is evident within 1 h and lasts for at least 72 h after nicotine exposure (and up to 8 d after repeated nicotine administration). This effect cannot be prevented by systemic injection of either alpha7-nAChR (nicotinic ACh receptor)-selective [methyllycaconitine (MLA)] or beta2*-nAChR-selective [mecamylamine (MEC)] antagonists but is prevented by coinjection of MLA and MEC. In either nAChR alpha7 or beta2 subunit knock-out mice, systemic exposure to nicotine still increases the AMPA/NMDA ratio. Preinjection in rats of a NMDA receptor antagonist MK-801((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), but neither DA receptor antagonists [SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) plus haloperidol] nor a calcineurin inhibitor (cyclosporine), prevents the nicotine-induced increase in AMPA/NMDA ratio. After systemic exposure to nicotine, glutamatergic (but not GABAergic) transmission onto rat VTA DA neuronal inputs is enhanced. Correspondingly, DA neuronal firing measured 24 h after nicotine exposure using extracellular single-unit recording in vivo is significantly faster, and there is conversion of silent to active DA neurons. Collectively, these findings demonstrate that systemic nicotine acting via either alpha7- or beta2*-nAChRs increases presynaptic and postsynaptic glutamatergic function, and consequently initiates glutamatergic synaptic plasticity, which may be an important, early neuronal adaptation in nicotine reward and reinforcement.
ESTHER : Gao_2010_J.Neurosci_30_13814
PubMedSearch : Gao_2010_J.Neurosci_30_13814
PubMedID: 20943922

Title : Salmonella paratyphi C: genetic divergence from Salmonella choleraesuis and pathogenic convergence with Salmonella typhi - Liu_2009_PLoS.One_4_e4510
Author(s) : Liu WQ , Feng Y , Wang Y , Zou QH , Chen F , Guo JT , Peng YH , Jin Y , Li YG , Hu SN , Johnston RN , Liu GR , Liu SL
Ref : PLoS ONE , 4 :e4510 , 2009
Abstract : BACKGROUND: Although over 1400 Salmonella serovars cause usually self-limited gastroenteritis in humans, a few, e.g., Salmonella typhi and S. paratyphi C, cause typhoid, a potentially fatal systemic infection. It is not known whether the typhoid agents have evolved from a common ancestor (by divergent processes) or acquired similar pathogenic traits independently (by convergent processes). Comparison of different typhoid agents with non-typhoidal Salmonella lineages will provide excellent models for studies on how similar pathogens might have evolved. METHODOLOGIES/PRINCIPAL FINDINGS: We sequenced a strain of S. paratyphi C, RKS4594, and compared it with previously sequenced Salmonella strains. RKS4594 contains a chromosome of 4,833,080 bp and a plasmid of 55,414 bp. We predicted 4,640 intact coding sequences (4,578 in the chromosome and 62 in the plasmid) and 152 pseudogenes (149 in the chromosome and 3 in the plasmid). RKS4594 shares as many as 4346 of the 4,640 genes with a strain of S. choleraesuis, which is primarily a swine pathogen, but only 4008 genes with another human-adapted typhoid agent, S. typhi. Comparison of 3691 genes shared by all six sequenced Salmonella strains placed S. paratyphi C and S. choleraesuis together at one end, and S. typhi at the opposite end, of the phylogenetic tree, demonstrating separate ancestries of the human-adapted typhoid agents. S. paratyphi C seemed to have suffered enormous selection pressures during its adaptation to man as suggested by the differential nucleotide substitutions and different sets of pseudogenes, between S. paratyphi C and S. choleraesuis. CONCLUSIONS: S. paratyphi C does not share a common ancestor with other human-adapted typhoid agents, supporting the convergent evolution model of the typhoid agents. S. paratyphi C has diverged from a common ancestor with S. choleraesuis by accumulating genomic novelty during adaptation to man.
ESTHER : Liu_2009_PLoS.One_4_e4510
PubMedSearch : Liu_2009_PLoS.One_4_e4510
PubMedID: 19229335
Gene_locus related to this paper: salty-BIOH , salty-FES , salty-IROD , salty-IROE , salty-P74847 , salty-STM0332 , salty-STY1441 , salty-STY2428 , salty-yafa , salty-YBFF , salty-ycfp , salty-YFBB

Title : Hypertriglyceridemia in Watanabe heritable hyperlipidemic rabbits was associated with increased production and reduced catabolism of very-low-density lipoproteins - Zhang_2009_Pathobiology_76_315
Author(s) : Zhang C , Jin Y , Liu T , Liu F , Ito T
Ref : Pathobiology , 76 :315 , 2009
Abstract : Watanabe heritable hyperlipidemic (WHHL) rabbit is an animal model for human familial hypercholesterolemia. Recently, we segregated a new mutant of WHHL rabbits with plasma levels of triglycerides (TG) >500 mg/dl (designated as TGH-WHHL). To investigate the underlying mechanisms for hypertriglyceridemia, we compared TGH-WHHL with WHHL rabbits with lower plasma TG levels (<250 mg/dl, designated as TGL-WHHL). A Triton WR-1339 injection experiment revealed that TGH-WHHL rabbits had increased secretion and decreased clearance of TG-rich lipoproteins. Furthermore, TGH-WHHL rabbits had lower a post-heparin activity of lipoprotein lipase and a higher cholesterol ester transfer protein activity than TGL-WHHL rabbits. Cultured hepatocytes isolated from TGH-WHHL rabbits showed a higher secretion rate of TG and cholesterol than those of TGL-WHHL rabbits. In addition, TGH-WHHL rabbits exhibited marked insulin resistance. These data suggest that hypertriglyceridemia exhibited by WHHL rabbits is caused by both increased production and impaired catabolism of TG-rich lipoproteins and associated with insulin resistance.
ESTHER : Zhang_2009_Pathobiology_76_315
PubMedSearch : Zhang_2009_Pathobiology_76_315
PubMedID: 19955843

Title : A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans - Jospin_2009_PLoS.Biol_7_e1000265
Author(s) : Jospin M , Qi YB , Stawicki TM , Boulin T , Schuske KR , Horvitz HR , Bessereau JL , Jorgensen EM , Jin Y
Ref : PLoS Biol , 7 :e1000265 , 2009
Abstract : In the nematode Caenorhabditis elegans, cholinergic motor neurons stimulate muscle contraction as well as activate GABAergic motor neurons that inhibit contraction of the contralateral muscles. Here, we describe the composition of an ionotropic acetylcholine receptor that is required to maintain excitation of the cholinergic motor neurons. We identified a gain-of-function mutation that leads to spontaneous muscle convulsions. The mutation is in the pore domain of the ACR-2 acetylcholine receptor subunit and is identical to a hyperactivating mutation in the muscle receptor of patients with myasthenia gravis. Screens for suppressors of the convulsion phenotype led to the identification of other receptor subunits. Cell-specific rescue experiments indicate that these subunits function in the cholinergic motor neurons. Expression of these subunits in Xenopus oocytes demonstrates that the functional receptor is comprised of three alpha-subunits, UNC-38, UNC-63 and ACR-12, and two non-alpha-subunits, ACR-2 and ACR-3. Although this receptor exhibits a partially overlapping subunit composition with the C. elegans muscle acetylcholine receptor, it shows distinct pharmacology. Recordings from intact animals demonstrate that loss-of-function mutations in acr-2 reduce the excitability of the cholinergic motor neurons. By contrast, the acr-2(gf) mutation leads to a hyperactivation of cholinergic motor neurons and an inactivation of downstream GABAergic motor neurons in a calcium dependent manner. Presumably, this imbalance between excitatory and inhibitory input into muscles leads to convulsions. These data indicate that the ACR-2 receptor is important for the coordinated excitation and inhibition of body muscles underlying sinusoidal movement.
ESTHER : Jospin_2009_PLoS.Biol_7_e1000265
PubMedSearch : Jospin_2009_PLoS.Biol_7_e1000265
PubMedID: 20027209

Title : Memory performance of hypercholesterolemic mice in response to treatment with soy isoflavones - Liu_2007_Neurosci.Res_57_544
Author(s) : Liu YQ , Xin TR , Lu XY , Ji Q , Jin Y , Yang HD
Ref : Neurosci Res , 57 :544 , 2007
Abstract : The aim of this study is to investigate the memory performance of hypercholesterolemic mice in response to soy isoflavones (SI) treatment and the mechanism involved. In this study, 64 mice were randomly divided into four groups: control, high lipid diet without SI, high lipid diet with a low SI level (50 mg/kg bw) and high lipid diet with a high SI level (100 mg/kg bw). The experimental period was 30 days. The results indicated that the mice given the different treatments showed the different percentages of good, medium and poor memory performance. chi(2) analysis revealed significant difference in memory performance (P<0.05) between the high lipid diet without SI group and the high lipid diet with a low SI level group or high lipid diet with a high SI level group. Moreover, SI treatment resulted in a decrease in blood cholesterol (TC) level (high lipid diet without SI group versus high lipid diet with a low SI level group or high lipid diet with a high SI level group, P<0.05) and triglyceride (TG) level (high lipid diet without SI group versus high lipid diet with a low SI level group or high lipid diet with a high SI level group, P<0.05). In addition, SI treatment resulted in a significant decrease in acetylcholinesterase (AChE) activity and significant increases in glutamic acid and aspartic acid contents in the frontal cerebral cortex and hippocampus. The results suggest that SI improve the memory performance of hypercholesterolemic mice, and the mechanism underlying the improvement might closely correlate with its roles in decreasing high blood lipid levels and modulating the metabolism of neurotransmitters such as acetylcholine and amino acids in brain areas of hypercholesterolemic mice.
ESTHER : Liu_2007_Neurosci.Res_57_544
PubMedSearch : Liu_2007_Neurosci.Res_57_544
PubMedID: 17289196

Title : Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms - Jin_2003_Toxicon_42_539
Author(s) : Jin Y , Lu Q , Zhou X , Zhu S , Li R , Wang W , Xiong Y
Ref : Toxicon , 42 :539 , 2003
Abstract : Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes.
ESTHER : Jin_2003_Toxicon_42_539
PubMedSearch : Jin_2003_Toxicon_42_539
PubMedID: 14529736

Title : The basement membrane components nidogen and type XVIII collagen regulate organization of neuromuscular junctions in Caenorhabditis elegans - Ackley_2003_J.Neurosci_23_3577
Author(s) : Ackley BD , Kang SH , Crew JR , Suh C , Jin Y , Kramer JM
Ref : Journal of Neuroscience , 23 :3577 , 2003
Abstract : Vertebrate neuromuscular junctions (NMJs) contain specialized basal laminas enriched for proteins not found at high concentrations extrasynaptically. Alterations in NMJ basement membrane components can result in loss of NMJ structural integrity and lead to muscular dystrophies. We demonstrate here that the conserved Caenorhabditis elegans basement membrane-associated molecules nidogen/entactin (NID-1) and type XVIII collagen (CLE-1) are associated with axons and particularly enriched near synaptic contacts. NID-1 is concentrated laterally, between the nerve cord and muscles, whereas CLE-1 is concentrated dorsal to the ventral nerve cord and ventral to the dorsal nerve cord, above the regions where synapses form. Mutations in these molecules cause specific and distinct defects in the organization of neuromuscular junctions. The mutant animals exhibit mild movement defects and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating altered synaptic function. Our results provide the first demonstration that basement membrane molecules are important for NMJ formation and/or maintenance in C. elegans and that collagen XVIII and nidogen can have important roles in synapse organization.
ESTHER : Ackley_2003_J.Neurosci_23_3577
PubMedSearch : Ackley_2003_J.Neurosci_23_3577
PubMedID: 12736328

Title : The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment - Clark_2003_Genome.Res_13_2265
Author(s) : Clark HF , Gurney AL , Abaya E , Baker K , Baldwin D , Brush J , Chen J , Chow B , Chui C , Crowley C , Currell B , Deuel B , Dowd P , Eaton D , Foster J , Grimaldi C , Gu Q , Hass PE , Heldens S , Huang A , Kim HS , Klimowski L , Jin Y , Johnson S , Lee J , Lewis L , Liao D , Mark M , Robbie E , Sanchez C , Schoenfeld J , Seshagiri S , Simmons L , Singh J , Smith V , Stinson J , Vagts A , Vandlen R , Watanabe C , Wieand D , Woods K , Xie MH , Yansura D , Yi S , Yu G , Yuan J , Zhang M , Zhang Z , Goddard A , Wood WI , Godowski P , Gray A
Ref : Genome Res , 13 :2265 , 2003
Abstract : A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.
ESTHER : Clark_2003_Genome.Res_13_2265
PubMedSearch : Clark_2003_Genome.Res_13_2265
PubMedID: 12975309
Gene_locus related to this paper: human-CES3 , human-CES4A

Title : Biochemical and biological properties of Trimeresurus jerdonii venom and characterization of a platelet aggregation-inhibiting acidic phospholipase A2 - Lu_2002_J.Nat.Toxins_11_25
Author(s) : Lu QM , Jin Y , Wei JF , Wang WY , Xiong YL
Ref : J Nat Toxins , 11 :25 , 2002
Abstract : Several biochemical and biological activities such as phospholipase A2, arginine esterase, proteolytic, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase, thrombin-like, anticoagulant, and hemorrhagic activities were determined for whole desiccated venom of Trimeresurus jerdonii. An acidic phospholipase (named TJ-PLA2) was purified by anionic exchange chromatography, gel filtration, and reverse phase HPLC. TJ-PLA2 had a molecular weight of 16,000 and a pI of 4.8. TJ-PLA2 was non-lethal to mice up to an i.p. dose of 15 mg/kg body weight and lacked neurotoxicity and myotoxicity. It induced edema in the footpads of mice. The purified enzyme inhibited ADP- and collagen-induced human platelet aggregation in a manner which was both dose- and time-dependent.
ESTHER : Lu_2002_J.Nat.Toxins_11_25
PubMedSearch : Lu_2002_J.Nat.Toxins_11_25
PubMedID: 11829058

Title : Genetic convergence during serial in vitro passage of a polyclonal squamous cell carcinoma - Heim_1989_Cytogenet.Cell.Genet_52_133
Author(s) : Heim S , Caron M , Jin Y , Mandahl N , Mitelman F
Ref : Cytogenet Cell Genet , 52 :133 , 1989
Abstract : A cell line was established from an in situ squamous cell carcinoma of the skin (Bowen's disease), and its in vitro karyotypic evolution was cytogenetically analyzed. Initially, considerable genetic heterogeneity was evident. Nine cytogenetically abnormal clones, eight of which were apparently unrelated, were found among the 83 metaphases analyzed from the primary culture and the first passage. With increasing time in culture this complexity was reduced, so that a single clone dominated passages 7-11. The clone that emerged from this genetic convergence had a t(12;17)(p13;q21) as the sole abnormality. Our findings indicate that the cytogenetic multiclonality that has been repeatedly detected in short-term cultures of squamous cell carcinomas is not caused by the in vitro conditions. Instead, the principles of Darwinian selection apply: the altered, but stable, selection pressure facing a newly established and initially multiclonal cell line will lead to a reduction of genetic heterogeneity until the one clone that now has the proliferative advantage outgrows the other subpopulations.
ESTHER : Heim_1989_Cytogenet.Cell.Genet_52_133
PubMedSearch : Heim_1989_Cytogenet.Cell.Genet_52_133
PubMedID: 2630184