Xiong Y

References (35)

Title : Role of Mn-LIPA in Sex Hormone Regulation and Gonadal Development in the Oriental River Prawn, Macrobrachium nipponense - Cai_2024_Int.J.Mol.Sci_25_
Author(s) : Cai P , Zhang W , Jiang S , Xiong Y , Qiao H , Yuan H , Gao Z , Zhou Y , Jin S , Fu H
Ref : Int J Mol Sci , 25 : , 2024
Abstract : This study investigates the role of lysosomal acid lipase (LIPA) in sex hormone regulation and gonadal development in Macrobrachium nipponense. The full-length Mn-LIPA cDNA was cloned, and its expression patterns were analyzed using quantitative real-time PCR (qPCR) in various tissues and developmental stages. Higher expression levels were observed in the hepatopancreas, cerebral ganglion, and testes, indicating the potential involvement of Mn-LIPA in sex differentiation and gonadal development. In situ hybridization experiments revealed strong Mn-LIPA signaling in the spermatheca and hepatopancreas, suggesting their potential role in steroid synthesis (such as cholesterol, fatty acids, cholesteryl ester, and triglycerides) and sperm maturation. Increased expression levels of male-specific genes, such as insulin-like androgenic gland hormone (IAG), sperm gelatinase (SG), and mab-3-related transcription factor (Dmrt11E), were observed after dsMn-LIPA (double-stranded LIPA) injection, and significant inhibition of sperm development and maturation was observed histologically. Additionally, the relationship between Mn-LIPA and sex-related genes (IAG, SG, and Dmrt11E) and hormones (17beta-estradiol and 17alpha-methyltestosterone) was explored by administering sex hormones to male prawns, indicating that Mn-LIPA does not directly control the production of sex hormones but rather utilizes the property of hydrolyzing triglycerides and cholesterol to provide energy while influencing the synthesis and secretion of self-sex hormones. These findings provide valuable insights into the function of Mn-LIPA in M. nipponense and its potential implications for understanding sex differentiation and gonadal development in crustaceans. It provides an important theoretical basis for the realization of a monosex culture of M. nipponense.
ESTHER : Cai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Cai_2024_Int.J.Mol.Sci_25_
PubMedID: 38338678

Title : Discovery of seven-membered ring berberine analogues as highly potent and specific hCES2A inhibitors - Yang_2023_Chem.Biol.Interact_378_110501
Author(s) : Yang Y , Xiong Y , Zhu G , Sun M , Zou K , Zhao Y , Zhang Y , Xu Z , Li Y , Zhu W , Jia Q , Li B , Ge G
Ref : Chemico-Biological Interactions , 378 :110501 , 2023
Abstract : Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC(50) = 1.66 microM) and excellent selectivity over hCES1A (IC(50) > 100 microM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K(i) value of 1.035 microM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
ESTHER : Yang_2023_Chem.Biol.Interact_378_110501
PubMedSearch : Yang_2023_Chem.Biol.Interact_378_110501
PubMedID: 37080375

Title : Enzyme-targeted near-infrared fluorescent probe for organophosphorus pesticide residue detection - Luo_2023_Anal.Bioanal.Chem__
Author(s) : Luo S , Peng R , Wang Y , Liu X , Ren J , Li W , Xiong Y , Yi S , Wen Q
Ref : Anal Bioanal Chem , : , 2023
Abstract : Pesticide residues significantly affect food safety and harm human health. In this work, a series of near-infrared fluorescent probes were designed and developed by acylating the hydroxyl group of the hemicyanine skeleton with a quenching moiety for monitoring the presence of organophosphorus pesticides in food and live cells. The carboxylic ester bond on the probe was hydrolyzed catalytically in the presence of carboxylesterase and thereby the fluorophore was released with near-infrared emission. Notably, the proposed probe 1 exhibited excellent sensitivity against organophosphorus based on the carboxylesterase inhibition mechanism and the detection limit for isocarbophos achieved 0.1734 microg/L in the fresh vegetable sample. More importantly, probe 1 allowed for situ visualization of organophosphorus in live cells and bacteria, meaning great potential for tracking the organophosphorus in biological systems. Consequently, this study presents a promising strategy for tracking pesticide residues in food and biological systems.
ESTHER : Luo_2023_Anal.Bioanal.Chem__
PubMedSearch : Luo_2023_Anal.Bioanal.Chem__
PubMedID: 37433954

Title : Integrative Analysis of Transcriptome and Metabolome to Illuminate the Protective Effects of Didymin against Acute Hepatic Injury - Pang_2023_Mediators.Inflamm_2023_6051946
Author(s) : Pang L , Xiong Y , Feng Z , Li C , Fang B , Huang Q , Lin X
Ref : Mediators Inflamm , 2023 :6051946 , 2023
Abstract : Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-kappaB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-kappaB pathways.
ESTHER : Pang_2023_Mediators.Inflamm_2023_6051946
PubMedSearch : Pang_2023_Mediators.Inflamm_2023_6051946
PubMedID: 36687218

Title : The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [(14)C] cetagliptin in healthy volunteers - Lu_2022_Xenobiotica_52_38
Author(s) : Lu J , Bian Y , Zhang H , Tang D , Tian X , Zhou X , Xu Z , Xiong Y , Gu Z , Yu Z , Wang T , Ding J , Yu Q
Ref : Xenobiotica , 52 :38 , 2022
Abstract : The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50microCi [(14)C] cetagliptin.The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [(14)C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulphate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and faeces at low levels, except that metabolite M640B was not detected in faeces. All metabolites were observed with <10% of parent compound systemic exposure after oral administration.
ESTHER : Lu_2022_Xenobiotica_52_38
PubMedSearch : Lu_2022_Xenobiotica_52_38
PubMedID: 34743655

Title : Discovery and Characterization of the Naturally Occurring Inhibitors Against Human Pancreatic Lipase in Ampelopsis grossedentata - Qin_2022_Front.Nutr_9_844195
Author(s) : Qin XY , Hou XD , Zhu GH , Xiong Y , Song YQ , Zhu L , Zhao DF , Jia SN , Hou J , Tang H , Ge GB
Ref : Front Nutr , 9 :844195 , 2022
Abstract : Pancreatic lipase (PL) inhibitor therapy has been validated as an efficacious way for preventing and treating obesity and overweight. In the past few decades, porcine PL (pPL) is widely used as the enzyme source for screening the PL inhibitors, which generates a wide range of pPL inhibitors. By contrast, the efficacious inhibitors against human PL (hPL) are rarely reported. This study aims to discover the naturally occurring hPL inhibitors from edible herbal medicines (HMs) and to characterize the inhibitory mechanisms of the newly identified hPL inhibitors. Following the screening of the inhibition potentials of more than 100 HMs against hPL, Ampelopsis grossedentata extract (AGE) displayed the most potent hPL inhibition activity. After that, the major constituents in AGE were identified and purified, while their anti-hPL effects were assayed in vitro. The results clearly showed that two abundant constituents in AGE (dihydromyricetin and iso-dihydromyricetin) were moderate hPL inhibitors, while myricetin and quercetin were strong hPL inhibitors [half-maximal inhibitory concentration (IC (50)) values were around 1.5 microM]. Inhibition kinetic analyses demonstrated that myricetin and quercetin potently inhibited hPL-catalyzed near-infrared fluorogenic substrate of human pancreatic lipase (DDAO-ol) hydrolysis in a non-competitive inhibition manner, with K (i) values of 2.04 and 2.33 microM, respectively. Molecular dynamics simulations indicated that myricetin and quercetin could stably bind on an allosteric site of hPL. Collectively, this study reveals the key anti-obesity constituents in AGE and elucidates their inhibitory mechanisms against hPL, which offers convincing evidence to support the anti-obesity and lipid-lowering effects of this edible herb.
ESTHER : Qin_2022_Front.Nutr_9_844195
PubMedSearch : Qin_2022_Front.Nutr_9_844195
PubMedID: 35284458

Title : Electrochemical (Bio)Sensors for the Detection of Organophosphorus Pesticides Based on Nanomaterial-Modified Electrodes: A Review - Ding_2022_Crit.Rev.Anal.Chem__1
Author(s) : Ding R , Li Z , Xiong Y , Wu W , Yang Q , Hou X
Ref : Crit Rev Analytical Chemistry , :1 , 2022
Abstract : Organophosphorus pesticides were easily remained in fruits and vegetables which would be harm to the environmental safety and human health. In recent years, due to the simple preparation process, fast response and high sensitivity, the electrochemical (bio)sensors have received increasing attention, which were extensively used as the sensing platform for the detection of OPPs. The mechanisms for the determination of OPPs mainly included redox of nitrophenyl OPPs, enzyme hydrolysis and inhibition, immunosensor, aptasensor. Nowadays, the mainly explored electrode material has focused on metal-organic frameworks, metal and metal derivatives, carbon materials (carbon nanotube, graphene, g-C(3)N(4)), MXene, etc. These nanomaterials played important roles in the electrochemical (bio)sensors, which included: (a) as an electrocatalyst to promote the redox reaction, (b) as a carrier to load the enzyme or aptamer, (c) as a recognizer to identify the targets. The nanomaterials-based electrochemical (bio)sensor was a rapid, cost-effective methods to detect OPPs with high sensitivity. Besides, this review compared the analytical performance of different nanomaterials-based electrochemical (bio)sensors, and also identified the key challenges in the future. It would provide new ideas and insights to the further development and application of electrochemical (bio)sensors and the detection of pesticides in real samples.
ESTHER : Ding_2022_Crit.Rev.Anal.Chem__1
PubMedSearch : Ding_2022_Crit.Rev.Anal.Chem__1
PubMedID: 35235478

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

Title : Effect of extrusion technology on hempseed (Cannabis sativa L.) oil cake: Polyphenol profile and biological activities - Leonard_2021_J.Food.Sci__
Author(s) : Leonard W , Zhang P , Ying D , Xiong Y , Fang Z
Ref : J Food Sci , : , 2021
Abstract : Effects of extrusion with varying barrel temperature, moisture content, and screw speed on hempseed oil cake were studied for the first time. Extrusion at lower moisture (30%) and higher screw speed (300 rpm) significantly increased the proportion of free polyphenols, flavonoids, and phenylpropionamide content, and alpha -glucosidase and acetylcholinesterase inhibition activities. Full factorial design confirmed the three-way interactions among all extrusion parameters for all chemical assays with the bound phenolic fraction, total flavonoid content, and DPPH inhibition activity of the free phenolic fraction. HPLC-DAD-ESI-QTOF-MS/MS analysis tentatively identified 26 phenylpropionamides, and the contents of N-trans-caffeoyltyramine (66.26 microg/g) and total phenylpropionamides (85.77 microg/g) were significantly increased after extrusion at the lower moisture and higher screw speed extrusion conditions. The higher alpha -glucosidase inhibition activity at higher screw speed could be due to the N-trans-caffeoyltyramine (r = 0.99, p < 0.01), while the AChE inhibition activity appeared to be influenced more by the cannabisins A-C, M (r > 0.8, p < 0.01). PRACTICAL APPLICATION: Hempseed oil cake is a byproduct of oil extraction, with high protein and high fiber contents. The results of this research could be used directly in food industry to improve the nutritional and commercial value of hempseed oil cake by extrusion technology.
ESTHER : Leonard_2021_J.Food.Sci__
PubMedSearch : Leonard_2021_J.Food.Sci__
PubMedID: 34176120

Title : Soluble ligands as drug targets for treatment of inflammatory bowel disease - Tong_2021_Pharmacol.Ther__107859
Author(s) : Tong X , Zheng Y , Li Y , Xiong Y , Chen D
Ref : Pharmacol Ther , :107859 , 2021
Abstract : Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by persistent inflammation in a hereditarily susceptible host. In addition to gastrointestinal symptoms, patients with IBD frequently suffer from extra-intestinal complications such as fibrosis, stenosis or cancer. Mounting evidence supports the targeting of cytokines for effective treatment of IBD. Cytokines can be included in a newly proposed classification "soluble ligands" that has become the third major target of human protein therapeutic drugs after enzymes and receptors. Soluble ligands have potential significance for research and development of anti-IBD drugs. Compared with traditional drug targets for IBD treatment, such as receptors, at least three factors contribute to the increasing importance of soluble ligands as drug targets. Firstly, cytokines are the main soluble ligands and targeting of them has demonstrated efficacy in patients with IBD. Secondly, soluble ligands are more accessible than receptors, which are embedded in the cell membrane and have complex tertiary membrane structures. Lastly, certain potential target proteins that are present in membrane-bound forms can become soluble following cleavage, providing further opportunities for intervention in the treatment of IBD. In this review, 49 drugs targeting 25 distinct ligands have been evaluated, including consideration of the characteristics of the ligands and drugs in respect of IBD treatment. In addition to approved drugs targeting soluble ligands, we have also assessed drugs that are in preclinical research and drugs inhibiting ligand-receptor binding. Some new types of targetable soluble ligands/proteins, such as epoxide hydrolase and p-selectin glycoprotein ligand-1, are also introduced. Targeting soluble ligands not only opens a new field of anti-IBD drug development, but the circulating soluble ligands also provide diagnostic insights for early prediction of treatment response. In conclusion, soluble ligands serve as the third-largest protein target class in medicine, with much potential for the drugs targeting them.
ESTHER : Tong_2021_Pharmacol.Ther__107859
PubMedSearch : Tong_2021_Pharmacol.Ther__107859
PubMedID: 33895184

Title : Understanding the Modulatory Effects of Cannabidiol on Alzheimer's Disease - Xiong_2021_Brain.Sci_11_
Author(s) : Xiong Y , Lim CS
Ref : Brain Sci , 11 : , 2021
Abstract : Alzheimer's disease (AD), the most common neurodegenerative disease, is characterized by progressive cognitive impairment. The deposition of amyloid beta (Abeta) and hyperphosphorylated tau is considered the hallmark of AD pathology. Many therapeutic approaches such as Food and Drug Administration-approved cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have been used to intervene in AD pathology. However, current therapies only provide limited symptomatic relief and are ineffective in preventing AD progression. Cannabidiol (CBD), a phytocannabinoid devoid of psychoactive responses, provides neuroprotective effects through both cannabinoid and noncannabinoid receptors. Recent studies using an AD mouse model have suggested that CBD can reverse cognitive deficits along with Abeta-induced neuroinflammatory, oxidative responses, and neuronal death. Furthermore, CBD can reduce the accumulation of Abeta and hyperphosphorylation of tau, suggesting the possibility of delaying AD progression. Particularly, the noncannabinoid receptor, peroxisome proliferator-activated receptor gamma, has been suggested to be involved in multiple functions of CBD. Therefore, understanding the underlying mechanisms of CBD is necessary for intervening in AD pathology in depth and for the translation of preclinical studies into clinical settings. In this review, we summarize recent studies on the effect of CBD in AD and suggest problems to be overcome for the therapeutic use of CBD.
ESTHER : Xiong_2021_Brain.Sci_11_
PubMedSearch : Xiong_2021_Brain.Sci_11_
PubMedID: 34573232

Title : Synthesis and Structure-Activity Relationships of 3-Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors - Zhao_2021_ChemMedChem_16_388
Author(s) : Zhao Y , Xiong Y , Dong S , Guan X , Song Y , Yang Y , Zou K , Li Z , Zhang Y , Fang S , Li B , Zhu W , Chen K , Jia Q , Ge G
Ref : ChemMedChem , 16 :388 , 2021
Abstract : Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC(50) =0.68microM, K(i) =0.36microM) and excellent specificity (more than 147.05-fold over hCES1A). Moreover, 4a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3h, with an IC(50) value of 0.41microM. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3h and 4a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.
ESTHER : Zhao_2021_ChemMedChem_16_388
PubMedSearch : Zhao_2021_ChemMedChem_16_388
PubMedID: 32935462

Title : Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials - Li_2021_Medicine.(Baltimore)_100_e26662
Author(s) : Li X , Wang Y , Liu J , Xiong Y , Chen S , Han J , Xie W , Wu Q
Ref : Medicine (Baltimore) , 100 :e26662 , 2021
Abstract : BACKGROUND: Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD. METHODS: The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay. RESULTS: Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P<.0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P=.002). Seventeen studies showed that perioperative sedation with alpha2-adrenergic receptor agonists prevented POD (P=.0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P=.002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P<.00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay. CONCLUSION: Measures including intraoperative monitoring of bispectral index, supplemental analgesia, alpha2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.
ESTHER : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedSearch : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedID: 34398027

Title : Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans - Zhang_2021_Chem.Biol.Interact_351_109744
Author(s) : Zhang F , Li HX , Zhang TT , Xiong Y , Wang HN , Lu ZH , Xiong L , He YQ , Ge GB
Ref : Chemico-Biological Interactions , 351 :109744 , 2021
Abstract : Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed K(m) values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.
ESTHER : Zhang_2021_Chem.Biol.Interact_351_109744
PubMedSearch : Zhang_2021_Chem.Biol.Interact_351_109744
PubMedID: 34774545
Gene_locus related to this paper: human-CES1

Title : In Situ Assessment of Donghu Lake China Using Rare Minnow (Gobiocypris rarus) - Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
Author(s) : Xiong X , Qiu N , Su L , Hou M , Xu C , Xiong Y , Dong X , Song Z , Wang J
Ref : Archives of Environmental Contamination & Toxicology , 79 :246 , 2020
Abstract : In this work, rare minnow (Gobiocypris rarus) was applied as a sentinel organism and set in cages at control and test sampling sites in Donghu Lake for 4 weeks in March, June, September, and December 2016 to assess the biological toxicity of in situ water. Sampling for active biomonitoring and physicochemical variables was performed weekly. The control was obtained from the outdoor pool of the Institute of Hydrobiology, China. Superoxide dismutase, lipoperoxidation, metallothioneins, acetylcholinesterase activity, and Vtg mRNA expression were determined as biomarkers during the field exposure period. Survival and growth also were monitored to evaluate the overall physiological condition of the fish. The seasonal changes of organic pollutants and trace metals (As, Hg, Cr, Cu, Zn, Cd, Pb) in surface water were determined. The integrated biomarker response (IBR) index was applied to summarize biomarker responses and correlate stress levels with concentrations of organic pollutants and trace metals in the surface water. Results indicated that complex pollution by persistent organic pollutants and heavy metals was present in Donghu Lake and that the in situ exposed organisms were stressed. Moreover, the complex pollution of Donghu Lake in summer and autumn was more serious than that in spring and winter. Active biomonitoring combined with IBR analysis enabled good discrimination among different exposure seasons. The proposed protocol with caged rare minnow revealed marked biological effects caused by the investigated Lake and a useful approach that can easily be extended to monitor water pollution.
ESTHER : Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
PubMedSearch : Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
PubMedID: 32607658

Title : The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea - Zou_2020_BMC.Complement.Med.Ther_20_236
Author(s) : Zou Y , Hu J , Huang W , Zhu L , Shao M , Dordoe C , Ahn YJ , Wang D , Zhao Y , Xiong Y , Wang X
Ref : BMC Complement Med Ther , 20 :236 , 2020
Abstract : BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human beta-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC(50) from 292.0 to 673.9 microg/mL. Fourteen samples presented potent inhibitory activity against human BACE1 with EC(50) from 236.0 to 881.1 microg/mL. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC(50) from 2.7 to 14.4mG/Ml, 0.9 to 12.7mG/Ml, 5.0 to > 25mG/Ml, 2.7 to 17.7mG/Ml, and 2.4 to 8.7mG/Ml, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.
ESTHER : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedSearch : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedID: 32711521

Title : Pentacyclic triterpenoid acids in Styrax as potent and highly specific inhibitors against human carboxylesterase 1A - Wang_2020_Food.Funct_11_8680
Author(s) : Wang L , Guan XQ , He RJ , Qin WW , Xiong Y , Zhang F , Song YQ , Huo PC , Song PF , Tang H , Ge GB
Ref : Food Funct , 11 :8680 , 2020
Abstract : Human carboxylesterase 1A1 (hCES1A) is a promising target for the treatment of hyperlipidemia and obesity-associated metabolic diseases. To date, the highly specific and efficacious hCES1A inhibitors are rarely reported. This study aims to find potent and highly specific hCES1A inhibitors from herbs, and to investigate their inhibitory mechanisms. Following large-scale screening of herbal products, Styrax was found to have the most potent hCES1A inhibition activity. After that, a practical bioactivity-guided fractionation coupling with a chemical profiling strategy was used to identify the fractions from Styrax with strong hCES1A inhibition activity and the major constituents in these bioactive fractions were characterized by LC-TOF-MS/MS. The results demonstrated that seven pentacyclic triterpenoid acids (PTAs) in two bioactive fractions from Styrax potently inhibit hCES1A, with IC50 values ranging from 41 nM to 478 nM. Among all the identified PTAs, epibetulinic acid showed the most potent inhibition activity and excellent specificity towards hCES1A. Both inhibition kinetic analyses and in silico analysis suggested that epibetulinic acid potently inhibited hCES1A in a mixed inhibition manner. Collectively, our findings demonstrate that some PTAs in Styrax are potent and highly specific inhibitors of hCES1A and these constituents can be used as promising lead compounds for the development of more efficacious hCES1A inhibitors.
ESTHER : Wang_2020_Food.Funct_11_8680
PubMedSearch : Wang_2020_Food.Funct_11_8680
PubMedID: 32940318

Title : Extrusion improves the phenolic profile and biological activities of hempseed (Cannabis sativa L.) hull - Leonard_2020_Food.Chem_346_128606
Author(s) : Leonard W , Zhang P , Ying D , Xiong Y , Fang Z
Ref : Food Chem , 346 :128606 , 2020
Abstract : The impact of extrusion at different barrel temperature and screw speed on the hempseed hull was investigated. The extrusion treatments showed significant (p < 0.05) increase in total phenolic content, proportion of free phenolic compounds, and DPPH and ABTS radical scavenging activities. At low screw speed (150 rpm), significantly (p < 0.05) higher alpha-glucosidase and acetylcholinesterase inhibition activities were observed in the extruded samples. The full factorial model revealed a significant interaction between extrusion parameters on total phenolic/flavonoid content and antioxidant activities for free fraction, and alpha-glucosidase and acetylcholinesterase inhibition for whole fraction. A total of 26 phenylpropionamides, including hydroxycinnamic acid amides and lignanamides, were identified by HPLC-ESI-QTOF-MS/MS. HPLC-DAD analysis showed a 25-78% increase in total phenylpropionamide content in hempseed hull after extrusion. Pearson's correlation displayed significant (p < 0.05) positive correlation of N-trans-caffeoyltyramine, the most abundant phenylpropionamide, with all biological activities (r = 0.832-0.940).
ESTHER : Leonard_2020_Food.Chem_346_128606
PubMedSearch : Leonard_2020_Food.Chem_346_128606
PubMedID: 33388667

Title : Identification of novel uracil derivatives incorporating benzoic acid moieties as highly potent Dipeptidyl Peptidase-IV inhibitors - Huang_2019_Bioorg.Med.Chem_27_644
Author(s) : Huang J , Deng X , Zhou S , Wang N , Qin Y , Meng L , Li G , Xiong Y , Fan Y , Guo L , Lan D , Xing J , Jiang W , Li Q
Ref : Bioorganic & Medicinal Chemistry , 27 :644 , 2019
Abstract : Dipeptidyl Peptidase-IV (DPP-4) is a validated therapeutic target for type 2 diabetes. Aiming to interact with both residues Try629 and Lys554 in S2' site, a series of novel uracil derivatives 1a-l and 2a-i incorporating benzoic acid moieties at the N3 position were designed and evaluated for their DPP-4 inhibitory activity. Structure-activity relationships (SAR) study led to the identification of the optimal compound 2b as a potent and selective DPP-4 inhibitor (IC50=1.7nM). Docking study revealed the additional salt bridge formed between the carboxylic acid and primary amine of Lys554 has a key role in the enhancement of the activity. Furthermore, compound 2b exhibited no cytotoxicity in human hepatocyte LO2 cells up to 50muM. Subsequent in vivo evaluations revealed that the ester of 2b robustly improves the glucose tolerance in normal mice. The overall results have shown that compound 2b has the potential to a safe and efficacious treatment for T2DM.
ESTHER : Huang_2019_Bioorg.Med.Chem_27_644
PubMedSearch : Huang_2019_Bioorg.Med.Chem_27_644
PubMedID: 30642693

Title : Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi - Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
Author(s) : Zhang X , Wang TT , Xu QL , Xiong Y , Zhang L , Han H , Xu K , Guo WJ , Xu Q , Tan RX , Ge HM
Ref : Angew Chem Int Ed Engl , 57 :8184 , 2018
Abstract : Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.
ESTHER : Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
PubMedSearch : Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184
PubMedID: 29797385
Gene_locus related to this paper: necsz-ntng , artsz-atng

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 : Streptococcuspantholopis sp. nov., isolated from faeces of the Tibetan antelope (Pantholops hodgsonii) - Bai_2016_Int.J.Syst.Evol.Microbiol_66_3281
Author(s) : Bai X , Xiong Y , Lu S , Jin D , Lai X , Yang J , Niu L , Hu S , Meng X , Pu J , Ye C , Xu J
Ref : Int J Syst Evol Microbiol , 66 :3281 , 2016
Abstract : Two bacterial strains were isolated from faecal samples of Tibetan antelopes. The isolates were Gram-stain-positive, catalase-negative, coccus-shaped organisms that were tentatively identified as representing a novel streptococcal species based on their morphological features, biochemical test results and phylogenomic findings. Comparative 16S rRNA gene sequencing studies confirmed that the organisms were members of the genus Streptococcus, but they did not correspond to any recognized species of the genus. The nearest phylogenetic relative of the unknown coccus was Streptococcus ursoris NUM 1615T (93.4 % 16S rRNA gene sequence similarity). Analysis of groEL and rpoB gene sequences of the novel isolates showed interspecies divergence of 27.0 and 22.2 %, respectively, from the type strain of its closest 16S rRNA gene phylogenetic relative, S. ursoris. The complete genome of strain TA 26T has been sequenced. Digital DNA-DNA hybridization studies between strain TA 26T and other species of the genus Streptococcus deposited in the GenBank database showed less than 70 % DNA-DNA relatedness, supporting a novel species status of the strain. On the basis of their genotypic and phenotypic differences from recognized Streptococcus species, the two isolates represent a novel species of the genus Streptococcus, for which the nameStreptococcus pantholopis sp. nov. (type strain TA 26T=CGMCC 1.15667T=DSM 102135T) is proposed.
ESTHER : Bai_2016_Int.J.Syst.Evol.Microbiol_66_3281
PubMedSearch : Bai_2016_Int.J.Syst.Evol.Microbiol_66_3281
PubMedID: 27226124
Gene_locus related to this paper: 9stre-a0a172q9u9

Title : An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo - Tang_2013_J.Biol.Chem_288_1307
Author(s) : Tang J , Majeti J , Sudom A , Xiong Y , Lu M , Liu Q , Higbee J , Zhang Y , Wang Y , Wang W , Cao P , Xia Z , Johnstone S , Min X , Yang X , Shao H , Yu T , Sharkov N , Walker N , Tu H , Shen W , Wang Z
Ref : Journal of Biological Chemistry , 288 :1307 , 2013
Abstract : Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). Small molecule DPP-IV inhibitors have been used as treatments for type 2 diabetes to improve glucose tolerance. However, each of the marketed small molecule drugs has its own limitation in terms of efficacy and side effects. To search for an alternative strategy of inhibiting DPP-IV activity, we generated a panel of tight binding inhibitory mouse monoclonal antibodies (mAbs) against rat DPP-IV. When tested in vitro, these mAbs partially inhibited the GLP-1 cleavage activity of purified enzyme and rat plasma. To understand the partial inhibition, we solved the co-crystal structure of one of the mAb Fabs (Ab1) in complex with rat DPP-IV. Although Ab1 does not bind at the active site, it partially blocks the side opening, which prevents the large substrates such as GLP-1 from accessing the active site, but not small molecules such as sitagliptin. When Ab1 was tested in vivo, it reduced plasma glucose and increased plasma GLP-1 concentration during an oral glucose tolerance test in rats. Together, we demonstrated the feasibility of using mAbs to inhibit DPP-IV activity and to improve glucose tolerance in a diabetic rat model.
ESTHER : Tang_2013_J.Biol.Chem_288_1307
PubMedSearch : Tang_2013_J.Biol.Chem_288_1307
PubMedID: 23184939
Gene_locus related to this paper: ratno-dpp4

Title : Dynamics of fecal microbial communities in children with diarrhea of unknown etiology and genomic analysis of associated Streptococcus lutetiensis - Jin_2013_BMC.Microbiol_13_141
Author(s) : Jin D , Chen C , Li L , Lu S , Li Z , Zhou Z , Jing H , Xu Y , Du P , Wang H , Xiong Y , Zheng H , Bai X , Sun H , Wang L , Ye C , Gottschalk M , Xu J
Ref : BMC Microbiol , 13 :141 , 2013
Abstract : BACKGROUND: The sequences of the 16S rRNA genes extracted from fecal samples provide insights into the dynamics of fecal microflora. This potentially gives valuable etiological information for patients whose conditions have been ascribed to unknown pathogens, which cannot be accomplished using routine culture methods. We studied 33 children with diarrhea who were admitted to the Children's Hospital in Shanxi Province during 2006.
RESULTS: Nineteen of 33 children with diarrhea could not be etiologically diagnosed by routine culture and polymerase chain reaction methods. Eleven of 19 children with diarrhea of unknown etiology had Streptococcus as the most dominant fecal bacterial genus at admission. Eight of nine children whom three consecutive fecal samples were collected had Streptococcus as the dominant fecal bacterial genus, including three in the Streptococcus bovis group and three Streptococcus sp., which was reduced during and after recovery. We isolated strains that were possibly from the S. bovis group from feces sampled at admission, which were then identified as Streptococcus lutetiensis from one child and Streptococcus gallolyticus subsp. pasteurianus from two children. We sequenced the genome of S. lutetiensis and identified five antibiotic islands, two pathogenicity islands, and five unique genomic islands. The identified virulence genes included hemolytic toxin cylZ of Streptococcus agalactiae and sortase associated with colonization of pathogenic streptococci.
CONCLUSIONS: We identified S. lutetiensis and S. gallolyticus subsp. pasteurianus from children with diarrhea of unknown etiology, and found pathogenic islands and virulence genes in the genome of S. lutetiensis.
ESTHER : Jin_2013_BMC.Microbiol_13_141
PubMedSearch : Jin_2013_BMC.Microbiol_13_141
PubMedID: 23782707

Title : Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii - Seim_2013_Nat.Commun_4_2212
Author(s) : Seim I , Fang X , Xiong Z , Lobanov AV , Huang Z , Ma S , Feng Y , Turanov AA , Zhu Y , Lenz TL , Gerashchenko MV , Fan D , Hee Yim S , Yao X , Jordan D , Xiong Y , Ma Y , Lyapunov AN , Chen G , Kulakova OI , Sun Y , Lee SG , Bronson RT , Moskalev AA , Sunyaev SR , Zhang G , Krogh A , Wang J , Gladyshev VN
Ref : Nat Commun , 4 :2212 , 2013
Abstract : Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat.
ESTHER : Seim_2013_Nat.Commun_4_2212
PubMedSearch : Seim_2013_Nat.Commun_4_2212
PubMedID: 23962925
Gene_locus related to this paper: myobr-s7mf99 , myobr-s7n4r2 , myobr-s7neb7 , myobr-s7ney7 , myobr-s7n9l2 , myobr-s7nk13 , myobr-s7mh20 , myobr-s7pbt8 , myobr-s7mux2 , myobr-s7mjb5 , myobr-s7n6x5 , myobr-s7nnt6 , myobr-s7n728.2 , myobr-s7n728.3 , myobr-s7n8d2 , myobr-s7nqw0 , myobr-s7mju4 , myolu-g1nth4 , myobr-s7mij5 , myobr-s7pr94 , myolu-g1q4e3 , myolu-g1p353

Title : A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China - Xiong_2012_PLoS.One_7_e36144
Author(s) : Xiong Y , Wang P , Lan R , Ye C , Wang H , Ren J , Jing H , Wang Y , Zhou Z , Bai X , Cui Z , Luo X , Zhao A , Zhang S , Sun H , Wang L , Xu J
Ref : PLoS ONE , 7 :e36144 , 2012
Abstract : An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7.
ESTHER : Xiong_2012_PLoS.One_7_e36144
PubMedSearch : Xiong_2012_PLoS.One_7_e36144
PubMedID: 22558360
Gene_locus related to this paper: ecoli-ycfp , ecoli-YFBB , ecoli-yqia , ecoli-Z1341

Title : The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors - Graham_2012_Bioorg.Med.Chem.Lett_22_658
Author(s) : Graham TH , Shen HC , Liu W , Xiong Y , Verras A , Bleasby K , Bhatt UR , Chabin RM , Chen D , Chen Q , Garcia-Calvo M , Geissler WM , He H , Lassman ME , Shen Z , Tong X , Tung EC , Xie D , Xu S , Colletti SL , Tata JR , Hale JJ , Pinto S , Shen DM
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :658 , 2012
Abstract : Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied.
ESTHER : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedSearch : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedID: 22079761
Gene_locus related to this paper: human-PRCP

Title : Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors - Shen_2011_Bioorg.Med.Chem.Lett_21_1299
Author(s) : Shen HC , Ding FX , Zhou C , Xiong Y , Verras A , Chabin RM , Xu S , Tong X , Xie D , Lassman ME , Bhatt UR , Garcia-Calvo MM , Geissler W , Shen Z , Chen D , SinhaRoy R , Hale JJ , Tata JR , Pinto S , Shen DM , Colletti SL
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :1299 , 2011
Abstract : A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC(50)'s were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
ESTHER : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedSearch : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedID: 21315588
Gene_locus related to this paper: human-PRCP

Title : Lipoprotein lipase gene polymorphisms and risks of childhood obesity in Chinese preschool children - Wang_2011_Eur.J.Pediatr_170_1309
Author(s) : Wang LN , Yu Q , Xiong Y , Liu LF , Zhang Z , Zhang XN , Cheng H , Wang B
Ref : Eur J Pediatr , 170 :1309 , 2011
Abstract : Childhood obesity is increasingly prevalent in the community and is related to many adult diseases. Lipoprotein lipase (LPL) plays a central role in dyslipidemia, and polymorphisms of the LPL gene may result in the disturbance in the lipid's metabolism. The aim of this study is to test the hypothesis that genetic variants of LPL and serum lipid levels are associated with the risk of childhood obesity. We genotyped +495T > G and PvuII T > C in an LPL gene and measured the serum lipid levels in a case-control study of 124 obese children and 346 frequency-matched normal controls in preschool Chinese children. The variant genotypes of LPL + 495GG and PvuII CC were associated with a significantly increased risk of childhood obesity [adjusted odds ratio (OR) = 2.39, 95% CI = 1.09-5.23 for +495 GG; adjusted OR = 2.00, 95% CI = 1.04-3.83 for PvuII CC], compared with their wild-type genotypes, respectively. In addition, compared with the lower serum level cut off by the control median, the higher level of serum triglyceride (TG) (>0.59 mmol/L) was associated with a 1.32-fold increased risk of childhood obesity, and the higher level of high density lipoprotein cholesterol (HDLC) (>1.14 mmol/L) was associated with a 36% decrease in risk of childhood obesity. Furthermore, the median levels of TG were higher in obese children carrying LPL +495TT/TG and PvuII TT/CT genotypes than those in controls, the HDLC levels were lower in obese children carrying LPL +495TG and PvuII CT/CC genotypes than those in controls. In conclusion, the LPL gene +495T > G and PvuII T > C polymorphisms may modulate the magnitude of dyslipidemia in Chinese early-onset obesity.
ESTHER : Wang_2011_Eur.J.Pediatr_170_1309
PubMedSearch : Wang_2011_Eur.J.Pediatr_170_1309
PubMedID: 21431783

Title : Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity - Zhou_2010_J.Med.Chem_53_7251
Author(s) : Zhou C , Garcia-Calvo M , Pinto S , Lombardo M , Feng Z , Bender K , Pryor KD , Bhatt UR , Chabin RM , Geissler WM , Shen Z , Tong X , Zhang Z , Wong KK , Roy RS , Chapman KT , Yang L , Xiong Y
Ref : Journal of Medicinal Chemistry , 53 :7251 , 2010
Abstract : Prolylcarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 microM) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP(-/-) and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a 1% reduction in PrCP KO mice.
ESTHER : Zhou_2010_J.Med.Chem_53_7251
PubMedSearch : Zhou_2010_J.Med.Chem_53_7251
PubMedID: 20857914
Gene_locus related to this paper: human-PRCP

Title : Clinical, experimental, and genomic differences between intermediately pathogenic, highly pathogenic, and epidemic Streptococcus suis - Ye_2009_J.Infect.Dis_199_97
Author(s) : Ye C , Zheng H , Zhang J , Jing H , Wang L , Xiong Y , Wang W , Zhou Z , Sun Q , Luo X , Du H , Gottschalk M , Xu J
Ref : J Infect Dis , 199 :97 , 2009
Abstract : BACKGROUND: Streptococcus suis emerged to cause an unusual outbreak of streptococcal toxic-shock-like syndrome (STSLS) in 2005. The mechanisms involved are unknown. METHODS: Clinical, laboratory, and epidemiologic data on patients infected with culture-confirmed S. suis were analyzed. The strain involved in the outbreak, "epidemic" strain ST7, was compared with both a classical highly pathogenic strain, ST1, and an intermediately pathogenic strain, ST25, to determine both its capacity to induce cytokines in experimentally infected mice and its genomic difference. RESULTS: Of 38 patients infected with culture-confirmed S. suis, 14 presented with STSLS. During the early phase of the disease, serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, interferon-gamma, and tumor necrosis factor-alpha were more elevated in patients with STSLS than in those with meningitis only. Serum levels of proinflammatory cytokines were significantly higher in mice infected with ST7 than in those infected with either ST1 or ST25. Genomic comparisons with ST25 showed that ST1 had acquired 132 genomic islands, including 5 pathogenicity islands, and that ST7, the epidemic strain, had acquired an additional 5 genomic islands. CONCLUSION: Intermediately pathogenic strain ST25 has evolved to become highly pathogenic strain ST1, which, in turn, has more recently evolved to become epidemic strain ST7. ST7 has the ability to stimulate the production of massive amounts of proinflammatory cytokines, leading to STSLS.
ESTHER : Ye_2009_J.Infect.Dis_199_97
PubMedSearch : Ye_2009_J.Infect.Dis_199_97
PubMedID: 19016627
Gene_locus related to this paper: strsu-a4vws4 , strsu-q673u2 , strsy-a4vus4

Title : Evaluation of alpha7 nicotinic acetylcholine receptor agonists and positive allosteric modulators using the parallel oocyte electrophysiology test station - Malysz_2009_Assay.Drug.Dev.Technol_7_374
Author(s) : Malysz J , Gronlien JH , Timmermann DB , Hakerud M , Thorin-Hagene K , Ween H , Trumbull JD , Xiong Y , Briggs CA , Ahring PK , Dyhring T , Gopalakrishnan M
Ref : Assay Drug Dev Technol , 7 :374 , 2009
Abstract : Neuronal acetylcholine receptors (nAChRs) of the alpha7 subtype are ligand-gated ion channels that are widely distributed throughout the central nervous system and considered as attractive targets for the treatment of various neuropsychiatric and neurodegenerative diseases. Both agonists and positive allosteric modulators (PAMs) are being developed as means to enhance the function of alpha7 nAChRs. The in vitro characterization of alpha7 ligands, including agonists and PAMs, relies on multiple technologies, but only electrophysiological measurements assess the channel activity directly. Traditional electrophysiological approaches utilizing two-electrode voltage clamp or patch clamp in isolated cells have very low throughput to significantly impact drug discovery. Abbott (Abbott Park, IL) has developed a two-electrode voltage clamp-based system, the Parallel Oocyte Electrophysiology Test Station (POETs()), that allows for the investigation of ligand-gated ion channels such as alpha7 nAChRs in a higher-throughput manner. We describe the utility of this technology in the discovery of selective alpha7 agonists and PAMs. With alpha7 agonists, POETs experiments involved both single- and multiple-point concentration-response testing revealing diverse activation profiles (zero efficacy desensitizing, partial, and full agonists). In the characterization of alpha7 PAMs, POETs testing has served as a reliable primary or secondary screen identifying compounds that fall into distinct functional types depending on the manner in which current potentiation occurred. Type I PAMs (eg, genistein, NS1738, and 5-hydroxyindole) increase predominantly the peak amplitude response, type II PAMs affect the peak current and current decay (eg, PNU-120,596 and 4-(naphthalen-1-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) , and anothertype slowing the current decay kinetics in the absence of increases in the peak current. In summary, POETs technology allows for significant impact on higher throughput in the testing of alpha7 agonists and PAMs and for identification of compounds with unique profiles that could prove valuable in identifying an optimum in vitro profile in the development of therapeutics for which the alpha7 subtype is considered.
ESTHER : Malysz_2009_Assay.Drug.Dev.Technol_7_374
PubMedSearch : Malysz_2009_Assay.Drug.Dev.Technol_7_374
PubMedID: 19689206

Title : The 2008 update of the Aspergillus nidulans genome annotation: a community effort - Wortman_2009_Fungal.Genet.Biol_46 Suppl 1_S2
Author(s) : Wortman JR , Gilsenan JM , Joardar V , Deegan J , Clutterbuck J , Andersen MR , Archer D , Bencina M , Braus G , Coutinho P , von Dohren H , Doonan J , Driessen AJ , Durek P , Espeso E , Fekete E , Flipphi M , Estrada CG , Geysens S , Goldman G , de Groot PW , Hansen K , Harris SD , Heinekamp T , Helmstaedt K , Henrissat B , Hofmann G , Homan T , Horio T , Horiuchi H , James S , Jones M , Karaffa L , Karanyi Z , Kato M , Keller N , Kelly DE , Kiel JA , Kim JM , van der Klei IJ , Klis FM , Kovalchuk A , Krasevec N , Kubicek CP , Liu B , Maccabe A , Meyer V , Mirabito P , Miskei M , Mos M , Mullins J , Nelson DR , Nielsen J , Oakley BR , Osmani SA , Pakula T , Paszewski A , Paulsen I , Pilsyk S , Pocsi I , Punt PJ , Ram AF , Ren Q , Robellet X , Robson G , Seiboth B , van Solingen P , Specht T , Sun J , Taheri-Talesh N , Takeshita N , Ussery D , vanKuyk PA , Visser H , van de Vondervoort PJ , de Vries RP , Walton J , Xiang X , Xiong Y , Zeng AP , Brandt BW , Cornell MJ , van den Hondel CA , Visser J , Oliver SG , Turner G
Ref : Fungal Genet Biol , 46 Suppl 1 :S2 , 2009
Abstract : The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology.
ESTHER : Wortman_2009_Fungal.Genet.Biol_46 Suppl 1_S2
PubMedSearch : Wortman_2009_Fungal.Genet.Biol_46 Suppl 1_S2
PubMedID: 19146970
Gene_locus related to this paper: emeni-axe1 , emeni-c8v4m7 , emeni-faec , emeni-ppme1 , emeni-q5ara9 , emeni-q5arf0 , emeni-q5as30 , emeni-q5ase8 , emeni-q5av79 , emeni-q5aw09 , emeni-q5awc3 , emeni-q5awc7 , emeni-q5awu9 , emeni-q5aww4 , emeni-q5ax50 , emeni-q5ay37 , emeni-q5ay57 , emeni-q5ay59 , emeni-q5ayk9 , emeni-q5ays5 , emeni-q5az32 , emeni-q5az91 , emeni-q5az97 , emeni-q5azp1 , emeni-q5b0i6 , emeni-q5b1h2 , emeni-q5b2a9 , emeni-q5b2p7 , emeni-q5b3d2 , emeni-q5b4q7 , emeni-q5b5u7 , emeni-q5b5y4 , emeni-q5b9e7 , emeni-q5b9i0 , emeni-q5b364 , emeni-q5b446 , emeni-q5b938 , emeni-q5ba78 , emeni-q5bcd1 , emeni-q5bcd2 , emeni-q5bde7 , emeni-q5bdr0 , emeni-q5bf92 , emeni-q7si80 , emeni-q5bdv9 , emeni-c8vu15 , 9euro-a0a3d8t644 , emeni-q5b719 , emeni-q5ax97 , emeni-tdia , emeni-afoc , emeni-dbae

Title : Reaction pathways and free energy barriers for alkaline hydrolysis of insecticide 2-trimethylammonioethyl methylphosphonofluoridate and related organophosphorus compounds: electrostatic and steric effects - Xiong_2004_J.Org.Chem_69_8451
Author(s) : Xiong Y , Zhan CG
Ref : J Org Chem , 69 :8451 , 2004
Abstract : Reaction pathways and free energy barriers for alkaline hydrolysis of the highly neurotoxic insecticide 2-trimethylammonioethyl methylphosphonofluoridate and related organophosphorus compounds were studied by performing first-principles electronic structure calculations on representative methylphosphonofluoridates, (RO)CH3P(O)F, in which R = CH2CH2N+(CH3)3, CH3, CH2CH2C(CH3)3, CH2CH2CH(CH3)2, CH(CH3)CH2N+(CH3)3, and CH(CH3)CH2N(CH3)2. The dominant reaction pathway was found to be associated with a transition state in which the attacking nucleophile OH- and the leaving group F- are positioned on opposite sides of the plane formed by the three remaining atoms attached to the phosphorus in order to minimize the electrostatic repulsion between these two groups. The free energy barriers calculated for the rate-determining step of the dominant pathway are 12.5 kcal/mol when R = CH2CH2N+(CH3)3, 15.5 kcal/mol when R = CH3, 17.9 kcal/mol when R = CH2CH2C(CH3)3, 16.5 kcal/mol when R = CH2CH2CH(CH3)2, 13.4 kcal/mol when R = CH(CH3)CH2N+(CH3)3, and 18.7 kcal/mol when R = CH(CH(3))CH(2)N(CH(3))(2). The calculated free energy barriers are in good agreement with available experimentally derived activation free energies, i.e. 14.7 kcal/mol when R = CH(3), 13.4 kcal/mol when R = CH2CH2N+(CH3)3, and 13.9 kcal/mol when R = CH(CH3)CH2N+(CH3)3. A detailed analysis of the calculated energetic results and available experimental data suggests that the net charge of the molecule (M) being hydrolyzed is a prominent factor affecting the free energy barrier (DeltaG) for the alkaline hydrolysis of phosphodiesters, phosphonofluoridates, and related organophosphorus compounds. The electrostatic interactions between the attacking nucleophile OH- and the molecule M being hydrolyzed favor such an order of the free energy barrier: DeltaG(M(+)+OH-) < DeltaG(M0+OH-) < DeltaG(M(-)+OH-), where M+, M0, and M- represent the cationic, neutral, and anionic molecules, respectively. The change of the substituent R in (RO)CH(3)P(O)F from CH3 to CH2CH2N+(CH3)3 is associated with both the electrostatic and steric effects on the free energy barrier, but the electrostatic effect dominates the substituent shift of the free energy barrier. This helps to better understand why the alkaline hydrolysis of (RO)CH3P(O)F with R = CH2CH2N+(CH3)3 and CH(CH3)CH2N+(CH3)3 is significantly faster than that with R = CH3. The effect of electrostatic interaction also helps to understand why the rate constants for the alkaline hydrolysis of phosphodiesters, such as intramolecular second messenger adenosine 3',5'-phosphate (cAMP), are generally smaller than those for the alkaline hydrolysis of the phosphonofluoridates and related phosphotriesters.
ESTHER : Xiong_2004_J.Org.Chem_69_8451
PubMedSearch : Xiong_2004_J.Org.Chem_69_8451
PubMedID: 15549820

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