Hu L

References (37)

Title : Bifunctional enzyme-mimicking metal-organic frameworks for sensitive acetylcholine analysis - Wen_2024_Talanta_275_126112
Author(s) : Wen Y , Xu W , Wu Y , Tang Y , Liu M , Sha M , Li J , Xiao R , Hu L , Lin Y , Zhu C , Gu W
Ref : Talanta , 275 :126112 , 2024
Abstract : The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk between different enzymes and the complexities and costs associated with detection. In this study, Pt nanoparticles (Pt NPs) were successfully supported on a Zr-based metal-organic framework (MOF-808) to create a composite catalyst named MOF-808/Pt NPs. This composite catalyst effectively mimics the functions of acetylcholinesterase (AChE) and peroxidase (POD). Leveraging this capability, we replaced AChE and POD with MOF-808/Pt NPs and constructed a biosensor for sensitive detection of acetylcholine (ACh). The MOF-808/Pt NPs catalyze the hydrolysis of ACh, resulting in the production of acetic acid. The subsequent reduction in pH value further enhances the POD-like activity of the MOFs, enabling signal amplification through the oxidation of a colorimetric substrate. This biosensor capitalizes on pH variations during the reaction to modulate the different enzyme-like activities of the MOFs, simplifying the detection process and eliminating cross-talk between different enzymes. The developed biosensor holds great promise for clinical diagnostic analysis and offers significant application value in the field.
ESTHER : Wen_2024_Talanta_275_126112
PubMedSearch : Wen_2024_Talanta_275_126112
PubMedID: 38677169

Title : Biomimetic single Al-OH site with high acetylcholinesterase-like activity and self-defense ability for neuroprotection - Xu_2023_Nat.Commun_14_6064
Author(s) : Xu W , Cai X , Wu Y , Wen Y , Su R , Zhang Y , Huang Y , Zheng Q , Hu L , Cui X , Zheng L , Zhang S , Gu W , Song W , Guo S , Zhu C
Ref : Nat Commun , 14 :6064 , 2023
Abstract : Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al(3+) is engineered onto the nodes of metal-organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al(3+) Lewis acid sites with a strong polarization effect unite the highly electronegative -OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage.
ESTHER : Xu_2023_Nat.Commun_14_6064
PubMedSearch : Xu_2023_Nat.Commun_14_6064
PubMedID: 37770453

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

Title : Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos - Yang_2023_Toxics_11_353
Author(s) : Yang Q , Deng P , Xing D , Liu H , Shi F , Hu L , Zou X , Nie H , Zuo J , Zhuang Z , Pan M , Chen J , Li G
Ref : Toxics , 11 :353 , 2023
Abstract :
ESTHER : Yang_2023_Toxics_11_353
PubMedSearch : Yang_2023_Toxics_11_353
PubMedID: 37112580

Title : Nickel Single-Atom Catalyst-Mediated Efficient Redox Cycle Enables Self-Checking Photoelectrochemical Biosensing with Dual Photocurrent Readouts - Tan_2023_ACS.Sens__
Author(s) : Tan R , Qin Y , Liu M , Wang H , Li J , Luo Z , Hu L , Gu W , Zhu C
Ref : ACS Sens , : , 2023
Abstract : Developing a self-checking photoelectrochemical biosensor with dual photocurrent signals could efficiently eliminate false-positive or false-negative signals. Herein, a novel biosensor with dual photocurrent responses was established for the detection of acetylcholinesterase activity. To achieve photocurrent polarity-switchable behavior, the iodide/tri-iodide redox couple was innovatively introduced to simultaneously consume the photoexcited electrons and holes, which circumvents the inconvenience caused by the addition of different hole- and electron-trapping agents in the electrolyte. Importantly, benefiting from the high catalytic activity, the enhanced photoelectric responsivity can be realized after decorating the counter electrode with nickel single-atom catalysts, which promotes a more efficient iodide/tri-iodide redox reaction under low applied voltages. It is envisioned that the proposed photocurrent polarity switching system offers new routes to sensitive and reliable biosensing.
ESTHER : Tan_2023_ACS.Sens__
PubMedSearch : Tan_2023_ACS.Sens__
PubMedID: 36624088

Title : Increasing Linker Chain Length and Intestinal Stability Enhances Lymphatic Transport and Lymph Node Exposure of Triglyceride Mimetic Prodrugs of a Model Immunomodulator Mycophenolic Acid - Han_2023_Mol.Pharm__
Author(s) : Han S , Quach T , Hu L , Lim SF , Zheng D , Leong NJ , Sharma G , Bonner D , Simpson JS , Trevaskis NL , Porter CJH
Ref : Mol Pharm , : , 2023
Abstract : Targeted delivery of immunomodulators to the lymphatic system has the potential to enhance therapeutic efficacy by increasing colocalization of drugs with immune targets such as lymphocytes. A triglyceride (TG)-mimetic prodrug strategy has been recently shown to enhance the lymphatic delivery of a model immunomodulator, mycophenolic acid (MPA), via incorporation into the intestinal TG deacylation-reacylation and lymph lipoprotein transport pathways. In the current study, a series of structurally related TG prodrugs of MPA were examined to optimize structure-lymphatic transport relationships for lymph-directing lipid-mimetic prodrugs. MPA was conjugated to the sn-2 position of the glyceride backbone of the prodrugs using linkers of different chain length (5-21 carbons) and the effect of methyl substitutions at the alpha and/or beta carbons to the glyceride end of the linker was examined. Lymphatic transport was assessed in mesenteric lymph duct cannulated rats, and drug exposure in lymph nodes was examined following oral administration to mice. Prodrug stability in simulated intestinal digestive fluid was also evaluated. Prodrugs with straight chain linkers were relatively unstable in simulated intestinal fluid; however, co-administration of lipase inhibitors (JZL184 and orlistat) was able to reduce instability and increase lymphatic transport (2-fold for a prodrug with a 6-carbon spacer, i.e., MPA-C6-TG). Methyl substitutions to the chain resulted in similar trends in improving intestinal stability and lymphatic transport. Medium- to long-chain spacers (C12, C15) between MPA and the glyceride backbone were most effective in promoting lymphatic transport, consistent with increases in lipophilicity. In contrast, short-chain (C6-C10) linkers appeared to be too unstable in the intestine and insufficiently lipophilic to associate with lymph lipid transport pathways, while very long-chain (C18, C21) linkers were also not preferred, likely as a result of increases in molecular weight reducing solubility or permeability. In addition to more effectively promoting drug transport into mesenteric lymph, TG-mimetic prodrugs based on a C12 linker resulted in marked increases (>40 fold) in the exposure of MPA in the mesenteric lymph nodes in mice when compared to administration of MPA alone, suggesting that optimizing prodrug design has the potential to provide benefit in targeting and modulating immune cells.
ESTHER : Han_2023_Mol.Pharm__
PubMedSearch : Han_2023_Mol.Pharm__
PubMedID: 36996486

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

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

Title : MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR - Wang_2022_Front.Vet.Sci_9_948873
Author(s) : Wang J , Hao Z , Hu L , Qiao L , Luo Y , Hu J , Liu X , Li S , Zhao F , Shen J , Li M , Zhao Z
Ref : Front Vet Sci , 9 :948873 , 2022
Abstract : In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep.
ESTHER : Wang_2022_Front.Vet.Sci_9_948873
PubMedSearch : Wang_2022_Front.Vet.Sci_9_948873
PubMedID: 35990270

Title : Effect of propeptide mutations on the directed evolution of Rhizomucor miehei lipase - Wang_2022_Protein.Pept.Lett__
Author(s) : Wang J , Bai R , Wu N , Zhang Y , Hu L
Ref : Protein Pept Lett , : , 2022
Abstract : BACKGROUND: A series of mutants of Rhizomucor miehei lipase (RML) screened through four rounds of directed evolution was studied as the research object. The hydrolysis activity of mutants to triglycerides was determined, and their genes were sequenced. Results showed that mutations in the propeptide can improve the activity of RML during the evolution. Two parts of propeptide (wild-type and mutant) and mature region were connected by molecular simulation technology. METHODS: The spatial structure of the most positive mutants containing the mutations in the propeptide was mainly characterized by the increase in the opening angle of the lid structure in the mature region of RML, the enhancement of the hydrophobicity of the active center, and the triad of the active center shifted outward. RESULTS: The three indexes above explain the mechanism of propeptide mutations on the activity change of the target protein. In addition, statistical analysis of all the mutants screened in directed evolution showed that: (1) most of the mutants with increased activity contained mutations of the propeptide; (2) In the later stage of directed evolution, the number of active mutants decreased gradually, and the mutations of inactivated protein mainly occurred in the mature region; and (3) In the last round of directed evolution, the mutations distributed in the propeptide improved the mutant activity further. The results show the propeptide down the evolutionary pressure of RML and delayed emergence of the evolutionary platform. CONCLUSION: These findings reveal the role of propeptide in the evolution of RML and provide strategies for the molecular transformation of other lipases.
ESTHER : Wang_2022_Protein.Pept.Lett__
PubMedSearch : Wang_2022_Protein.Pept.Lett__
PubMedID: 35289250
Gene_locus related to this paper: rhimi-lipas

Title : Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry - Zhao_2021_Bioorg.Chem_108_104656
Author(s) : Zhao S , Xu J , Zhang S , Han M , Wu Y , Li Y , Hu L
Ref : Bioorg Chem , 108 :104656 , 2021
Abstract : In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).
ESTHER : Zhao_2021_Bioorg.Chem_108_104656
PubMedSearch : Zhao_2021_Bioorg.Chem_108_104656
PubMedID: 33548731

Title : [Serum C-reactive protein, cholinesterase and prealbumin are correlated with prognosis of severe coronavirus disease 2019 patients] - Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
Author(s) : Wang H , Hu L , Bai GQ , Liu Z , Yu GG , Wang W , Sun L
Ref : Zhonghua Nei Ke Za Zhi , 60 :134 , 2021
Abstract : Objective: To retrospectively analyze the relationship between serum C-reactive protein (CRP), serum cholinesterase (ChE), prealbumin (PA) and mortality in severe patients with coronavirus disease 2019 (COVID-19). Methods: During the period from January 29 to March 30, 2020, a total of 344 COVID-19 patients were admitted to west branch of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. One-hundred and ninety-two patients were diagnosed with common type and excluded, and 34 patients were transferred to LeiShenShan or other medical units. The remaining 118 patients were severe cases, and 18 cases were excluded due to incomplete data. A total of 100 severe COVID-19 patients were finally collected. According to the outcome, the patients were divided into death group (37 cases) and survival group(63 cases), and the levels of serum CRP, ChE and PA were compared. Statistical analysis were performed by SPSS25.0. Results: There were 53 male patients in this study. The level of CRP in death group was significantly more elevated compare to the survival group [(95.72+/-39.56) mg/L vs. (22.21+/-20.75) mg/L, P<0.01]. On the contrary, serum ChE in death group was remarkably decreased [(5 082+/-1 566) U/L vs. (7 075+/-1 680) U/L, P<0.01]. Also, serum PA in death group was significantly lower [(86.18+/-47.94) mg/L vs. (167.40+/-57.82) mg/L, P<0.01]. Univariate analysis showed that CRP and PA had an impact on the survival of critical patients, but multivariate Cox regression analysis suggested that CRP was the independent factor affecting the survival of critical patients. Conclusions: CRP is generally elevated in severe patients with COVID-19, and serum ChE and PA accordingly decrease. CRP and PA have influence on patients' survival, but only CRP demonstrates predictive value for prognosis in critical patients with COVID-19.
ESTHER : Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
PubMedSearch : Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
PubMedID: 33503724

Title : Iridium Single-Atomic Site Catalysts with Superior Oxygen Reduction Reaction Activity for Sensitive Monitoring of Organophosphorus Pesticides - Luo_2021_Anal.Chem__
Author(s) : Luo X , Luo Z , Wei X , Jiao L , Fang Q , Wang H , Wang J , Gu W , Hu L , Zhu C
Ref : Analytical Chemistry , : , 2021
Abstract : Tremendous efforts have been made in developing single-atomic site catalysts (SASCs) for oxygen reduction reaction (ORR), which is regarded as a pivotal cornerstone in electrochemical energy conversion. However, SASCs for ORR have not been explored for electrochemical sensing. Herein, a template-sacrificed strategy is reported for the synthesis of atomically dispersed Ir SASCs, serving as a sensing platform to detect organophosphorus pesticides (OPs) with high sensitivity and selectivity. Owing to abundant Ir single-atom active sites, Ir SASCs show excellent ORR activity and stability in a neutral medium. It is found that the ORR activity of Ir SASCs can be inhibited by thiocholine, which is the hydrolysate of acetylthiocholine. After being integrated with acetylcholinesterase (AChE), the AChE-Ir SASC-based electrochemical sensor is established and shows a superior sensitivity, which shows a wide detection range of 0.5-500 ng mL(-1) with a low detection limit of 0.17 ng mL(-1) for OPs. This work exhibits a broad application prospect of ORR for sensitive detection of biomolecules.
ESTHER : Luo_2021_Anal.Chem__
PubMedSearch : Luo_2021_Anal.Chem__
PubMedID: 34969242

Title : Identification and synthesis of selective cholesterol esterase inhibitor using dynamic combinatorial chemistry - Zhao_2021_Bioorg.Chem_119_105520
Author(s) : Zhao S , Wu Y , Hu L
Ref : Bioorg Chem , 119 :105520 , 2021
Abstract : In this study, the concept of dynamic combinatorial chemistry (DCC) was applied to explore novel cholesterol esterase (CEase) inhibitors. In the presence of enzyme, two substrates (A1H3 and A2H3) were amplified from the dynamic combinatorial library (DCL), which was generated through reversible acylhydrazone formation reaction. In the in vitro biological evaluation, compound A1H3 exhibited not only potent (IC(50) in nanomolar range) but also selective inhibition (>120 folds of selectivity for CEase over AChE). Furthermore, the binding pattern and possible binding mechanism were investigated in the kinetic experiment and molecular docking study, respectively.
ESTHER : Zhao_2021_Bioorg.Chem_119_105520
PubMedSearch : Zhao_2021_Bioorg.Chem_119_105520
PubMedID: 34864280

Title : Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry - Xu_2020_Int.J.Biol.Macromol_150_1184
Author(s) : Xu J , Zhao S , Zhang S , Pei J , Li Y , Zhang Y , He X , Hu L
Ref : Int J Biol Macromol , 150 :1184 , 2020
Abstract : In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride.
ESTHER : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedSearch : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedID: 31758986

Title : Dissociable photoelectrode materials boost ultrasensitive photoelectrochemical detection of organophosphorus pesticides - Qin_2020_Anal.Chim.Acta_1130_100
Author(s) : Qin Y , Wu Y , Chen G , Jiao L , Hu L , Gu W , Zhu C
Ref : Anal Chim Acta , 1130 :100 , 2020
Abstract : Generally, the photoactive materials are always tightly fixed on the photoelectrode of photoelectrochemical (PEC) sensors to produce excellent photocurrent response, while obvious and constant background currents will appear as well and then hamper the ultrasensitive sensing of target molecules. In this work, ultrasensitive detection of organophosphorus pesticides (OPs) is successfully fulfilled by using dissociable photoelectrode based on CdS nanocrystal-functionalized MnO(2) nanosheets. With the assistance of acetylcholinesterase (AChE), acetylthiocholine (ATCh) is hydrolyzed into thiocholine (TCh) which can effectively etch the ultrathin MnO(2) nanosheets, resulting in the dissociation of MnO(2)-CdS from the photoelectrode. Benefiting from the dissociation of photoactive materials, the background photocurrent induced by semiconductor itself dramatically decreases. OPs, as a specific inhibitor for AChE activity, can prevent the generation of TCh and the dissociation of MnO(2) nanosheets, building a relationship between OPs concentration and photocurrent. Under the optimized test conditions, the PEC sensor for the detection of paraoxon displays a wide linear range from 0.05 to 10 ng/mL with a detection limit of 0.017 ng/mL. Furthermore, the PEC sensor shows good sensitivity, stability, and promising application in practical samples.
ESTHER : Qin_2020_Anal.Chim.Acta_1130_100
PubMedSearch : Qin_2020_Anal.Chim.Acta_1130_100
PubMedID: 32892929

Title : Circumdatin D Exerts Neuroprotective Effects by Attenuating LPS-Induced Pro-Inflammatory Responses and Downregulating Acetylcholinesterase Activity In Vitro and In Vivo - Zhang_2020_Front.Pharmacol_11_760
Author(s) : Zhang C , Hu L , Liu D , Huang J , Lin W
Ref : Front Pharmacol , 11 :760 , 2020
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with multifactorial causes, of which systemic inflammation may play a key role to promote neurodegeneration, and acetylcholinesterase (AChE) is a target protein to induce cholinergic transmission. Inhibitors toward inflammation and targeting AChE are regarded to promote cholinergic signaling of the central nervous system in AD therapy. During the search for neuroprotection agents from marine-derived compounds, seven circumdatin-type alkaloids from a coral-associated fungus Aspergillus ochraceus LZDX-32-15 showed potent inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production and activation of NF-kappaB report gene along with anti-AChE activities. Among the tested compounds, circumdatin D showed the most potent inhibitory effect against AChE activity and NO production. In vivo experiments using AD-like nematode models demonstrated that circumdatin D effectively delayed paralysis of CL4176 worms upon temperature up-shift via suppression of AChE activity and inflammatory-related gene expression. Moreover, circumdatin D interfered with inflammatory response by inhibiting the secretion of pro-inflammatory cytokines in LPS-induced BV-2 and primary microglia cells. Mechanistically, circumdatin D modulated Toll-like receptor 4 (TLR4)-mediated NF-kappaB, MAPKs and JAK/STAT inflammatory pathways in LPS-stimulated BV-2 cells, and protected primary neurons cells from LPS-induced neurotoxicity. Thus, circumdatin D is a potential agent for neuroprotective effects by the multi-target strategy.
ESTHER : Zhang_2020_Front.Pharmacol_11_760
PubMedSearch : Zhang_2020_Front.Pharmacol_11_760
PubMedID: 32523534

Title : Silicon-mediated multiple interactions: Simultaneous induction of rice defense and inhibition of larval performance and insecticide tolerance of Chilo suppressalis by sodium silicate - Wang_2020_Ecol.Evol_10_4816
Author(s) : Wang J , Xue R , Ju X , Yan H , Gao Z , Esmail Abdalla Elzaki M , Hu L , Zeng R , Song Y
Ref : Ecol Evol , 10 :4816 , 2020
Abstract : The rice striped stem borer (SSB, Chilo suppressalis) is one of the most destructive pests of rice plants. Si-mediated rice defense against various pests has been widely reported, and sodium silicate (SS) has been used as an effective source of silicon for application to plants. However, there is quite limited information about the direct effects of Si application on herbivorous insects. SSB larval performance and their insecticide tolerance were examined after they had been reared either on rice plants cultivated in nutrient solution containing 0.5 and 2.0 mM SS or on artificial diets with 0.1% and 0.5% SS. SS amendment in either rice culture medium or artificial diets significantly suppressed the enzymatic activities of acetylcholinesterase, glutathione S-transferases, and levels of cytochrome P450 protein in the midgut of C. suppressalis larvae. Larvae fed on diets containing SS showed lower insecticide tolerance. Additionally, RNA-seq analysis showed that SS-mediated larval insecticide tolerance was closely associated with fatty acid biosynthesis and pyruvate metabolism pathways. Our results suggest that Si not only enhances plant resistance against insect herbivore, but also impairs the insect's capacity to detoxify the insecticides. This should be considered as another important aspect in Si-mediated plant-insect interaction and may provide a novel approach of pest management.
ESTHER : Wang_2020_Ecol.Evol_10_4816
PubMedSearch : Wang_2020_Ecol.Evol_10_4816
PubMedID: 32551063

Title : Diagnostic value of complete blood count in paraquat and organophosphorus poisoning patients - Tang_2018_Toxicol.Ind.Health__748233718770896
Author(s) : Tang Y , Hu L , Hong G , Zhong D , Song J , Zhao G , Lu Z
Ref : Toxicol Ind Health , :748233718770896 , 2018
Abstract : Complete blood count (CBC) is one of the most extensively used tests in clinical practice. In order to determine the diagnostic value of the CBC in paraquat (PQ) and organophosphorus (OPPs) poisoning, the CBC indices of PQ- and OPPs-poisoned patients were investigated in this study. A total of 96 PQ poisoning patients, 90 OPPs poisoning patients, and 188 healthy subjects were included in this study. The PQ- and OPPs-poisoned patients were divided into different groups according to their clinical symptoms. All CBC indices were analyzed by Fisher discriminant, partial least-squares discriminant analysis (PLS-DA), variance analysis, and receiver operating characteristic (ROC). The discriminant results showed that 87.7% of original grouped cases correctly classified between PQ-poisoned patients, OPPs-poisoned patients, and healthy subjects. The PLS-DA results showed that the important variable order was different in PQ- and OPPs-poisoned patients. Both white blood cell (WBC) and neutrophil (NE) counts were the most important indexes in PQ- and OPPs-poisoned patients. In OPPs poisoning patients, WBC and NE showed statistical differences between the severe poisoning group and the moderate poisoning group. Their areas under the ROC curve (AUC) were 0.673 (WBC) and 0.669 (NE), which were higher than cholinesterase (CHE; AUC 0.326). In conclusion, the CBC indices had a diagnostic value in PQ and OPPs poisoning; WBC and NE were the first responses and had clinical significance in PQ and OPPs poisoning; moreover, they are better than CHE in diagnosing OPPs poisoning.
ESTHER : Tang_2018_Toxicol.Ind.Health__748233718770896
PubMedSearch : Tang_2018_Toxicol.Ind.Health__748233718770896
PubMedID: 29669481

Title : Biodegradation of phenanthrene by endophytic fungus Phomopsis liquidambari in vitro and in vivo - Fu_2018_Chemosphere_203_160
Author(s) : Fu W , Xu M , Sun K , Hu L , Cao W , Dai C , Jia Y
Ref : Chemosphere , 203 :160 , 2018
Abstract : Phenanthrene, as a widespread polycyclic aromatic hydrocarbons (PAHs) contaminant in vitro and in vivo of plant, has the characteristics of carcinogenicity, teratogenicity and mutagenicity. This work aimed to explore the phenanthrene metabolic mechanism by Phomopsis liquidambari in vitro, as well as the bioremediation ability through P. liquidambari-rice combination. This strain was able to use phenanthrene as source of carbon and energy to grow, more than 77% of added 50mgL(-1) phenanthrene was removed after 10d in MSM. We identified the metabolic products via HPLC-MS and proposed two possible degradation pathways. Phenanthrene was firstly combined with oxygen to become phenanthrene 9,10-oxide, and then degraded to 9-phenanthrol, followed by oxidization to 9,10-dihydroxyphenanthrene. In addition, that epoxide (phenanthrene 9,10-oxide) was also hydrolyzed to phenanthrene trans-9,10-dihydrodiol, and then dehydrogenized to 9,10-dihydroxyphenanthrene, which was further degraded to 9,10-phenanthrenequinone; during this metabolic pathway, the changes of P450 monooxygenase, epoxide hydrolase, dehydrogenase and catechol 2,3-dioxygenase activities and their corresponding gene transcription levels were closely related. What's more, P. liquidambari could combine with rice to eliminate phenanthrene accumulated in vivo of rice seedlings, and the removal rate in inoculation treatment represented a significant difference (increased 25.68%) compared with uninoculation treatment after cultivation 30d. Therefore, we concluded that P. liquidambari could not only respond to phenanthrene pollution stress in vitro but also exert a mitigation effect on plants accumulated phenanthrene. This work provides a foundation for applying endophytic fungi to PAHs bioremediation in vitro and in vivo.
ESTHER : Fu_2018_Chemosphere_203_160
PubMedSearch : Fu_2018_Chemosphere_203_160
PubMedID: 29614409

Title : Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson's Disease and Related Dementia - Dong_2017_Biomed.Res.Int_2017_1524107
Author(s) : Dong MX , Xu XM , Hu L , Liu Y , Huang YJ , Wei YD
Ref : Biomed Res Int , 2017 :1524107 , 2017
Abstract : OBJECTIVE: This study aim to determine changes of serum butyrylcholinesterase (BChE) activity in PD patients and related dementia. PATIENTS AND
METHODS: Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC) curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia.
RESULTS: Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson's Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L.
CONCLUSIONS: Serum BChE activity can be regarded as a biomarker for PD and related dementia.
ESTHER : Dong_2017_Biomed.Res.Int_2017_1524107
PubMedSearch : Dong_2017_Biomed.Res.Int_2017_1524107
PubMedID: 28840123

Title : Hepatectomy combined with microwave ablation of the spleen for treatment of hepatocellular carcinoma complicated with splenomegaly: A retrospective study - Han_2017_Mol.Clin.Oncol_6_204
Author(s) : Han JB , Kong FW , Ding H , Zhang YF , Liu JM , Wei Q , Hu L , Zhao L , Xu CJ , Yi YX
Ref : Mol Clin Oncol , 6 :204 , 2017
Abstract : The present retrospective study aimed to investigate the mid-term safety and efficacy of hepatectomy combined with microwave ablation of the partial spleen for treatment of liver cancer complicated with hypersplenism. A retrospective analysis was performed on 23 patients who underwent hepatectomy combined with microwave ablation of the partial spleen for liver cancer, complicated with hypersplenism that was secondary to cirrhosis. The splenic and ablated volumes were calculated according to a contrast-enhanced computed tomography scan prior to and 2 weeks after the operation. Complete blood count and liver function tests were examined prior to and following the surgery, and complications and changes in the blood tests were monitored for 6 months. Over this period of investigation, the splenic volume was reduced by a mean value of 34.0%. The levels of serum alanine aminotransferase and aspartate aminotransferase were increased on the first day after the operation (P<0.05), although they recovered to the normal level within 1 week (P<0.05). The total level of bilirubin increased slightly, along with moderately decreased levels of albumin and cholinesterase on the first day, although these changes were not significant compared with the baseline (P>0.05). The white blood cell count was persistently significantly higher compared with the baseline over the course of the 6 months (P>0.05). The platelet count did not increase significantly for the first week after the operation (P>0.05); however, it was revealed to be significantly increased 1 month after the surgery (P<0.05). No significant complications were occurred during the follow-up period. In conclusion, hepatectomy combined with microwave ablation of the spleen was demonstrated to be a safe and effective procedure for patients with liver cancer and hypersplenism in the mid-term.
ESTHER : Han_2017_Mol.Clin.Oncol_6_204
PubMedSearch : Han_2017_Mol.Clin.Oncol_6_204
PubMedID: 28357095

Title : Effects of the antidepressant, mianserin, on early development of fish embryos at low environmentally relevant concentrations - Yang_2017_Ecotoxicol.Environ.Saf_150_144
Author(s) : Yang M , Liu S , Hu L , Zhan J , Lei P , Wu M
Ref : Ecotoxicology & Environmental Safety , 150 :144 , 2017
Abstract : Pharmaceuticals have been considered as emerging organic contaminants in the environment that might pose huge risk to the non-target aquatic organisms. Mianserin, a tetracyclic antidepressant, is present at low detectable concentrations in the aquatic environment; however, limited attention has been devoted to its potential adverse effects on the aquatic animals. In the present study, we first performed an acute toxicity test for mianserin exposure using zebrafish (Danio rerio) embryos during 4-124h post fertilization (hpf). Time-dependent lethal concentrations of mianserin exposure on the zebrafish embryos were firstly determined at mg/L levels. Then, a series of sublethal concentrations of 0.01, 0.1, 1, 10, 100, and 1000mug/L of mianserin were prepared for the short-term exposure of zebrafish embryos for 120h. The results showed that mianserin exposure reduced the body length of zebrafish larvae, in addition to altering multiple physiological and biochemical parameters in the exposed embryos/larvae. A dose-dependent inhibition of the total antioxidant capacity and total cholinesterase activity was revealed in the exposed fish larvae upon increasing the concentrations of mianserin exposure. A U-shaped concentration-dependent response curve was observed for the adrenocorticotropic hormone; however, an inversed U-shaped response curve was obtained for the monoamine oxidase level in response to mianserin exposure. Activities of the total adenosine triphosphatase (T-ATPase), Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase were significantly increased in the fish larvae exposed to relatively high doses of mianserin; interestingly however, low dose of mianserin at 10ng/L inhibited their Na(+)/K(+)-ATPase and T-ATPase activities. Additionally, the coordinated regulation of cyclic adenosine monophosphate and protein kinase A was observed in the mianserin-exposed fish larvae, implying a reserved signaling pathway involved in the fish response to the antidepressant. Therefore, our study demonstrated that mianserin exposure significantly affected the early development of fish embryos at environmentally relevant concentrations, and suggested that the risk of pharmaceutical contamination of the aquatic environment, even at low doses, should receive more attention.
ESTHER : Yang_2017_Ecotoxicol.Environ.Saf_150_144
PubMedSearch : Yang_2017_Ecotoxicol.Environ.Saf_150_144
PubMedID: 29272719

Title : The potential neurotoxicity of emerging tetrabromobisphenol A derivatives based on rat pheochromocytoma cells - Liu_2016_Chemosphere_154_194
Author(s) : Liu Q , Ren X , Long Y , Hu L , Qu G , Zhou Q , Jiang G
Ref : Chemosphere , 154 :194 , 2016
Abstract : Tetrabromobisphenol A (TBBPA) can cause diverse adverse effects including neurotoxicity. Emerging TBBPA derivatives, with high structure similarity to the parent compound, are now being concerned. In this study, the potential neurotoxicities of four TBBPA derivatives and their parent compound were studied by cell viability inhibition in rat pheochromocytoma cells (PC12) and the corresponding molecular mechanisms were investigated. The cellular toxicity was correlated with the chemical hydrophobicity. Tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE) exhibited the highest cellular toxicity to PC12 due to its lowest hydrophobicity among these 5 tested compounds. Further experiments showed that TBBPA-BHEE disturbed dopamine (DA) secretion and altered acetylcholinesterase (AChE) enzymatic activity in PC12 cells. The molecular mechanism study indicated that TBBPA-BHEE induced cellular toxicity to PC12 cells through ROS-mediated caspase activation to a large extent, which was partially attenuated by the anti-oxidation of Vitamin E. Moreover, in contrast to TBBPA, the occurrence of TBBPA-BHEE toxicity to PC12 was not attributed to activation of mitogen-activated protein kinases (MAPKs) or thyroid hormone (TH) signaling pathway. These findings suggest TBBPA derivatives, especially TBBPA-BHEE, as potential neurotoxins need urgent attention.
ESTHER : Liu_2016_Chemosphere_154_194
PubMedSearch : Liu_2016_Chemosphere_154_194
PubMedID: 27055180

Title : Removal of the Side Chain at the Active-Site Serine by a Glycine Substitution Increases the Stability of a Wide Range of Serine beta-Lactamases by Relieving Steric Strain - Stojanoski_2016_Biochemistry_55_2479
Author(s) : Stojanoski V , Adamski CJ , Hu L , Mehta SC , Sankaran B , Zwart P , Prasad BV , Palzkill T
Ref : Biochemistry , 55 :2479 , 2016
Abstract : Serine beta-lactamases are bacterial enzymes that hydrolyze beta-lactam antibiotics. They utilize an active-site serine residue as a nucleophile, forming an acyl-enzyme intermediate during hydrolysis. In this study, thermal denaturation experiments as well as X-ray crystallography were performed to test the effect of substitution of the catalytic serine with glycine on protein stability in serine beta-lactamases. Six different enzymes comprising representatives from each of the three classes of serine beta-lactamases were examined, including TEM-1, CTX-M-14, and KPC-2 of class A, P99 of class C, and OXA-48 and OXA-163 of class D. For each enzyme, the wild type and a serine-to-glycine mutant were evaluated for stability. The glycine mutants all exhibited enhanced thermostability compared to that of the wild type. In contrast, alanine substitutions of the catalytic serine in TEM-1, OXA-48, and OXA-163 did not alter stability, suggesting removal of the Cbeta atom is key to the stability increase associated with the glycine mutants. The X-ray crystal structures of P99 S64G, OXA-48 S70G and S70A, and OXA-163 S70G suggest that removal of the side chain of the catalytic serine releases steric strain to improve enzyme stability. Additionally, analysis of the torsion angles at the nucleophile position indicates that the glycine mutants exhibit improved distance and angular parameters of the intrahelical hydrogen bond network compared to those of the wild-type enzymes, which is also consistent with increased stability. The increased stability of the mutants indicates that the enzyme pays a price in stability for the presence of a side chain at the catalytic serine position but that the cost is necessary in that removal of the serine drastically impairs function. These findings support the stability-function hypothesis, which states that active-site residues are optimized for substrate binding and catalysis but that the requirements for catalysis are often not consistent with the requirements for optimal stability.
ESTHER : Stojanoski_2016_Biochemistry_55_2479
PubMedSearch : Stojanoski_2016_Biochemistry_55_2479
PubMedID: 27073009

Title : Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs - Zhuang_2015_Pharmacology_95_243
Author(s) : Zhuang Z , Tang M , Zheng Y , Hu L , Lin F
Ref : Pharmacology , 95 :243 , 2015
Abstract : BACKGROUND: Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats.
METHODS: Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method.
RESULTS: The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0-infinity), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t1/2, CL and Tmax for phenacetin, tolbutamide and midazolam.
CONCLUSIONS: A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks. (c) 2015 S. Karger AG, Basel.
ESTHER : Zhuang_2015_Pharmacology_95_243
PubMedSearch : Zhuang_2015_Pharmacology_95_243
PubMedID: 25967365

Title : Genome and transcriptome of the porcine whipworm Trichuris suis - Jex_2014_Nat.Genet_46_701
Author(s) : Jex AR , Nejsum P , Schwarz EM , Hu L , Young ND , Hall RS , Korhonen PK , Liao S , Thamsborg S , Xia J , Xu P , Wang S , Scheerlinck JP , Hofmann A , Sternberg PW , Wang J , Gasser RB
Ref : Nat Genet , 46 :701 , 2014
Abstract : Trichuris (whipworm) infects 1 billion people worldwide and causes a disease (trichuriasis) that results in major socioeconomic losses in both humans and pigs. Trichuriasis relates to an inflammation of the large intestine manifested in bloody diarrhea, and chronic disease can cause malnourishment and stunting in children. Paradoxically, Trichuris of pigs has shown substantial promise as a treatment for human autoimmune disorders, including inflammatory bowel disease (IBD) and multiple sclerosis. Here we report whole-genome sequencing at approximately 140-fold coverage of adult male and female T. suis and approximately 80-Mb draft assemblies. We explore stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs.
ESTHER : Jex_2014_Nat.Genet_46_701
PubMedSearch : Jex_2014_Nat.Genet_46_701
PubMedID: 24929829
Gene_locus related to this paper: 9bila-a0a085nui3 , 9bila-a0a085mx66 , 9bila-a0a085lsb8 , 9bila-a0a085mja7 , 9bila-a0a085ly55 , 9bila-a0a085nlc5 , 9bila-a0a085nb82 , 9bila-a0a085n057 , 9bila-a0a085mjs6

Title : Genome of the Chinese tree shrew - Fan_2013_Nat.Commun_4_1426
Author(s) : Fan Y , Huang ZY , Cao CC , Chen CS , Chen YX , Fan DD , He J , Hou HL , Hu L , Hu XT , Jiang XT , Lai R , Lang YS , Liang B , Liao SG , Mu D , Ma YY , Niu YY , Sun XQ , Xia JQ , Xiao J , Xiong ZQ , Xu L , Yang L , Zhang Y , Zhao W , Zhao XD , Zheng YT , Zhou JM , Zhu YB , Zhang GJ , Wang J , Yao YG
Ref : Nat Commun , 4 :1426 , 2013
Abstract : Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.
ESTHER : Fan_2013_Nat.Commun_4_1426
PubMedSearch : Fan_2013_Nat.Commun_4_1426
PubMedID: 23385571
Gene_locus related to this paper: tupch-l9l8p0 , tupch-l9l7d8.1 , tupch-l9l7d8.2 , tupch-l9l7d8.3 , tupch-l8y4e3 , tupch-l9jqg5 , tupch-l9l3m0 , tupch-l9kxg8 , tupch-l9knn8 , tupch-l9kf47 , tupch-l9ja32 , tupch-l9l5b1 , tupch-l9khv5

Title : [Effects of soybean trypsinase inhibitor and defense signaling compounds on detoxification enzymes in Spodoptera litura (F.) larvae] - Wu_2012_Ying.Yong.Sheng.Tai.Xue.Bao_23_1952
Author(s) : Wu GZ , Hu L , Ye M , Wang RL , Zhu KY , Zeng RS , Cai W
Ref : Ying Yong Sheng Tai Xue Bao , 23 :1952 , 2012
Abstract : In a long history of interactions between insects and plants, plants have developed various anti-insect compounds and defense signaling transduction pathways to defend against herbivorous insects, while insects have responded with sophisticated detoxification enzyme systems to protect against the toxicity of anti-insect compounds. In this study, the 2nd or 3rd instar of Spodoptera litura larvae were successively fed with the diets containing 0.5% soybean trypsinase inhibitor (SBTI) for six generations to evaluate the effects of SBTI and defense signaling compounds on the activities of detoxification enzymes carboxylesterase (CarE) and glutathione-S-transferase (GST) in the midgut and fatbody of the larvae. After fed with the diets, the CarE and GST activities in the 5th instar larvae increased significantly. The CarE activity in the midgut and fatbody of the second generation larvae was the highest, being 2.06 and 2.40 times, and 1.96 and 2.70 times of that of the control, and the GST activity in the midgut and fatbody of the fourth and second generations was the highest, being 7.03 and 11.58 times, and 5.71 and 3.60 times of that of the control, respectively. These induced enzyme activities decreased gradually when the larvae continuously grew with the SBTI-containing diets. In addition, when the S. litura larvae were pre-exposed to methyl jasmonate (MeJA) or methyl salicylate (MeSA) for 48 h or fed with the diets containing 0.5% SBTI, the activities of CarE and GST in the midgut and fatbody increased significantly, and, when the 2nd instar larvae were pre-exposed to MeJA and MeSA for 48 h, the effects of SBTI on the GST activity in larval midgut and fatbody were reduced.
ESTHER : Wu_2012_Ying.Yong.Sheng.Tai.Xue.Bao_23_1952
PubMedSearch : Wu_2012_Ying.Yong.Sheng.Tai.Xue.Bao_23_1952
PubMedID: 23173473

Title : Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins - Wang_2009_J.Biol.Chem_284_32116
Author(s) : Wang H , Hu L , Dalen K , Dorward H , Marcinkiewicz A , Russell D , Gong D , Londos C , Yamaguchi T , Holm C , Rizzo MA , Brasaemle D , Sztalryd C
Ref : Journal of Biological Chemistry , 284 :32116 , 2009
Abstract : Lipolysis is an important metabolic pathway controlling energy homeostasis through degradation of triglycerides stored in lipid droplets and release of fatty acids. Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells. We applied fluorescence microscopic tools to analyze proteins in situ in cultured Chinese hamster ovary cells using fluorescence recovery after photobleaching and anisotropy Forster resonance energy transfer. Fluorescence recovery after photobleaching data show that ADFP and LSDP5 exchange between lipid droplet and cytoplasmic pools, whereas perilipin A does not. Differences in protein mobility do not correlate with PAT protein-mediated control of lipolysis catalyzed by HSL or endogenous lipases. Forster resonance energy transfer and co-immunoprecipitation experiments reveal that each of the three PAT proteins bind HSL through interaction of the lipase with amino acids within the highly conserved amino-terminal PAT-1 domain. ADFP and LSDP5 bind HSL under basal conditions, whereas phosphorylation of serine residues within three amino-terminal protein kinase A consensus sequences of perilipin A is required for HSL binding and maximal lipolysis. Finally, protein kinase A-mediated phosphorylation of HSL increases lipolysis in cells expressing ADFP or LSDP5; in contrast, phosphorylation of perilipin A exerts the major control over HSL-mediated lipolysis when perilipin is the main lipid droplet protein.
ESTHER : Wang_2009_J.Biol.Chem_284_32116
PubMedSearch : Wang_2009_J.Biol.Chem_284_32116
PubMedID: 19717842

Title : Monitoring enzyme reaction and screening enzyme inhibitor based on MALDI-TOF-MS platform with a matrix of oxidized carbon nanotubes - Hu_2006_J.Am.Soc.Mass.Spectrom_17_1616
Author(s) : Hu L , Jiang G , Xu S , Pan C , Zou H
Ref : J Am Soc Mass Spectrom , 17 :1616 , 2006
Abstract : A matrix assisted laser desorption/ionization time-of-flight mass spectrometry platform for quantitatively monitoring enzyme activity and screening enzyme inhibitors has been demonstrated. The described method employs a new matrix of oxidized carbon nanotubes. Compared with the traditional fluorescence approach, this label-free method has the advantage of directly identifying the substrates and products in enzymatic reactions. Moreover, the method could be conveniently carried out with any commercial mass spectrometer without modification. We quantitatively monitored the acetylcholinesterase activity and screened acetylcholinesterase inhibitors with a detection rate of about 3.3 s per sample.
ESTHER : Hu_2006_J.Am.Soc.Mass.Spectrom_17_1616
PubMedSearch : Hu_2006_J.Am.Soc.Mass.Spectrom_17_1616
PubMedID: 16905330

Title : Two-dimensional protein database of human pancreas - Hu_2004_Electrophoresis_25_512
Author(s) : Hu L , Evers S , Lu ZH , Shen Y , Chen J
Ref : Electrophoresis , 25 :512 , 2004
Abstract : We report here the two-dimensional protein database of human pancreas. The proteins were analyzed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Totally, 302 proteins were identified, of which about 27% were enzymes with a broad range of catalytic activities. Several of these are specifically expressed in pancreas, such as pancreatic amylase, pancreatic stone protein, pancreatitis-associated protein, pancreatic lipase, pancreatic elastase, etc. Structural and cytoskeletal proteins are also strongly represented on the gels. Thus, the pancreatic proteome reflects the organ's function. This work paves the way for further studies on pancreatic protein expression in health and disease, such as diabetes and pancreatic cancer.
ESTHER : Hu_2004_Electrophoresis_25_512
PubMedSearch : Hu_2004_Electrophoresis_25_512
PubMedID: 14760645

Title : The impact of Abeta-plaques on cortical cholinergic and non-cholinergic presynaptic boutons in alzheimer's disease-like transgenic mice - Hu_2003_Neurosci_121_421
Author(s) : Hu L , Wong TP , Cote SL , Bell KF , Cuello AC
Ref : Neuroscience , 121 :421 , 2003
Abstract : A previous study in our laboratory, involving early stage, amyloid pathology in 8-month-old transgenic mice, demonstrated a selective loss of cholinergic terminals in the cerebral and hippocampal cortices of doubly transgenic (APP(K670N,M671L)+PSl(M146L)) mice, an up-regulation in the single mutant APP(K670N,M671L) mice and no detectable change in the PSl(M146L) transgenics [J Neurosci 19 (1999) 2706]. The present study investigates the impact of amyloid plaques on synaptophysin and vesicular acetylcholine transporter (VAChT) immunoreactive bouton numbers in the frontal cortex of the three transgenic mouse models previously described. When compared as a whole, the frontal cortices of transgenic and control mice show no observable differences in the densities of synaptophysin-immunoreactive boutons. An individual comparison of layer V of the frontal cortex, however, shows a significant increase in density in transgenic models. Analysis of the cholinergic system alone shows significant alterations in the VAChT-immunoreactive bouton densities as evidenced by an increased density in the single (APP(K670N,M671L)) transgenics and a decreased density in the doubly transgenics (APP(K670N,M671L)+PSl(M146L)). In investigating the impact of plaque proximity on bouton density at early stages of the amyloid pathology in our doubly (APP(K670N,M671L)+PSl(M146L)) transgenic mouse line, we observed that plaque proximity reduced cholinergic pre-synaptic bouton density by 40%, and yet increased synaptophysin-immunoreactive pre-synaptic bouton density by 9.5%. Distance from plaques (up to 60 microm) seemed to have no effect on bouton density; however a significant inverse relationship was visible between plaque size and cholinergic pre-synaptic bouton density. Finally, the number of cholinergic dystrophic neurites surrounding the truly amyloid, Thioflavin-S(+) plaque core, was disproportionately large with respect to the incidence of cholinergic boutons within the total pre-synaptic bouton population. Confocal and electron microscopic observations confirmed the preferential infiltration of dystrophic cholinergic boutons into fibrillar amyloid aggregates. We therefore hypothesize that extracellular Abeta aggregation preferentially affects cholinergic terminations prior to progression onto other neurotransmitter systems. This is supported by the observable presence of non-cholinergic sprouting, which may be representative of impending neuritic degeneration.
ESTHER : Hu_2003_Neurosci_121_421
PubMedSearch : Hu_2003_Neurosci_121_421
PubMedID: 14522000

Title : Evidence against a major role of PEG1\/MEST in Silver-Russell syndrome - Riesewijk_1998_Eur.J.Hum.Genet_6_114
Author(s) : Riesewijk AM , Blagitko N , Schinzel AA , Hu L , Schulz U , Hamel BC , Ropers HH , Kalscheuer VM
Ref : Eur J Hum Genet , 6 :114 , 1998
Abstract : Silver-Russell syndrome (SRS) is a heterogeneous disorder characterised by interauterine and postnatal growth retardation, with or without additional dysmorphic features. Most cases are sporadic but a few familial cases have been described. A subset of patients exhibit maternal uniparental disomy for chromosome 7 (mUPD7) strongly suggesting that genomic imprinting plays a role in the aetiology of the disease. We and others have recently characterised the human PEG1/MEST gene, the first imprinted gene known to be located on chromosome 7. Although the function of PEG1/MEST is unknown, the paternal-specific expression of this gene and its location at 7q32, render it a promising candidate for SRS. As a prerequisite for mutation screening in 49 patients with SRS and 9 with primordial growth retardation (PGR), we determined the complete genomic structure of the PEG1/MEST gene which consists of 12 exons. Apart from one silent mutation and two novel polymorphisms, nucleotide changes were not detected in any of these patients. Moreover, methylation patterns of the 5' region of PEG1/MEST were found to be normal in 35 SRS and 9 PGR patients and different from the pattern seen in patients with mUPD7. These findings strongly argue against a role of PEG1/MEST in the majority of Silver-Russell syndrome cases.
ESTHER : Riesewijk_1998_Eur.J.Hum.Genet_6_114
PubMedSearch : Riesewijk_1998_Eur.J.Hum.Genet_6_114
PubMedID: 9781054

Title : Monoallelic expression of human PEG1\/MEST is paralleled by parent-specific methylation in fetuses - Riesewijk_1997_Genomics_42_236
Author(s) : Riesewijk AM , Hu L , Schulz U , Tariverdian G , Hoglund P , Kere J , Ropers HH , Kalscheuer VM
Ref : Genomics , 42 :236 , 1997
Abstract : We have isolated the human PEG1/MEST gene and have investigated its imprinting status and parental-specific methylation. FISH mapping assigned the gene to chromosome 7q32, and homologous sequences were identified on the short arm of human chromosomes 3 and 5. Through the use of a newly identified intragenic polymorphism, expression analysis revealed that PEG1/MEST is monoallelically transcribed in all fetal tissues examined. In two informative cases, expression was shown to be confined to the paternally derived allele. In contrast to the monoallelic expression observed in fetal tissues, biallelic expression was evident in adult blood lymphocytes. Biallelic expression in blood is supported by the demonstration of PEG1/MEST transcripts in a lymphoblastoid cell line with maternal uniparental disomy 7. The human PEG1/MEST gene spans a genomic region of approximately 13 kb. Sequence analysis of the 5' region of PEG1/MEST revealed the existence of a 620-bp-long CpG island that extends from the putative promoter region into intron 1. We demonstrate that this CpG island is methylated in a parent-of-origin-specific manner. All MspI/HpaII sites were unmethylated on the active paternal allele but methylated on the inactive maternal one.
ESTHER : Riesewijk_1997_Genomics_42_236
PubMedSearch : Riesewijk_1997_Genomics_42_236
PubMedID: 9192843
Gene_locus related to this paper: human-MEST

Title : Differential modulation of the cholinergic phenotype of the nucleus basalis magnocellularis neurons by applying NGF at the cell body or cortical terminal fields - Hu_1997_Exp.Neurol_143_162
Author(s) : Hu L , Cote SL , Cuello AC
Ref : Experimental Neurology , 143 :162 , 1997
Abstract : Although it is well known that exogenous nerve growth factor (NGF) can dramatically affect the phenotype of the basal forebrain cholinergic neurons in normal, aged, or lesioned animals, whether its actions are restricted to the terminal field level of these cholinergic neurons has yet to be established. In most cases, NGF has been applied into the cerebroventricle space giving it access to both the terminal fields and somatodendritic regions. The recent demonstration that TrkA, the essential component of high-affinity NGF receptors, is expressed not only at the distal fields (terminals and distal axons) but also at the proximal fields (cell bodies, dendrites, and proximal axons) of the basal forebrain cholinergic neurons has provoked renewed interest in this problem. More recently, it was further demonstrated that in Alzheimer's disease (AD), the NGF peptide increased throughout the brain but decreased in the nucleus basalis magnocellularis (NBM), suggesting that there is an impaired retrograde transport of NGF from the cortex to the NBM. Thus, it will be crucial to clarify whether or not the TrkA receptors on the somatodendritic fields of the NBM cholinergic neurons respond to exogenous NGF in order to support the rationale for site-directed neurotrophic factor therapy in AD or other neurological disorders. To clarify this issue, we delivered 2.5S purified mouse NGF locally into the cortex or corpus striatum adjacent to the NBM of naive and cortically devascularized mature male Wistar rats. The local distribution of exogenous NGF was demonstrated by immunohistochemical staining. In naive rats, an NGF dose of 84.00 or 16.80 microg infused into either the cortex or the corpus striatum for 2 weeks caused ipsilateral hypertrophy of the cholinergic neurons of the NBM. In cortically devascularized animals, an NGF dose of 84.00 microg delivered into the cortex and 84.00 microg or 16.80 microg infused into the striatum adjacent to the NBM for 2 weeks rescued the ipsilateral cholinergic phenotype of NBM neurons of the basolocortical pathway from retrograde degeneration. Thus, exogenous NGF can affect the cholinergic phenotype of the NBM regardless of whether it is presented to their nerve terminal fields or their somatodendritic region. The present results provide new evidence that the TrkA receptors present in the somatodendritic region of the cholinergic neurons of the NBM are functional and capable of modulating neuronal phenotype in the naive and lesioned CNS, when applied pharmacologically.
ESTHER : Hu_1997_Exp.Neurol_143_162
PubMedSearch : Hu_1997_Exp.Neurol_143_162
PubMedID: 9000455

Title : NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to cortical infarction in adult post-hypothyroid rats but does not restore cell size compared to euthyroid [correction of euthroid] rats - Figueiredo_1996_J.Chem.Neuroanat_12_15
Author(s) : Figueiredo BC , Hu L , Bedard AM , Tetzlaff W , Cuello AC
Ref : Journal of Chemical Neuroanatomy , 12 :15 , 1996
Abstract : We have tested the hypotheses that nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infarction. In addition, we assessed the expression of p75NGFR and p140trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of 1 month. At this time both the pups and their dams continued to receive 0.05% propylthiouracil in their diet and the pups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75NGFR and p140trkA mRNAs in methylene blue stained cells (day 75) and choline acetyltransferase immunostaining (day 105). The mean number of silver grains (pixels) per microns2 (mean +/- S.E.M.) of cell body cross-sectional area for p75NGFR mRNA in the nucleus basalis magnocellularis of euthyroid rats was 3.43 +/- 0.89, which was not statistically different from post-hypothyroid animals (4.02 +/- 1.07). A similar finding was noted for p140trkA mRNA: mean number of grains in the euthyroid group was 5.54 +/- 0.96 and was not statistically different from the post-hypothyroid group (6.32 +/- 1.45). Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).
ESTHER : Figueiredo_1996_J.Chem.Neuroanat_12_15
PubMedSearch : Figueiredo_1996_J.Chem.Neuroanat_12_15
PubMedID: 9001945