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  1. Article ; Online: Progressive expansion of albumin adducts for organophosphorus nerve agent traceability based on single and group adduct collection.

    Wang, Jin / Lu, Xiaogang / Gao, Runli / Pei, Chengxin / Wang, Hongmei

    Analytical and bioanalytical chemistry

    2024  

    Abstract: Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the ... ...

    Abstract Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the active nonapeptide in butyrylcholinesterase (BChE). To explore stable and reliable protein adducts and increase the accuracy of OPNAs traceability further, we gradually expanded OPNAs-albumin adducts based on single and group adduct collection. Several stable peptides were found via LC-MS/MS analysis in human serum albumin (HSA) exposed to OPNAs in a large exposure range. These adducts were present in HSA samples exposed to OPNAs of each concentration, which provided data support for the reliability and stability of using adducts to trace OPNAs. Meanwhile, the formation mechanism of OPNAs-cysteine adduct was clarified via computer simulations. Then, these active sites found and modified peptides were used as raw materials for progressive expansion of albumin adducts. We constructed an OPNAs-HSA adducts group, in which a specific agent is the exposure source, and three or more active peptides constitute data sets for OPNAs traceability. Compared with single or scattered protein adducts, the OPNAs-HSA adduct group improves OPNAs identification by mutual verification using active peptides or by narrowing the identity range of the exposure source. We also determined the minimum detectable concentration of OPNAs for the adduct group. Two or more peptides can be detected when there is an exposure of 50 times the molar excess of OPNAs in relation to HSA. This improved the accuracy of OPNAs exposure and identity confirmation. A collection of OPNAs-albumin adducts was also examined. The collection was established by collecting, classifying, and integrating the existing albumin adducts according to the species to which each albumin belongs, the types of agents, and protease. This method can serve as a reference for discovering new albumin adducts, characteristic phosphonylated peptides, and potential biomarkers. In addition, to avoid a false negative for OPNAs traceability using albumin adducts, we explored OPNAs-cholinesterase adducts because cholinesterase is more reactive with OPNAs than albumin. Seven active peptides in red blood cell acetylcholinesterase (RBC AChE) and serum BChE can assist in OPNAs exposure and identity confirmation.
    Language English
    Publishing date 2024-05-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 201093-8
    ISSN 1618-2650 ; 0016-1152 ; 0372-7920
    ISSN (online) 1618-2650
    ISSN 0016-1152 ; 0372-7920
    DOI 10.1007/s00216-024-05311-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Synthesis, biological evaluation and molecular docking of novel nereistoxin derivatives containing phosphonates as insecticidal/AChE inhibitory agents.

    Yan, Qiaoli / Lu, Xiaogang / Wang, Jin / Zhang, Zixuan / Gao, Runli / Pei, Chengxin / Wang, Hongmei

    RSC advances

    2024  Volume 14, Issue 6, Page(s) 3996–4004

    Abstract: In continuation of our program aimed at the discovery and development of natural product-based insecticidal agents, a series of novel nereistoxin derivatives containing phosphonate were synthesized and characterized ... ...

    Abstract In continuation of our program aimed at the discovery and development of natural product-based insecticidal agents, a series of novel nereistoxin derivatives containing phosphonate were synthesized and characterized by
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d3ra08004h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Application of chemical attribution in matching OPNAs-exposed biological samples with exposure sources- based on the impurity profiles via GC × GC-TOFMS analysis.

    Wang, Jin / Lu, Xiaogang / Zhang, Zixuan / Gao, Runli / Pei, Chengxin / Wang, Hongmei

    Journal of chromatography. A

    2024  Volume 1718, Page(s) 464718

    Abstract: Chemical attribution is a vital tool to attribute chemicals or related materials to their origins in chemical forensics via various chemometric methods. Current progress related to organophosphorus nerve agents (OPNAs) has mainly focused on the ... ...

    Abstract Chemical attribution is a vital tool to attribute chemicals or related materials to their origins in chemical forensics via various chemometric methods. Current progress related to organophosphorus nerve agents (OPNAs) has mainly focused on the attribution of chemical sources and synthetic pathways. It has not yet been applied in matching exposed biological samples to their sources. This work used chemical attribution to explore organic impurity profiles in biological samples exposed to various OPNAs. Chemical attribution was first used to identify the exposure source of biological samples based on the full-scan data via comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometer (GC × GC-TOFMS). Taking peak area as the only variable, it can quickly match exposed samples to their sources by applying unsupervised or supervised models, screen difference compounds via one-way ANOVA or t-tests, and then identify valuable impurities that can distinguish different types of exposed samples. To further obtain the impurity profile only applicable to a certain weapon' samples, the irrelevant components were removed via conventional methods. The findings showed there were 53 impurities that can promote distinguishing six groups of OPNA exposed samples, as well as 42 components that can be used as valuable impurities to distinguish class G and class V samples. These were all unique impurities that appear in a certain weapon' samples. The outcomes can be a reference for tracing the source for OPNA-exposed samples, which was beneficial to the further development in source matching of forensic samples. Moreover, the chemical attribution for impurity profiles in biological samples after weapons exposure may inspire research into the characteristics of impurity profile in biological samples as well as practical applications of chemical attribution for OPNA-exposed samples, that may expand potential biomarkers and break the limits of existing markers in the future.
    MeSH term(s) Nerve Agents ; Mass Spectrometry ; Chromatography, Gas/methods
    Chemical Substances Nerve Agents
    Language English
    Publishing date 2024-02-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1171488-8
    ISSN 1873-3778 ; 0021-9673
    ISSN (online) 1873-3778
    ISSN 0021-9673
    DOI 10.1016/j.chroma.2024.464718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Current Progress for Retrospective Identification of Nerve Agent Biomarkers in Biological Samples after Exposure.

    Wang, Jin / Lu, Xiaogang / Gao, Runli / Pei, Chengxin / Wang, Hongmei

    Toxics

    2022  Volume 10, Issue 8

    Abstract: Organophosphorus neurotoxic agents (OPNAs) seriously damage the nervous system, inhibiting AChE activity and threatening human health and life. Timely and accurate detection of biomarkers in biomedical samples is an important means for identifying OPNA ... ...

    Abstract Organophosphorus neurotoxic agents (OPNAs) seriously damage the nervous system, inhibiting AChE activity and threatening human health and life. Timely and accurate detection of biomarkers in biomedical samples is an important means for identifying OPNA exposure, helping to recognize and clarify its characteristics and providing unambiguous forensic evidence for retrospective research. It is therefore necessary to summarize the varieties of biomarkers, recognize their various characteristics, and understand the principal research methods for these biomarkers in the retrospective detection of OPNA exposure. Common biomarkers include mainly intact agents, degradation products and protein adducts. Direct agent identification in basic experimental research was successfully applied to the detection of free OPNAs, however, this method is not applicable to actual biomedical samples because the high reactivity of OPNAs promotes rapid metabolism. Stepwise degradation products are important targets for retrospective research and are usually analyzed using a GC-MS, or an LC-MS system after derivatization. The smaller window of detection time requires that sampling be accomplished within 48 h, increasing the obstacles to determining OPNA exposure. For this reason, the focus of retrospective identification of OPNA exposure has shifted to protein adducts with a longer lifetime. Compared to the fluoride-induced reactivation method, which cannot be used for aged adducts, digestive peptide analysis is the more elegant method for detecting various adducts, identifying more active sites, exploring potential biomarkers and excavating characteristic ions. Retrospective identification of biomarkers after OPNA poisoning is of primary importance, providing unambiguous evidence for forensic analysis in actual cases and judgment of chemical accidents. At present, degradation products, the nonapeptide from BChE adducts and Y411 from human serum adducts are used successfully in actual cases of OPNA exposure. However, more potential biomarkers are still in the discovery stage, which may prove inconclusive. Therefore, there is an urgent need for research that screens biomarker candidates with high reactivity and good reliability from the potential candidates. In addition, mass spectrometry detection with high resolution and reactivity and an accurate data processing system in the scanning mode must also be further improved for the retrospective identification of unknown agents.
    Language English
    Publishing date 2022-08-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2733883-6
    ISSN 2305-6304 ; 2305-6304
    ISSN (online) 2305-6304
    ISSN 2305-6304
    DOI 10.3390/toxics10080439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: First Display of Haloalkane Dehalogenase LinB on the Surface of

    Wang, Fuli / Liu, Xiujie / Song, Tianyu / Pei, Chengxin / Huang, Qibin / Jiang, Hui / Xi, Hailing

    Protein and peptide letters

    2023  Volume 30, Issue 11, Page(s) 959–965

    Abstract: Background: LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode.: Objectives: In order to display ... ...

    Abstract Background: LinB, as a Haloalkane dehalogenase, has good catalytic activity for many highly toxic and recalcitrant compounds, and can realize the elimination of chemical weapons HD in a green non-toxic mode.
    Objectives: In order to display Haloalkane dehalogenase LinB on the surface of
    Methods: We have constituted the
    Results: Data revealed that LinB can display on spore surface successfully. The hydrolyzing HD analogue 2-chloroethyl ethylsulfide (2-CEES) activity of displayed LinB spores was 4.30±0.09 U/mL, and its specific activity was 0.78±0.03U/mg. Meanwhile, LinB spores showed a stronger stress resistance activity on 2-CEES than free LinB. This study obtained B. subtilis spores of LinB (phingobium japonicum UT26) with enzyme activity that was not reported before.
    Conclusion: Spore surface display technology uses resistance spore as the carrier to guarantee LinB activity, enhances its stability, and reduces the production cost, thus expanding the range of its application.
    MeSH term(s) Bacillus subtilis/genetics ; Spores, Bacterial/genetics ; Hydrolases/genetics ; Hydrolases/chemistry ; Bacterial Proteins/genetics
    Chemical Substances haloalkane dehalogenase (EC 3.8.1.5) ; 2-chloroethyl ethyl sulfide (693-07-2) ; Hydrolases (EC 3.-) ; Bacterial Proteins
    Language English
    Publishing date 2023-11-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1280776-x
    ISSN 1875-5305 ; 0929-8665
    ISSN (online) 1875-5305
    ISSN 0929-8665
    DOI 10.2174/0109298665238177231020044054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Facile synthesis and nematicidal activity evaluation of thiophosphinyl amide [(Pz)

    Chen, Xiao / Lu, Xiaogang / Liu, Haibo / Wang, Hongmei / Pei, Chengxin

    RSC advances

    2021  Volume 11, Issue 57, Page(s) 36250–36256

    Abstract: A series of thiophosphinyl amide [(Pz) ...

    Abstract A series of thiophosphinyl amide [(Pz)
    Language English
    Publishing date 2021-11-10
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d1ra06232h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Chemometrics-assisted analysis of chemical impurity profiles of tabun nerve agent using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

    Lu, Xiaogang / Zhu, Xiaxia / Gao, Runli / Tang, Hui / Pei, Chengxin / Wang, Hongmei / Xiao, Junhua

    Journal of chromatography. A

    2022  Volume 1685, Page(s) 463643

    Abstract: A route determination strategy through non-targeted screening of chemical attribution signatures was developed to identify tabun samples from three different synthetic routes. The CAS profiles of tabun samples were obtained by comprehensive two- ... ...

    Abstract A route determination strategy through non-targeted screening of chemical attribution signatures was developed to identify tabun samples from three different synthetic routes. The CAS profiles of tabun samples were obtained by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometer (GC×GC-TOFMS). The structures of 109 CAS were identified by NIST library and mass spectrometry fragment analysis. A few identified compounds could be traced to impurities in precursor compounds used in tabun synthesis. Based on the gas chromatography/mass spectrometry peak data of the selected CAS, partial least squares-discriminant analysis (PLS-DA) was used to extract the chemical attribution signatures of the characteristic compounds. The trained PLS-DA model performed well, with the lowest specificity and sensitivity values of 1.000 and 0.882, respectively. The performance of the PLS-DA model was further verified by unknown sample test set. The model demonstrated its ability to differentiate all the unknown tabun samples. The stability of chemical attribution signatures from different time periods was also investigated, and was further evaluated.
    MeSH term(s) Nerve Agents ; Chemometrics ; Gas Chromatography-Mass Spectrometry ; Mass Spectrometry
    Chemical Substances tabun (S45M750QSH) ; Nerve Agents
    Language English
    Publishing date 2022-11-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1171488-8
    ISSN 1873-3778 ; 0021-9673
    ISSN (online) 1873-3778
    ISSN 0021-9673
    DOI 10.1016/j.chroma.2022.463643
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin.

    Wang, Jin / Sun, Fengjuan / Lu, Xiaogang / Gao, Runli / Pei, Chengxin / Wang, Hongmei

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 10979

    Abstract: Organophosphorus nerve agents (OPNAs) that damage the central nervous system by inhibiting acetylcholinesterase activity, pose severe threats to human health and life security. Reliable biomarkers that quickly and accurately detect OPNAs exposure are ... ...

    Abstract Organophosphorus nerve agents (OPNAs) that damage the central nervous system by inhibiting acetylcholinesterase activity, pose severe threats to human health and life security. Reliable biomarkers that quickly and accurately detect OPNAs exposure are urgently needed to help diagnose quickly and treat in time. Albumins that covalently bind to OPNAs could serve as important targets for retrospective verification of OPNAs exposure. The goal of this study is to explore the potential biomarkers in albumins with high reactivity and good stability and expand the group of potential biomarkers in different species for detecting the exposure of V-type OPNAs including O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). Taking human serum albumin (HSA), bovine serum albumin (BSA) and rabbit serum albumin (RSA) as the research objectives, multiple active sites including phosphonylation and disulfide adduct sites were observed in albumins from different species. Numerous phosphonylation sites labeled by all agents in one type of albumin were found. Among the different species, four shared phosphonylation sites with high reactivity include K499, K549, K249, and Y108. In addition, Y108 on ETY*GEMADCCAK, Y287 on Y*ICENQDSISSK, Y377 on TY*ETTLEK and Y164 on YLY*EIAR in HSA were stably phosphonylated by all agents in gradient concentration, making them stable and suitable potential biomarkers for V-type OPNAs exposure. Notably, Y108 on ETY*GEMADCCAK in HSA, on DTY*GDVADCCEK in RSA, and on ETY*GDMADCCEK in BSA were highly reactive to all V-type agents, regardless of species. It was also successfully labeled in HSA exposed to class V agents in gradient concentration. Y108 is expected to be used to screen and identify the exposure of V-type agents in the retrospective research. Disulfide adducts sites, consisted of four sites in HSA and two sites in BSA were also successfully labeled by V-type agents, and characteristic ion fragments from these disulfide adducts were also identified by secondary mass spectrometry. Molecular simulation of the stably modified sites were conducted to discover the promoting factors of covalent adduct formation, which help further clarify formation mechanism of albumin adducts at active sites.
    MeSH term(s) Acetylcholinesterase ; Animals ; Biomarkers ; Disulfides/chemistry ; Nerve Agents/metabolism ; Rabbits ; Retrospective Studies ; Serum Albumin/metabolism ; Serum Albumin, Human/metabolism
    Chemical Substances Biomarkers ; Disulfides ; Nerve Agents ; Serum Albumin ; Acetylcholinesterase (EC 3.1.1.7) ; Serum Albumin, Human (ZIF514RVZR)
    Language English
    Publishing date 2022-06-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-15198-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Qualitative Analysis of Novel Flavonoid Adducts from Nerve Agent Tabun-Exposed

    Xing, Zhongfang / Zhang, Ruiqian / Zhao, Zhehui / Yuan, Ling / Yu, Huilan / Yang, Yang / Yang, Yuntao / Liu, Shilei / Pei, Chengxin

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 6

    Abstract: Flavonoids are a kind of secondary metabolite which widely exist in plants. They contain a lot of active hydroxyls, which can react with toxic chemicals to produce potential exposure biomarkers. In this article, the model ... ...

    Abstract Flavonoids are a kind of secondary metabolite which widely exist in plants. They contain a lot of active hydroxyls, which can react with toxic chemicals to produce potential exposure biomarkers. In this article, the model plant
    MeSH term(s) Flavonoids/chemistry ; Nerve Agents ; Arabidopsis ; Tandem Mass Spectrometry/methods ; Retrospective Studies ; Chromatography, High Pressure Liquid/methods ; Plants
    Chemical Substances Flavonoids ; tabun (S45M750QSH) ; Nerve Agents
    Language English
    Publishing date 2023-03-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28062581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Self-Assembly Nanostructure of Myristoylated ω-Conotoxin MVIIA Increases the Duration of Efficacy and Reduces Side Effects

    Ding, Xiufang / Wang, Yue / Zhang, Sida / Zhang, Ruihua / Chen, Dong / Chen, Long / Zhang, Yu / Luo, Shi-Zhong / Xu, Jianfu / Pei, Chengxin

    Mar Drugs. 2023 Apr. 01, v. 21, no. 4

    2023  

    Abstract: Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca²⁺ channels (Caᵥ2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow ... ...

    Abstract Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca²⁺ channels (Caᵥ2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow therapeutic window, severe neurological side effects and low stability associated with peptide MVIIA have restricted its widespread use. Fortunately, self-assembly endows the peptide with high stability and multiple functions, which can effectively control its release to prolong its duration of action. Inspired by this, MVIIA was modified with appropriate fatty acid chains to render it amphiphilic and easier to self-assemble. In this paper, an N-terminal myristoylated MVIIA (Myr-MVIIA, medium carbon chain length) was designed and prepared to undergo self-assembly. The present results indicated that Myr-MVIIA can self-assemble into micelles. Self-assembled micelles formed by Myr-MVIIA at higher concentrations than MVIIA can prolong the duration of the analgesic effect and significantly reduce or even eliminate the side effects of tremor and coordinated motor dysfunction in mice.
    Keywords analgesic effect ; calcium ; carbon ; fatty acids ; micelles ; nanomaterials ; pain ; peptides ; therapeutics
    Language English
    Dates of publication 2023-0401
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2175190-0
    ISSN 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md21040229
    Database NAL-Catalogue (AGRICOLA)

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