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Microglia lactylation in relation to central nervous system diseases

Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina department of clinical laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina department of clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai department of clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina department of Radiology and Nuclear medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China Chemistry 2025年第01期 377-384页

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao Key laboratory of Environmental medicine Engineering Ministry of Education School of Public Health Southeast University Key laboratory of Modern Toxicology of Ministry of Education Department of Hygienic Analysis and Detection School of Public HealthNanjing Medical University department of Psychosomatics and Psychiatry Zhongda Hospital School of Medicine Southeast University

The measurement of amino acid and monoamine neurotransmitters（NTs） in serum plays a central role in the identification and monitoring of clinical panic disorder（PD）. However, the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely challenging. Herein, we developed a strategy that integrated solid phase extraction based on magnetic Fe3O4coated with polydopamine（Fe3O4@PDA） and direct analysis of mass spectrometry in real time（DART-MS） for quantification of 10 NTs. We systematically investigated the optimal conditions of this strategy to achieve good accuracy and precision. Compared with existing magnetic solid phase extraction methods for NTs detection in biological samples, this strategy could adsorb more targets while having similar adsorption efficiencies, and the total process time was reduced by an average of 69.42%. We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic accuracy. In addition, an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this strategy. Our results highlighted the potential ability of Fe3O4@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

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Antiviral activity of five Asian medicinal pant crude extracts against highly pathogenic H5N1 avian influenza virus

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Asian Pacific Journal of Tropical medicine 2017年第9期10卷 871-876页

作者： Benjaporn Sornpet Teerapong Potha Yingmanee Tragoolpua Kidsadagon Pringproa Central veterinary diagnostic laboratory Faculty of Veterinary MedicineChiang Mai UniversityChiang Mai 50100Thailand department of Biology Faculty of SciencesChiang Mai UniversityChiang Mai 50200Thailand department of veterinary Biosciences and veterinary Public Health Faculty of Veterinary MedicineChiang Mai UniversityChiang Mai 50100Thailand

Objective: To study the antiviral properties of the five Asian medicinal plants against in vitro infection by the highly pathogenic avian influenza virus(H5N1).Methods: Crude extracts of Andrographis paniculata, Curcuma longa(C. longa),Gynostemma pentaphyllum, Kaempferia parviflora(K. parviflora), and Psidium guajava obtained by both water and ethanol extractions were investigated for their cytotoxicity in the Madin–Darby canine kidney cells. Thereafter, they were investigated in vitro for antiviral activity and cytokine response upon H5N1 virus ***: The results revealed that both water and ethanol extracts of all the five studied plants showed significant antiviral activity against H5N1 virus. Among these plants,C. longa and K. parviflora showed strong anti-H5N1 activity. Thus, they were selected for further studies on their cytokine response upon virus infection. It was found that ethanol and water crude extracts of C. longa and K. parviflora induced significant upregulation of TNF-a and IFN-b m RNA expressions, suggesting their roles in the inhibition of H5N1 virus ***: To the best of the authors' knowledge, this study is among the earliest reports to illustrate the antiviral property of these Asian medicinal plants against the highly pathogenic avian H5N1 influenza virus. The results of this study shed light on alternative therapeutic sources for treatment of H5N1 influenza virus infection in the future.

关键词： Antiviral activity H5N1 influenza virus Medicinal plants Cytokine response

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A nanobody-based blocking enzyme-linked immunosorbent assay for detecting antibodies against pseudorabies virus glycoprotein E

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Journal of Integrative Agriculture 2024年第4期23卷 1354-1368页

作者： Huanhuan Lü Pinpin Ji Siyu Liu Ziwei Zhang Lei Wang Yani Sun Baoyuan Liu Lizhen Wang Qin Zhao department of Preventive veterinary medicine College of Veterinary MedicineNorthwest A&F University/Shaanxi Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic TechnologyMinistry of Agriculture and Rural AffairsYangling 712100China

Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry *** glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA)has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some *** has the advantages of small size and easy genetic engineering and has been a promising diagnostic ***,there were few reports about developing nanobody-based ELISA for detecting anti-PRV-gE *** the present study,the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian ***,two nanobodies against PRV-gE were screened from the immunized camel by phage display ***,two nanobody-HRP fusion proteins were expressed with HEK293T *** PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA(bELISA)to detect anti-PRV-gE *** optimizing the conditions of bELISA,the amount of coated antigen was 200 ng per well,and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:*** cut-off value of bELISA was 24.20%,and the sensitivity and specificity were 96.43 and 92.63%,*** detecting 233 clinical pig sera with the developed bELISA and a commercial kit,the results showed that the coincidence rate of two assays was 93.99%.Additionallly,epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV ***,great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were *** bELISA could be used for monitoring and eradicating PR.

关键词： nanobody nanobody-HRP blocking ELISA PRV-gE antibody

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A microfluidic biosensor for the diagnosis ofchronic wasting disease

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Microsystems & Nanoengineering 2023年第4期9卷 263-279页

作者： Sura A.Muhsin Amjed Abdullah Estela kobashigawa Muthana Al-Amidie Sherri Russell Michael Z.Zhang Shuping Zhang Mahmoud Almasri University of Missouri–Columbia Electrical Engineering and Computer ScienceColumbiaMOUSA University of Missouri–Columbia College of Veterinary MedicineVeterinary Medical Diagnostic LaboratoryColumbiaMOUSA Missouri department of Conservation ColumbiaMOUSA

Cervids are affected by a neurologic disease that is always fatal to individuals and has population effects. This disease iscalled chronic wasting disease (CWD) and is caused by a misfolded prion protein. The disease is transmitted viacontact with contaminated body fluids and tissue or exposure to the environment, such as drinking water or *** CWD diagnosis depends on ELISA screening of cervid lymph nodes and subsequent immunohistochemistry(IHC) confirmation of ELISA-positive results. The disease has proven to be difficult to control in part because ofsensitivity and specificity issues with the current test regimen. We have investigated an accurate, rapid, and low-costmicrofluidic microelectromechanical system (MEMS) biosensing device for the detection of CWD pathologic prions inretropharyngeal lymph nodes (RLNs), which is the current standard type of CWD diagnostic sample. The deviceconsists of three novel regions for concentrating, trapping, and detecting the prion. The detection region includes anarray of electrodes coated with a monoclonal antibody against pathologic prions. The experimental conditions wereoptimized using an engineered prion control antigen. Testing could be completed in less than 1 hour with highsensitivity and selectivity. The biosensor detected the engineered prion antigen at a 1:24 dilution, while ELISA detectedthe same antigen at a 1:8 dilution. The relative limit of detection (rLOD) of the biosensor was a 1:1000 dilution of aknown strong positive RLN sample, whereas ELISA showed a rLOD of 1:100 dilution. Thus, the biosensor was 10 timesmore sensitive than ELISA, which is the currently approved CWD diagnostic test. The biosensor’s specificity andselectivity were confirmed using known negative RPLN samples, a negative control antibody (monoclonal antibodyagainst bovine coronavirus BCV), and two negative control antigens (bluetongue virus and Epizootic hemorrhagicdisease virus). The biosensor’s ability to detect pathogenic prions was

关键词： fir diagnosis specificity

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KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma

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Journal of Genetics and Genomics 2021年第7期48卷 618-630页

作者： Kevin Christian Montecillo Gulay Keisuke Aoshima Yuki Shibata Hironobu Yasui Qin Yan Atsushi Kobayashi Takashi Kimura laboratory of Comparative Pathology Department of Clinical SciencesFaculty of Veterinary MedicineHokkaido UniversitySapporoHokkaido 060-0818 Japan laboratory of Radiation Biology Department of Applied Veterinary SciencesFaculty of Veterinary MedicineHokkaido UniversitySapporoHokkaido 060-0818 Japan department of Pathology Yale School of MedicineNew HavenCT 06510USA

Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been *** this study,we find that lysine-specific demethylase 2 b(KDM2 B)is highly expressed in HSA cell lines compared with normal canine endothelial *** of KDM2 B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA ***,doxycycline-induced KDM2 B silencing in tumor xenografts results in decreased tumor sizes compared with the ***,KDM2 B is also highly expressed in clinical cases of *** hypothesize that pharmacological KDM2 B inhibition can also induce HSA cell death and can be used as an alternative treatment for *** treat HSA cells with GSK-J4,a histone demethylase inhibitor,and find that GSK-J4 treatment also induces apoptosis and cell *** addition,GSK-J4 treatment decreases tumor ***,we demonstrate that KDM2 B acts as an oncogene in HSA by enhancing the DNA damage ***,we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.

关键词： DNA repair Epigenetics Hemangiosarcoma KDM2B Oncogene

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Comparative study of heavy metal and pathogenic bacterial contamination in sludge and manure in biogas and non-biogas swine farms

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Journal of Environmental Sciences 2011年第6期23卷 991-997页

作者： Phitsanu Tulayakul Alongkot Boonsoongnern Suwicha Kasemsuwan Srisamai Wiriyarampa Juree Pankumnoed Suwanna Tippayaluck Hathairad Hananantachai Ratchaneekorn Mingkhwan Ramnaree Netvichian Sutha Khaodhiar department of veterinary Public Health and diagnostic Services Faculty of Veterinary MedicineKasetsart UniversityNakorn-Pathom 73140Thailand department of Farm Resources and Production medicine Faculty of Veterinary MedicineKasetsart UniversityNakorn-Pathom 73140Thailand Central laboratory Units Faculty of Tropical MedicineMahidol UniversityBangkok 10400Thailand department of Environmental Engineering Faculty of EngineeringChulalongkorn UniversityBangkok 10330Thailand

The objective of this study is to determine and compare the heavy metal（Zn,Cu,Cd,Pb） and bacterial（***,coliform and Salmonella spp.） contamination between swine farms utilizing biogas and non-biogas systems in the central part of *** showed that average levels of ***,coliform,BOD,COD,Zn,Cu and Pb in sludge from the post-biogas pond were higher than the standard ***,the levels of ***,coliform,Cd and Pb were also higher than the standard limits for dry *** levels of ***,coliform and BOD on biogas farms were lower than on non-biogas *** isolation of Salmonella spp.,it was found that Salmonella serovars Rissen was the most abundant at 18.46%（12/65）,followed by Anatum 12.31%（8/65）,and Kedougou 9.23%（6/65）.The pathogenic strains of Salmonella serovars Paratyphi B *** and Typhimurium were present in equal amounts at 4.62%（3/65） in samples from all swine *** study revealed that significant reduction in *** and coliform levels in sludge from covered lagoon biogas systems on swine *** presence of Salmonella as well as Cd and Pb,in significant amount in dry manure,suggests that there is a high probability of environmental contamination if it is used for agricultural ***,careful waste and manure disposal from swine farms and the regular monitoring of wastewater is strongly recommended to ensure the safety of humans,other animals and the environment.

关键词： pathogenic bacteria heavy metal manure biogas sludge swine

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Recent advances in exploring new blood-based biomarkers for the early diagnosis of gastric cancer

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Science China Chemistry 2025年第1期 35-45页

作者： Xinyu Peng Qian Ma Da Han School of Life Science Shanghai University Institute of Molecular medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University department of Research and Development Intellinosis Biotechnologies Co.Ltd.

Gastric cancer(GC) is a prevalent and lethal malignancy worldwide, and the 5-year survival rate is less than 30%. The absence of distinctive symptoms often leads to late-stage diagnosis, contributing to a grim prognosis. Early detection is pivotal for improving the survival rates and outcomes of GC patients. Traditional diagnostic methods, including gastroscopy and histopathological examination, are restricted in the early diagnosis of GC. Conventional protein biomarkers, such as carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), and carbohydrate antigen 72-4(CA72-4), exhibit insufficient sensitivity and specificity for GC screening, which diminishes their clinical value. Recently, novel circulating biomarkers, such as circulating tumor cells(CTCs), circulating tumor cell DNA(ct DNA), and circulating free RNA(cf RNA), have emerged as promising candidates in the burgeoning field of liquid biopsy due to their superior sensitivity and specificity. This review focuses on the latest research on blood-based biomarkers for GC diagnosis and examines the clinical potentials and challenges associated with these emerging biomarkers.

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HLA-B-associated transcript 3 (Bat3) stabilizes and activates p53 in a HAUSP-dependent manner

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Journal of Molecular Cell Biology 2020年第2期12卷 99-112页

作者： Rui Zhang Di Cui TengXue Yue Lang Yunfan Zhang Lianjie Li Haili Sun Yu Kuang Gebin Li Jun Tang department of Basic veterinary College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China State Key laboratory of Agrobiotechnology China Agricultural UniversityBeijing 100193China department of clinical veterinary College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China clinical Research Institute Zhejiang Provincial People's HospitalPeople's Hospital of Hangzhou Medical CollegeHangzhou 310014China

The p53 pathway is a highly complex signaling network including several key *** is a critical component of the p53 pathway acting as a deubiquitinase for both p53 and its key repressor ***,we identified a novel HAUSP-interacting protein,HLA-B-associated transcript 3(Bat3)and found it to be capable of inducing p53 stabilization and activation via a HAUSP-dependent mechanism,resulting in cell growth ***,the deubiquitylating enzymatic activity of HAUSP was not required for this ***-immunoprecipitation showed that p53 coexisted in a complex with Bat3 and HAUSP in vivo,and HAUSP may serve as a binding mediator to enhance the interaction between p53 and *** studies revealed that formation of this three-protein complex interfered with the binding of p53 to its proteasome receptor S5a and promoted the accumulation of p53 in ***,Mdm2 protein abundance is also regulated by Bat3 in the presence of *** of Bat3 and HAUSP increases Mdm2 protein levels without influencing the p53–Mdm2 interaction and Mdm2-mediated p53 ubiquitination,indicating that Bat3–HAUSP-mediated protein stabilization is not specific to p53 and different mechanisms may be involved in Bat3-mediated regulation of p53–Mdm2 ***,our study unravels a novel mechanism by which p53 is stabilized and activated by HAUSP-mediated interaction with Bat3 and implies that Bat3 might function as a tumor suppressor through the stabilization of p53.

关键词： Bat3 p53 stabilization HAUSP S5a proteasome recognition

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