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Copper homeostasis and neurodegenerative diseases

Neural Regeneration Research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang international Research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Opinion on pharmacology research and new drug development from precision medicine

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中国药理学与毒理学杂志 2017年第8期31卷 779-785页

作者： Michael SPEDDING James BARRETT Ying ZHAO international union of pharmacology IUPHAR Chinese Pharmacological Society CNPHARS

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical *** medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

关键词： Opinion on pharmacology research and new drug development from precision medicine

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Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Institute of Clinical pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

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Hippocampal neurogenesis and pro-neurogenic therapies for Alzheimer's disease

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Animal Models and Experimental Medicine 2022年第1期5卷 3-14页

作者： Jie Zheng Department of pharmacology Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of EducationKey Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiChina

Adult hippocampal neurogenesis(AHN)facilitates hippocampal circuits plasticity and regulates hippocampus-dependent cognition and ***,AHN malfunction has been widely reported in both human and animal models of Alzheimer's disease(AD),the most common form of dementia in the *** therapies including rescuing innate AHN,cell engraftment and glianeuron reprogramming hold great potential for compensating the neuronal loss and rewiring the degenerated neuronal network in AD,but there are still great challenges to be *** review covers recent advances in unraveling the involvement of AHN in AD and highlights the prospect of emerging proneurogenic remedies.

关键词： Alzheimer's disease cognitive deficit hippocampus neurogenesis pro-neurogenic therapy

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Protective effects of Dendrobium nobile Lindl. alkaloids on amyloid beta(25–35)-induced neuronal injury

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Neural Regeneration Research 2017年第7期12卷 1131-1136页

作者： Wei Zhang Qin Wu Yan-liu Lu Qi-hai Gong Feng Zhang Jing-shan Shi Key Laboratory of Basic pharmacology of Ministry of Education and Joint international Research Laboratory of Ethnomedicine of Ministry ofEducation Zunyi Medical University Zunyi Guizhou Province China

Dendrobium nobile ***（DNLA）,the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose ***,it is not clear whether DNLA reduces amyloid-beta（Aβ）-induced neuronal *** this study,cortical neurons were treated with DNLA at different concentrations（0.025,0.25,and 2.5 mg/L）for 24 hours,followed by administration of Aβ（25-35）（10μM）.Aβ（25-35） treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial *** damage caused by Aβ（25-35） on these cellular properties was markedly attenuated when cells were pretreated with *** with Aβ（25-35）down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with *** findings suggest that DNLA reduces the cytotoxicity induced by Aβ（25-35） in rat primary cultured *** protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.

关键词： nerve regeneration Dendrobium nobile Lindl. alkaloids amyloid beta neurons synapse synaptophysin postsynaptic density-95 cognitive impairment neuroprotection neural regeneration

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Glycoproteomics analysis of plasma proteins associated with Opisthorchis viverrini infection-induced cholangiocarcinoma in hamster model

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1142-1147页

作者： Pramote Sriwanitchrak Atchara Paemanee Sittiruk Roytrakul Vithoon Viyanant Kesara Na-Bangchang Graduate Program in Biomedical Sciences Faculty of Allied Health SciencesThammasat University Proteomics Research Laboratory National Center for Genetic Engineering and Biotechnology Graduate Program in Bioclinical Sciences Center of Excellence in Pharmacology and Molecular Biology of Malaria and CholangiocarcinomaChulabhorn International College of Medicine Center of Excellence in pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhorn International College of Medicine Excellence Center in pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat University

Objective: To apply lectin affinity chromatography and glycoproteomics-based LC-MS/MS to preliminarily investigate the possible potential plasma biomarkers of Opisthorchis viverrini(OV)-associated CCA in OV/dimethylnitrosamine(DMN)-induced CCA hamster model. Methods: Nine Syrian hamsters were divided into 3 groups as follows(n=3 each): normal(healthy control group); OV group; and OV/DMN group(CCA group). Pooled plasma samples collected from animals in each group at the 6th month post-infection with OV metacercarae were subjected to glycoproteomics analysis. Glycoproteins in the pooled sample from each group were initially isolated by concanavilin A(Con A)-based affinity chromatography. The expression of glycoproteins isolated by both enrichment methods were determined using LCMS/MS. Results: Among the 24 Con A-binding glycoproteins isolated, two proteins, N-myc downstream regulated gene 1(NDRG1) and fetuin-B(FETUB) were found up-regulated only in the samples from the OV and control groups, but not in the OV/DMN(CCA) groups. On the other hand, one protein, i.e., NSFL1 cofactor p47 isoform x3(NSFL1C) was found only in the samples from OV/DMN(CCA) and control groups, but not in the OV group. The remaining 21 proteins were upregulated in the samples from all groups. Conclusions: NDRG1, FETUB and NSFL1 C glycoproteins isolated by Con A-based affinity chromatography could be potential biomarkers for CCA. Plasma samples with negative for NDRG1 and FETUB proteins but positive for NSFL1 C are likely to be OV-associated CCA. Nevertheless, this conclusion remains to be confirmed whether this battery test can discriminate OV-associated CCA from other risk factors.

关键词： Cholangiocarcinoma Opisthorchis viverrini Glycoprotein Hamster model ConA binding protein LC-MS/MS

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Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

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Asian Pacific Journal of Tropical Biomedicine 2020年第10期10卷 442-451页

作者： Uzma Saleem Shingraf Zaib Sana Khalid Fareeha Anwar Muhammad Furqan Akhtar Bashir Ahmad Department of pharmacology Faculty of Pharmaceutical SciencesGovernment College University FaisalabadPakistan Riphah Institute of Pharmaceutical Sciences Riphah International University LahorePakistan

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. ***: Safety was assessed by acute oral toxicity(OECD 425) study. Anti-arthritic activity was explored by in vitro(inhibition of protein denaturation) and in vivo(Complete Freund’s adjuvantinduced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H2O2 scavenging assays. Furthermore, molecular docking was done to check interactions between the plant constituents and cyclooxygenases(COX-1 and COX-2). Quercetin, gallic acid, caffeic acid, syringic acid, sinapic acid, and vanillic acid were quantified by HPLC and eight compounds were identified by GC-MS analysis. Results: No mortality and abnormality in biochemical parameters were observed in the toxicity study. Histological analysis of vital organs also supported these biochemical results. The in vitro and in vivo studies showed that the methanolic extract of leaves of Convolvulus arvensis exhibited dose-dependent anti-arthritic and anti-oxidant potential. Molecular docking showed better interactions of plant compounds with cyclooxygenases as compared to standard ibuprofen. Conclusions: Convolvulus arvensis exhibits strong anti-arthritic activity, justifying the traditional use of the herbal drug.

关键词： Antioxidant organs herbal

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Gastroprotective effect of the aqueous leaf extract of Guiera senegalensis in Albino rats

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 771-775页

作者： Akuodor GC Essien AD David-Oku E Chilaka kC Akpan JL Ezeokpo B Ezeonwumelu JOC Department of pharmacology College of Medical SciencesUniversity of Calabar Department of Biochemistry of Medical SciencesUniversity of Calabar Department of pharmacology and Therapeutic College of Health SciencesNnamdi Azikiwe University Department of pharmacology and Therapeutic Faculty of Clinical MedicineEbonyi State University School of Pharmacy Kampala International University

Objective:To evaluate the effect of aqueous leaf extract of Guiera senegalensis(***)on gastric mucosal damage using different ulcer ***:Considering the above claims,the present study was undertaken to validate the gastroprotective potential of the aqueous leaf extract of this plant against ethanol,water immersion and Aspirin induced ulcer ***:The leaf extract(50,100 and 200 mg/kg,p.o.)significantly(P<0.05)decreased the ulcer index in all assays ***:The results obtained,provide strong evidence of antiulcer activity of the leaf extract of *** and support the traditional uses of the plant for the treatment of ulcer.

关键词： Guiera senegalensis Aqueous extract Ethanol Aspirin Stress induced gastric ulcers

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Magnesium acetyltaurate prevents retinal damage and visual impairment in rats through suppression of NMDA-induced upregulation of NF-κB,p53 and AP-1(c-Jun/c-Fos)

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Neural Regeneration Research 2021年第11期16卷 2330-2344页

作者： Lidawani Lambuk Igor Iezhitsa Renu Agarwal Puneet Agarwal Anna Peresypkina Anna Pobeda Nafeeza Mohd Ismail Center for Neuroscience Research(NeuRon) Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSelangorMalaysia School of Medicine International Medical UniversityKuala LumpurMalaysia Department of pharmacology and Clinical pharmacology Institute of MedicineBelgorod State National Research UniversityBelgorodRussia

Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell *** current study investigated the involvement of nuclear factor kappa-B(NF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against NMDA-induced retinal *** this study,Sprague-Dawley rats were randomized to undergo intravitreal injection of vehicle,NMDA or MgAT as pre-treatment to *** days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRN3A *** outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain *** phospho-NF-κB,phospho-p53 and AP-1 levels were evaluated using western blot *** visual functions were evaluated using visual object recognition *** retrograde labelling and BRN3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of *** indicated that pre-treatment with MgAT partially preserved the functional activity of NMDA-exposed *** abolished NMDA-induced increase of retinal phospho-NF-κB,phospho-p53 and AP-1 expression and suppressed NMDA-induced transcriptional activity of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(*** with different shapes)after NMDA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with *** conclusion,pre-treatment with MgAT prevents NMDA induced retinal injury by inhibiting NMDA-induced neuronal apoptosis via downr

关键词： AP-1(c-Jun/c-Fos) electroretinography magnesium acetyltaurate neuroprotection NF-κB N-methyl-D-aspartate object recognition tasks p53 retinal excitotoxicity retrograde labelling

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Crimean-Congo hemorrhagic fever: etiology, diagnosis, management and potential alternative therapy

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Asian Pacific Journal of Tropical Medicine 2020年第4期13卷 143-151页

作者： Mohammad Saleem Muiz Tanvir Muhammad Furqan Akhtar Ammara Saleem Department of pharmacology Punjab University College of PharmacyUniversity of the PunjabLahorePakistan Department of pharmacology Faculty of Pharmaceutical SciencesGovernment College University FaisalabadFaisalabadPakistan Riphah Institute of Pharmaceutical Sciences Riphah International UniversityLahore CampusPakistan

Crimean-Congo hemorrhagic fever(CCHF)virus belongs to the genus Nairovirus and family *** is a tickborne disease that has mostly been reported from Asia,Africa and *** diagnosis of CCHF is essential for patient care and preventing its spread to normal *** of CCHF is mostly limited to the use of ribavirin and palliative *** practice of using interferon and vaccines has also been proved to be ineffective and unsafe.A search for an effective alternative treatment of the CCHF still ***,the current review focusses on the cause,prevalence,mode of transmission,pathophysiology,signs,symptoms,diagnostic features and treatment options of *** review also highlights the possible alternative therapy in the form of antiviral medicinal plants which are effective against viral hemorrhagic *** medicinal plants have shown convincing evidence for their activities against different viral hemorrhagic fevers and may be used alone or in combination with existing therapies to achieve an optimum therapeutic response.

关键词： Congo fever Dengue fever Alternative therapy Antiviral plants

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