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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli clinical medical college of fujian medical university Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina fujian provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha Department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina fujian provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Institute of Laboratory Animal Center Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina Department of Hyperbaric Oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei college of Pharmacy and First clinical medical college Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

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Activatable chemiluminescence probe based on four-arm PEGconjugated-pyropheophorbide-a for in vivo autofluorescence-free imaging of peroxynitrite

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Science China Chemistry 2025年

作者： Jianmei Ke Lei Ding Ronggui Lian Cheng Zheng Wenjun Li Aixian Zheng Yupeng Sun Ming Wu Yongyi Zeng Xiaolong Liu Maochun Hong Xiaolong Zhang The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Ganjiang Innovation Academy Chinese Academy of Sciences School of Rare Earths University of Science and Technology of China college of Chemistry Fuzhou University State Key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences

Peroxynitrite（ONOO-） is a highly reactive nitrogen species that plays pivotal roles in cell signal transduction and physiological or pathological progresses. However, commonly used ONOO-optical imaging probes are still hampered by high background/autofluorescence（fluorescence probe）, short emission wavelength, or poor selectivity in the case of chemiluminescence. Herein,we report a facile method to prepare an activatable chemiluminescence probe（PPA-PEG） with good biocompatibility and functionality for in vivo autofluorescence-free imaging of ONOO-. The PPA-PEG consists of pyropheophorbide-a（PPA）, a typical deep red photosensitizer that acts as both the recognition and signaling element, and 4-arm poly（ethylene glycol）(4-arm PEG), which improves the biosafety and water solubility of probe. These components can self-assemble into nanoparticles（namely PPA-PEG nanoprobe） in aqueous solution. The PPA-PEG nanoprobe showed an ultra-low chemiluminescence signal before interacting with ONOO-, but exhibited good selectivity, high sensitivity and a fast response toward ONOO-. The PPAPEG was successfully applied to image cellular ONOO-changes, as well as the endogenous ONOO-changes in inflammation models and subcutaneous or orthotopic hepatocellular carcinoma（HCC） tumors models in living mice. In vitro and in vivo studies verified the good detection and imaging capabilities of PPA-PEG for peroxynitrite, demonstrating suitable tissue penetration and a high signal-to-background ratio（SBR）. Thus, our nanoprobe can serve as a valuable activatable chemiluminescence imaging tool for studying important peroxynitrite-related chemical and biological applications.

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Association between plasma immunoproteasome and 90-day prognosis after first-ever ischemic stroke

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Neural Regeneration Research 2021年第4期16卷 795-800页

作者： Xing-Yong Chen Ming Fu Shao-Fen Wan Xu Zhang Yin-Zhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina

Many blood biomarkers are reportedly helpful for predicting post-stroke cognitive impairment(PSCI),but no biomarkers are widely used in clinical *** purpose of this study was to investigate the association between the plasma immunoproteasome and patients’90-day prognosis after first-ever acute ischemic *** our prospective,single-center study,259 patients with first-ever acute ischemic stroke were enrolled from the Department of Neurology,fujian provincial Hospital,China,from March to September *** these,27 patients(10.4%)had unfavorable outcomes as assessed by the Modified Rankin Scale(scores of 3–6).The National Institutes of Health Stroke Scale score on admission,plasma N-terminal pro-B-type natriuretic peptide(NT-pro-BNP)levels,and immunopro-teasome subunit(low molecular mass peptide[LMP]2,LMP5,and LMP7)levels were significantly higher in the unfavorable outcome group than in the favorable outcome *** predict unfavorable outcomes,the optimal cutoff points were National Institutes of Health Stroke Scale score>12,NT-pro-BNP level>1883.5 pg/mL,and LMP2 level>841.4 pg/*** the 193 patients that were able to complete the Mini-Mental State Examination at 90 days poststroke,66 patients(34.2%)had *** levels of NT-pro-BNP and LMP2 were higher in patients with PSCI than in those without *** predict PSCI,the optimal cutoff values were age>70.5 years and LMP2 level>630.5 pg/*** findings indicate that plasma LMP2 may serve as a new prognostic biomarker of poor outcome and PSCI at 90 days after *** study was approved by the Ethics Committee of fujian provincial Hospital,provincial clinical medical college of fujian medical university(approval No.K2014-01-003)on January 15,2014.

关键词： behavior biomarker brain clinical trial cognitive impairment immune function neurological function protein stroke

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Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells

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Current medical Science 2024年第4期44卷 789-798页

作者： Chai-ming ZENG Bin SHAO Yan-ping CHEN Gui-sheng DING Department of Geriatric Medicine Shengli Clinical Medical College of Fujian Medical UniversityFujian Key Laboratory of Geriatrics DiseasesFujian Provincial Center for GeriatricsFujian Provincial HospitalFuzhou350001China Department of Rehabilitation Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China Department of Gynecology Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China Department of Ultrasonography Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China

Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular *** further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating *** This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC *** experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these *** Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic ***,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin ***,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned *** results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 ***,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by *** Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.

关键词： mitofusin-2 epithelial-mesenchymal transition sorafenib resistance apoptosis hepatocellular carcinoma

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Cytotoxic Activities of Total Saponins from Plena Clematis on Human Tumor Cell Lines In Vitro

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Chinese Journal of Integrative Medicine 2018年第10期24卷 763-767页

作者： ZHU Fu-rong LI Yong-ning HE Shu-lan CHEN Qian-shun XU Xun-yu Department of Pharmacy Fujian Health College provincial clinical college of fujian medical university Department of Thoracic Surgery Fujian Provincial Hospital

Objective： To investigate the anti-proliferative effects of saponins prepared from Plena Clematis （PC） cultured in fujian Province, China on 4 human tumor cell lines and its possible anti-tumor mechanism. Methods： The growth inhibition assays of saponins on human esophageal squamous carcinoma cell line （EC9706）, human hepatoma cell line （HepG-2）, human oral cancer cell line （KB） and human gastric cancer cell line （BGC-823） were evaluated in vitro by thiazolyl blue （MTT） method. The inhibitory effects on EC9706 treated with different concentrations of saponins （15.62, 31.25, 62.50, 125, 250 and 500 μg/mL） were performed in vitro by MTT method. The morphology and nuclear staining with acridine orange/ethidium bromide of EC9706 calls treated with saponins were illustrated under an inverted phase fluorescence microscope. The apoptotic effects of saponins were further evaluated by annexin-V/propidium iodide dual staining experiment to examine the occurrence of phosphatidylserine externalization onto the call surface by a flow cytometer. Results： MTT assay showed that the saponins could inhibit the proliferation of 4 tumor cell lines. Among them, the maximum inhibition rate of 73.1% was detected in EC9706 cells at the saponins concentration of 250 μg/mL for 24 h. Further investigation indicated that the saponins induced EC9706 cells apoposis. The EC9706 cells presented apoptotic characteristics when treated with saponins, including that the morphologies of EC9706 cells were appeared round-shaped with higher refraction, and the cell nuclear stained orange with EB after 250 μ g/mL saponins exposure. The flow cytometry analysis results showed that the induction of cell cycle arrest in apoptotic system may participate in the anti-proliferative activity of saponins on EC9706 cells. Conclusion： The saponins from PC exhibited significant cytotoxicity against human EC9706, KB, BGC-823, and HepG-2 cells and might be beneficial to development of ethnic pharmaceutical plant for pote

关键词： Plena Clematis Clematis florida var. plena D cytotoxic activity saponins human esophageal cancer cell

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Matrix metalloproteinase 9 level as an indicator for restenosis following cervical and intracranial angioplasty and stenting

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Neural Regeneration Research 2015年第4期10卷 631-635页

作者： Jun-peng Liu Yin-zhou Wang Yong-kun Li Qiong Cheng Zheng Zheng Department of Neurology Fujian Provincial HospitalProvincial Clinical Department of Fujian Medical University

Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that resteno-sis occurred in 30% （3/10） of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% （2/17） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% （1/23） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically signiifcant （P 〉 0.05）. Experimental ifndings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervi-cal and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.

关键词： nerve regeneration matrix metalloproteinase 9 cervical and intracranial angioplasty and stenting restenosis intracranial artery stenosis neural regeneration

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