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Contribution of presynaptic HCN channels in GABAergic substantia gelatinosa neurons from GAD67-GFP transgenic mice

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Contribution of presynaptic HCN channels in GABAergic substa...

Characterization of the T-type calcium channels in rat spinal substantia gelatinosa neurons

中国神经科学学会第十二届全国学术会议

作者： Si-cong Peng Jing Wu da-ying zhang Chang-ning Xie Ling-hui Xiao Tao Liu Department of Pediatrics the First Affiliated Hospital of Nanchang University Department of Pain Clinic the First Affiliated Hospital of Nanchang University

Aim of Investigation: Hyperpolarization-activated cyclic nucleotide-gated（HCN） channels induced an inward Na+-K+ mixed currents（Ih） which is involved in the nociceptive transmission and neuropathic pain. The expression of Ih was found in spinal lamina II（also named substantia gelatinosa, SG） neurons, especially in the GABAergic neurons which labelled green fluorescent protein（GFP） in GAD67-GFP mice. To know in detail the role of HCN channels in regulating nociceptive transmission, we investigated the contribution of presynaptic HCN channels to excitatory and inhibitory inputs of GABAergic SG neurons. Methods: Juvenile（3-5 weeks） male GAD67-GFP C57/BL6 transgenic mice were used. Whole-cell patch-clamp recordings were applied to SG neurons in transverse spinal cord slices to investigate the spontaneous excitatory and inhibitory postsynaptic currents（s EPSCs and s IPSCs）. Results: Consist with previous studies, 88.9%（n = 136/153 neurons） of recorded GFPlabelled SG neurons expressed Ih and the average amplitude was 217.9 ± 15.2 p A. Perfusion of 10 mM of ZD7288（an antagonist of HCN channel） did not affect the s EPSCs of GFP-labelled neurons（103 ± 5% of control, n = 9/9 neurons）. Neither did 50 mM of forskoin（113 ± 6% of control, n = 7/7 neurons）, an activator of adenylate cyclase. However, ZD7288 significantly decreased s IPSC frequency by 37 ± 6% but not affect their amplitude in 78%（n = 7/9 neurons） of GFP-labelled neurons. In the remaining two neurons, no detectable effects of ZD7288 on s EPSCs were found in one of them, but ZD7288 increased the s EPSC frequency by 45% in the other neuron. Consistently, forskolin dramatically increased s IPSC frequency by 64 ± 29% in 50%（n = 5/10 neurons） of GFP-labelled neurons. In the remaining five neurons, no detectable effects of forskolin on s EPSCs were found in two of them, but forskolin decreased the s EPSC frequency by 34 ± 6% in the other three neurons. Conclusions: The expression of the HCN channels is different between e

关键词： Hyperpolarization-activated cyclic nucleotide-gated channels substantia gelatinosa excitatory postsynaptic currents inhibitory postsynaptic currents GABAergic whole-cell patch-clamp

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Characterization of the T-type calcium channels in rat spina...

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

中国神经科学学会第十二届全国学术会议

作者： Jing Wu Si-cong Peng da-ying zhang Chang-ning Xie Ling-hui Xiao Tao Liu Department of Pediatrics the First Affiliated Hospital of Nanchang University Department of Pain Clinic the First Affiliated Hospital of Nanchang University

Objective: T-type calcium channels are widely distributed in central and peripheral nervous system including spinal lamina II(also named substantia gelatinosa, SG) neurons. Activation of T-type channels induces an inward Ca current(I) which contribute to regulation of nociceptive transmission. In order to know in detail the cell-specific expression and function of I in SG neurons, we investigated the pharmacological characterization of I and the morphology of the SG neurons with or without I. Methods: Whole-cell patch-clamp recordings were applied to SG neurons in spinal cord slices prepared from male juvenile Sprague–dawley rats. Neurobiotin 488 was added to the intracellular solutions to label the somata, dendrites and axon in a fraction of SG neurons recorded. Results: I was recorded in nearly 46% of the SG neurons(n = 177/384) with the average amplitude of 85.80 ± 7.49 p A. The slope of activation curve and voltage for half-maximal current(V) of I is 3.75 and-53.18 m V, respectively. The slope and V of inactivation curve was-7.31 and V =-79.69 m V, respectively. Moreover, NiCl, an antagonist of Ttype calcium channels, inhibited I in a concentration-dependent manner and the IC50 was 89.2 mM when fitted with a Hill equation(Hill coefficient = 1.7). In morphological experiments, 111 SG neurons were used for analysis. Five major cell types were identified: islet, central, radial, vertical, and unclassified cells. Among them, I was recorded in 23 neurons(21 %). Moreover, the proportion of I in each subtypes of SG neurons were: islet(35 %, n = 8/23), central(21 %, n = 5/23), radial(9 %, n = 2/23), vertical(22 %, n = 5/23), and unclassified(13%, n = 3/23) neurons. Conclusions: Most SG neurons showed a functional I that was blocked by NiCl in a concentration-dependent and reversible manner. The expression ratio of I is highest in islet neurons and lowest in radial neurons. Altogether, current study will help us better understand the role of calcium channels in nocicepti

关键词： T-type calcium channel spinal substantia gelatinosa neurons Whole-cell patch-clamp recording

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng ying Chen Jiali Pu Baorong zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats

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World Journal of Gastroenterology 2025年第1期31卷 93-109页

作者： Ping zhang ying Zhu Pu Chen Tong Zhou Zhe-Yi Han Jun Xiao Jian-Feng Ma Wen Ma Peng Zang ying Chen Graduate School Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Key Laboratory of Aerospace Nutrition and Food Engineering China Astronaut Research and Training CenterBeijing 100094China Department of Gastroenterology The Air Force Medical CenterBeijing 100142China Department of Blood Transfusion Air Force Medical CenterBeijing 100142China

BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility *** pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal ***,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal *** cells are the pacemakers of gastrointestinal *** To investigate the effects of Bifidobacterium lactis(***)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit *** The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 *** tail group was given *** BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/***&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and *** fecal flora and mucosal flora of rats in each group were detected by 16S *** Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic *** microgravity reduced the expressions of SCF and c-kit,and increased the express

关键词： Simulated microgravity Rat Intestinal flora Gastrointestinal motility Stem cell factor/c-kit signaling pathway

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

Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi zhang Yu-ying Tan Li zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China Department of Liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

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Traditional Medicine Research 2025年第2期10卷 16-29页

作者： Xia-Jie Quan Hao Liang Yong-Hong Tang Li Jiang Xiong-ying Ji Feng-ying zhang Ping zhang Bo Ouyang Department of Information The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Neurology The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Gastroscopy The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Traditional Chinese Medicine The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of ***,the specific mechanism of action of SXLJF remains ***:The mouse model of insomnia was established by intraperitoneal injection of ***-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive *** open field test and pentobarbital-induced sleeping test were ***-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating ***,key targets were validated using ***:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep *** and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of ***,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,***-qPCR results supported the role of TH in the mechanism of SXLJF in treating ***:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

关键词： Shangxia Liangji formula insomnia metabolomics network pharmacology tyrosine hydroxylase tyrosine metabolism

An Efficient Boron Source Activation Strategy for the Low‑Temperature Synthesis of Boron Nitride Nanotubes

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Nano-Micro Letters 2025年第1期17卷 548-558页

作者： ying Wang Kai zhang Liping Ding Liyun Wu Songfeng E Qian He Nanyang Wang Hui Zuo Zhengyang Zhou Feng Ding Yue Hu Jin zhang Yagang Yao National Laboratory of Solid State Microstructures College of Engineering and Applied SciencesJiangsu Key Laboratory of Artificial Functional Materialsand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093People’s Republic of China School of Electronic Information and Artificial Intelligence Shaanxi University of Science&TechnologyXian 710000People’s Republic of China College of Bioresources Chemical and Materials Engineering Shaanxi University of Science&TechnologyXian 710000People’s Republic of China Key Laboratory of Carbon Materials of Zhejiang Province College of Chemistry and Materials EngineeringWenzhou UniversityWenzhou 325000People’s Republic of China Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen 518000People’s Republic of China College of Chemical and Molecular Engineering Peking UniversityBeijing 100871People’s Republic of China

Lowering the synthesis temperature of boron nitride nanotubes(BNNTs)is crucial for their *** primary reason for adopting a high temperature is to enable the effective activation of highmelting-point solid *** this study,we developed a novel approach for efficiently activating boron by introducing alkali metal compounds into the conventional MgO–B *** approach can be adopted to form various low-melting-point AM–Mg–B–O growth *** growth systems have improved catalytic capability and reactivity even under low-temperature conditions,facilitating the synthesis of BNNTs at temperatures as low as 850℃.In addition,molecular dynamics simulations based on density functional theory theoretically demonstrate that the systems maintain a liquid state at low temperatures and interact with N atoms to form BN *** findings offer novel insights into the design of boron activation and are expected to facilitate research on the low-temperature synthesis of BNNTs.

关键词： Boron nitride nanotubes Low-temperature Boron activation Density functional theory

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： ying Wang Xiang zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator