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Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang Stephen Temitayo Bello department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for Regenerative medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator

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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan Han Li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health Sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain Sciences University of MacaoMacao Special Administrative RegionChina department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina department of Emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina department of Laboratory medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina department of Laboratory medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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Exploring Mechanism of Electroacupuncture in Modulating Neuroinflammation Based on Intestinal Flora and Its Metabolites

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Chinese Journal of Integrative medicine 2025年第2期31卷 183-192页

作者： YE Hai-min LI Zhuo-yan ZHANG Peng KANG Zhen ZHOU De-sheng School of Integrated Chinese and Western medicine Hunan University of Chinese MedicineChangsha(410208)China Neurology department The Second Affiliated Hospital of Hunan University of Chinese MedicineChangsha(410005)China Acupuncture and Moxibustion Massage Rehabilitation department The Second Affiliated Hospital of Hunan University of Chinese MedicineChangsha(410005)China Neurology department The First Hospital of Hunan University of Chinese MedicineChangsha(410011)China

Neuroinflammatory responses play an important role in the pathogenesis of various diseases,particularly those affecting the central nervous *** of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system *** intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory *** flora metabolites such as short-chain fatty acids,indoles and their derivatives,lipopolysaccharides,trimethylamine oxide,and secondary bile acids exert direct or indirect effects on *** have shown that electroacupuncture(EA)modulates the composition of the intestinal microbiota and its metabolites,while also suppressing neuroinflammation by targeting the TLR4/NF-κB,NLRP3/caspase-1,and microglial cell M2-type transformation *** review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites,providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.

关键词： electroacupuncture intestinal flora metabolites of intestinal flora neuroinflammation nervous system disease review

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Effect of electroacupuncture on pain after periodontal flap surgery:a randomized controlled trial

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Journal of Traditional Chinese medicine 2025年第1期45卷 184-191页

作者： Emre Bulut Didem ?zkal Emino?lu Yasemin ?ay?r department of Periodontology Faculty of DentistryAtatürk University department of Family medicine Faculty of MedicineAtatürk University

OBJECTIVE: To examine the effect of electroacupuncture(EA) application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery. METHODS: In this prospective, randomized and controlled study, patients planned for periodontal surgery were divided into two groups [EA group(n = 22): patients who received electroacupuncture and control group(n = 22): patients who did not receive electroacupuncture]. Electroacupuncture was applied bilaterally to the Hegu(LI4), Daying(ST5), and Jiache(ST5) points of the patients in the EA group immediately before and after the flap surgery for 30 min at a frequency of 50 Hz to each point at a current that the patient could tolerate. The patients in the control group underwent flap surgery without applying electroacupuncture. Patients were asked to record their pain levels on the visual analog scale and the number of analgesic tablets they took during the 7 postoperative days on the given form. RESULTS: The total mean score of pain felt in the EA group(16.60 ± 2.78) was found to be significantly lower than that in the control group(31.37 ± 2.78)(P = 0.001). No significant difference was found between the groups regarding the amount of analgesics taken(4.77 ± 4.72, 5.82 ± 3.11)(P = 0.111). CONCLUSIONS: Our study shows that electroacupuncture application is beneficial in reducing pain after periodontal flap surgery. Overall, more research is needed to fully understand the effects of electroacupuncture on postoperative pain.

关键词： analgesics electroacupuncture pain, postoperative periodontitis randomized controlled trial

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Pharmacological Mechanism of Chinese medicine in Systemic Lupus Erythematosus:A Narrative Review

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Chinese Journal of Integrative medicine 2025年第2期31卷 157-169页

作者： ZHU Bo-yu LIU Zhi-chao ZHAO Zhen-xi HUANG Hui-ping ZHANG Na XIA Jia CHEN Wei-wei department of Rheumatology Shanghai Municipal Hospital of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghai(200071)China

Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder affecting multiple systems,characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and *** medicine(CM)plays a role in mitigating complications,enhancing treatment effectiveness,and reducing toxicity of concurrent medications,and ensuring a safe ***,CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process,therefore,its treatment mechanism is often complicated,involving many molecular *** review introduces the research progress of pathogenesis of SLE from the aspects of genetics,epigenetics,innate immunity and acquired immunity,and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.

关键词： systemic lupus erythematosus Chinese medicine natural extracts treatment review

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Impact of Spinal Manipulative Therapy on Brain Function and Pain Alleviation in Lumbar Disc Herniation:A Resting-State fMRI Study

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Chinese Journal of Integrative medicine 2025年第2期31卷 108-117页

作者： ZHOU Xing-chen WU Shuang WANG Kai-zheng CHEN Long-hao WEI Zi-cheng LI Tao HUA Zi-han XIA Qiong LYU Zhi-zhen LYU Li-jiang department of Spine The Third Affiliated Hospital of Zhejiang Chinese Medicine UniversityHangzhou(310053)China department of Spine The Third School of Clinical MedicineZhejiang Chinese Medicine UniversityHangzhou(310053)China Research Institute of Tuina(Spinal Disease) Zhejiang Chinese Medicine UniversityHangzhou(310053)China

Objective:To elucidate how spinal manipulative therapy(SMT)exerts its analgesic effects through regulating brain function in lumbar disc herniation(LDH)patients by utilizing resting-state functional magnetic resonance imaging(rs-f MRI).Methods:From September 2021 to September 2023,we enrolled LDH patients(LDH group,n=31)and age-and sex-matched healthy controls(HCs,n=28).LDH group underwent rs-f MRI at 2 distinct time points(TPs):prior to the initiation of SMT(TP1)and subsequent to the completion of the SMT sessions(TP2).SMT was administered once every other day for 30 min per session,totally 14 treatment sessions over a span of 4 *** did not receive SMT treatment and underwent only one f MRI ***,participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale(VAS)and the Japanese Orthopedic Association(JOA)score,whereas HCs did not undergo clinical scale *** effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations(ALFF)and regional homogeneity(Re Ho).Correlation analyses were conducted between specific brain regions and clinical ***:Following SMT treatment,pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the *** comparison to TP1,TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L(voxelwise P30;FDR correction).Additionally,the most substantial enhancement in Re Ho values was observed for the Cuneus_R,while the most prominent reduction was noted for the Olfactory_R(voxelwise P30;FDR correction).Moreover,a comparative analysis revealed that,in contrast to HCs,LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L(voxelwise P30;FDR correction).Fur

关键词： functional magnetic resonance imaging lumbar disc herniation spinal manipulative therapy pain

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Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

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World Journal of Gastroenterology 2025年第6期31卷 44-61页

作者： Han-Ning Xuan Yuan Hyun Sung Kim Gye Ryeol Park Jae Eun Ryu Ji Eun Kim In Young Kang Hye Young Kim Seung Min Lee Ju Hee Oh Eileen L Yoon Dae Won Jun department of Internal medicine Hanyang University School of MedicineSeoul 04763South Korea department of Pathology Hanyang University School of MedicineSeoul 04763South Korea department of Translational medicine Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoul 04763South Korea department of Obstetrics and Gynecology Institute of Women’s Medical Life ScienceYonsei Cancer CenterSeverance HospitalYonsei University College of MedicineSeoul 04763South Korea department of Internal medicine Sanggye Paik HospitalInje University College of MedicineSeoul 01757South Korea

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver *** study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease *** focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related *** To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver *** Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various *** human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate ***,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver *** While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and ***,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid *** MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease *** MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

关键词： RAW 264.7 cell Cell death Necroptosis Mixed lineage kinase domain-like protein Non-alcoholic fatty liver disease Mixed lineage kinase domain-like protein adenosine triphosphate binding inhibitor Alcoholic liver disease

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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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