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Immune cells:potential carriers or agents for drug delivery to the central nervous system

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Military Medical Research 2025年第1期12卷 121-153页

作者： Shan-Shan Zhang Ruo-Qi Li Zhong Chen Xiao-Ying Wang Aaron S.Dumont Xiang Fan School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key laboratory of neuropharmacology and Translational Medicine of Zhejiang Province Zhejiang Chinese Medical UniversityHangzhou 310053China Clinical Neuroscience Research Center Department of Neurosurgery and NeurologyTulane University School of MedicineNew OrleansLA 70122USA

Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted ***,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain *** cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug ***,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain *** subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS ***,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.

关键词： Drug delivery systems Immune cells Blood-brain barrier Central nervous system

DNA2 knockout aggravates cerebral ischemia/reperfusion injury by reducing postsynaptic Homer1a

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Zoological Research 2025年第01期 87-102页

作者： Ting Ma Yu-Meng Li Peng-Yu Ren Shi-Quan Wang Xiang-Long Liu Wen-Bo Lv Wu-Gang Hou Wen-Qiang Zuo Wei-Qiang Lin Jian Sima An-Qi Geng laboratory of Aging Neuroscience and neuropharmacology School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University Research & Development Institute of Northwestern Polytechnical University in Shenzhen Xi'an Key laboratory of Stem Cell and Regenerative Medicine Xi'an Key Laboratory of Special Medicine and Health Engineering Institute of Medical Research Northwestern Polytechnical University Sanhang Institute for Brain Science and Technology Northwestern Polytechnical University Department of Anesthesiology and Perioperative Medicine Xijing Hospital Fourth Military Medical University College of Pharmacy Shaanxi University of Chinese Medicine International Institutes of Medicine Fourth Affiliated Hospital School of Medicine Zhejiang University

DNA2, a multifunctional enzyme with structure-specific nuclease, 5'-to-3' helicase, and DNA-dependent ATPase activities, plays a pivotal role in the cellular response to DNA damage. However, its involvement in cerebral ischemia/reperfusion(I/R) injury remains to be *** study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout(cKO) mice(Nestin-Cre) subjected to middle cerebral artery occlusion(MCAO), an established model of cerebral I/R. Results demonstrated a gradual up-regulation of DNA2 expression,peaking at 72 h post-MCAO. Notably, DNA2 cKO mice exhibited more pronounced brain injury, neurological deficits, and neuronal apoptosis within the penumbra following MCAO. Additionally, DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation(OGD/R) cell culture model, and DNA2 knockdown(KD)exacerbated neuronal apoptosis and oxidative *** analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice. Furthermore, in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis. Collectively, these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a, highlighting a novel regulatory axis in ischemic neuroprotection.

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Dissection of voltage-gated sodium channels in developing cochlear sensory epithelia

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Protein & Cell 2015年第6期6卷 458-462页

作者： You Zhou Fang-Hao Fang Zhi-Rui Liu Yong-Hua Ji laboratory of neuropharmacology and Neurotoxicology ShanghaiUniversity Shanghai 200436 China

Dear Editor Hair cells （HCs） clustered produce spontaneous spike n cochlear sensory epithelia and evoked action potentials during the developmental stage of auditory, which rely on many ion channels, such as Ca2＋ channels, K＋ channels and Na＋ channels （Housley et al., 2006; Marcotti et al., 2003）. As the dominant molecule acting in action potentials in most of excitable cells, Na＋ channels （VGSCs） were deemed to be indispensable in the spontaneous and evoked action po- tentials of HCs （Marcotti et al., 2003）.

关键词： voltage-gated sodium developing cochlear sensory epithelia

Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins

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Protein & Cell 2011年第6期2卷 437-444页

作者： Zhi-Rui Liu Pin Ye Yong-Hua Ji laboratory of neuropharmacology and Neurotoxicology Shanghai UniversityShanghai 200444China

Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the *** extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act as sodium channel-specific modulators and have therefore been widely used to study VGSCs.α-type neurotoxins,named BmK I,BmKαIV and BmK abT,bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of *** contrast,β-type neurotoxins,named BmK AS,BmK AS-1,BmK IT and BmK IT2,occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium *** evidence from binding assays of scorpion neurotoxins on VGSCs,however,indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simpleα-type and β-type neurotoxin *** the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region-and/or speciesspecific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse *** this review,we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3-or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.

关键词： voltage-gated sodium channel receptor sites scorpion neurotoxins

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Promising effects of Persian shallot extract on the serum markers and blood pressure of patients with metabolic syndrome:a double-blinded randomized controlled trial

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Journal of Traditional Chinese Medicine 2025年第1期45卷 100-106页

作者： Neda Naimipoor Zahra Bagheri-Hosseinabadi Mohammad Reza Hajizadeh Mitra Abbasifard Mohammad Reza Mirzaei Akram Ghadiri Anari Maryam Mohammad-Sadeghipour Mehdi Mahmoodi Department of Clinical Biochemistry School of MedicineRafsanjan University of Medical Sciences Department of Internal Medicine School of MedicineAli-Ibn Abi-Talib HospitalRafsanjan University of Medical Sciences Molecular Medicine Research Center Research Institute of Basic Medical SciencesRafsanjan University of Medical Sciences Diabetes Research Center Shahid Sadoughi University of Medical Sciences Department of Clinical Biochemistry Afzalipour School of MedicineKerman University of Medical Sciences Physiology Research Center Institute of NeuropharmacologyKerman University of Medical Sciences

OBJECTIVE: To evaluate the effect of Persian shallot extract on the serum markers and blood pressure of patients with metabolic syndrome(MetS). METHODS: Fifty patients with Met S diagnosis were randomly assigned to the intervention(Persian shallot extract) and the control(placebo) group. Both groups received treatment for three months. Before the study and at the end of the study, 5 mL peripheral blood was taken from each patient. The measured factors included total antioxidant capacity(TAC), superoxide dismutase enzyme(SOD), malondialdehyde, oxidized low-density lipoprotein(Ox-LDL), apolipoprotein H(Apo-H), fasting blood glucose(FBS), total cholesterol, triglycerides, high-density lipoprotein(HDL), LDL, and systolic and diastolic blood pressure. RESULTS: At baseline, the evaluated parameters were not significantly different between the intervention and control groups. At the end of the study, the mean serum levels of malondialdehyde and ox-LDL were significantly lower in the intervention group. The mean FBS, cholesterol, triglycerides, and LDL were significantly lower in the intervention group. The mean TAC and HDL were significantly higher in the intervention group(P < 0.05). Moreover, the intervention group significantly reduced systolic and diastolic blood pressure. No other significant association was observed. CONCLUSION: Persian shallot extract has several beneficial effects in Met S patients, including optimizing oxidative balance, reducing blood pressure, fasting blood sugar, and blood lipid profile.

关键词： antioxidants medicine, Persian metabolic syndrome shallots

Dopaminergic Remodeling During a Critical Developmental Window:Linking Drug Use to Adult Aggression

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Neuroscience Bulletin 2024年第6期40卷 845-848页

作者： Dadao An Lingyan Zheng Zhengyi Xu Yanrong Zheng Zhong Chen Key laboratory of neuropharmacology and Translational Medicine of Zhejiang Province Zhejiang Chinese Medical UniversityHangzhou310053China

Behaviors can be shaped and modulated by the dopamine system,which can be remodeled in adolescents due to environmental factors,including pharmacologic exposure,stress,and rewarding experiences,leading to various adolescentonset neuropsychiatric disorders[1-3].A deficiency of dopamine transporter(DAT),responsible for reuptaking extracellular DA.

关键词： Window shaped Dopamine

Targeting the Central Histamine H, Receptor: New Hope for Schizophrenia?

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Neuroscience Bulletin 2024年第1期40卷 143-145页

作者： Wenkai Lin Xuemin Yu Xinyan Zhu Key laboratory of neuropharmacology and Translational Medicine of Zhejiang Province Zhejiang Chinese Medical UniversityHangzhou 310053China

Histamine is a neurotransmitter and neuromodulator in the central nervous system,which plays its function through binding with diferent histamine receptors,such as H_(1)receptor(H_(1)R),H_(2)receptor(H_(2)R),H_(3)receptor(H_(3)R),and H_(4)receptor(H_(4)R)[1,2].Although both H_(1)R and H_(2)R,as post-synaptic receptors,are expressed in most brain areas,they captured different attention from scientists.H,R is well stud-ied and believed to play critical roles in many physiological and pathological processes,including sleep and wakefulness.

关键词： superficial intake cortex

β-AGKISTRODOTOXIN: A PRESYNAPTIC NEUROTOXIN FROM VENOM OF THE PIT VIPER (Agkistrodon blomhoffii brevicaudus STEJNEGER)

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Chinese Science Bulletin 1990年第14期35卷 1145-1155页

作者：徐科 laboratory of Molecular neuropharmacology Shanghai Institute of Physiology Academia Sinica Shanghai 200031 PRC

About 20 species of poisonous snakes have been found in the continent of China. Among them the pit viper classified as agkistrodon halys Pallas(A. halys) from genus agkistrodon, family Crotalidae is the widely distributed and the most numerous poisonous snake. Therefore, it gives more troubles to the health and life of related residents than all the other poisonous snakes in China. In 1976 on the basis of physiological observations we concluded that there might be both the presynaptic and the postsynaptic components in the venom of the pit viper(A. halys)collected in Jiangsu and Zhejiang provinces, China. A year later we first succeeded in isolating from the venom a

关键词： snake classified venom continent physiological Pallas Jiangsu numerous concluded invariant