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Pharmacological intervention for chronic phase of spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1377-1389页

作者： Chihiro Tohda section of Neuromedical Science Institute of Natural MedicineUniversity of ToyamaToyamaJapan

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidat

关键词： axonal growth chronic phase clinical study pharmacotherapy spinal cord injury

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

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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

Liver parasites:A global endemic and journey from infestation to intervention

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World Journal of Gastroenterology 2025年第1期31卷 8-15页

作者： Yumna Shahid Bushra Emman Shahab Abid Department of Medicine Section of GastroenterologyAga Khan University HospitalKarachi 75500SindhPakistan Aga Khan Medical College Aga Khan University HospitalKarachi 75500SindhPakistan

Parasites have coexisted with humans throughout history,forming either symbiotic relationships or causing significant morbidity and *** liver is particularly vulnerable to parasitic infections,which can reside in,pass through,or be transported to the liver,leading to severe *** editorial explores various parasites that infect the liver,their clinical implications,and diagnostic considerations,as discussed in the article“Parasites of the liver:A global problem?”.Parasites reach the liver primarily through oral ingestion,mucosal penetration,or the bloodstream,with some larvae even penetrating the *** parasites such as cestodes(Echinococcus),trematodes(Clonorchis,Opisthorchis),nematodes(Ascaris),and protozoa(Entamoeba histolytica)can also cause systemic infections like visceral leishmaniasis,malaria,cryptosporidiosis,and *** infections like clonorchiasis and opisthorchiasis are linked to persistent hepatobiliary inflammation,potentially progressing to cholangiocarcinoma,a fatal bile duct cancer,particularly prevalent in Southeast *** global nature of liver parasite infestations is alarming,with hundreds of millions affected ***,control over treatment quality remains *** the significant public health threat posed by these parasites,international medical organizations must prioritize improved diagnosis,treatment,and preventive *** educational efforts and enhancing healthcare provider training are critical steps toward mitigating the global impact of parasitic liver diseases.

关键词： Liver flukes Nematodes Cestodes Trematodes Protozoa Parasites

Cannabidiol preferentially binds TRPV2: a novel mechanism of action

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Neural Regeneration Research 2022年第12期17卷 2693-2694页

作者： Elisa Landucci Domenico E.Pellegrini-Giampietro Alessandra Gianoncelli Giovanni Ribaudo Department of Health Sciences Section of Clinical Pharmacology and OncologyUniversity of FlorenceFirenzeItaly Department of Molecular and Translational Medicine University of BresciaBresciaItaly

Plants from the genus Cannabis,and strains of Cannabis sativa in particular,have been used in medicine since ancient *** Cannabis plant contains more than 500 chemical compounds,with two main phytocannabinoids consisting of Δ9-tetrahydrocannabinol(THC),the psychoactive constituent,and cannabidiol(CBD),which does not bear this *** paper aims at providing a perspective on the potential therapeutic effects of CBD based on its preferential interaction with transient potential receptor V2(TRPV2).Many formulations based on Cannabis extract have been licensed for therapeutic use in some Western *** these,the most relevant are Sativex(THC+CBD,used mainly for the treatment of spasticity in multiple sclerosis)and Epidyolex(purified plant-derived CBD,used for some rare childhood epilepsies).

关键词： effect mechanism formulation

Comparative research between Bai-hua Qian-hu,a Chinese traditional plant, and its active ingredient on nuclear factor-κB and tumor necrosis factor-α in isolated ischemia-reperfusion heart of rat

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Chinese Medical Journal 2004年第3期117卷 461-463页

作者：王弛常天辉 Department of clinical pharmacology China Medical University

Ischemia-reperfusion (I/R) injury is a complicated pathophysiological process, which is involved in calcium overload, free radical production, metabolic abnormalities, and inflammatory reaction. With the development of modern molecular biology, the expression and regulation of gene in myocardial I/R injury are focused on NF-κB.1Inflammatory reactions play an important role in I/R injury.2 TNF-α, an important inflammatory cytokine, is regulated by NF-κB and counteracts the activation of NF-κB. Sometimes, improper activation of NF-κB can induce excessive inflammatory responses and injury, so, modulation of NF-κB activation may dedicate a new target in alleviation of myocardial I/R injury.3Our previous studies have proved that Bai-hua Qian-hu (Peucedanum praeruptorum Dunn, BQ), a Chinese traditional plant had cardioprotective action in I/R animals.4 Its active ingredient Pd-Ia, a Ca2+-influx blocker5 and K+-channel opener,6 had similar effects. Meanwhile, it relieved inflammatory reaction and apoptosis in I/R myocardium through inhibition of interleukin-6 and Fas, bax, bcl-2 protein expression.7 However, the effects of BQ and Pd-Ia on the activation of NF-κB and the expression of TNF-α in I/R myocardium have not been clear yet. In this study, the effects of BQ and Pd-Ia on these two factors were investigated to further ascertain the molecular protective mechanism of BQ in I/R myocardium.

关键词： Peucedanum praeruptorum Dunn · dl-praeruptorin A · myocardium · ischemia · reperfusion · nuclear factor-κB · t umor necrosis factor-α

Fibrinogen’s potential role in connecting cerebrovascular abnormalities with glymphatic dysfunction in Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 203-204页

作者： Vishal Singh Arnab Choudhury Hyung Jin Ahn Department of pharmacology Physiology and NeurosciencesRutgers-New Jersey Medical SchoolNewarkNJUSA Brain Health Institute Rutgers UniversityPiscatawayNJUSA

Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated ***,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological *** often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and *** models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).

关键词： cerebrovascular dysfunction Alzheimer

“Pharmacogenetics of Cancer”-Cancer Drug Resistance special issue

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Cancer Drug Resistance 2020年第2期3卷 225-231页

作者： Enrico Mini Stefania Nobili Department of Health Sciences Section of Clinical Pharmacology and OncologyUniversity of FlorenceFlorence 50139Italy Cancer pharmacology Working Group of the Italian Society of pharmacology Milan 20129Italy

Pharmacogenetics and pharmacogenomics have expanded rapidly over the past years and represent one of the bases of precision *** application of pharmacogenetic and pharmacogenomic approaches and tools for the selection of medications and their dosage to improve patient care is nowadays substantially increased[1,2].Prescription drug information sheets in several therapeutic areas(psychiatric,cardiovascular,analgesic,antiviral,and anticancer drugs)provide current information on pharmacogenetic and pharmacogenomic biomarkers for over 200 medicines including mandatory or recommended biomarker testing prior to initiating therapy[3].

关键词： dosage bases initiating