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Neural Regeneration Research 2024年第6期19卷 1199-1200页

作者： Francesco Margiotia Lorenzo Di Cesare Mannelli Antonino Morabito Carla Ghelardini Elena Lucarini Department of Neuroscience Psychology Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section University of Florence Department of Neuroscience Psychology Drug Research and Child Health-NEUROFARBA University of Florence 3. Meyer Children's Hospital IRCCS

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs), affecting about 20% of the global population(Grundy et al., 2019). Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects, hence the need to identify novel molecular and cellular targets for drug development. The pathophysiology of visceral-abdominal pain,

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Commentary on“Synchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain”

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Neural Regeneration Research 2024年第4期19卷 728-728页

作者： Lorenzo Di Cesare Mannelli Carla Ghelardini Department of Neuroscience PsychologyDrug Research and Child Health-Neurofarba-Section of Pharmacology and ToxicologyUniversity of Florence

In pat i e nt s,a s well as in animal mod e l s,hypersensitivity to external stimuli(hyperalgesia and allodynia)or spontaneous pain is often the first,and the most disabling,symptom of neuropathy(Davis et al.,2020).The increased activity of sensitive neurons drives pain development,making ion channel modulation a fundamental target for current pharmacotherapy as well as one of the most investigated by the R&D departments of pharmaceutical companies(Bennett et al.,2019).

关键词： companies pain ent

The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

Stereoselective recognition of morphine enantiomers by μ-opioid receptor

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National Science Review 2024年第3期11卷 183-191页

作者： Yibo Wang Van A.Ngo Xiaohui Wang Laboratory of Chemical Biology Changchun Institute of Applied ChemistryChinese Academy of Sciences Advanced Computing for Life Sciences and Engineering Group Science Engagement Section National Center for Computational Sciences Oak Ridge National Lab School of Applied Chemistry and Engineering University of Science and Technology of China Beijing National Laboratory for Molecular Sciences

Stereospecific recognition of chiral molecules plays a crucial role in biological systems. The μ-opioid receptor（MOR） exhibits binding affinity towards（-）-morphine, a well-established gold standard in pain management, while it shows minimal binding affinity for the（+）-morphine enantiomer, resulting in a lack of analgesic activity. Understanding how MOR stereoselectively recognizes morphine enantiomers has remained a puzzle in neuroscience and pharmacology for over half-a-century due to the lack of direct observation techniques. To unravel this mystery, we constructed the binding and unbinding processes of morphine enantiomers with MOR via molecular dynamics simulations to investigate the thermodynamics and kinetics governing MOR's stereoselective recognition of morphine enantiomers. Our findings reveal that the binding of（-）-morphine stabilizes MOR in its activated state, exhibiting a deep energy well and a prolonged residence time. In contrast,（+）-morphine fails to sustain the activation state of ***, the results suggest that specific residues, namely D1142.50and D1473.32, are deprotonated in the active state of MOR bound to（-）-morphine. This work highlights that the selectivity in molecular recognition goes beyond binding affinities, extending into the realm of residence time.

关键词： stereoselective recognition thermodynamics and kinetics residence time morphine enantiomers μ-opioid receptor

Interferon-gamma and neuropathy: balance between pain and neuroprotection

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Neural Regeneration Research 2022年第12期17卷 2700-2701页

作者： Valentina Ferrara Alessandra Toti Carla Ghelardini Lorenzo Di Cesare Mannelli Department of Neuroscience PsychologyDrug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology SectionUniversity of FlorenceFlorenceItaly

Chronic pain is sustained by a phenomenon of hyper-activation of nociceptive neurons both at peripheral(peripheral sensitization)and central(central sensitization)*** onset and maintenance of pain,however,is to be found in the interaction among the various cell populations in the nervous tissue including neurons and glia(Nam et al.,2016).The pathogenesis of neuropathic pain is extremely complex depending on the primary cause of nerve damage,*** nerve injury is associated with a robust inflammatory response while chemotherapy-induced pain is characterized by a modest phlogistic component(Di Cesare Mannelli et al.,2013).Despite these differences,a powerful common concept to explain the cellular mechanisms underlying pain is the activation of glia.

关键词： pain sustained

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

Corrigendum to“Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review”[***.14(2024)100919]

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Journal of Pharmaceutical Analysis 2024年第6期14卷 934-936页

作者： Hemanth P.R.Vikram Tegginamath Pramod Kumar Gunjan Kumar Narasimha M.Beeraka Rajashree Deka Sheik Mohammed Suhail Sandeep Jat Namitha Bannimath Gayatiri Padmanabhan Ravandur S.Chandan Pramod Kumar Bannimath Gurupadayya Department of Pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare Pvt.Ltd. New Delhi110076India Department of Pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Human Anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation Department of pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal Physiology and Biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India Department of pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India Department of pharmacology University of GalwayGalwayH91 TK33Ireland

Original statement in the section 2:*** search Our primary screening of 180 articles yielded the relevant data for this *** selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially *** the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.

关键词： statement initially spanning

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