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On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál department of physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing *** challenged weaned piglets

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1278-1291页

作者： Matthias Dierick Ruben Ongena Daisy Vanrompay Bert Devriendt Eric Cox Laboratory of Immunology Department of Translational PhysiologyInfectiology and Public HealthFaculty of Veterinary MedicineGhent UniversitySalisburylaan 1339820 MerelbekeBelgium Laboratory for Immunology and Animal Biotechnology Faculty of Bioscience EngineeringGhent UniversityCoupure links 6539000 GhentBelgium

Background Post-weaned piglets suffer from F18+Escherichia coli(***)infections resulting in post-weaning diar-rhoea or oedema *** used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial *** antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being *** has shown promising results against porcine enterotoxigenic *** strains,both in vitro and in *** We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned ***,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing ***(STEC)***,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC *** did not affect theα-andβ-***,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal *** analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF *** Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned ***,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut ***,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

关键词： E.coli Immune modulation Lactoferrin Microbiome

K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

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Neural Regeneration Research 2024年第7期19卷 1403-1404页

作者： Kaizhen Li Daria Savitska Olga Garaschuk Laboratory of Systems Neuroscience Department of PhysiologyUniversity of BernBernSwitzerland Institute of physiology Department of NeurophysiologyEberhard Karls University of TübingenTübingenGermany

De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental ***,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).

关键词： disorders atrophy

The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration Research 2024年第11期19卷 2411-2420页

作者： Shuangchan Wu Wensheng Lin department of Neuroscience University of MinnesotaMinneapolisMNUSA Institute for translational Neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded *** UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein *** also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum *** research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous ***,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano department of Orthopedic Surgery Keio University School of Medicine department of physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

Mechanism of Cu entry into the brain:many unanswered questions

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Neural Regeneration Research 2024年第11期19卷 2421-2429页

作者： Shubhrajit Roy Svetlana Lutsenko department of physiology Johns Hopkins University School of MedicineBaltimoreMDUSA

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical *** requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional *** imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and *** the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well *** review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

关键词： ATOX1 ATP7A ATP7B blood-brain barrier brain choroid plexus copper SLC31A1

REGENERATION FACTOR 1, a peptide boost for wound healing and plant biotechnology

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Molecular Plant 2024年第9期17卷 1333-1334页

作者： Andreas Schaller University of Hohenheim Department of Plant Physiology and Biochemistry70593 StuttgartGermany

Plants respond to wounding such as caused by insect herbivores by activating their defenses and thus increasing their resistance against attacking pests and opportunistic pathogens(Howe and Schaller,2008).The phenomenon was first described more than 50 years ago by Green and Ryan,who reported that wounding triggers tomato and potato plants to produce proteinase inhibitors that inhibit digestive proteases in the gut of leaf-eating insects to starve them of nutrients(Green and Ryan,1972).They also observed that the accumulation of proteinase inhibitors is not restricted to wounded leaves but occurs throughout the aerial parts of the *** search for a chemical signal that is released locally in response to wounding and that mediates systemic activation of defense gene expression led to the identification of systemin,the first ever peptide with hormonelike activity in plants(Pearce et al.,1991).These seminal findings sparked much research into systemic defense responses and peptide signaling in general,and we know now that systemin is one of many phytocytokines that regulate a multitude of immune responses in plants(Schilmiller and Howe,2005;Gust et al.,2017).

关键词： wound activation defense

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National translational Science Center for Molecular Medicine & department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

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World Journal of Gastroenterology 2024年第17期30卷 2294-2297页

作者： Fabiola Di Dato Raffaele Iorio department of translational Medical Science Section of PediatricsUniversity of Naples Federico IINaples 80131Italy

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular *** the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis ***,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the *** are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment *** editorial addresses key questions about the topic and whether indications for treatment should be expanded.

关键词： Hepatitis B virus Interferon Nucleos(t)ide analogues Functional cure Children