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Context-dependent role of sirtuin 2 in inflammation

Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of pharmaceutical sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA division of pharmaceutical sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Silk damping in scalar-induced gravitational waves:a novel probe for new physics

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Science China(Physics,Mechanics & Astronomy) 2025年第1期68卷 75-81页

作者： Yan-Heng Yu Sai Wang Theoretical Physics division Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China School of Physics University of Chinese Academy of SciencesBeijing 100049China

Silk damping is well known in the study of cosmic microwave background(CMB)and accounts for suppression of the angular power spectrum of CMB on large angular *** this article,we study the effect of Silk damping on the scalar-induced gravitational waves(SIGWs).Resulting from the dissipation of cosmic fluid,the Silk damping notably suppresses the energy-density spectrum of SIGWs on scales comparable to a diffusion scale at the decoupling time of weakly-interacting *** effect offers a novel observable for probing the underlying particle interaction,especially for those mediated by heavy gauge bosons beyond the standard model of *** anticipate that pulsar timing arrays are sensitive to gauge bosons with mass∼10^(3)-10^(4)GeV,while space-and ground-based interferometers to those with mass∼10^(7)-10^(12)GeV,leading to essential comple-ments to on-going and future experiments of high-energy physics.

关键词： scalar-induced gravitational waves Silk damping new physics

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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Antiepileptic activity and potential mechanism of full-spectrum hemp extract

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Fundamental Research 2025年第1期5卷 379-380页

作者： Zengliang Jin Zhuo Huang Department of pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking UniversityHealth Science CenterBeijing 100191China IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China

Epilepsy is the fourth most common neuropsychiatric *** the approval of Epidiolex has ignited hope for patients,there is still a large gap in the field of anti-seizure *** effect and underlying mechanism of full-spectrum hemp extract(HE)remains *** this study investigated the anti-seizure effect of HE on seizure *** results showed that HE significantly reduced seizure susceptibility and prolonged seizure latency with better pharmacokinetic performance compared to *** article then further explored the anti-seizure active components and their possible mechanism in *** results indicated that cannabichromene(CBC)and cannabinol(CBN)were involved in the anti-seizure process,especially CBC showed a strong allosteric enhancement effects on CBD binding site of the GABAA receptor,which implied that the GABAA receptor seemed to be the primary anti-epileptic target of *** article not only presents the great potential of HE as a candidate for new anti-epileptic drugs with less psychoactive,but also provides a valuable contribution to subsequent mechanism research and drug development on ***:Epilepsy is the fourth most coneuropsychiatric *** the approval of Epidiolex has ignited hope for patients,there is still a large gap in the field of anti-seizure *** effect and underlying mechanism of full-spectrum hemp extract remains *** this study investigated the anti-seizure effect of HE on seizure *** results showed that HE significantly reduced seizure susceptibility and prolonged seizure latency with better pharmacokinetic performance compared to *** article then further explored the anti-seizure active components and their possible mechanism in *** results indicated that cannabichromene and cannabinol were involved in the anti-seizure process,especially CBC showed a strong allosteric enhancement effects on CBD binding site of the GABAA receptor,which implied that the GABAA

关键词： Hemp Cannabinoids Pharmacokinetics Anti-seizure drugs GABA_(A)receptor

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Capsaicin(CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo

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Chinese Journal of Natural Medicines 2025年第2期23卷 191-202页

作者： Zhiru Yang Haolin Guo Pengfei Zhang Kairui Liu Junli Ba Xue Bai Shiti Shama Bo Zhang Xiaoning Gao Jun Kang School of Life sciences Tianjin University School of Traditional Chinese Medicine Beijing University of Chinese Medicine Tianjin pharmaceutical and Cosmetic Evaluation and Inspection Center Institute for TCM-X MOE Key Laboratory of Bioinformatics Bioinformatics Division BNRist Department of Automation Tsinghua University Institute of Biomedical Research Henan Academy of Sciences

Ethanol(EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin(CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4(CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65(NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.

关键词： Capsaicin Chemokine signaling Gastric mucosal damage NF-κB p65

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A quinolinyl analog of resveratrol improves neuronal damage after ischemic stroke by promoting Parkin-mediated mitophagy

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Chinese Journal of Natural Medicines 2025年第2期23卷 214-224页

作者： Qingqi Meng Yan Mi Libin Xu Yeshu Liu Dong Liang Yongping Wang Yan Wang Yueyang Liu Guoliang Chen Yue Hou Key Laboratory of Bioresource Research and Development of Liaoning Province College of Life and Health Sciences National Frontiers Science Center for Industrial Intelligence and Systems Optimization Key Laboratory of Data Analytics and Optimization for Smart Industry Ministry of Education Northeastern University State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical Sciences Guangxi Normal University Shenyang Key Laboratory of Vascular Biology Science and Research Center Department of Pharmacology Shenyang Medical College Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education School of Pharmaceutical Engineering Shenyang Pharmaceutical University

Ischemic stroke(IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc.(commonly known as Japanese knotweed), has been recognized for its potent neuroprotective ***, the neuroprotective efficacy of its derivative,(E)-4-(3,5-dimethoxystyryl) quinoline(RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species(ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.

关键词： (E)-4-(3,5-dimethoxystyryl) quinoline Ischemic stroke Mitophagy Parkin Resveratrol

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA division of pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Geochemistry of shales of middle Permian Barren Measures Formation,West Bokaro Basin,India:Implications on provenance,paleodepositional and paleoclimatic conditions

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Journal of Palaeogeography 2025年第01期14卷 40-65页

作者： Mritunjoy Banerjee Biplab Bhattacharya Arnab Bhattacharya Aniruddha Pathak Partha Pratim Banerjee Department of Earth sciences Indian Institute of Technology Natural Resource division Tata Steel Limited

Geochemical analyses of fine-grained clastic sedimentary rocks,such as shales,are significant since they portray the nature of the control factors from source to sink in a sedimentary basin,and help characterizing the heterogeneity in potential source and/or reservoir *** rock geochemistry（including major element oxides,trace elements and rare earth elements） of 20 shale samples from the Permian Barren Measures Formation,West Bokaro Basin,Peninsular India,is presented to decipher the provenance,paleoweathering,paleotectonic,paleodepositional and paleoredox conditions of the basin within the Lower Gondwana paleogeographic framework.X-ray diffraction（XRD） peaks and scanning electron microscopy（SEM）reveal an abundance of quartz,muscovite and clay minerals,viz.,illite,kaolinite,etc.,with less abundant feldspar and *** concentrations of major element oxides,trace elements and rare earth elements（REEs） of the shale samples are compared with predefined standards such as PAAS and *** CIA（chemical index of alteration） and the A-CN-K values,based on the ratios of the major element oxides,signify intense chemical *** ratios of Sr/Cu versus Rb/Sr and K2O/Al2O3versus Ga/Rb,and high ∑REE values indicate a temperate *** of the major element oxides（e.g.,K2O/Na2O versus SiO2） suggest a passive tectonic *** Eu/Eu*and（Gd/Yb）_n values depict predominantly post-Archean granitic and gneissic source *** ratios of trace elements,viz.,Th/Sc,Th/Co,Th/Cr,La/Sc and Eu/Eu*,and the distribution pattern of the REEs（higher LREE in comparison to HREE） attest to a felsic-intermediate source from a nearby *** redox-sensitive trace elements,such as V and Ni,indicate a dysoxic condition that prevailed during *** ratios of Fe2O3versus MgO and Log（MgO/Al2O3） versus Log（K2O/Al2O3）,and the ternary plots of Fe2O3-MgO-SiO2/Al2O3suggest a non-marine to deltaic transitional *** evidence of marine influences during

关键词： Guadalupian Lower Gondwana Passive margin rift basin Fluvial–marine transition Anoxic condition West Bokaro Basin

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