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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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Small modifications of endo-functionalized cavities lead to large changes in molecular interaction in water

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Science China Chemistry 2025年第1期 369-376页

作者： Song-Meng Wang Hao Nian Yan-Fang Wang Li-Shuo Zheng Yu-Tao Zheng Yi-Wei Dong Liping Huang Xiaoping Wang Wei Jiang Liu-Pan Yang department of Chemistry Southern University of Science and Technology School of Chemistry and pharmaceutical Sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesGuangxi Normal University School of pharmaceutical Science Hengyang Medical School University of South China

Studying molecular recognition in aqueous environments is crucial for understanding biological processes. Herein, we present a series of N-doped endo-functionalized anthracene-based cavities by introducing inward-directed pyridine units. The subtle modifications can significantly affect the binding properties of these receptors, which is similar to the mutations in biological systems. Combining theoretical calculations and molecular recognition experiments demonstrated that these “mutations” have an impact on the hydrophobicity and charge distribution of the hosts, consequently significantly influencing molecular *** is crucial for understanding the intricate mechanisms of molecular-level interactions in biological receptors.

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Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese department of Pharmacy-pharmaceutical Science University of Bari Aldo MoroBariItaly department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Breaking new ground in photocatalysis: lutetium texaphyrin as a trigger for pyroptosis through biomolecular photoredox reactions

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Science China Chemistry 2025年第1期 1-2页

作者： Qihang Ding Mengrong He Meijia Gu department of Chemistry Korea University department of Ultrasound Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) School of Pharmaceutical Sciences Wuhan University

Malignant neoplasms consistently pose a significant threat to global public health [1,2]. In recent years, immunotherapy has demonstrated remarkable clinical success; however, its efficacy is limited by the scarcity of immune cell infiltration within tumor microenvironments. Cell pyroptosis, a gasdermin-mediated process characterized by cellular swelling,rupture, and the release of intracellular contents such as IL-1β, IL-18, ATP, HMGB1, plays a crucial role in this context[3,4].

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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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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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Oncology research 2025年第1期33卷 225-234页

作者： Wei Zhang Weicheng Wang Rui Wang Xiao Han Lijun Zhu Wenjie Guo Yanhong Gu department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China. department of Oncology The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou 225300 China. State Key Laboratory of pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing 210023 China.

Background:As a novel blocker of vascular endothelial growth factor receptor (VEGFR), fruquintinib has been approved for treating colorectal cancer (CRC). However, its dosage and therapeutic efficacy are limited by its widespread adverse reactions. Venetoclax, recognized as the initial inhibitor of B-cell lymphoma protein 2 (BCL2), has shown potential in boosting the effectiveness of immunotherapy against CRC. This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax's efficacy against tumors. Then we employed various techniques to evaluate different aspects of the experimental outcomes. Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues. Western blot analysis was utilized to examine the occurrence of cell apoptosis, and flow cytometry to quantitate immune cells within the tumor tissues. Moreover, immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax, as opposed to individual drug use. Venetoclax was found to amplify the impact of fruquintinib, leading to decreased cancer cell proliferation, increased cancer cell apoptosis, lowered angiogenesis, better vascular structure normalization, and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment. Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC. Venetoclax holds promise in being assimilated into anticancer medications for CRC.

关键词： Anti-angiogenesis B-cell lymphoma protein 2 (BCL2) Colorectal cancer (CRC) Fruquintinib Immunotherapy Vascular endothelial growth factor receptor (VEGFR) Venetoclax

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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan Han Li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina department of pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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