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

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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Context-dependent role of sirtuin 2 in inflammation

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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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Mycotoxin binder improves growth rate in piglets associated with reduction of toll-like receptor-4 and increase of tight junction protein gene expression in gut mucosa

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Journal of animal Science and Biotechnology 2018年第2期9卷 351-360页

作者： Linghong Jin Wei Wang Jeroen Degroote Noémie Van Noten Honglin Yan Maryam Majdeddin Mario Van Poucke Luc Peelman Anne Goderis Kurt Van De Mierop Ronny Mombaerts Stefaan De Smet Joris Michiels department of Applied Biosciences Ghent University Laboratory for animal nutrition and animal Product quality Department of Animal Production Ghent University department of nutrition Genetics and EthologyFaculty of Veterinary Medicine Ghent University Nutrex

Background: Deoxynivalenol(DON) is a mycotoxin produced by Fusarium species in the field, commonly found in cereal grains, which negatively affects performances and health of animals. Mycotoxin binders are supposed to reduce the toxicity of ***: The effect of a mycotoxin binder(containing acid-activated bentonite, clinoptilolite, yeast cell walls and organic acids) on growth performance and gut health was studied. Hundred and twenty weaning piglets were allocated to 4 treatments, with 5 pens of 6 piglets each, arranged in a 2 × 2 factorial design: control diet; control diet with 1 kg/t binder; control diet with DON; and control diet with DON and 1 kg/t binder. From d0–14,the diet of DON-challenged groups was artificially contaminated with a mixture of DON(2.6 mg/kg), 3-acetyldeoxynivalenol(0.1 mg/kg) and 15-acetyl-deoxynivalenol(0.3 mg/kg), after which the total contamination level was reduced to 1 mg/kg, until d37. On d14, one pig from each pen was euthanized and distal small intestinal mucosa samples were collected for the assessment of intestinal permeability, and gene expression of tight junction proteins, toll-like receptor 4, inflammatory cytokines and intestinal alkaline ***: After 37 d, there were no differences in growth performance between control and DON-challenged groups(P > 0.05). Nevertheless, groups that received diets with binder had a significantly higher average daily gain(ADG) and average daily feed intake(ADFI) for the first 14 d as well as for the whole period, compared to groups without binder(P ≤ 0.05). Groups with binder in the diet also exhibited lower expression of toll-like receptor 4 in distal small intestinal mucosa at d14, compared to groups without binder(P ≤ 0.05). Interestingly, comparing the two DON treatments, piglets fed DON and binder had significantly higher ADFI and ADG compared to those with only DON for the first 14-d(P ≤ 0.05). Addition of binder to DON contaminated diets, also down-regulated th

关键词： Binder Deoxynivalenol Gut barrier Gut health Mycotoxin Pigs

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Suitability of Hermetia illucens larvae meal and fat in broiler diets:effects on animal performance,apparent ileal digestibility,gut histology,and microbial metabolites

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Journal of animal Science and Biotechnology 2022年第5期13卷 1386-1401页

作者： Kristina Hartinger Katharina Froschl Marco Antonio Ebbing Barbara Bruschek-Pfleger Karl Schedle Christiane Schwarz Martin Gierus department of Agrobiotechnology Institute of Animal NutritionLivestock Productsand Nutrition PhysiologyUniversity of Natural Resources and Life SciencesViennaAustria

Background:The possibility of partially replacing soybean meal(SBM)with Hermetia illucens(HI)defatted larvae meal in broiler nutrition has frequently been *** sustainability reasons,however,the larvae fat produced during defatting should also be used and could be particularly beneficial regarding gut health due to its fatty acid *** evaluate the suitability of HI larvae as protein and fat source,a 2×3 factorial arrangement with two types of protein,***(S)or SBM and 15%of its crude protein replaced by HI larvae meal(L),and three levels of fat sources,namely 0(0 L),50%(50 L)or 100%HI larvae fat(100 L)at the expense of soybean oil was ***:In the starter phase,an interaction showed higher body weight(BW),average daily gain(ADG)and improved feed conversion ratio(FCR)if 50%or 100%HI larvae fat was fed with HI larvae ***,BW,ADG and FCR improved when feeding HI larvae meal as protein ***,we observed an increased average daily feed intake in the grower,finisher,and overall phase in the L groups and an improved FCR in 0 L compared to 50 L groups during the overall *** apparent ileal digestibility,HI larvae meal feeding increased dry matter,organic matter,and fat *** HI larvae meal as protein source decreased the concentrations of agmatine,spermidine,spermine and ammonia in the caecal digesta,whereas fat source affected agmatine with higher concentrations in 50 L compared to 0 L in the colonic *** contrast,caecal ethanolamine concentrations increased in HI larvae meal groups compared to *** butyric acid concentrations decreased with HI larvae meal *** interaction was found for the jejunal villus area,being higher in L+100 L compared to S+100 ***,L groups had greater villus ***:A partial replacement of SBM with HI larvae meal and soybean oil with HI larvae fat in broiler diets without impairing animal performance or gut health seems possible

关键词： Broiler chicken Hermetia illucens Larvae fat Larvae meal Lauric acid Microbial metabolites Performance

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The main physical properties of planosol in maize(Zea mays L.) cultivation under different long-term reduced tillage practices in the Baltic region

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Journal of Integrative Agriculture 2015年第7期14卷 1309-1320页

作者： K?stutis Romaneckas Egidijus ?arauskis Dovil? Avi?ienyt? Sidona Buragien? David Arney Institute of Agrosystems and Soil Sciences Aleksandras Stulginskis University Institute of Agricultural Engineering and Safety Aleksandras Stulginskis University department of nutrition and animal products quality Institute of Veterinary Medicine and Animal Sciences Estonian University of Life Sciences

The impact of sustainable reduced tillage （RT） on the physical properties of soil is well documented worldwide; however, there is no precise information about the influence of long-term RT or no-till （NT） on the soils at the boundary for grain maize-growing in the semi-humid subarctic climate conditions of the Baltic states, especially on the formation of a hard- ened upper soil layer （10-15 cm in depth） --＂loosening hardpan＂. This study was carried out at the Research Station of Aleksandras Stulginskis University, Lithuania from 2009-2012. The investigations were based on a long-term （since 1988） field experiment. The aim of the investigation was to ascertain the influence of reduced primary tillage on the main soil＇s physical properties. This study examined soils that were deep ploughing （DP）, shallow ploughing （SP）, deep cultivation （DC）, shallow cultivation （SC）, and no-till （NT）. Reducing the tillage intensity to NT had no significant effect on the structural soil＇s composition; however, the stability of the structure of the 〉1 and 〉0.25 mm-size fractions was significantly higher in the non-reversibly tilled （DC, SC） and NT plots. The penetration resistance of the DP soils was less after primary tillage and wintering, and became similar to the NT plots at the end of the maize growth season. After primary tillage and wintering, the soil moisture content in the upper soil layer （0-5 cm depth） of the NT plots was 17-49 and 16-18% higher than that in the DP. Long-term reduction of primary tillage up to NT generally had no significant effect on the moisture content and soil bulk density of the 0-10 and 10-20 cm layers. The results showed that long-term RT stabilized the physical quality of soil. Less soil penetration resistance was established in the DP plots compared to both RT and NT, however, indicators of the formation of a uniform ＂loosening hardpan＂ layer were not found. It is summarized that long-term RT or NT systems stabilize, or may increase, the physical

关键词： bulk density maize moisture content penetration resistance reduced tillage soil aggregation

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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

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Early inoculation with caecal fermentation broth alters small intestine morphology,gene expression of tight junction proteins in the ileum,and the caecal metabolomic profiling of broilers

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Journal of animal Science and Biotechnology 2020年第2期11卷 440-452页

作者： Yujie Gong Wenrui Xia Xueting Wen Wentao Lyu Yingping Xiao Hua Yang Xiaoting Zou Key Laboratory for Molecular animal nutrition of Ministry of Education Feed Sciences InstituteCollege of Animal SciencesZhejiang University(Zijingang Campus)Hangzhou 310058China State Key Laboratory for quality and Safety of Agro-products Institute of Quality and Standards for Agro-productsZhejiang Academy of Agricultural SciencesHangzhou 310021China

Background:The establishment of stable microbiota in early life is beneficial to the *** in the intestinal environment during early life play a crucial role in modulating the gut ***,early intervention to change the intestinal environment can be regarded as a new regulation strategy for the growth and health of ***,the effects of intestinal environmental changes on host physiology and metabolism are rarely *** study was conducted to investigate the effects of early inoculation with caecal fermentation broth on small intestine morphology,gene expression of tight junction proteins in the ileum,and cecum microbial metabolism of ***:Our data showed that early inoculation with caecal fermentation broth could improve intestine *** small intestine villus height was significantly increased(P<0.05)in the intervened broilers compared to the control group,especially on day 28.A similar result was observed in the ratio of villus height to crypt depth(P<0.05).Meanwhile,we found early inoculation significantly increased(P<0.05)the expression levels of zonula occludens-1(ZO1)on days 14 and 28,claudin-1(CLDN1)on day 28,whereas the gene expression of claudin-2(CLDN2)was significantly decreased(P<0.05)on days 14 and *** chromatography time-of-flight/mass spectrometry(GC-TOF/MS)technology was further implemented to systematically evaluate the microbial metabolite *** component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)displayed a distinct trend towards separation between the fermentation broth group(F group)and the control group(C group).The differentially expressed metabolites were identified,and they were mainly functionally enriched in beta-alanine metabolism and biosynthesis of unsaturated fatty *** addition,1,3-diaminopropane was selected as a key biomarker that responded to early inoculation with caecal fermentation ***:These re

关键词： Broilers Early inoculation Gene expression Intestine morphology Metabolomics profiling

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Fermented liquid feed for pigs： an ancient technique for the future

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Journal of animal Science and Biotechnology 2016年第1期7卷 1-9页

作者： Joris AM Missotten Joris Michiels Jeroen Degroote Stefaan De Smet Laboratory for animal nutrition and animal Product quality Department of Animal ProductionGhent UniversityGhentBelgium department of Applied Biosciences Ghent UniversityValentin Vaerwyckweg 1B-9000 GhentBelgium

Fermented liquid feed is feed that has been mixed with water at a ratio ranging from 1：1.5 to 1：4. By mixing with water lactic acid bacteria and yeasts naturally occurring in the feed proliferate and produce lactic acid, acetic acid and ethano which reduces the pH of the mixture. This reduction in pH inhibits pathogenic organisms from developing in the feed. In addition, when this low pH mixture is fed, it reduces the pH in the stomach of pigs and prevents the proliferation of pathogens such as coliforms and Salmonella in the gastrointestinal tract. For piglets, the use of fermented liquid feed offers the possibility of simultaneously providing feed and water, which may facilitate an easier transition from sow＇s milk to solid feed. Secondly, offering properly produced fermented liquid feed may strengthen the role of the stomach as the first line of defense against possible pathogenic infections by lowering the pH in the gastrointestinal tract thereby helping to exclude enteropathogens. Finally, feeding fermented liquid feed to pigs has been shown to improve the performance of suckling pigs, weaner pigs and growing-finishing pigs. In this review, current knowledge about the use of fermented liquid feed in pig diets will be discussed. This will include a discussion of the desirable properties of fermented liquid feed and factors affecting fermentation. In addition, advantages and disadvantages of fermented liquid feed will be discussed including its effects on gastrointestinal health, intestinal pH and the types of bacteria found in the gastrointestinal tract as well as the effects of fermented liquid feeds on pig performance.

关键词： Fermented liquid feed Lactobacillus spp Pigs Probiotics Yeasts

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A comparative study to determine the effects of breed and feed restriction on glucose metabolism of chickens

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animal nutrition 2023年第2期13卷 261-269页

作者： Pengfei Du Huanjie Wang Xiuwen Shi Xiangli Zhang Yao Zhu Wen Chen Huaiyong Zhang Yanqun Huang College of animal Science and Technology Key Laboratory of Animal Biochemistry and NutritionMinistry of AgricultureHenan Agricultural UniversityZhengzhou 450002HenanChina Laboratory for animal nutrition and animal Product quality Department of Animal Sciences and Aquatic EcologyGhent UniversityGhent9000Belgium

The glucose metabolism of poultry draws wide attention as they have nearly twice the fasting blood glucose than that of *** define the relationship between glucose metabolism and breed of chicken,the outcomes from different growth rate chickens showed that Arbor Acres(AA)broilers,a well-known fast-growing breed,had a lower fasting blood glucose concentration and glucose clearance rate when compared to Silky chickens,a Chinese traditional medicinal chicken with black skin and a slow growth ***,AA broilers had a relatively slow rise in blood glucose in response to oral glucose solution than the Silky chickens on 21 and 42 d(P<0.05),which is probably attributed to downregulated expression of pancreatic insulin(INS),and upregulated transcription of phosphoenolpyruvate carboxy kinase 1(PCK1)and glucose transporter 2(GLUT2)in the liver of AA broilers(P<0.05).In response to feeding restriction from 7 to 21 d,both the fasting blood glucose and the response speed of AA broilers to oral glucose were increased on d 21(P<0.05),and the serum glucose concentrations after 3 weeks compensatory growth were improved by early feed restriction in AA *** restriction could also upregulate the mRNA level of pancreatic INS on d 21 and 42,as well as decrease the expressions of PCK1,glucose-6-phosphatase catalytic(G6PC),and GLUT2 in the liver on d 21(P<0.05)when compared to the free feeding *** results revealed that Silky chickens have a stronger capability to regulate glucose homeostasis than AA broilers,and feed restriction could improve the fasting blood glucose and the response to oral glucose of AA broilers.

关键词： Silky chicken AA broiler Feed restriction Glucose tolerance Pancreas

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Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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Science China Life Sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Shandong Key Laboratory of animal Bioengineering and Disease Prevention College of Animal Science and Technology Shandong Agricultural University department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine Shanghai Institute of nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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