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Redox dysregulation as a driver for dNA damage and its relationship to neurodegenerative diseases

Translational Neurodegeneration 2023年第1期12卷 604-637页

作者： Sina Shadfar Sonam Parakh Md Shafi Jamali julie d.atkin Centre for Motor Neuron disease Research Macquarie Medical SchoolMacquarie UniversitySydneyNSW 2109Australia La Trobe Institute for Molecular Science La Trobe UniversityBundooraMelbourneVIC 3086Australia

Redox homeostasis refers to the balance between the production of reactive oxygen species(ROS)as well as reactive nitrogen species(RNS),and their elimination by *** is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant *** stress perturbs many cellular activities,including processes that maintain the integrity of *** acids are highly reactive and therefore particularly susceptible to *** dNA damage response detects and repairs these dNA *** dNA repair processes are therefore essential for maintaining cellular viability,but they decline considerably during *** damage and deficiencies in dNA repair are increasingly described in age-related neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s ***,oxidative stress has long been associated with these ***,both redox dysregulation and dNA damage increase significantly during aging,which is the biggest risk factor for neurodegenerative ***,the links between redox dysfunction and dNA damage,and their joint contributions to pathophysiology in these conditions,are only just *** review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of dNA damage in neurodegenerative *** these connections may facilitate a better understanding of disease mechanisms,and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and dNA damage.

关键词： Redox dysregulation dNA damage Neurodegeneration Reactive oxygen species Oxidative stress

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Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows

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Journal of Animal Science and Biotechnology 2024年第5期15卷 2031-2043页

作者： Sai Zhang Juan C.Marini Vengai Mavangira Andrew Claude julie Moore Mahmoud A.Mohammad Nathalie L.Trottier department of Animal Science Michigan State UniversityEast Lansing 48824USA State Key Laboratory of Swine and Poultry Breeding Industry Key Laboratory of Animal Nutrition and Feed Science in South ChinaMinistry of Agriculture and Rural AffairsGuangdong Provincial Key Laboratory of Animal Breeding and NutritionInstitute of Animal ScienceGuangdong Academy of Agricultural SciencesGuangzhou 510640PR China USdA/ARS Children’s Nutrition Research Center and Pediatric Critical Care Medicine Department of PediatricsBaylor College of MedicineHoustonTX 77030USA department of Large Animal Clinical Sciences Michigan State UniversityEast LansingMI 48824USA Present address:department of Animal Science Cornell UniversityFrank Morrison Hall507 Tower RoadIthacaNY 14853‑4801USA

Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein *** lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets(10.80 MJ/kg net energy):control(CON;19.24%CP)and reduced CP with“optimal”AA profile(OPT;14.00%CP).Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1,14,18,and 21 of *** d 14 and 18,a subset of 9 sows(CON=4,OPT=5)was infused with a mixed solution of 3-[methyl-2H3]histidine(bolus injection)and[13C]bicarbonate(priming dose)first,then a constant 2-h[13C]bicarbonate infusion followed by a 6-h primed constant[1-13C]lysine *** blood and milk sampling were performed to determine plasma and milk Lys enrichment,Lys oxidation rate,whole body protein turnover,and muscle protein *** Over the 21-d lactation period,compared to CON,sows fed OPT had greater litter growth rate(Pd to CON,sows fed OPT had greater efficiency of Lys(Pd whole-body protein turnover efficiency(Pd to CON,sows fed OPT tended to have lower whole body protein breakdown rate(P=0.069).Muscle protein breakdown rate did not differ between OPT and CON(P=0.197).Conclusion Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein *** results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.

关键词： Amino acid Efficiency Lactating sows Protein breakdown Protein turnover Reduced protein diet

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Assessment of the Recent Hydromorphological Features of Nokoue Lake and Its Channels (South-East Benin)

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Open Journal of Modern Hydrology 2024年第1期14卷 33-55页

作者： Tètchodiwèï julie-Billard Yonouwinhi Gérard Alfred Franck Assiom d’Almeida Felix Kofi Abagale Akuemaho Virgile Onésime Akowanou Laboratory of Applied Hydrology (LHA) National Institute of water (INE) African Centre of Excellence for Water and Sanitation (C2EA) University of Abomey-Calavi (UAC) Cotonou Benin International Chair in Mathematical Physics and Applications (ICMPA–UNESCO Chair) University of Abomey-Calavi (UAC) Cotonou Benin Laboratory of Geology Mining and Environment (LGME) Faculty of Science and Technology (FAST) University of Abomey-Calavi (UAC) Cotonou Benin West African Centre for Water Irrigation and Sustainable Agriculture (WACWISA) University of Development Studies (UDS) Tamale Ghana Laboratory of Sciences and Technology for Water and Environment (LSTEE) University of Abomey-Calavi (UAC) Cotonou Benin

Based on 2022 and 2023 hydrometric data and satellite images (Sentinel 2022, SPOT 2010), this study aims to present the Nokoué Lake and its channels’ re-cent hydromorphological characteristics. Integrating flow, tributary morphology, and topography data determined specific power values along the axes studied. The values obtained range from 2.69 to 12.92 W/m2 for Ouémé River and 2.46 to 10.99 W/m2 for Sô River. The resulting water erosion on banks and bottoms is of linear, areolar, or gully and claw types. Lake bathymetry varies from -0.5 to -2.6 m (low flow period) and -1 to -4 m;in the Ouémé, Sô, and Totchè rivers, it varies from -5 m to -7 m, reaching -10 m at the Cotonou channel entrance (flood period). Bathymetric profiles reveal varied “U”, “V” and “Intermediate” bottom morphologies, influenced by erosion/sedimentation processes and human activities. The flow facies identified are lentic in the northern tributaries and lotic in the Cotonou and Totchè canals. Spatial analysis identified nine (09) thematic classes. In 2022, the surface area of the water body has increased from 274 km2 at low water to 280 km2 at high water, whereas in 2010 (a recent year of exceptional flooding), the surface area was 270 km2 at low water and 277 km2 at high water. Significant changes in land use are observed between 2010 and 2022. The floodplain area decreased slightly, from 421 km2 in 2010 (year of exceptional flooding) to 419 km2 in 2022. The evolution of land use shows a progressive expansion of the urban environment to the detriment of the natural environment. In the medium to long term, this trend could threaten the hydromorphological balance and even the existence of this important lagoon ecosystem.

关键词： Nokoué Lake Ouémé River Sô River Cotonou Channel Hydromorphology

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肌萎缩侧索硬化蛋白激活小胶质细胞NLRP3炎性体

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神经损伤与功能重建 2022年第1期17卷 F0003-F0003页

作者： Vandana deora John d Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson julie d atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff School of Biomedical Sciences Faculty of MedicineThe University of QueenslandSt.LuciaQueenslandAustralia University of Queensland Centre for Clinical Research Faculty of MedicineThe University of QueenslandHerstonQueenslandAustralia Institute for Molecular Bioscience and Centre for Inflammation and Disease ResearchThe University of QueenslandSt.LuciaQueenslandAustralia School of Chemistry and Molecular Biosciences Faculty of ScienceMedicine and HealthUniversity of WollongongWollongongNew South WalesAustralia Illawarra Health and Medical Institute University of WollongongWollongongNew South WalesAustralia Faculty of Medicine and Health Sciences Department of Biomedical SciencesCentre for MND ResearchMacquarie UniversityNew South WalesAustralia School of Chemistry and Molecular Biosciences The University of QueenslandSt.LuciaQueenslandAustralia

小胶质细胞NLRP3炎症小体激活正在成为神经退行性变期间神经炎症的关键因素。β-淀粉样蛋白和α-突触核蛋白等致病蛋白的聚集体可触发小胶质细胞NLRP3激活,并导致半胱氨酸天冬氨酸酶激活和白介素-1β分泌。半胱氨酸天冬氨酸酶和白介素-... 详细信息

小胶质细胞NLRP3炎症小体激活正在成为神经退行性变期间神经炎症的关键因素。β-淀粉样蛋白和α-突触核蛋白等致病蛋白的聚集体可触发小胶质细胞NLRP3激活,并导致半胱氨酸天冬氨酸酶激活和白介素-1β分泌。半胱氨酸天冬氨酸酶和白介素-1β均促进肌萎缩侧索硬化(ALS)小鼠SOd1G93A模型的疾病进展,这提示小胶质细胞NLRP3在该进程中起作用。然而,先前的研究表明SOd1G93A模型小鼠的小胶质细胞并不表达NLRP3,并且SOd1G93A蛋白在小胶质细胞中产生白介素-1β不依赖于NLRP3。本研究展示了使用Nlrp3-GFP基因敲入小鼠,在SOd1G93A小鼠中小胶质细胞表达NLRP3。结果表明,聚集和可溶性SOd1G93A均以剂量和时间依赖性方式激活小鼠原代小胶质细胞中的炎性体,导致半胱氨酸天冬氨酸酶和白介素-1β裂解、ASC斑点形成和白介素-1β分泌。重要的是,SOd1G93A不能诱导缺乏Nlrp3的小胶质细胞或用特异性NLRP3抑制剂MCC950预处理的小胶质细胞分泌白介素-1β,这证实NLRP3是介导SOd1诱导的小胶质细胞白介素-1β分泌的关键炎性体复合物。在TdP-43Q331K ALS小鼠模型中也观察到小胶质细胞NLRP3上调,并且TdP-43野生型和突变蛋白也能以NLRP3依赖性方式激活小胶质细胞炎症小体。从机制上,本研究确定活性氧簇和ATP的产生是SOd1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,病理性ALS蛋白激活了小胶质细胞NLRP3炎性体。因此,抑制NLRP3可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。

关键词：白介素-1β 胶质细胞先天免疫运动神经元病

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肌萎缩性侧索硬化蛋白激活小胶质细胞NLRP3炎性小体

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神经损伤与功能重建 2020年第9期15卷 F0003-F0003页

作者： Vandana deora John d Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson julie d atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff 杜一星(编译) School of Biomedical Sciences Faculty of MedicineThe University of QueenslandSt.LuciaQueenslandAustralia University of Queensland Centre for Clinical Research Faculty of MedicineThe University of QueenslandHerstonQueenslandAustralia Institute for Molecular Bioscience and Centre for Inflammation and Disease ResearchThe University of QueenslandSt.LuciaQueenslandAustralia School of Chemistry and Molecular Biosciences Faculty of ScienceMedicine and HealthUniversity of WollongongWollongongNew SouthWalesAustralia Illawarra Health and Medical Institute University ofWollongongWollongongNew SouthWalesAustralia Faculty of Medicine and Health Sciences Department of Biomedical SciencesCentre for MND ResearchMacquarie UniversityNew SouthWalesAustralia School of Chemistry and Molecular Biosciences The University of QueenslandSt.LuciaQueenslandAustralia 不详

小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS... 详细信息

小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS)的SOd1G93A模型中,半胱天冬酶-1和IL-1β均促进疾病进展,提示小胶质NLRP3在该进程中发挥作用。然而先前的研究表明,SOd1G93A小鼠小胶质细胞不表达NLRP3,SOd1G93A蛋白在小胶质细胞中产生独立于NLRP3的IL-1β。本研究论证了使用Nlrp3-GFP基因敲入小鼠,在SOd1G93A小鼠中小胶质细胞表达NLRP3。本研究显示聚集和可溶性SOd1G93A均可激活小鼠原代小胶质细胞中的炎性小体,导致半胱天冬酶-1和IL-1β裂解,ASC斑点形成以及呈剂量和时间依赖性的IL-1β分泌。重要的是,SOd1G93A无法从缺乏Nlrp3的小胶质细胞或者用特异性NLRP3抑制剂MCC950预处理的小胶质细胞中诱导IL-1β分泌,从而证实NLRP3是介导SOd1诱导的小胶质细胞IL-1β分泌的关键炎症小体复合物。在TdP-43Q331K ALS小鼠模型中也观察到小胶质NLRP3上调,TdP-43野生型和突变蛋白亦可以NLRP3依赖性的方式激活小胶质炎性小体。从机制上讲,本研究确定了活性氧簇和ATP的生成是SOd1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,而病理ALS蛋白激活小胶质NLRP3炎性小体。因此,NLRP3抑制可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。

关键词：白介素-1β 胶质细胞先天免疫运动神经元病

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