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基于AGE/RAGE信号通路探讨半夏泻心汤改善血管性痴呆大鼠认知功能障碍的作用机制
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作者 梁书志 赵中敏 +3 位作者 侯苏寓 罗丹丹 张艳 刘西建 《中国实验方剂学杂志》 北大核心 2026年第3期10-21,共12页
目的:该研究旨在探讨半夏泻心汤(BXT)通过调控糖基化终产物/晚期糖基化终产物受体(AGE/RAGE)信号通路降低神经炎症反应,改善血管性痴呆(VD)大鼠认知功能障碍的作用机制。方法:采用超高效液相色谱-四极杆-轨道阱串联质谱(UPLC-Q-Orbitrap... 目的:该研究旨在探讨半夏泻心汤(BXT)通过调控糖基化终产物/晚期糖基化终产物受体(AGE/RAGE)信号通路降低神经炎症反应,改善血管性痴呆(VD)大鼠认知功能障碍的作用机制。方法:采用超高效液相色谱-四极杆-轨道阱串联质谱(UPLC-Q-Orbitrap-MS/MS)技术对BXT进行成分检测,运用网络药理学、分子对接技术筛选出核心成分与关键作用通路。60只SPF级SD雄性大鼠随机数字表法分为假手术组(Sham)、造模组,采用改良双侧颈总动脉结扎法(2-VO)复制VD模型,将造模成功的大鼠按照随机数字表法分为模型组(Model),半夏泻心汤低、中、高剂量组(BXT-L、BXT-M、BXT-H)和尼莫地平组(NMP),BXT-L、BXT-M、BXT-H分别给予BXT 3.7485、7.497、14.994 g·kg^(-1),NMP给予NMP 0.0027 g·kg^(-1),Sham、Model予等量生理盐水,连续14 d灌胃给药。Morris水迷宫、Y迷宫、新物体识别实验评估大鼠认知功能障碍。苏木素-伊红(HE)染色评估大鼠海马组织病理学变化。实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠海马组织晚期AGE、RAGE、磷酸化核转录因子-κB p65(p-NF-κB p65)mRNA水平。蛋白免疫印迹法(Western blot)和免疫组化法(IHC)检测大鼠海马组织AGE/RAGE通信通路的相关蛋白表达。酶联免疫吸附测定法(ELISA)检测大鼠血清神经递质和炎症因子。结果:UPLC-Q-Orbitrap-MS/MS技术检测BXT化学成分。网络药理学、分子对接技术筛选出AGE/RAGE信号通路作为关键通路。与Sham比较,Model大鼠成功潜伏期延长,穿越平台次数、自主交替率、进入新臂次数、偏好指数、辨别指数显著降低(P<0.01);与Model比较,BXT-H、BXT-M大鼠成功潜伏期显著缩短(P<0.01)、穿越平台次数、自主交替率、进入新臂次数、偏好指数、辨别指数明显增加(P<0.05,P<0.01)。HE结果显示,与Sham比较,Model大鼠细胞排列松散杂乱,细胞核固缩。与Model比较,BXT海马组织病理损伤明显改善。Real-time PCR结果显示,与Sham比较,Model大鼠海马组织AGE、RAGE、p-NF-κB p65 mRNA显著升高(P<0.01),与Model比较,BXT-H、BXT-M大鼠AGE、RAGE、p-NF-κB p65 mRNA显著降低(P<0.01),Western blot结果显示,与Sham比较,Model大鼠AGE、RAGE、p-NF-κB p65、肿瘤坏死因子-α(TNF-α)表达明显增加(P<0.05),与Model比较,BXT-H大鼠AGE、RAGE、p-NF-κB p65、TNF-α表达明显降低(P<0.05),IHC结果显示,与Sham比较,Model大鼠RAGE表达显著增加(P<0.01),与Model比较,BXT-H、BXT-M大鼠RAGE表达显著降低(P<0.01),ELISA结果显示,与Sham比较,Model大鼠血清TNF-α、白细胞介素-1β(IL-1β)水平显著升高,乙酰胆碱(ACh)和多巴胺(DA)水平显著降低(P<0.01),与Model比较,BXT-L各剂量组大鼠血清TNF-α、IL-1β水平明显降低(P<0.05),ACh和DA水平明显升高(P<0.05)。结论:BXT可能通过下调AGE/RAGE信号通路,减轻神经炎症反应,调节神经递质含量,从而改善VD认知功能障碍。 展开更多
关键词 半夏泻心汤 血管性痴呆 神经炎症 认知功能障碍 糖基化终产物/晚期糖基化终产物受体(AGE/RAGE)信号通路
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运用网络药理学和糖尿病大鼠模型研究荷芪散改善新诊断2型糖尿病胰岛素抵抗的作用机制
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作者 连李荣 舒晓 +5 位作者 黄宝利 谢伟 何金莲 李润泽 赵恒侠 刘良 《中国新药杂志》 北大核心 2026年第2期183-192,共10页
目的:本研究旨在探讨荷芪散改善新诊断2型糖尿病(type 2 diabetes mellitus,T2DM)胰岛素抵抗的作用及其潜在机制。方法:采用网络药理学方法预测荷芪散干预T2DM胰岛素抵抗的关键靶点与信号通路。随后构建T2DM胰岛素抵抗大鼠模型,设正常... 目的:本研究旨在探讨荷芪散改善新诊断2型糖尿病(type 2 diabetes mellitus,T2DM)胰岛素抵抗的作用及其潜在机制。方法:采用网络药理学方法预测荷芪散干预T2DM胰岛素抵抗的关键靶点与信号通路。随后构建T2DM胰岛素抵抗大鼠模型,设正常对照组、模型组、二甲双胍组、荷芪散高剂量组和低剂量组,评估荷芪散对血糖、胰岛素抵抗、血脂水平及肝脏病理变化的影响。采用Western blot与ELISA法检测肝组织及血清中相关蛋白和炎症因子的表达水平,进一步验证网络药理学预测关键通路的准确性。结果:网络药理学结果提示,荷芪散通过多成分、多靶点调控AGEs/RAGE/PI3K/AKT通路发挥作用。动物实验显示,荷芪散高剂量组可显著降低大鼠空腹血糖与HOMA-IR指数,改善胰岛素抵抗与血脂紊乱,减轻肝细胞脂肪变性。分子机制方面,荷芪散可抑制AGEs/RAGE表达与NF-κB活化,降低肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素6(interleukin-6,IL-6)炎症因子水平,解除PI3K/AKT通路抑制,提高葡萄糖转运蛋白2(glucose transporter-2,GLUT2)蛋白表达,增强肝糖代谢功能。结论:荷芪散通过调控AGEs/RAGE/PI3K/AKT信号通路改善胰岛素信号传导,减轻肝脏胰岛素抵抗,调节脂代谢与糖代谢,发挥降糖、调脂及护肝作用,为其用于新诊断T2DM胰岛素抵抗治疗提供实验依据。 展开更多
关键词 荷芪散 新诊断2型糖尿病 胰岛素抵抗 AGEs/RAGE/PI3K/AKT通路 网络药理学 糖脂代谢
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Global Age Assurance Standards Summit 2026
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《China Standardization》 2026年第2期36-36,共1页
April 14-16,Manchester,United KingdomThe Global Age Assurance Standards Summit2026 brings together the international age assurance community for three days of practical insight,shared learning and real-world experienc... April 14-16,Manchester,United KingdomThe Global Age Assurance Standards Summit2026 brings together the international age assurance community for three days of practical insight,shared learning and real-world experience focused on implementing age assurance systems in live environments. 展开更多
关键词 live environments age assurance systems global age assurance standards summit practical insight real world experience age assurance shared learning implementing age assurance systems
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Aging puzzle:A closer look on the complex dilemma of autologous stem cell therapy
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作者 Mahmood S Choudhery Taqdees Arif Ruhma Mahmood 《World Journal of Stem Cells》 2026年第1期8-24,共17页
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh... Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients. 展开更多
关键词 Regenerative medicine Autologous stem cell therapy Regenerative potential AGING Donor age Optimizing therapy Aged patients
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Cross-sectional analysis of hearing loss,age and tinnitus severity in a web-recruited cohort of 610 subjects
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作者 María Cuesta Pedro Cobo 《Journal of Otology》 2026年第1期38-49,共12页
Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for... Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for tinnitus while emotional disorders are risk factors for developing intrusive or bothersome tinnitus.Moreover,aging has also been identified as another risk factor.The aim of this paper was to analyse the correlation between hearing loss,age and tinnitus severity in a cohort of 610 tinnitus sufferers.Methods:Age,audiometric(hearing condition)and tinnitus(time duration and severity)data were assessed and analysed for all subjects just after recruiting(baseline).Furthermore,the average hearing loss(HL)curves of the participants for age groups were compared to these with the corresponding Age Related HL(ARHL).Results:For most of the age groups,the measured HL curves exceeded in 10-20 dB those of the ARHL.The average age of tinnitus onset(age minus tinnitus duration)was found to be 44-46 years in both men and women.Weak correlation between audiometric feature and tinnitus distress was observed.Conclusions:Hearing loss has been shown to be a clear risk factor for triggering tinnitus(86%of participants were hearing impaired).In this cohort,average measures of hearing loss showed,at most,weak associations with tinnitus-related distress,suggesting that non-audiological factors may play a predominant role. 展开更多
关键词 TINNITUS Age Hearing loss Tinnitus-related distress
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Dietary glycyrrhizin enhances reproductive performance by improving intestinal microbiota,liver lipid metabolism and ovarian senescence in aged breeder hens
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作者 Zhenwu Huang Huchuan Liu +5 位作者 Guangju Wang Huan Ge Yanru Shi Jinghai Feng Chunmei Li Minhong Zhang 《Journal of Animal Science and Biotechnology》 2026年第1期299-317,共19页
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha... Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period. 展开更多
关键词 Aged breeder hen GLYCYRRHIZIN Gut microbiota Lipid metabolism Reproductive performance
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Genetic variation in growth characteristics and stem quality of Acacia hybrid across three distinct locations in Vietnam
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作者 Hieu Van Trinh Kien Duc Nguyen +1 位作者 Duong Anh La Yue Li 《Journal of Forestry Research》 2026年第2期1-15,共15页
This study investigates the genetic variability and environmental adaptability of Acacia hybrid clones across three distinct ecological regions,providing insights into growth characteristics and stem quality for futur... This study investigates the genetic variability and environmental adaptability of Acacia hybrid clones across three distinct ecological regions,providing insights into growth characteristics and stem quality for future breeding strategies.42 natural hybrid clones were evaluated over a five-year period in three clonal trials in northern,central and southern Vietnam for height(HT),diameter at breast height(DBH),volume(VOL),trunk straightness(STR),branch size(BRA)and survival.Significant clonal differences were found in all traits across all three regions.From age 2-5,the clone repeatability(H_(C)^(2))for growth traits improved from 0.19 to 0.59,indicating substantial genetic control.Genotypic coefficients of variation(CVG)for volume ranged from 21%to 34%,suggesting significant potential for genetic improvement.Site-to-site genotypic correlations ranged from 0.53 to 0.78,pointing to the existence of genotype-environment interactions.Clones derived from Acacia mangium material demonstrated enhanced growth,while the hybrid clones exhibited superior stem quality,particularly in terms of straightness.The findings emphasize the importance of selecting clones that are adapted to specific environmental conditions,with both growth and quality traits considered in breeding programs. 展开更多
关键词 Acacia hybrid Clonal repeatability Inter-trait correlation Age
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当心,3种食物正在“摧毁”你的皮肤
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作者 罗增香 《医食参考》 2026年第3期47-47,共1页
现代人的健康意识增强,对皮肤健康的关注度也随之提高。为了拥有理想的皮肤,很多人在防晒、清洁等方面下足功夫,却忽视了饮食对皮肤健康的负面影响。3种食物对皮肤造成负面影响高糖食物高糖食物会影响人的皮肤健康。如果人体内糖分存积... 现代人的健康意识增强,对皮肤健康的关注度也随之提高。为了拥有理想的皮肤,很多人在防晒、清洁等方面下足功夫,却忽视了饮食对皮肤健康的负面影响。3种食物对皮肤造成负面影响高糖食物高糖食物会影响人的皮肤健康。如果人体内糖分存积量过大,多余的糖分就会与皮肤中的弹性蛋白、胶原蛋白相结合,形成AGEs,即晚期糖基化终末产物,导致胶原蛋白断裂、变硬,丧失支撑力与弹性,使皮肤变得松弛,出现很多细纹。AGEs为黄棕色,会让皮肤变得暗沉。 展开更多
关键词 AGES 高糖食物 健康 胶原蛋白 弹性蛋白
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Melatonin and mitochondrial stress: New insights into age-related neurodegeneration
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作者 Silvia Carloni Francesca Luchetti +3 位作者 Maria Gemma Nasoni Walter Balduini Walter Manucha Russel J.Reiter 《Neural Regeneration Research》 2026年第4期1564-1565,共2页
Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo... Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable. 展开更多
关键词 buildup changes neurodegenerative diseases aging neurodegenerative diseases MITOCHONDRIA mitochondrial stress MELATONIN age related neurodegeneration AGING
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Mineralization Characteristics of the Li-rich Muscovite Granite in the Mufushan Batholith,Central China:Insights into the Rare Metal Mineralization Models of Batholithic Complex
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作者 ZHANG Hao LI Peng +5 位作者 LI Jiankang YUAN Lulu JIANG Pengfei LIU Ze YIN Jin CHEN Zhuo 《Acta Geologica Sinica(English Edition)》 2026年第1期137-155,共19页
Elucidating the mineralization mechanisms of individual granitic stages and tracing magmatic evolution processes are critical for establishing mineralization models of large-scale batholiths.The Mufushan granitoid bat... Elucidating the mineralization mechanisms of individual granitic stages and tracing magmatic evolution processes are critical for establishing mineralization models of large-scale batholiths.The Mufushan granitoid batholith,renowned for multistage magmatism and large-scale rare metal mineralization,mainly comprises biotite,two-mica,and muscovite monzogranite.Existing research has predominantly focused on biotite and two-mica granite,whereas muscovite granite,as the most highly differentiated lithologic unit,remains understudied regarding its mineralization mechanisms and evolution characteristics.Focusing on two newly discovered Li-rich granites,namely tourmaline muscovite granite(TMG)from Shiniuchong and garnet muscovite granite(GMG)from Huanglongxiang,this study clarifies their intrusion ages,Li occurrence states and enrichment mechanisms,while establishing the magmatic evolutionary pathway.The results show that the U-Pb ages of columbite-tantalum and zircon are 130.2±1.0 Ma(TMG)and 138.2±1.0 Ma(GMG),respectively,confirming Early Cretaceous Li-rich magmatism.The Li concentrations in muscovite from the Li-rich muscovite granites are high(mean 3328 ppm),compared to those in Mufushan ordinary muscovite granites(<1500 ppm),but the dominant Li-bearing minerals are still classified as muscovite or phengite.Li enrichment of mica in this Li-rich granite system is controlled by the magmatic differentiation-dominated vector Si2LiAl-3,differing from that in cogenetic pegmatite systems,indicating distinct Li enrichment pathways between two mineralization processes and thereby endowing this system with the potential to evolve into granite-type Li deposits.Mica geochemistry and Rayleigh fractionation modeling indicate the Li-rich muscovite granites,along with biotite and two-mica granite in the Mufushan area,represent products of different stages of co-magmatic evolution.Crystal fractionation is the key mechanism controlling Li enrichment,requiring effective separation of at least 75%of the melt to drive preliminary Li enrichment in the highly differentiated granite.These findings significantly advance understanding of mineralization processes in large-scale batholiths,providing valuable insights for regional Li exploration. 展开更多
关键词 Li-rich muscovite monzogranite emplacement age enrichment mechanism Mufushan granitoid batholith magmatic evolution
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Zircon U-Pb ages of the volcanic rocks and their constraints on the ending of the Huoshiling Formation in the southeastern of Songliao Basin,NE China
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作者 Xue-jiao Qu Ming-kai Zhang +5 位作者 Pu-jun Wang Zhuo-long Yang You-feng Gao Kang-jun Wu Jia Wang Xian-feng Tan 《China Geology》 2026年第1期214-216,I0023,共4页
1.Objective The Songliao Basin(SB)is situated on the eastern margin of Eurasia continent(Northeast Asia).During the Late Jurassic to Early Cretaceous,hundreds of rifting basins developed in this area,and the SB is a u... 1.Objective The Songliao Basin(SB)is situated on the eastern margin of Eurasia continent(Northeast Asia).During the Late Jurassic to Early Cretaceous,hundreds of rifting basins developed in this area,and the SB is a unique case among them as it evolved into the largest rift basin.The rift basin filling of SB includes Huoshiling Formation,Shahezi Formation,and Yingcheng Formation in ascending order.The mega-rifting was controlled by the Mongol-Okhotsk Collisional Belt to the north and northwest and the Pacific Subduction Zone to the east(Wang PJ et al.,2016).As the first rifting succession,the Huoshiling Formation contains key information about the formation of the rifting basins and records the evolution of the Mongol-Okhotsk Collisional Belt and the Pacific Subduction Zone.However,the geological period of the Huoshiling Formation has not been well constrained for two main reasons.First,it is easily confused with the Yingcheng Formation,as both are dominated by volcanogenic-sedimentary successions.Second,there is lack of reliable dating samples from the uppermost part of the Huoshiling Formation due to its considerable burial depth. 展开更多
关键词 rift basin rift basinthe yingcheng formation ZIRCON U Pb ages rifting basins volcanic rocks huoshiling formationshahezi formationand
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Hevin/sparcl-1 as a potential biomarker and therapy in age-associated cognitive decline
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作者 Felipe Cabral-Miranda Flávia C.A.Gomes 《Neural Regeneration Research》 2026年第6期2357-2358,共2页
Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structu... Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain. 展开更多
关键词 synaptic function modulating synaptic transmissionneurovascular ASTROCYTES neuronal homeostasis age associated cognitive decline glial cellshave hevin sparcl therapy
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Neoproterozoic Overprinting on the Archean Western Dharwar Craton,Southern India:Records from LA-ICP-MS U-Pb Geochronology of Rutile and Monazite
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作者 HU Yuhua ZHAO Yan +5 位作者 LU Junsheng GOU Longlong PMGEORGE AO Wenhao ZHANG Chengli ZHAI Mingguo 《Acta Geologica Sinica(English Edition)》 2026年第1期82-98,共17页
This study provides new evidence for a significant Neoproterozoic tectono-thermal event in the southern Dharwar Craton,based on U-Pb dating of rutile and monazite from metamorphic rocks of the Sargur Group.Trace eleme... This study provides new evidence for a significant Neoproterozoic tectono-thermal event in the southern Dharwar Craton,based on U-Pb dating of rutile and monazite from metamorphic rocks of the Sargur Group.Trace element analysis of rutile in garnet-bearing amphibolite,amphibolite,garnet-bearing staurolite-kyanite schist,and grunerite-garnet schist suggests that their protoliths were primarily basaltic rocks,sediments with mafic component,pelitic sediments,and mixed sediments with both mafic and felsic components,respectively.Rutile U-Pb ages of 625±22 Ma(garnet-bearing amphibolite),752±5.1 Ma(amphibolite),836±4 Ma to 663±26 Ma(garnet-bearing staurolite kyanite schist)and 860±13 Ma(grunerite-garnet schist),along with a monazite U-Pb age of 789±4.4 Ma(garnet-bearing staurolite kyanite schist),record a significant Neoproterozoic(860-625 Ma)tectono-thermal event along the southern margin of the western Dharwar Craton.This event is most likely associated with aborted rift-related alkaline magmatism along the northern margin of the Southern Granulite Terrane(SGT)and the southern margin of the Dharwar Craton.Given the lack of direct evidence for the assembly of the Rodinia supercontinent in the Dharwar Craton and SGT,this Neoproterozoic event is unlikely to be related to the breakup of Rodinia. 展开更多
关键词 rutile and monazite U-Pb ages NEOPROTEROZOIC Sargur area western Dharwar Craton southern India
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Targeting Wallerian degeneration in glaucoma
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作者 Melissa Jöe Pete A.Williams 《Neural Regeneration Research》 2026年第2期693-694,共2页
Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of n... Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of neurodegenerative diseases with glaucoma being highly prevalent.Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells and their axons which make up the optic nerve.It is the leading cause of irreversible vision loss and affects an estimated 80 million people.The mammalian central nervous system is non-regenerative and,once lost or injured,retinal ganglion cells cannot regenerate an axon into the optic nerve under basal conditions.Thus,strategies that provide neuroprotection to stressed,dysfunctional,or dying retinal ganglion cells are likely to be of high therapeutic and translational value.Advancing age,genetics,and elevated intraocular pressure are all major risk factors for glaucoma,however,all clinically available glaucoma treatments focus on intraocular pressure management and do not directly address the neurodegenerative component of glaucoma. 展开更多
关键词 health burden neurodegenerative diseases aged population Wallerian degeneration GLAUCOMA vision loss economic burden retinal ganglion cells their axons
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Mechanism of action of synaptic mitochondrial damage in delayed cognitive recovery
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作者 Huihui Miao Qiang Liu +7 位作者 Yan-Ping Liu Bin-Bin Yan Xin-Hao Jiao Hai-Bi Wang Cheng-Hua Zhou Tianzuo Li Zhongcong Xie Yuqing Wu 《Neural Regeneration Research》 2026年第6期2457-2466,共10页
Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy s... Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment. 展开更多
关键词 acetylase aged mice cyclophilin D delayed neurocognitive recovery hippocampus long-term potentiation mitochondrial permeability transition pore sirtuin 3 synaptic mitochondria SYNAPTOSOME
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Risk factors for paternal perinatal depression in Chinese advanced maternal age couples:A regression mixture model
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作者 Xing Yin Juan Du +1 位作者 Shao-Lian Cai Xing-Qiang Chen 《World Journal of Psychiatry》 2026年第1期267-277,共11页
BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recogn... BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recognized in family-centered clinical practice.Concurrently,against the backdrop of rising rates of delayed marriage and China’s Maternity Incentive Policy,the proportion of women giving birth at an advanced maternal age is increasing.Nevertheless,research specifically examining PPD among spouses of older mothers remains critically scarce,both in China and globally.AIM To investigate PPD and its influencing factors in Chinese advanced maternal age families.METHODS This cross-sectional study included 358 participants;it was conducted among fathers of pregnant women of advanced maternal age at five hospitals in the Pearl River Delta region of China from September 2023 to June 2024.Data were collected via a general information questionnaire,the Social Support Rating Scale,and the Edinburgh Postnatal Depression Scale.Latent profile analysis and regression mixture models(RMMs)were adopted to analyze the latent PPD types and factors that influenced PPD.RESULTS The incidence of PPD was 16.48%,and three profiles were identified:Low-symptomatic(175 cases,48.89%),monophasic(140 cases,39.10%),and high-symptomatic(43 cases,12.01%).The RMM analysis revealed that first pregnancy,low income(<¥3000/month),part-time work,and a history of abnormal pregnancy were positively associated with the high-symptomatic type(P<0.05).Conversely,high subjective support and support utilization were negatively associated with the high-symptomatic type compared with the low-symptomatic type(P<0.05).Good couple relationships,high objective and subjective support,and high support utilization were negatively associated with monophasic disorder(P<0.05).CONCLUSION PPD incidence is high among Chinese fathers with advanced maternal age partners,and the characteristics of depression are varied.Healthcare practitioners should prioritize individuals with low levels of social support. 展开更多
关键词 Advanced maternal age Paternal perinatal depression Fathers’mental health Regression mixture model Advanced-age pregnancy Latent profile analysis
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当归补血汤通过AGEs/RAGE/NF-κB通路保护糖尿病肾病大鼠肾脏的机制研究
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作者 王月 郑琳琳 +3 位作者 吕哲 裴天琦 侯明君 郭登洲 《安徽中医药大学学报》 2026年第1期71-77,共7页
目的 基于晚期糖基化终末产物(advanced glycation end products,AGEs)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)/核因子-κB(nuclear transcription factor-kappa B,NF-κB)通路探讨当归补血汤对... 目的 基于晚期糖基化终末产物(advanced glycation end products,AGEs)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)/核因子-κB(nuclear transcription factor-kappa B,NF-κB)通路探讨当归补血汤对大鼠糖尿病肾病(diabetic kidney disease,DKD)的作用及其机制。方法 采用高糖高脂饲料联合腹腔注射链脲佐菌素方法复制DKD大鼠模型;将大鼠随机分为正常组,模型组,恩格列净组(0.01g/kg),当归补血汤高、中、低剂量组(2.88、1.44、0.72g/kg),每组8只;各给药组大鼠灌胃相应药物,正常组、模型组大鼠给予等体积生理盐水灌胃,每日灌胃1次,持续20周。检测各组大鼠24h尿蛋白、血清肌酐(serum creatinine,SCr)水平;ELISA法检测大鼠血清白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1beta,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平;光学显微镜下观察大鼠肾脏组织病理形态变化;Western blot法检测大鼠肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平;RT-qPCR法检测大鼠肾脏组织中RAGE、NF-κB p65mRNA表达水平。结果 与正常组比较,模型组大鼠24h尿蛋白、SCr水平均显著升高(P<0.05),血清IL-6、IL-1β、TNF-α水平均显著升高(P<0.05),肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平显著升高(P<0.05),肾脏组织中RAGE、NF-κB p65mRNA表达水平显著升高(P<0.05);肾小球体积增大,基底膜增厚,系膜增生。与模型组比较,各给药组大鼠24h尿蛋白、SCr水平均显著降低(P<0.05),血清中IL-6、IL-1β、TNF-α水平均显著降低(P<0.05),肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平显著降低(P<0.05),肾脏组织中RAGE、NF-κB p65mRNA表达水平显著降低(P<0.05);肾脏组织病理学改变有不同程度减轻。结论 当归补血汤可能通过抑制AGEs/RAGE/NF-κB通路的表达,减轻炎症反应,降低肾脏病理损伤,减少蛋白尿,从而有效保护肾脏,缓解DKD进展。 展开更多
关键词 当归补血汤 糖尿病肾病 AGEs/RAGE/NF-κB通路 炎症
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DYNAMICAL ANALYSIS OF AN AGE-STRUCTURED TUBERCULOSIS MODEL DRIVEN BY THE NOVEL M72/AS01_(E)VACCINE IN CONTAMINATED ENVIRONMENTS
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作者 Qian JIANG Zhijun LIU Lianwen WANG 《Acta Mathematica Scientia》 2026年第1期330-360,共31页
To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en... To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB. 展开更多
关键词 tuberculosis model age structure contaminated environments M72/AS01_(E)vaccine STABILITY
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胰腺导管腺癌KRASG12D抑制剂耐药细胞系的构建及耐药机制研究
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作者 张良 刘敬毅 +5 位作者 王红瑞 刘禹搏 赵婷 李俊强 王榕林 苏海川 《中国医药导报》 2026年第4期45-51,共7页
目的构建对KRASG12D抑制剂MRTX1133耐药的胰腺导管腺癌(PDAC)细胞系,并探讨其耐药机制。方法采用浓度梯度递增法诱导人PDAC AsPC-1细胞,构建MRTX1133耐药细胞系AsPC-1.RE。通过克隆形成实验评估MRTX1133对细胞增殖能力的影响;利用转录... 目的构建对KRASG12D抑制剂MRTX1133耐药的胰腺导管腺癌(PDAC)细胞系,并探讨其耐药机制。方法采用浓度梯度递增法诱导人PDAC AsPC-1细胞,构建MRTX1133耐药细胞系AsPC-1.RE。通过克隆形成实验评估MRTX1133对细胞增殖能力的影响;利用转录组测序技术筛选差异表达基因,并进行基因本体功能与京都基因与基因组数据库(KEGG)通路富集分析;采用RT-qPCR验证关键通路中差异基因的表达水平。结果亲本细胞的MRTX1133 IC50值小于耐药细胞(P<0.01),耐药指数为19.87。耐药细胞对照组克隆形成数量少于亲本细胞对照组(P<0.01);耐药细胞MRTX1133处理组克隆形成数量多于亲本细胞(P<0.01)。KEGG富集分析显示差异基因显著富集于细胞外基质重塑、PI3K/Akt及AGE/RAGE等信号通路。RT-qPCR实验显示,与亲本细胞AsPC-1比较,耐药细胞AsPC-1.RE中COL1A1、ITGA3、PIK3CG、Akt3、AGER、NFKB1、CCL2、TGFB2、BCL2 mRNA表达上调,而BAX表达下调(P<0.05)。结论本研究成功构建MRTX1133耐药的PDAC细胞模型,并通过转录组分析与RT-qPCR验证,初步揭示细胞外基质重塑、PI3K/Akt和AGE/RAGE等信号通路的异常激活在MRTX1133耐药中的潜在作用,为克服临床耐药提供实验与理论依据。 展开更多
关键词 胰腺肿瘤 KRAS 肿瘤耐药性 MRTX1133 PI3K/Akt/mTOR通路 AGE/RAGE通路
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Neutralizing hepatic apolipoprotein E enhances aged bone fracture healing
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作者 Mingjian Huang Abhinav Reddy Balu +2 位作者 Kristin Happ Molitoris Akshay Bareja Gurpreet Singh Baht 《Bone Research》 2026年第1期210-221,共12页
Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hep... Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration. 展开更多
关键词 hepatic apolipoprotein E Wnt catenin pathway deletion hepatic apoe expression apoe month old apoe aged bmscs bone fracture healing LRP apolipoprotein E neutralizing antibody tissue culture modelsrna seqwestern blotimmunofluorescenceand
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