Degeneration

变性
  • 文章类型: Journal Article
    Degenerative lesions specific to the basal nuclei have not been described as a background finding in Beagle dogs. This report comprises a documentation of seven cases. In the context of a nonclinical safety studies, the authors suggest documenting the lesion descriptively as degeneration neuropil, basal nuclei, bilateral as it is characterized by (1) vacuolation, neuropil; (2) gliosis (astro- and/or microgliosis); and (3) demyelination. This novel lesion is considered a potential new background change for several reasons: (1) It occurred in animals from test item-treated and also vehicle-treated groups; (2) no dose dependency was observed; (3) in one of six affected test item-treated dogs, the given compound was shown not to penetrate the blood-brain barrier; and (4) statistical comparison between the proportions of affected dogs in the treatment and control groups did not yield a statistically significant difference. The etiology remains unknown and is subject to further investigations.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    Optimized nitrogen (N) management (OPT), with reduced total N input and more N applied during panicle development, has been proved to increase grain yield of rice through panicle enlargement. However, the changes in panicle architecture and source of variation are not well understood. A hybrid rice variety named Tianyou 3618 was subjected to OPT and farmer\'s fertilizer practice (FFP) in early cropping seasons of 2016 and 2017. With 16.7 % less N input, OPT increased panicle size by 8.6 % and 27.4 %, and grain yield by 13.8 % and 12.3 % for 2016 and 2017, respectively. OPT had greater dry matter accumulation and N uptake from panicle initiation to heading, which bolstered panicle enlargement. The number of surviving florets per branch was quite constant under different N treatments for all primary, secondary, and tertiary branches, implying that panicle size was mainly determined by the number of branches rather than the number of florets per branch. Little change was observed between OPT and FFP in differentiation, degeneration and survival of primary branches and their florets. Surviving secondary and tertiary branches and their florets were significantly more under OPT than those under FFP. The increase in surviving secondary branches under OPT resulted from both enhanced differentiation and reduced degeneration. While the increase in surviving tertiary branches under OPT was merely from enhanced differentiation though their degeneration was also dramatically increased. Among the increased differentiated florets under OPT, 32.4%-36.3 % and 61.6%-67.7 % came from secondary and tertiary branches, respectively. Among the increased surviving florets under OPT, 62.2%-65.2 % and 32.5%-37.8 % came from secondary and tertiary branches, respectively. Both secondary branches and tertiary branches were principal contributors to the increase in panicle size of OPT. To our knowledge, this is the first report on the detailed changes in panicle architecture and their involvement in panicle enlargement and yield gain under OPT.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    介绍糖尿病和骨关节炎(OA)是普遍存在的慢性疾病,经常同时发生,使患者管理复杂化。虽然每种情况对功能损害的个人影响是有据可查的,他们的综合效果仍然知之甚少。本研究旨在阐明糖尿病与OA相关功能损害之间的关系。方法这是一项对290名单侧膝关节OA参与者的横断面研究。他们的人口统计,临床,并收集糖尿病数据。使用西安大略省和麦克马斯特大学骨关节炎指数-风湿病中心(WOMAC-CRD)评估功能障碍。统计分析调查了糖尿病之间的关系,OA严重程度,和功能损害。结果糖尿病患者的身体功能和整体残疾均显著恶化,WOMAC-CRD分数较低。糖尿病和非糖尿病组的平均WOMAC-CRD疼痛评分分别为6.46(SD=1.088)和6.48(SD=1.101),分别。糖尿病和非糖尿病组的平均WOMAC-CRD硬度评分分别为6.48(SD=1.101)和6.56(SD=1.083)。糖尿病参与者的平均WOMAC-CRD身体功能评分为55.93(SD=2.484),相比之下,非糖尿病参与者为64.02(SD=2.542)。糖尿病参与者的平均WOMAC总分为68.80(SD=2.857),非糖尿病参与者的平均WOMAC总分为77.06(SD=2.933)。较长的糖尿病病程与身体功能和WOMAC总分呈负相关。讨论研究结果表明,糖尿病会加剧OA患者的功能损害,特别是影响身体功能和整体残疾。慢性炎症和晚期糖基化终产物的积累可能导致观察到的关节功能恶化。结论针对糖尿病和OA的综合管理策略对于优化患者护理至关重要。
    Introduction Diabetes and osteoarthritis (OA) are prevalent chronic conditions, often occurring concurrently and complicating patient management. While the individual impact of each condition on functional impairment is well documented, their combined effect remains poorly understood. This study aims to elucidate the relationship between diabetes and OA-related functional impairment. Methodology This was a cross-sectional study of 290 participants with unilateral knee OA. Their demographic, clinical, and diabetes data were collected. Functional impairment was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index-Center for Rheumatic Diseases (WOMAC-CRD). Statistical analyses investigated the relationships between diabetes, OA severity, and functional impairment. Result Diabetic participants showed significantly worse physical function and overall disability, with lower WOMAC-CRD scores. Mean WOMAC-CRD pain scores were 6.46 (SD = 1.088) and 6.48 (SD = 1.101) for the diabetic and non-diabetic groups, respectively. Mean WOMAC-CRD stiffness scores were 6.48 (SD = 1.101) and 6.56 (SD = 1.083) for diabetic and non-diabetic groups. Diabetic participants had a mean WOMAC-CRD physical function score of 55.93 (SD = 2.484), compared to 64.02 (SD = 2.542) for non-diabetic participants. The mean total WOMAC score was 68.80 (SD = 2.857) for diabetic participants and 77.06 (SD = 2.933) for non-diabetic participants. Longer diabetes duration correlated negatively with physical function and total WOMAC scores. Discussion The findings suggest that diabetes exacerbates functional impairment in OA patients, particularly affecting physical function and overall disability. Chronic inflammation and the accumulation of advanced glycation end-products may contribute to the observed deterioration in joint function. Conclusion Integrated management strategies addressing both diabetes and OA are essential for optimizing patient care.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:异常闭塞和衰老是颞下颌关节(TMJ)变性的两个主要风险。
    目的:评估咬合和年龄对TMJ椎间盘的综合影响。
    方法:为了避免性别的混杂影响,目前,126只雌性C57BL/6J小鼠,63名年轻人,6周龄和63名成年人,28周龄,被使用。通过将金属管安装到下颌切牙上,创建了实验性的双侧前牙咬合(BAC)关系。在第3、7和11周处死小鼠(n=9)。此外,在去除组中,在7周时将已安装的试管取出,在另外4周后对TMJ进行采样(n=9).通过组织形态学检测到椎间盘的变化,免疫组织化学,和蛋白质印迹分析。
    结果:BAC组椎间盘变形明显。典型的变化是椎间盘后部区域的增生,其中有明显的炎症细胞浸润。炎症标志物的表达,包括肿瘤坏死因子-α和白细胞介素-1β,和分解代谢标记,包括纤连蛋白(FN),FN-末端片段,血管内皮生长因子A,都增加了。这种变化在成年人中比在年轻人中更明显。去除BAC减轻了青少年的炎症和分解代谢变化,但是成人的炎症标志物几乎没有恢复。
    结论:TMJ椎间盘通过变性和炎症对BAC有反应,并通过康复来应对BAC移除。与年轻人的椎间盘相比,成人椎间盘对BAC的变性反应更严重,对BAC的抗炎能力水平较低。动物不能等同于人类。人类椎间盘对咬合变化的反应值得进一步探讨。
    BACKGROUND: Aberrant occlusion and aging are two main risks for temporomandibular joint (TMJ) degeneration.
    OBJECTIVE: To assess the combined impact of occlusion and age on TMJ disc.
    METHODS: To avoid the confounding impact of gender, presently, 126 female C57BL/6J mice, 63 youngsters, 6-week old and 63 adults, 28-week old, were used. An experimental bilateral anterior crossbite (BAC) relation was created by installing metal tubes onto the mandibular incisors. Mice were sacrificed at 3, 7 and 11 weeks (n = 9). Additionally, the installed tubes were removed at 7 weeks in removal groups and the TMJs were sampled after another 4 weeks (n = 9). Disc changes were detected by histomorphology, immunohistochemistry, and western blot assays.
    RESULTS: Disc deformation was obvious in BAC groups. The typical change was hyperplasia at the posterior region of the disc where there was significant infiltration of inflammatory cells. Expressions of the inflammatory markers, including tumour necrosis factor-α and interleukin-1β, and the catabolic markers, including fibronectin (FN), FN N-terminal fragments, and vascular endothelial growth factor-A, were all increased. The changes were more obvious in adults than in youngsters. Removal of BAC attenuated inflammatory and catabolic changes in the youngsters, but the inflammatory markers recovered little in the adults.
    CONCLUSIONS: TMJ disc responds to BAC by degeneration and inflammation, and respond to BAC removal by rehabilitation. Adult discs show severer degeneration responses to BAC and a lower level of anti-inflammatory capability to BAC removal than the youngster\'s discs. Animals cannot be equated with humans. The human disc response to occlusion changes worth further exploration.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:女性脉络膜血症携带者存在一系列疾病严重程度。不像男人,疾病进展的速度在携带者中没有得到很好的表征。这项纵向研究旨在确定脉络膜血症携带者的视网膜变性率,使用多模态成像和显微视野。
    方法:以前在2012年至2017年在牛津眼科医院(英国)就诊的脉络病携带者在2015年至2023年期间返回进行测试,提供了长达11年的随访数据。参与者进行了光学相干断层扫描,进行眼底追踪显微视野和眼底自发荧光(FAF)成像。
    结果:使用多模态成像检查了17个脉络膜携带者的34只眼。基线时中位年龄为44(范围:15-73)岁,中位随访时间为7(范围:1-11)年。在基线,表型分类为细(n=5眼),粗糙(n=13眼),地理(n=12眼)或男性模式(n=4眼)。13例患者表型分类无变化,4例显示与脉络膜血症相关的视网膜变性相关的轻微变化。尽管如此,患有严重视网膜表型的携带者的平均视网膜敏感性在统计学上有显着下降(每年-0.7dB和-0.8dB,分别,p<0.001),由FAF定义的地理损失面积(每年+2.5mm2和+3.7mm2,分别,p<0.001)和感光复合物的变薄(每年高达-2.8微米和-10.3微米,p<0.001)。
    结论:脉络病携带者,特别是那些有严重视网膜表型的人,表现出进行性视网膜变性,多模态成像生物标志物和功能测试证明了这一点。临床医生不应仅依靠视网膜严重程度分类来评估疾病进展。
    OBJECTIVE: Female choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to determine the rate of retinal degeneration in choroideremia carriers, using multimodal imaging and microperimetry.
    METHODS: Choroideremia carriers previously seen at Oxford Eye Hospital (United Kingdom) between 2012 and 2017 returned for testing between 2015 and 2023, providing up to 11 years\' follow-up data. Participants had optical coherence tomography, fundus-tracked microperimetry and fundus autofluorescence (FAF) imaging performed.
    RESULTS: Thirty-four eyes of 17 choroideremia carriers were examined using multimodal imaging. Median age was 44 (range: 15-73) years at baseline and median follow-up duration was 7 (range: 1-11) years. At baseline, phenotype was classified as fine (n=5 eyes), coarse (n=13 eyes), geographic (n=12 eyes) or male pattern (n=4 eyes). Thirteen patients showed no change in phenotype classification, four showed slight changes associated with choroideremia-related retinal degeneration. Despite this, carriers with severe retinal phenotypes had a statistically significant decline in average retinal sensitivity (-0.7 dB and -0.8 dB per year, respectively, p<0.001), area of geographic loss defined by FAF (+2.5 mm2 and +3.7 mm2 per year, respectively, p<0.001) and thinning of the photoreceptor complex (up to -2.8 microns and -10.3 microns per year, p<0.001).
    CONCLUSIONS: Choroideremia carriers, particularly those with severe retinal phenotypes, exhibit progressive retinal degeneration, as evident by multimodal imaging biomarkers and functional testing. Clinicians should not rely on retinal severity classification alone to assess disease progression.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    椎间盘(IVD)变性引起的慢性腰痛,也称为慢性椎间盘源性下腰痛(CD-LBP),是最常见的肌肉骨骼疾病之一。IVD中的退化过程,如炎症和细胞外基质分解,导致神经营养蛋白释放。局部升高的神经营养蛋白水平将刺激感觉神经元的发芽和神经支配。此外,直接连接到相邻背根神经节的发芽的感觉神经已显示出增加小胶质细胞激活,有助于疼痛的维持和慢性化。目前的疼痛治疗已经表明对于长期使用是不足的或不充分的。此外,大多数针对椎间盘退变潜在发病机制的治疗方法侧重于修复和再生,而忽略了慢性疼痛。生物分子疗法如何影响退行性IVD环境,疼痛信号级联,感觉神经元的神经支配和兴奋性通常仍不清楚。这篇综述讨论了CD-LBP慢性疼痛治疗相对不足的领域,并总结了针对CD-LBP的治疗效果,特别强调慢性疼痛。已经显示基于阻断促炎介质或神经营养蛋白活性的方法阻碍神经元向内生长到椎间盘中。此外,细胞外基质成分或移植的间充质干细胞的组织再生和神经抑制特性是潜在的有趣的生物分子方法,不仅可以阻断IVD变性,还可以阻止疼痛敏化。目前,大多数生物分子疗法基于急性IVD变性模型,因此不能反映CD-LBP患者的真实临床慢性疼痛情况.未来的研究应旨在研究治疗性干预措施在包含已建立的感觉神经向内生长的慢性退化椎间盘中的作用。深入了解生物分子疗法对CD-LBP疼痛(慢性化)途径和疼痛缓解的影响,有助于缩小新型CD-LBP疗法的临床前工作台和临床床边之间的差距,并优化疼痛治疗。
    Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:研究USH2A视网膜病变中椭球区(EZ)宽度的长期自然史。
    方法:光学相干断层扫描的EZ宽度测量来自55例分子证实为双等位基因USH2A视网膜病变的参与者的110只眼。我们使用分层贝叶斯方法来构建和比较描述EZ宽度长期下降的不同数学模型。
    结果:与线性和二次模型相比,指数下降最好地代表了基于偏差信息准则得分的EZ宽度的长期损失。对数变换的EZ宽度在30年的推断疾病持续时间内线性下降(中位数:0.063(IQR:0.040-0.086)log(µm)/年)。与原始EZ宽度下降率相比,对数变换的EZ宽度下降率需要减少48%的患者才能实现相同功效的1年试验(38对73名参与者).LogEZ宽度下降率与基线EZ宽度(Spearmanρ=-0.18,p=0.06)和年龄(ρ=-0.10,p=0.31)脱钩。患有Usher综合征的眼睛表现出黄斑EZ宽度丢失的中位发病年龄较早(18.8(IQR:13.1-24.7)vs28.1(IQR:18.5-35.8),p<0.001),但具有可比性的logEZ宽度下降率(0.060(IQR:0.035-0.100)vs0.065(IQR:0.050-0.079)log(µm)/年;p=0.42)。
    结论:EZ宽度跟随USH2A视网膜病变的指数下降。与原始EZ宽度下降率相比,对数变换的EZ宽度下降率可能是临床试验的最佳终点。综合征眼表现出黄斑EZ宽度损失的较早发作,但进展速度与非综合征眼相当。
    OBJECTIVE: To investigate the long-term natural history of ellipsoid zone (EZ) width in USH2A-retinopathy.
    METHODS: EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic USH2A-retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width.
    RESULTS: Compared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040-0.086) log (µm)/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman ρ=-0.18, p=0.06) and age (ρ=-0.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1-24.7) vs 28.1 (IQR: 18.5-35.8) years, p<0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035-0.100) vs 0.065 (IQR: 0.050-0.079) log (µm)/year; p=0.42).
    CONCLUSIONS: EZ width follows an exponential decline in USH2A-retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    蚕是一种非常有价值的昆虫,通过它的丝腺产生丝绸。在这个器官中,由于其能够降解丝心蛋白,因此已鉴定并命名了丝素酶。丝腺中丝素酶的表达在幼虫-p期显着增加,这可能与丝腺的退化有关。在这项研究中,纤维蛋白酶在中部和后部的丝腺中都被过表达并被特别地击倒。分别,使用转基因技术。对这些转基因蚕的丝腺发育的研究表明,纤维蛋白酶在加速丝腺变性中起直接作用。在转基因蚕的丝腺中进行的染色分析表明,纤维蛋白酶参与了丝腺变性过程中的自噬和凋亡过程。进一步的实验表明,纤维蛋白酶,作为溶酶体调节剂,通过mTOR(雷帕霉素的机制靶标)途径负调节自噬。此外,在细胞凋亡期间,纤维蛋白酶可以通过增加BmCaspase1的活性来激活Caspase3,最终加速细胞凋亡过程。这些发现增强了我们对纤维蛋白酶在促进丝腺变性中的生理作用的理解,丝腺中的蛋白质分解,协调自噬和凋亡的调节。
    The silkworm is an incredibly valuable insect that produces silk through its silk gland. Within this organ, Fibroinase has been identified and named due to its ability to fibroin degradation. The expression of Fibroinase in the silk gland significantly increases during the larval-pupal stage, which might be associated with the degeneration of the silk gland. In this study, Fibroinase was overexpressed and knocked down specifically both in the middle and posterior silk glands, respectively, using transgenic technology. The investigation of silk gland development in these transgenic silkworms showed that Fibroinase plays a direct role in accelerating silk gland degeneration. The staining analyses performed in the silk glands of transgenic silkworms suggest that Fibroinase is involved in the processes of autophagy and apoptosis during silk gland degeneration. Further experiments demonstrated that Fibroinase, acting as a lysosomal regulator, negatively regulates autophagy via the mTOR (mechanistic target of rapamycin) pathway. Moreover, during apoptosis, Fibroinase could activate Caspase3 by increasing the activity of BmCaspase1, ultimately accelerating the apoptosis process. These findings enhance our understanding of the physiological role of Fibroinase in promoting silk gland degeneration, which plays a role in breaking down proteins in the silk gland and coordinating the regulation of autophagy and apoptosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    脊髓挫伤导致脊髓轴突束的Wallerian变性,这是运动功能所必需的。挫伤部位轴突肿胀和轴突密度损失,瓦勒变性的特征,在受伤后几小时内开始。Tempol,超氧化物歧化酶模拟物,先前在脊髓挫伤的实验模型中显示出减少脊髓白质的损失并改善运动功能,提示tempol治疗可能抑制脊髓轴突的Wallerian变性。这里,我们报道tempol部分抑制Wallerian变性,从而改善运动恢复。我们以前报道过,醛糖还原酶(AR)抑制剂可以减少Wallerian变性,在多元醇途径中将葡萄糖转化为山梨糖醇。我们观察到tempol抑制受损脊髓中的山梨糖醇产生的程度与AR抑制剂相同,Sorbinil.Tempol还阻止了挫伤后变性轴突内AR(AKR1B10)蛋白表达的上调,如先前观察到的AR抑制剂。此外,我们假设tempol通过防止由于多元醇途径活性导致的谷胱甘肽库的损失来抑制轴突变性。与我们的假设一致,tempol治疗导致受损脊髓中谷胱甘肽含量增加,这与γ-谷氨酰半胱氨酸连接酶(γGCL;EC6.3.2.2)的表达和活性增加有关,谷胱甘肽合成的限速酶。施用γGCL抑制剂丁硫氨酸亚砜胺消除了tempol施用的所有观察到的效果。一起,这些结果支持谷胱甘肽耗竭中多元醇途径活化的病理作用,导致脊髓损伤后的Wallerian变性。有趣的是,甲基强的松龙,oxandrolone,还有瘦肉精,已知在脊髓损伤后备用轴突束,在抑制多元醇途径激活方面同样有效。这些结果表明,预防AR激活是许多不同的SCI后干预措施的共同目标。
    Spinal cord contusion injury results in Wallerian degeneration of spinal cord axonal tracts, which are necessary for locomotor function. Axonal swelling and loss of axonal density at the contusion site, characteristic of Wallerian degeneration, commence within hours of injury. Tempol, a superoxide dismutase mimetic, was previously shown to reduce the loss of spinal cord white matter and improve locomotor function in an experimental model of spinal cord contusion, suggesting that tempol treatment might inhibit Wallerian degeneration of spinal cord axons. Here, we report that tempol partially inhibits Wallerian degeneration, resulting in improved locomotor recovery. We previously reported that Wallerian degeneration is reduced by inhibitors of aldose reductase (AR), which converts glucose to sorbitol in the polyol pathway. We observed that tempol inhibited sorbitol production in the injured spinal cord to the same extent as the AR inhibitor, sorbinil. Tempol also prevented post-contusion upregulation of AR (AKR1B10) protein expression within degenerating axons, as previously observed for AR inhibitors. Additionally, we hypothesized that tempol inhibits axonal degeneration by preventing loss of the glutathione pool due to polyol pathway activity. Consistent with our hypothesis, tempol treatment resulted in greater glutathione content in the injured spinal cord, which was correlated with increased expression and activity of γ-glutamylcysteine ligase (γGCL; EC 6.3.2.2), the rate-limiting enzyme for glutathione synthesis. Administration of the γGCL inhibitor buthionine sulfoximine abolished all observed effects of tempol administration. Together, these results support a pathological role for polyol pathway activation in glutathione depletion, resulting in Wallerian degeneration after spinal cord injury. Interestingly, methylprednisolone, oxandrolone, and clenbuterol, which are known to spare axonal tracts after spinal cord injury, were equally effective in inhibiting polyol pathway activation. These results suggest that prevention of AR activation is a common target of many disparate post-SCI interventions.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    这项研究调查了雄性和雌性小鼠后爪和背根神经节(DRG)中紫杉醇(PTX)引起的持续性疼痛性神经病进展过程中基因表达变化的时间过程。在最后一个PTX后1、16和31天,使用BulkRNA-seq检查这些基因表达变化。在这些时间点,差异表达基因(DEGs)主要与上皮的减少或增加有关,皮肤,骨头,肌肉发育和血管生成,髓鞘形成,轴突发生,和神经发生。这些过程伴随着与细胞骨架相关的DEGs的调节,细胞外基质组织,和细胞能量生产。在持续性疼痛性神经病的进展过程中,这种基因可塑性可以解释为与组织再生/变性有关的生物学过程。相比之下,与免疫过程相关的基因可塑性在PTX后1-31天最小。还指出,尽管男性和女性在生物学过程和疼痛慢性方面有相似之处,具体的DEGs根据性别有很大差异。本研究的主要结论是,PTX神经病变进展过程中后爪和DRG的基因表达可塑性与组织再生和变性相似,对免疫系统过程的影响最小,并且在个体基因水平上严重依赖性别。
    This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis. These processes are accompanied by the regulation of DEGs related to the cytoskeleton, extracellular matrix organization, and cellular energy production. This gene plasticity during the progression of persistent painful neuropathy could be interpreted as a biological process linked to tissue regeneration/degeneration. In contrast, gene plasticity related to immune processes was minimal at 1-31 days after PTX. It was also noted that despite similarities in biological processes and pain chronicity between males and females, specific DEGs differed dramatically according to sex. The main conclusions of this study are that gene expression plasticity in hindpaw and DRG during PTX neuropathy progression similar to tissue regeneration and degeneration, minimally affects immune system processes and is heavily sex-dependent at the individual gene level.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号