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Nuclear Medicine Imaging Techniques in Glioblastomas 胶质母细胞瘤的核医学成像技术。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04233-6
Emirhan Harbi, Michael Aschner

Glioblastomas are the most common primary malignant grade 4 tumors of the central nervous system (CNS). The treatment and management of such tumors requires a multidisciplinary approach and nuclear medicine techniques play an important role in this process. Glioblastoma, which recurs despite current treatments and becomes resistant to treatments, is among the tumors with the lowest survival rate, with a survival rate of approximately 8 months. Currently, the standard treatment of glioblastoma is adjuvant chemoradiotherapy after surgical resection. There have been many recent advances in the field of Nuclear Medicine in glioblastoma. PET scans are critical in determining tumor localization, pre-surgical planning, evaluation of post-treatment response and detection of recurrence. Advances in the treatment of glioblastoma and a better understanding of the biological characteristics of the disease have contributed to the development of nuclear medicine techniques. This review, in addition to other studies, is intended as a general imaging summary guide and includes some new expressions discovered in glioblastoma. This review discusses recent advances in nuclear medicine in glioblastoma.

胶质母细胞瘤是中枢神经系统(CNS)最常见的原发性四级恶性肿瘤。此类肿瘤的治疗和管理需要采用多学科方法,而核医学技术在这一过程中发挥着重要作用。胶质母细胞瘤在目前的治疗方法下仍会复发,并对治疗产生耐药性,是存活率最低的肿瘤之一,存活期约为 8 个月。目前,胶质母细胞瘤的标准治疗方法是手术定位后的辅助化放疗。最近,核医学在胶质母细胞瘤领域取得了许多进展。正电子发射计算机断层扫描对于确定肿瘤定位、手术前计划、评估治疗后反应和检测复发至关重要。胶质母细胞瘤治疗的进步以及对该疾病生物学特性的深入了解促进了核医学技术的发展。除其他研究外,本综述旨在作为一般成像总结指南,并包括一些在胶质母细胞瘤中发现的新表达。本综述讨论了胶质母细胞瘤核医学的最新进展。
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引用次数: 0
The Involvement of the Ventral Tegmental Area in the Electroacupuncture Alleviation of Anxiety-Like Behaviors Induced by Chronic Restraint Stress in Mice 电针缓解小鼠慢性束缚应激诱发的焦虑样行为与腹侧被盖区的关系
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-27 DOI: 10.1007/s11064-024-04229-2
Hua-Min Zhang, Jiang-Fan Li, Jing-Wei Zhao, Jing Shao

Emotional stress is a significant environmental risk factor for various mental health disabilities, such as anxiety. Electroacupuncture (EA) has been demonstrated to have pronounced anxiolytic effects. However, the neural mechanisms underlying these effects and their contribution to behavioral deficits remain poorly understood. Here, we addressed these issues using a classical mouse anxiety model induced by chronic restraint stress (CRS).Anxiety-like behaviors were evaluated with the open field test and elevated plus maze. Neuronal activation in various brain regions was marked using c-Fos, followed by calculations of interregional correlation to characterize a network that became functionally active following EA at the HT7 acupoint (EA-HT7). We selected the hub regions and further investigated their functions and connections in regulating anxiety-like behaviors by using a combination of chemogenetic manipulations and behavioral testing. CRS exposure induced anxiety-like behaviors. Interestingly, EA-HT7 mitigated these behavioral abnormalities. The c-Fos expression in 30 brain areas revealed a vital brain network for acupuncture responsiveness in naïve mice. Neural activity in the NAcSh (nucleus accumbens shell), BNST (bed nucleus of the stria terminalis), VMH (Ventromedial Hypothalamus), ARC (arcuate nucleus), dDG (dorsal dentate gyrus), and VTA (ventral tegmental area) was significantly altered following acupuncture. Notably, both c-Fos immunostaining and brain functional connectivity analysis revealed the significant activation of VTA following EA-HT7. Interestingly, blocking the VTA eliminated the anxiolytic effects of EA-HT7, whereas chemogenetic activation of the VTA replicated the therapeutic effects of EA-HT7. EA-HT7 has demonstrated benefits in treating anxiety and enhances brain functional connectivity. The VTA is functionally associated with the anxiolytic effects of EA-HT7.

情绪压力是导致焦虑等各种精神疾病的重要环境风险因素。电针(EA)已被证明具有明显的抗焦虑作用。然而,人们对这些效应的神经机制及其对行为缺陷的影响仍知之甚少。在此,我们使用慢性束缚应激(CRS)诱导的经典小鼠焦虑模型来解决这些问题。我们使用 c-Fos 标记了不同脑区的神经元激活情况,然后计算了区域间相关性,从而确定了 HT7 穴位 EA(EA-HT7)后功能活跃网络的特征。我们选取了这些枢纽区域,并通过化学遗传操作和行为测试相结合的方法进一步研究了它们在调节焦虑样行为中的功能和连接。CRS暴露会诱发焦虑样行为。有趣的是,EA-HT7 可减轻这些行为异常。30个脑区的c-Fos表达揭示了针灸反应的重要脑网络。针刺后,NAcSh(伏隔核)、BNST(纹状体末端床核)、VMH(内下丘脑)、ARC(弓状核)、dDG(齿状回背侧)和VTA(被盖区腹侧)的神经活动发生了显著变化。值得注意的是,c-Fos免疫染色和大脑功能连接分析均显示,针刺EA-HT7后VTA被显著激活。有趣的是,阻断VTA消除了EA-HT7的抗焦虑作用,而化学激活VTA复制了EA-HT7的治疗效果。EA-HT7在治疗焦虑症和增强大脑功能连接方面具有明显的疗效。VTA在功能上与EA-HT7的抗焦虑作用有关。
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引用次数: 0
The Interplay of Carveol and All-Trans Retinoic Acid (ATRA) in Experimental Parkinson’s Disease: Role of Inflammasome-Mediated Pyroptosis and Nrf2 卡维醇和全反式维甲酸(ATRA)在实验性帕金森病中的相互作用:炎症体介导的脓毒症和 Nrf2 的作用。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-27 DOI: 10.1007/s11064-024-04226-5
Asmaa Jan Muhammad, Faisal F Al-baqami, Fawaz E. Alanazi, Abdullah Alattar, Reem Alshaman, Najeeb Ur Rehman, Yassine Riadi, Fawad Ali Shah

Parkinson’s disease (PD) is a debilitating and the second most common neurodegenerative disorder with a high prevalence. PD has a multifaceted etiology characterized by an altered redox state and an excessive inflammatory response. Extensive research has consistently demonstrated the role of the nuclear factor E2-related factor (Nrf2) and inflammasomes, notably NLRP3 in neurodegenerative diseases. In this study, our focus was on exploring the potential neuroprotective properties of carveol in Parkinson’s disease. Our findings suggest that carveol may exhibit these effects through Nrf2 and by suppressing pyroptosis. Male albino mice were treated with carveol, and the animal PD model was induced through a single intranigral dose of 2 µg/2µl lipopolysaccharide (LPS). To further demonstrate the essential role of the Nrf2 pathway, we utilized all-trans retinoic acid (ATRA) to inhibit the Nrf2. Our finding showed the induction of pyroptosis as evidenced by increased levels of NLRP3 and other inflammatory mediators, including IL-1β, iNOS, p-NFKB, and apoptotic cell death indicated by positive fluoro Jade B (FJB) staining. Moreover, increased levels of lipid peroxides and reactive oxygen species indicated a significant rise in oxidative stress due to LPS. The administration of carveol mitigates oxidative stress and suppresses inflammatory pathways through the augmentation of intrinsic antioxidant defenses, primarily via the activation of the Nrf2. Conversely, ATRA reversed carveol protective effects by increasing FJB-positive cells, inflammatory and oxidative biomarkers. Taken together, our findings suggest that carveol mitigated LPS-induced Parkinson-like symptoms, partially through the activation of the Nrf2 and downregulation of pyroptosis notably NLRP3.

帕金森病(Parkinson's disease,PD)是一种使人衰弱的疾病,也是第二大最常见的神经退行性疾病,发病率很高。帕金森病的病因是多方面的,以氧化还原状态改变和过度炎症反应为特征。大量研究不断证明,核因子 E2 相关因子(Nrf2)和炎性体(尤其是 NLRP3)在神经退行性疾病中的作用。在这项研究中,我们的重点是探索香芹醇在帕金森病中的潜在神经保护特性。我们的研究结果表明,香芹酚可能是通过 Nrf2 和抑制化脓作用来发挥这些作用的。用卡维醇治疗雄性白化小鼠,并通过单次鞘内注射 2 µg/2µl 脂多糖(LPS)诱导动物帕金森病模型。为了进一步证明Nrf2通路的重要作用,我们利用全反式维甲酸(ATRA)来抑制Nrf2。我们的研究结果表明,NLRP3和其他炎症介质(包括IL-1β、iNOS、p-NFKB)水平的升高,以及氟玉B(FJB)阳性染色所显示的细胞凋亡,都诱导了脓毒症。此外,脂质过氧化物和活性氧水平的增加表明 LPS 导致氧化应激显著增加。施用卡维醇可缓解氧化应激,并通过增强内在抗氧化防御能力(主要是通过激活 Nrf2)抑制炎症途径。相反,ATRA 通过增加 FJB 阳性细胞、炎症和氧化生物标志物逆转了卡维醇的保护作用。综上所述,我们的研究结果表明,卡维醇减轻了 LPS 诱导的帕金森样症状,部分原因是通过激活 Nrf2 和显著下调 NLRP3 来实现的。
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引用次数: 0
Retraction Note: Neuroprotective Effect of Hesperidin on Aluminium Chloride Induced Alzheimer’s Disease in Wistar Rats 撤稿说明:橙皮甙对氯化铝诱导的 Wistar 大鼠阿尔茨海默病的神经保护作用。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-23 DOI: 10.1007/s11064-024-04232-7
Arokiasamy Justin Thenmozhi, Tharsius Raja William Raja, Udaiyappan Janakiraman, Thamilarasan Manivasagam
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引用次数: 0
Age- and Sex-Associated Wnt Signaling Dysregulation is Exacerbated from the Early Stages of Neuropathology in an Alzheimer’s Disease Model 阿尔茨海默病模型中与年龄和性别相关的 Wnt 信号传导失调会在神经病理学的早期阶段加剧
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-21 DOI: 10.1007/s11064-024-04224-7
Elizabeth Colín-Martínez, César Espino-de-la-Fuente, Clorinda Arias

Emerging studies suggest that Wnt signaling is dysregulated in the brains of AD patients, suggesting that this pathway may also contribute to disease progression. However, it remains to be determined whether alterations in the Wnt pathway are the cause or consequence of this disease and which elements of Wnt signaling mainly contribute to the appearance of AD histopathological markers early in disease compared to what occurs during normal aging. The present study aimed to describe the status of several canonical Wnt pathway components and the expression of the AD marker p-tau in the hippocampi of female and male 3xTg-AD mice during disease progression compared to those during normal aging. We analyzed the levels of the canonical Wnt components Wnt7a, Dkk-1, LRP6 and GSK3β as well as the levels of p-tau and BDNF at 3, 6, 9–12 and 18 months of age. We found a gradual increase in Dkk-1 levels during aging prior to Wnt7a and LRP5/6 depletion, which was strongly exacerbated in 3xTg-AD mice even at young ages and correlated with GSK3β activation and p-tau-S202/Thr205 expression. Dkk-1 upregulation, as well as the level of p-tau, was significantly greater in females than in males. Our results suggest that Dkk-1 upregulation is involved in the expression of several features of AD at early stages, which supports the possibility of positively modulating the canonical Wnt pathway as a therapeutic tool to delay this disease at early stages.

新近的研究表明,AD 患者大脑中的 Wnt 信号传导失调,这表明这一通路也可能导致疾病进展。然而,Wnt通路的改变是这种疾病的原因还是结果,以及与正常衰老过程相比,Wnt信号转导的哪些因素主要导致了疾病早期AD组织病理学标志物的出现,这些问题仍有待确定。本研究旨在描述雌性和雄性3xTg-AD小鼠海马中几种典型Wnt通路成分的状态以及AD标志物p-tau的表达。我们分析了小鼠3、6、9-12和18个月大时典型Wnt组分Wnt7a、Dkk-1、LRP6和GSK3β的水平以及p-tau和BDNF的水平。我们发现,在Wnt7a和LRP5/6耗竭之前,Dkk-1水平在衰老过程中逐渐升高,而在3xTg-AD小鼠中,这种升高即使在幼年也会强烈加剧,并与GSK3β激活和p-tau-S202/Thr205表达相关。雌性小鼠的 Dkk-1 上调和 p-tau 水平明显高于雄性小鼠。我们的研究结果表明,Dkk-1的上调参与了早期AD几种特征的表达,这支持了积极调节典型Wnt通路作为一种治疗工具在早期阶段延缓这种疾病的可能性。
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引用次数: 0
Pre-electroacupuncture Ameliorates Cerebral Ischemia-reperfusion Injury by Inhibiting Microglial RhoA/pyrin/GSDMD Signaling Pathway 针刺前通过抑制小胶质细胞RhoA/pyrin/GSDMD信号通路改善脑缺血再灌注损伤
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-21 DOI: 10.1007/s11064-024-04228-3
Hao Fang, Ling-Ling Fan, Ye-Ling Ding, Dan Wu, Jia-Yi Zheng, Ye-Feng Cai, Yan Huang, Li-Jun Qiao, Shi-Jie Zhang, Jie Zhan

Cerebral ischemia reperfusion injury is a severe neurological impairment that occurs after blood flow reconstruction in stroke, and microglia cell pyroptosis is one of its important mechanisms. Electroacupuncture has been shown to be effective in mitigating and alleviating cerebral ischemia reperfusion injury by inhibiting neuroinflammation, reducing cellular pyroptosis, and improving neurological function. In this experiment, we divided the rats into three groups, including the sham operation (Sham) group, the middle cerebral artery occlusion/reperfusion (MCAO/R) group, and the pre-electroacupuncture (EAC) group. Pre-electroacupuncture group was stimulated with electroacupuncture of a certain intensity on the Baihui (GV 20) and Dazhui (GV 14) of the rat once a day from the 7th day to the 1st day before the MCAO/R operation. The extent of cerebral infarction was detected by TTC staining. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. The number of neurons and morphological changes were accessed by Nissl staining and HE staining. The cellular damage was detected by TUNEL staining. In addition, the expression levels of RhoA, pyrin, GSDMD, Caspase1, cleaved-Caspase1, Iba-1, CD206, and ROCK2 were examined by western blotting and immunofluorescence. The results found that pre-electroacupuncture significantly attenuated neurological impairment and cerebral infarction compared to the post-MCAO/R rats. In addition, pre-electroacupuncture therapy promoted polarization of microglia to the neuroprotective (M2) phenotype. In addition, pre-electroacupuncture inhibited microglia pyroptosis by inhibiting RhoA/pyrin/GSDMD signaling pathway, thereby reducing neuronal injury and increasing neuronal survival in the MCAO/R rats. Taken together, these results demonstrated that pre-acupuncture could attenuate cerebral ischemia-reperfusion injury by inhibiting microglial pyroptosis. Therefore, pre-electroacupuncture might be a potential preventive strategy for ischemic stroke patients.

脑缺血再灌注损伤是脑卒中血流重建后出现的严重神经功能损害,而小胶质细胞嗜热是其重要机制之一。电针通过抑制神经炎症、减少细胞凋亡、改善神经功能,可有效减轻和缓解脑缺血再灌注损伤。本实验将大鼠分为三组,包括假手术组(Sham)、大脑中动脉闭塞再灌注组(MCAO/R)和电针前组(EAC)。电针前组在MCAO/R手术前第7天至第1天,每天一次对大鼠的百会(GV 20)和大椎(GV 14)进行一定强度的电针刺激。通过 TTC 染色检测脑梗死的程度。采用改良的Zea-Longa五点评分法测定MCAO大鼠的神经功能。通过 Nissl 染色和 HE 染色检测神经元数量和形态学变化。细胞损伤通过 TUNEL 染色检测。此外,还通过 Western 印迹和免疫荧光检测了 RhoA、pyrin、GSDMD、Caspase1、cleaved-Caspase1、Iba-1、CD206 和 ROCK2 的表达水平。结果发现,与MCAO/R后大鼠相比,电针前大鼠的神经功能损伤和脑梗死程度明显减轻。此外,预针刺疗法还能促进小胶质细胞向神经保护(M2)表型极化。此外,预针刺疗法通过抑制 RhoA/pyrin/GSDMD 信号通路,抑制了小胶质细胞的脓毒症,从而减轻了 MCAO/R 大鼠神经元损伤,提高了神经元存活率。综上所述,这些结果表明,针刺前可以通过抑制小胶质细胞凋亡减轻脑缺血再灌注损伤。因此,预针灸可能是缺血性中风患者的一种潜在预防策略。
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引用次数: 0
Therapeutic Options of Crystallin Mu and Protein Disulfide Isomerase A3 for Cuprizone-Induced Demyelination in Mouse Hippocampus 晶体蛋白 Mu 和蛋白二硫异构酶 A3 对铜绿素诱导的小鼠海马脱髓鞘的治疗方案
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-20 DOI: 10.1007/s11064-024-04227-4
Kyu Ri Hahn, Hyun Jung Kwon, Dae Won Kim, In Koo Hwang, Yeo Sung Yoon

This study investigates the changes in hippocampal proteomic profiles during demyelination and remyelination using the cuprizone model. Employing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry for protein profiling, we observed significant alterations in the expression of ketimine reductase mu-crystallin (CRYM) and protein disulfide isomerase A3 precursor (PDIA3) following exposure to and subsequent withdrawal from cuprizone. Immunohistochemical staining validated these protein expression patterns in the hippocampus, revealing that both PDIA3 and CRYM were downregulated in the hippocampal CA1 region during demyelination and upregulated during remyelination. Additionally, we explored the potential protective effects of CRYM and PDIA3 against cuprizone-induced demyelination by synthesizing cell-permeable Tat peptide-fusion proteins (Tat-CRYM and Tat-PDIA3) to facilitate their crossing through the blood–brain barrier. Our results indicated that administering Tat-CRYM and Tat-PDIA3 mitigated the reduction in proliferating cell and differentiated neuroblast counts compared to the group receiving cuprizone alone. Notably, Tat-PDIA3 demonstrated significant effects in enhancing myelin basic protein expression alongside phosphorylation of CREB in the hippocampus, suggesting its potential therapeutic role in the prevention or treatment of demyelination, and by extension, in conditions such as multiple sclerosis.

本研究利用铜绿素模型研究了脱髓鞘和再髓鞘化过程中海马蛋白质组的变化。利用二维凝胶电泳和液相色谱-串联质谱进行蛋白质谱分析,我们观察到在接触并随后停用铜松后,酮还原酶μ结晶素(CRYM)和蛋白二硫异构酶A3前体(PDIA3)的表达发生了显著变化。免疫组化染色验证了这些蛋白在海马中的表达模式,发现在脱髓鞘过程中,PDIA3和CRYM在海马CA1区下调,而在再髓鞘化过程中上调。此外,我们还通过合成细胞渗透性 Tat 肽融合蛋白(Tat-CRYM 和 Tat-PDIA3)来促进它们通过血脑屏障,从而探索 CRYM 和 PDIA3 对铜绿素诱导的脱髓鞘的潜在保护作用。我们的研究结果表明,与单用铜绿素组相比,服用 Tat-CRYM 和 Tat-PDIA3 可减轻增殖细胞和分化神经母细胞数量的减少。值得注意的是,Tat-PDIA3在增强海马中髓鞘碱性蛋白表达和CREB磷酸化方面具有显著效果,这表明它在预防或治疗脱髓鞘以及多发性硬化症等疾病方面具有潜在的治疗作用。
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引用次数: 0
Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism 自闭症临床前模型纹状体星形胶质细胞的自发钙瞬态记录
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-09 DOI: 10.1007/s11064-024-04218-5
Hugo Saavedra-Bonilla, Durairaj Ragu Varman, Daniel Reyes-Haro

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

众所周知,自闭症谱系障碍(ASD)是一组神经发育疾病,除了社交和感知运动障碍外,还包括刻板和重复行为。解剖学和功能学证据表明,纹状体的成熟不典型。星形胶质细胞调节突触回路的成熟和可塑性,而钙信号受损与重复行为和非典型社会交往有关。通过产前暴露于丙戊酸(VPA),在ASD临床前模型中对大鼠纹状体星形胶质细胞中记录的自发钙瞬态(SCT)进行了研究。我们的研究结果表明,在 VPA 模型中,感觉运动延迟、神经胶质纤维酸性蛋白(一种典型的星形胶质细胞表达的中间丝蛋白)增加、GABAA-ρ3 表达减少、SCT 频率增加且潜伏期缩短,从而导致振幅减小。惊厥剂picrotoxin是一种GABAA(γ-氨基丁酸A型)受体拮抗剂,它能降低两个实验组的SCT频率,但在临床前ASD模型中却能将这一参数恢复到控制水平。在两个实验组中,微毒素都降低了SCT的振幅和潜伏期。GABA摄取抑制剂尼泊金酸只降低了对照组的平均振幅。然而,尼泊金酸盐增加了两个实验组的频率,但减少了潜伏期。因此,我们得出结论,纹状体星形胶质细胞表现出受 GABAA 介导的信号调节的 SCT,而出生前暴露于 VPA 会干扰这种调节。
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引用次数: 0
Circ_0001361/miR-490-5p/IGF2 Axis Regulates the Viability and Apoptosis of Neuroblastoma Cells Circ_0001361/miR-490-5p/IGF2轴调控神经母细胞瘤细胞的活力和凋亡
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-07 DOI: 10.1007/s11064-024-04225-6
Jian Bian, Hao Ding, Anla Hu, Jian Wang

Background: Circular RNAs (circRNAs) are involved in the neuroblastoma (NB) development. Objectie: The study aimed to determine the biological behaviors of circ_0001361 and explore its underlying mechanism in NB. Methods: The circ_0001361, miR-490-5p, and IGF2 levels were measured using quantitative real-time polymerase chain reaction. Cellular processes were analyzed using MTT assay or fluorescence-activated cell sorting (FACS). Phosphorylated (p)-PI3K, p-AKT, Bax, and caspase-3 were tested by western blot. Dual-luciferase reporter analysis together with RNA pull-down analysis were utilized to evaluate the correlation of miR-490-5p and circ_0001361 or IGF2. Results: The results in this study illustrated that an elevation of circ_0001361 levels was observed in NB. Depletion of circ_0001361 suppressed the viability but facilitated apoptosis of NB cells. Circ_0001361 sponged miR-490-5p, which targeted to regulate IGF2. Inhibition of miR-490-5p rescued the effect induced by circ_0001361 knockdown, while deletion of IGF2 rescued the effect induced by the miR-490-5p inhibitor. Conclusions: In summary, a loss of circ_0001361 inhibited NB progression via targeting the miR-490-5p/IGF2 axis, suggesting that circ_0001361 may be a novel therapeutical target of NB.

背景:环状 RNA(circRNA)参与了神经母细胞瘤(NB)的发育。目的本研究旨在确定circ_0001361的生物学行为并探索其在NB中的内在机制:方法:采用实时定量聚合酶链反应检测 circ_0001361、miR-490-5p 和 IGF2 的水平。采用 MTT 法或荧光激活细胞分选法(FACS)分析细胞过程。磷酸化(p)-PI3K、p-AKT、Bax和caspase-3通过Western印迹进行检测。利用双荧光素酶报告分析和 RNA 拉取分析来评估 miR-490-5p 与 circ_0001361 或 IGF2 的相关性:结果:研究结果表明,在NB中观察到了circ_0001361水平的升高。结果:该研究结果表明,在 NB 中观察到了 circ_0001361 水平的升高,消耗 circ_0001361 会抑制 NB 细胞的活力,但会促进其凋亡。circ_0001361能疏导miR-490-5p,而miR-490-5p是调控IGF2的靶标。抑制miR-490-5p可挽救circ_0001361敲除诱导的效应,而缺失IGF2可挽救miR-490-5p抑制剂诱导的效应:总之,circ_0001361的缺失通过靶向miR-490-5p/IGF2轴抑制了NB的进展,这表明circ_0001361可能是NB的一个新的治疗靶点。
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引用次数: 0
Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury 铁诱导脑损伤后去甲肾上腺素能合成和多巴胺β-羟化酶活性对氧化应激的响应变化
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-06 DOI: 10.1007/s11064-024-04222-9
Antonio Verduzco-Mendoza, Daniel Mota-Rojas, Adriana Olmos-Hernández, Alberto Avila-Luna, Karla García-García, Arturo Gálvez-Rosas, Alberto Hidalgo-Bravo, Camilo Ríos, Carmen Parra-Cid, Sergio Montes, Julieta García-López, Laura E. Ramos-Languren, Francisca Pérez-Severiano, Rigoberto González-Piña, Antonio Bueno-Nava

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

在大脑皮层损伤后的最初几小时和几天内,去甲肾上腺素(NA)水平会发生变化。NA调节运动功能的恢复。本研究探讨了铁诱导的大脑皮层损伤是否会调节大鼠大脑皮层、脑桥和小脑的去甲肾上腺素能合成和多巴胺 beta- 羟化酶(DBH)活性,以应对氧化应激。78 只大鼠分为两组:(a) 假组,皮质内注射载体溶液;(b) 损伤组,皮质内注射氯化亚铁。对受伤后 20 天的运动障碍进行评估。第 3 天和第 20 天,对大鼠实施安乐死,测量氧化应激指标(活性氧 (ROS)、还原型谷胱甘肽 (GSH) 和氧化型谷胱甘肽 (GSSG))、儿茶酚胺(NA、多巴胺 (DA))以及 DBH mRNA 和蛋白质水平。我们的研究结果表明,铁诱导的大脑皮层损伤会在损伤后 3 天增加大脑皮层、脑桥和小脑的去甲肾上腺素能合成和 DBH 活性,主要是在损伤的同侧,以应对氧化应激。观察到对侧去甲肾上腺素能活性代偿性增加,但小脑和脑桥的 DBH mRNA 和蛋白质水平没有变化。总之,铁诱导的大脑皮层损伤增加了大脑皮层、脑桥和小脑的去甲肾上腺素能反应,特别是在同侧,同时在对侧伴有代偿反应。抗氧化活性抵消了氧化应激,有利于运动障碍后的功能恢复。
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Neurochemical Research
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