scholarly journals Xiao-Yao-San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lina Liu ◽  
Fei Ge ◽  
Haoran Yang ◽  
Huilian Shi ◽  
Weiting Lu ◽  
...  
Keyword(s):  
Western Blot ◽  
Learning And Memory ◽  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
High Dose ◽  
Pi3k Signaling ◽  
Hippocampal Ca1 ◽  
Golgi Staining

Xiao-Yao-San (XYS) decoction is a traditional Chinese medicine formula. This study aimed to investigate the effect of XYS on cognitive abilities and its underlying mechanism in ovariectomized rats. Female Sprague-Dawley rats were ovariectomized and treated with XYS (3 g/kg or 9 g/kg) by gavage, with subcutaneous injection of 17-β estradiol (E2, 2 μg/kg) as a positive drug control and gavage of 1 ml saline (0.9%) as a placebo control. After 6 weeks of treatment, rats were examined using the Morris water maze test. The estradiol level in the serum and hippocampus was measured by ELISA. Golgi staining was performed to observe neuronal morphology in the hippocampus. Apoptosis of hippocampal cells was observed by TUNEL staining. The protein content of N-methyl-D-aspartate receptor (NMDAR) 2A and 2B in the hippocampal CA1 region was determined by Western blot and immunohistochemistry. Expression of estrogen receptor (ER) and PI3K signaling was detected by Western blot. Compared with the sham group, both learning and memory were impaired in ovariectomized rats. Rats treated with E2 or high-dose XYS showed better learning and memory compared with the saline-treated rats. High-dose XYS significantly reduced escape latency in the spatial acquisition trial; meanwhile, the cross times and duration in the probe quadrant were increased in the spatial probe trial. High-dose XYS promoted the de novo synthesis of E2 content in the hippocampus but had no significant effect on the serum E2 level. Golgi staining indicated that high-dose XYS could increase the branch number and density of dendritic spines in the hippocampal CA1 area. TUNEL staining showed that high-dose XYS alleviated ovariectomy-induced neuronal apoptosis. The expression level of NMDAR2A and NMDAR2B in hippocampal CA1 was upregulated by XYS treatment. The beneficial effect of XYS was through activating ERα-PI3K signaling. In conclusion, high-dose XYS treatment can improve the cognitive abilities of ovariectomized rats by protecting the hippocampal neurons and restoring the hippocampal E2 level.

scholarly journals Adiponectin Protects against Glutamate-Induced Excitotoxicity via Activating SIRT1-Dependent PGC-1αExpression in HT22 Hippocampal Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Liang Yue ◽  
Lei Zhao ◽  
Haixiao Liu ◽  
Xia Li ◽  
Bodong Wang ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Critical Role ◽  
Tunel Staining ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Expression Levels

Glutamate- (Glu-) induced excitotoxicity plays a critical role in stroke. This study aimed to investigate the effects of APN on Glu-induced injury in HT22 neurons. HT22 neurons were treated with Glu in the absence or the presence of an APN peptide. Cell viability was assessed using the MTT assay, while cell apoptosis was evaluated using TUNEL staining. Levels of LDH, MDA, SOD, and GSH-Px were detected using the respective kits, and ROS levels were detected using dichlorofluorescein diacetate. Western blot was used to detect the expression levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), cleaved caspase-3, Bax, and Bcl-2. In addition to the western blot, immunofluorescence was used to investigate the expression levels of SIRT1 and PGC-1α. Our results suggest that APN peptide increased cell viability, SOD, and GSH-Px levels and decreased LDH release, ROS and MDA levels, and cell apoptosis. APN peptide upregulated the expression of SIRT1, PGC-1α, and Bcl-2 and downregulated the expression of cleaved caspase-3 and Bax. Furthermore, the protective effects of the APN peptide were abolished by SIRT1 siRNA. Our findings suggest that APN peptide protects HT22 neurons against Glu-induced injury by inhibiting neuronal apoptosis and activating SIRT1-dependent PGC-1αsignaling.

scholarly journals Cynomorium songaricum Extract Alleviates Memory Impairment through Increasing CREB/BDNF via Suppression of p38MAPK/ERK Pathway in Ovariectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Fang-ze Tian ◽  
Hong-sheng Chang ◽  
Jian-xun Liu ◽  
Junchao Zheng ◽  
Dan Cheng ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Learning And Memory ◽  
Protein Kinases ◽  
Sham Group ◽  
Pyramidal Neurons ◽  
Mitogen Activated Protein Kinase ◽  
Ovariectomized Rats ◽  
Estradiol Valerate ◽  
Hippocampal Ca1 ◽  
Extracellular Regulated Protein Kinases

Cynomorium songaricum Rupr is a very important traditional Chinese medicine for tonifying the kidney, which has a significant effect on improving estrogen level on the long term. In many studies, it can improve the learning and memory function of ovariectomized (OVX) model animals. 10 of the 50 rats received only bilateral back surgery and were harvested with the same amount of fat as the ovaries without removing the ovaries as sham group; remains underwent bilateral ovariectomy and equally randomized into five groups: sham group, with OVX as model group, estradiol valerate (EV, 0.2 mg/kg) as positive control, with 3.3 and 33 mg/kg body weight/day of ethyl acetate extract of Cynomorium songaricum extract (CSE) as low and high dosage groups, respectively. The orally administered CSE to ovariectomized rats exerted an ameliorative effect on learning and memory in the Morris water maze tests. All rats were sacrificed after 8 weeks of treatment, and tissue was analyzed using histopathology and electron microscopy. To comprehensively examine the mechanism, brain derived neurotrophic factor (BDNF), p-p38 mitogen-activated protein kinase (p-p38MAPK), extracellular regulated protein kinases (ERK), p-extracellular regulated protein kinases (p-ERK), and p-cAMP-response element binding protein (p-CREB) were detected by Western blotting. Using histopathology and electron microscopy, it was clearly observed that the pyramidal neurons of the hippocampal CA1 area were reduced in the OVX groups, indicating that CSE could attenuate the loss of pyramidal neurons in hippocampal CA1 and revert the synaptic morphological variations produced by ovariectomy. Mechanistically, the expressions of p-p38MAPK and p-ERK levels were significantly downregulated by CSE intervention, whereas the BDNF and p-CREB were significantly upregulated by CSE as compared to the control. Concisely, Cynomorium songaricum Rupr exhibited potential therapeutic effect on Neuroprotection of ovariectomized rats, and its effect was possibly exerted by p-CREB/BDNF mediated down regulation of ERK/p38MAPK.

scholarly journals Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

2017 ◽  
Vol 41 (5) ◽  
pp. 1838-1850 ◽  
Author(s):  
Shuainan Ma ◽  
Di Zhong ◽  
Pingwei Ma ◽  
Guozhong Li ◽  
Wei Hua ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Western Blot ◽  
Cognitive Decline ◽  
Hippocampal Neurons ◽  
Tunel Staining ◽  
Spatial Learning And Memory ◽  
Apoptotic Pathway ◽  
Sodium Hydrosulfide ◽  
Mitochondrial Apoptotic Pathway ◽  
Increased Risk

Background: Diabetes-associated cognitive decline (DACD) is one of the complications of diabetes and leads to cognitive impairment and an increased risk of dementia. However, the exact mechanism of DACD has not been fully characterized, and a successful therapy for this issue has not been established. This study aimed to detect the anti-apoptotic and anti-inflammatory effects of hydrogen sulfide (H2S) on DACD. Methods: We used a behavioural scoring method, Western blot, TUNEL staining and immunofluorescence staining to investigate the expression of the mitochondrial apoptotic pathway and the IL-23/IL-17 axis in db/db mice with or without sodium hydrosulfide (NaHS) administration. Results: NaHS administration mice exhibited reduced time to find the platform and a shorter swimming distance (P<0.05), while the time spent in the target quadrant was increased compared to that of the db/db group (P<0.05). Pro-apoptotic proteins, including cleaved Caspase-3, cleaved Caspase-9, Bax and cytochrome C, were elevated in the db/db group (P<0.01) but were downregulated in the db/db+NaHS group (P<0.05). Exogenous H2S decreased the numbers of TUNEL-positive cells in the db/db mice (P<0.05). The Western blot analysis showed that the expression levels of IL-23/IL-17 were lower in the NaHS administration group than in the db/db group (P<0.05). Conclusion: We demonstrated that H2S improved the spatial learning and memory abilities of the db/db mice by modulating the mitochondrial apoptotic pathway and the IL-23/IL-17 axis, which were found to be associated with DACD. H2S treatment may help prevent the progression of apoptotic hippocampal neurons in db/db mice and inform the development of a new therapeutic target.

scholarly journals Calcium-/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibition Induces Learning and Memory Impairment and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jialu Wang ◽  
Xiaoxue Xu ◽  
Wanying Jia ◽  
Dongyi Zhao ◽  
Tomasz Boczek ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Memory Impairment ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Tunel Staining ◽  
Protein Activity ◽  
Calcium Calmodulin Dependent ◽  
Cultured Hippocampal Neurons

Objectives. Inhibition of calcium-/calmodulin- (CaM-) dependent kinase II (CaMKII) is correlated with epilepsy. However, the specific mechanism that underlies learning and memory impairment and neuronal death by CaMKII inhibition remains unclear. Materials and Methods. In this study, KN93, a CaMKII inhibitor, was used to investigate the role of CaMKII during epileptogenesis. We first identified differentially expressed genes (DEGs) in primary cultured hippocampal neurons with or without KN93 treatment using RNA-sequencing. Then, the impairment of learning and memory by KN93-induced CaMKII inhibition was assessed using the Morris water maze test. In addition, Western blotting, immunohistochemistry, and TUNEL staining were performed to determine neuronal death, apoptosis, and the relative signaling pathway. Results. KN93-induced CaMKII inhibition decreased cAMP response element-binding (CREB) protein activity and impaired learning and memory in Wistar and tremor (TRM) rats, an animal model of genetic epilepsy. CaMKII inhibition also induced neuronal death and reactive astrocyte activation in both the Wistar and TRM hippocampi, deregulating mitogen-activated protein kinases. Meanwhile, neuronal death and neuron apoptosis were observed in PC12 and primary cultured hippocampal neurons after exposure to KN93, which was reversed by SP600125, an inhibitor of c-Jun N-terminal kinase (JNK). Conclusions. CaMKII inhibition caused learning and memory impairment and apoptosis, which might be related to dysregulated JNK signaling.

scholarly journals Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

2012 ◽  
Vol 70 (11) ◽  
pp. 874-879 ◽  
Author(s):  
Reihaneh Sadeghian ◽  
Masoud Fereidoni ◽  
Mohammad Soukhtanloo ◽  
Hamid Azizi-Malekabadi ◽  
Mahmoud Hosseini
Keyword(s):  
Nitric Oxide ◽  
Learning And Memory ◽  
Memory Deficits ◽  
Ovariectomized Rats ◽  
Estradiol Valerate ◽  
High Dose ◽  
Trial Test ◽  
Learning And Memory Deficits ◽  
Underlying Mechanisms ◽  
Nitric Oxide Metabolites

The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1) than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively). Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001). These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

The Anti-tumor Activity and Mechanisms of rLj-RGD3 on Human Laryngeal Squamous Carcinoma Hep2 Cells

2020 ◽  
Vol 19 (17) ◽  
pp. 2108-2119
Author(s):  
Yang Jin ◽  
Li Lv ◽  
Shu-Xiang Ning ◽  
Ji-Hong Wang ◽  
Rong Xiao
Keyword(s):  
Wound Healing ◽  
Western Blot ◽  
Morphological Changes ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Dna Ladder ◽  
Western Blot Assay

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa’s staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. Conclusion: hese results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

scholarly journals Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qi Sun ◽  
Xin-Yu Nan ◽  
Fa-Ming Tian ◽  
Fang Liu ◽  
Shao-Hua Ping ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Lumbar Fusion ◽  
B Cell Lymphoma ◽  
Intervertebral Disk ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
Mineral Density ◽  
Vertebral Osteoporosis ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration

Abstract Background Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis. Methods An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated. Results RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group. Conclusions RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.

scholarly journals Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress

2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Caspase 3 ◽  
Visual Learning ◽  
Morris Water Maze Test ◽  
High Dose ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Neural Apoptosis ◽  
The Brain

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.

In utero exposure of high-dose di-n-butyl phthalate resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal male rat offspring

2017 ◽  
Vol 36 (12) ◽  
pp. 1236-1247 ◽  
Author(s):  
H Shen ◽  
K Liao ◽  
H-F Wu ◽  
H-C Lu ◽  
Y Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Apoptosis ◽  
In Utero ◽  
Male Rat ◽  
In Utero Exposure ◽  
High Dose ◽  
Testicular Cell ◽  
Rat Testis ◽  
Rat Offspring ◽  
Butyl Phthalate

Objective: To investigate the effects of in utero exposure to high-dose di- n-butyl phthalate (DBP) on testicular cell apoptosis in late embryonic and pubertal male rat offspring. Methods: Twenty pregnant Sprague-Dawley (SD) rats were divided into two groups. During gestation day (GD) 12 to GD 19, control group was given 1 ml day−1 of olive oil and experimental group was given DBP 500 mg kg−1 day−1 by gavage. On GD 19.5 and postnatal day (PND) 45, the testes were removed. Morphological analysis of the testes was observed by transmission electron microscopy and hematoxylin and eosin (H&E) staining. Testicular cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Bcl-2, Bax, and p53 was presented by immunohistochemistry (IHC) and western blot. Data of the two groups was compared using independent samples t-test and Mann–Whitney test by SPSS 20.0. Results: H&E staining showed that spermatogenetic cells were significantly decreased in DBP exposed pubertal rat testis. The apoptosis index of testes in DBP-treated group was significantly lower on GD 19.5 but higher on PND 45 than that of the controls ( p < 0.01). IHC and western blot revealed significantly increased expression of Bcl-2 in GD 19.5 rat testis and Bax and p53 in PND 45 rat testis after DBP exposure, compared with the control ( p < 0.05). Conclusion: In utero exposure of high-dose DBP resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal rat offspring. The overexpression of Bcl-2, Bax, and p53 might be related to the occurrence of abnormal apoptosis and finally produce male infertility.

scholarly journals Reappearance of Hippocampal CA1 Neurons after Ischemia is Associated with Recovery of Learning and Memory

2005 ◽  
Vol 25 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Olof Bendel ◽  
Tjerk Bueters ◽  
Mia von Euler ◽  
Sven Ove Ögren ◽  
Johan Sandin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Functions ◽  
Spatial Learning And Memory ◽  
Neuronal Marker ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 ◽  
The Brain

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

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