Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion

Pharmacology ◽  
2019 ◽  
Vol 103 (5-6) ◽  
pp. 324-332 ◽  
Author(s):  
Wenji Xie ◽  
Wenqin Xie ◽  
Zhenming Kang ◽  
Changcheng Jiang ◽  
Naizhen Liu
Keyword(s):  
Western Blot ◽  
Brachial Plexus ◽  
Expression Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Curcumin Treatment ◽  
Protein Levels ◽  
Brachial Plexus Avulsion ◽  
Tnf Α ◽  
Associated Proteins ◽  
Factor Α

Background/Aims: Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA. Methods: Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot. Results: After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression. Conclusions: Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

scholarly journals Tripterine up-regulates miR-223 to alleviate lipopolysaccharide-induced damage in murine chondrogenic ATDC5 cells

2019 ◽  
Vol 33 ◽  
pp. 205873841882452 ◽  
Author(s):  
Xuefu Li ◽  
Wei Wei ◽  
Zhongquan Zhao ◽  
Shuzhen Lv
Keyword(s):  
Western Blot ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inhibitory Effects ◽  
Tnf Α ◽  
Associated Proteins ◽  
Regulatory Effects ◽  
Induced Apoptosis

Tripterine, also known as celastrol, is a main natural ingredient in Tripterygium wilfordii. Tripterine has a variety of pharmacological functions, and the therapeutic potential of tripterine in many kinds of inflammation-linked diseases has been revealed. However, the function of tripterine on osteoarthritis still remains unclear. The objective of this study was to study the function of tripterine (TPR) on lipopolysaccharide (LPS)-injured chondrocyte. ATDC5 cells were treated with tripterine after LPS stimulation and then cell survival, the release of pro-inflammatory cytokines, and the expression of chondrogenic differentiation-associated proteins were assessed by performing CCK-8, flow cytometry, reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot. Moreover, the expression of miR-223 and core factors in PI3K/AKT and nuclear factor kappa B (NF-κB) signaling was tested by RT-qPCR/Western blot. LPS stimulation significantly reduced ATDC5 cells viability, induced apoptosis, and increased the release of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Tripterine protected ATDC5 cells against LPS-induced chondrocyte loss and the release of IL-6 and TNF-α. miR-223 was down-regulated by LPS, while was up-regulated by tripterine. The protective actions of tripterine were eliminated when miR-223 was silenced. Besides, tripterine inhibited hypertrophic differentiation induced by LPS, and the inhibitory effects of tripterine on hypertrophic differentiation could be abolished when miR-223 was silenced. Furthermore, tripterine activated PI3K/AKT pathway and deactivated NF-κB pathway. And the regulatory effects of tripterine on these two pathways were abolished by miR-223 silence. This study revealed that tripterine protected ATDC5 cells against LPS-induced cell damage possibly via up-regulation of miR-223 and modulation of NF-κB and PI3K/AKT pathways.

scholarly journals Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine Production

2017 ◽  
Vol 103 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Sepide E Nematian ◽  
Ramanaiah Mamillapalli ◽  
Trisha S Kadakia ◽  
Masoumeh Majidi Zolbin ◽  
Sarah Moustafa ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Cytokine Production ◽  
University Hospital ◽  
Regulatory Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Circulating Microrna ◽  
Protein Levels ◽  
Tnf Α ◽  
Factor Α ◽  
Macrophage Cytokine

Abstract Context Endometriosis is characterized by aberrant inflammation. We previously reported increased levels of microRNA (miRNA) 125b-5p and decreased levels of miRNA Let-7b-5p in serum of patients with endometriosis. Objective Determine the regulatory function of miRNAs 125b-5p and Let-7b-5p on production of proinflammatory cytokines in endometriosis. Design Case-control study. Setting University hospital. Patients Women with (20) and without (26) endometriosis; human U937 macrophage cell line. Intervention Sera were collected from surgically diagnosed patients and differentiated U937 cells that were transfected with miRNAs 125b-5p and Let-7b-5p mimics and inhibitor. Main Outcome Measures Enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β levels and quantitative real-time polymerase chain reaction for expression of miRNAs 125b-5p and Let-7b-5p in sera of patients with and without endometriosis. Transfected macrophages were evaluated for expression of inflammatory cytokines, intracellular production, and secretion of these cytokines. Results We noted substantial elevation of TNF-α, IL-1β, and IL-6, marked upregulation of miRNA 125b, and considerable downregulation of Let-7b in sera of patients with endometriosis vs control. There was a positive correlation between miRNA 125b levels and TNF-α, IL-1β, and IL-6 and a negative correlation between miRNA Let-7b levels and TNF-α in sera of patients with endometriosis. Transfection experiments showed a noteworthy upregulation of TNF-α, IL-1β, IL-6, and IL-8 in macrophages transfected with miRNA 125b mimic or Let-7b inhibitor. The secreted cytokine protein levels and intracellular imaging studies closely correlate with the messenger RNA changes. Conclusions Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.

scholarly journals Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Laifang Wang ◽  
Qing Zhao ◽  
Na Wang ◽  
Yanjie Ding ◽  
Lingli Kong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blot ◽  
Synovial Fibroblasts ◽  
Diagnostic Value ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Tnf Α ◽  
Malignant Changes ◽  
Factor Α

Abstract Background Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. Methods The expression of circ_0000396, microRNA (miR)-203 and HMG-box transcription factor 1 (HBP1) was detected using qRT-PCR and western blot. The proliferative and apoptotic capabilities of rheumatoid arthritis synovial fibroblasts (RASFs) were measured by colony formation, CCK-8, flow cytometry and western blot assays, respectively. The levels of interleukins (IL)-6, IL-1β, IL-8 and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The target correlations between miR-203 and circ_0000396 or HBP1 were validated using pull-down and dual-luciferase reporter assay. Results Circ_0000396 was decreased in RA synovial tissues and RASFs, and overexpression of circ_0000396 suppressed cell proliferation, induced cell apoptosis and reduced the release of inflammatory cytokine IL-6, IL-1β, IL-8 and TNF-α in RASFs, while circ_0000396 deletion functioned oppositely. MiR-203 was confirmed to be a target of circ_0000396, and miR-203 reversed the protective effects of circ_0000396 on the dysfunction and inflammation of RASFs. HBP1 was a target of miR-203, and silencing miR-203 inhibited RASFs malignant changes by regulating HBP1. In addition, circ_0000396 could regulate HBP1 by sponging miR-203, and HBP1 decrease attenuated the effects of circ_0000396 on RASF growth and inflammation. Conclusion Circ_0000396 inhibited the growth and inflammation in RASFs by regulating miR-203/HBP1 axis, providing a potential therapeutic target for RA.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

scholarly journals Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Zhao ◽  
Yihang Li ◽  
Dahong Yao ◽  
Ran Sun ◽  
Shifang Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Western Blot ◽  
Serum Uric Acid ◽  
Glucose Transporter ◽  
Serum Uric Acid Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
The Novel ◽  
Mice Model ◽  
Protein Levels ◽  
Anti Inflammatory

Background: The prevalence of hyperuricemia is considered high worldwide. Hyperuricemia occurs due to decreased excretion of uric acid, increased synthesis of uric acid, or a combination of both mechanisms. There is growing evidence that hyperuricemia is associated with a decline of renal function.Purpose: This study is aimed at investigating the effects of the novel compound on lowering the serum uric acid level and alleviating renal inflammation induced by high uric acid in hyperuricemic mice.Methods: Hyperuricemic mice model was induced by potassium oxonate and used to evaluate the effects of the novel compound named FxUD. Enzyme-linked immunosorbent assay was used to detect the related biochemical markers. Hematoxylin-eosin (HE) staining was applied to observe pathological changes. The mRNA expression levels were tested by qRT-PCR. The protein levels were determined by Western blot. In parallel, human proximal renal tubular epithelial cells (HK-2) derived from normal kidney was used to further validate the anti-inflammatory effects in vitro.Results: FxUD administration significantly decreased serum uric acid levels, restored the kidney function parameters, and improved the renal pathological injury. Meanwhile, treatment with FxUD effectively inhibited serum and liver xanthine oxidase (XOD) levels. Reversed expression alterations of renal inflammatory cytokines, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were observed in hyperuricemic mice. Western blot results illustrated FxUD down-regulated protein levels of inflammasome components. Further studies showed that FxUD inhibited the activation of NF-κB signaling pathway in the kidney of hyperuricemic mice. In parallel, the anti-inflammatory effect of FxUD was also confirmed in HK-2.Conclusion: Our study reveals that FxUD exhibits the anti-hyperuricemic and anti-inflammatory effects through regulating hepatic XOD and renal urate reabsorption transporters, and suppressing NF-κB/NLRP3 pathway in hyperuricemia. The results provide the evidence that FxUD may be potential for the treatment of hyperuricemia with kidney inflammation.

scholarly journals Application of Dexmedetomidine in Cardiopulmonary Bypass Prefilling

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093976 ◽  
Author(s):  
Li Wang ◽  
Shaowei Wang ◽  
Zhen Xing ◽  
Fulong Li ◽  
Jinliang Teng ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Anesthesia Induction ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective: The purpose of this study was to explore the application of dexmedetomidine (Dex) in cardiopulmonary bypass. Methods: A total of 60 patients undergoing elective cardiopulmonary bypass were divided into control (C) group and Dex group. In the Dex group, appropriate amount of Dex was added into the membrane lung prefilling solution before anesthesia induction, while those in control group were given normal saline. The levels of mean arterial pressure (MAP) and heart rate (HR) at different times were measured. The levels of cardiac troponin I (CTNI), malondialdehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) at different points (T0/T1/T2/T3/T4) in both groups were measured by enzyme-linked immunosorbent assay kits. Results: The intraoperative and postoperative levels of MAP and HR in the 2 groups were significantly lower than those preoperatively ( P < .05). The levels of MAP and HR in the Dex group were significantly lower than those of the C group ( P < .05). The levels of CTNI/MDA/IL-6/TNF-α at different points in both groups were significantly higher than those at T0 ( P < .05). The serum levels of CTNI, MDA, IL-6, and TNF-α in the Dex group at T1/T2/T3/T4 were significantly lower than those in the C group ( P < .05). The rate of arrhythmia in the Dex group was significantly lower than that in the C group ( P < .05). Conclusion: Dexmedetomidine has a stable effect in cardiopulmonary priming solution.

scholarly journals Heat stress combined with lipopolysaccharide alter the activity and superficial molecules of peripheral monocytes

2019 ◽  
Vol 33 ◽  
pp. 205873841982889
Author(s):  
Jiajing Luo ◽  
Yi Chen ◽  
Chengjia Ding ◽  
Jialing Qiu ◽  
Yulan Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Heat Stress ◽  
Western Blot ◽  
Inflammatory Mediators ◽  
Peripheral Blood ◽  
Heat Stroke ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Rt Pcr ◽  
Tnf Α

The purpose of this study was to focus on the underlying relationship between the hyperactivity for the peripheral monocytes and heat stroke by investigating the inflammatory oxidative activity of and the expression of superficial molecules. Peripheral blood samples were collected from 10 healthy adult volunteers. Human blood monocytes were isolated by density gradient centrifugation and sequent adherent culture. The objectives were divided into four groups: 43°C heat stress combined with lipopolysaccharide (LPS) group, 43°C heat stress group, LPS group, and control group. There were 10 cases in each group. An enzyme-linked immunosorbent assay (ELISA) test was used to measure the concentrations of supernatant inflammatory mediators (tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10)). After loaded by 2,7-Dichlorodi-hydrofluorescein-diacetate (DCFHDA) fluorescent probe, intracellular reactive oxygen species (ROS) levels were determined by a flow cytometry. After fluorescent microspheres incubation, the phagocytosis of monocytes was observed under a fluorescent microscope. Respectively, the flow cytometry and Western blot were used to evaluate the level of triggering receptor expressed on myeloid cells-1 (TREM-1) and Toll-like receptor-4 (TLR-4) on the monocytes. Furthermore, the mRNA expression of TREM-1 and TLR-4 was detected by real-time polymerase chain reaction (RT-PCR). The heat stress combined with LPS stimulation promoted the peripheral monocytes to produce inflammatory mediators (TNF-α, IL-1β, and IL-10) and release ROS. Otherwise, such complex strike significantly suppressed the phagocytic activity of monocytes in peripheral blood. Moreover, the expression of TREM-1, TLR-4 and CD86 was measured by the flow cytometry on peripheral monocytes which were respectively promoted by the union of heat stress and LPS. The results of Western blot and RT-PCR demonstrated the similar kinetics on these superficial molecules (TREM-1, TLR-4, and CD86) stimulated by the combination of heat stress and LPS. The underlying mechanism of the dysfunction for the peripheral monocytes may be related to the abnormal expression of superficial molecules TREM-1, TLR-4, and CD86 on the monocytes induced by heat stress and LPS.

Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

2005 ◽  
Vol 288 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Jiing Chyuan Luo ◽  
Vivian Yvonne Shin ◽  
Ying Hua Yang ◽  
William Ka Kei Wu ◽  
Yi Ni Ye ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Epithelial Cell Line ◽  
Epithelial Cell Proliferation ◽  
Protein Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Factor Α

TNF-α is a cytokine produced during gastric mucosal injury. We examined whether TNF-α could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-α treatment (1–10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-α treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-α on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-α on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-α plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-α receptor and activation of the arachidonic acid/PG pathway.

Upregulation of the thioredoxin-dependent redox system during differentiation of 3T3-L1 cells to adipocytes

2014 ◽  
Vol 395 (6) ◽  
pp. 667-677 ◽  
Author(s):  
Ann-Marie Rajalin ◽  
Mustafa Micoogullari ◽  
Helmut Sies ◽  
Holger Steinbrenner
Keyword(s):  
Hydrogen Peroxide ◽  
Redox System ◽  
Antioxidant Systems ◽  
Protein Levels ◽  
Glutathione Peroxidases ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Hydrogen Peroxide Generation ◽  
Factor Α ◽  
Thioredoxin Reductases

Abstract Hydrogen peroxide acts as a signaling molecule in early adipogenesis. In differentiating adipocytes, elevated hydrogen peroxide generation is balanced through induction of antioxidant enzymes such as catalase and peroxiredoxins. Thioredoxin reductases (TrxR) and glutathione peroxidases (GPx) are selenoenzymes that constitute part of the major thiol-dependent antioxidant systems in cells. Here we show that the protein levels of cytoplasmic/nuclear TrxR1 and mitochondrial TrxR2 increase in the course of adipocyte differentiation of 3T3-L1 cells together with the TrxR2 substrate thioredoxin 2 (Trx2), resulting in elevated TrxR activity in mature adipocytes. Gene and protein expression of the GPx isoenzyme GPx4 was also stimulated during adipogenesis. Chronic exposure of 3T3-L1 cells to the anti-adipogenic factors tumor necrosis factor α (TNF-α) or rapamycin during differentiation suppressed TrxR1 and Trx2 upregulation, concomitantly with inhibition of adipogenesis and lipogenesis. In contrast, TNF-α or rapamycin did not affect expression of TrxRs and their Trx substrates in mature adipocytes. These results indicate that upregulation of the thioredoxin-dependent redox system is linked to the development of an adipocyte phenotype.

scholarly journals Enhanced Cerebral Expression of MCT1 and MCT2 in a Rat Ischemia Model Occurs in Activated Microglial Cells

2009 ◽  
Vol 29 (7) ◽  
pp. 1273-1283 ◽  
Author(s):  
Tiago JTP Moreira ◽  
Karin Pierre ◽  
Fumihiko Maekawa ◽  
Cendrine Repond ◽  
Aleta Cebere ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Level ◽  
Protein Levels ◽  
Microglial Cell Line ◽  
Tnf Α ◽  
Ischemic Episode ◽  
Isolectin B4 ◽  
Factor Α ◽  
Necrosis Factor

Monocarboxylate transporters (MCTs) are essential for the use of lactate, an energy substrate known to be overproduced in brain during an ischemic episode. The expression of MCT1 and MCT2 was investigated at 48 h of reperfusion from focal ischemia induced by unilateral extradural compression in Wistar rats. Increased MCT1 mRNA expression was detected in the injured cortex and hippocampus of compressed animals compared to sham controls. In the contralateral, uncompressed hemisphere, increases in MCT1 mRNA level in the cortex and MCT2 mRNA level in the hippocampus were noted. Interestingly, strong MCT1 and MCT2 protein expression was found in peri-lesional macrophages/microglia and in an isolectin B4+/S100β+ cell population in the corpus callosum. In vitro, MCT1 and MCT2 protein expression was observed in the N11 microglial cell line, whereas an enhancement of MCT1 expression by tumor necrosis factor-α (TNF-α) was shown in these cells. Modulation of MCT expression in microglia suggests that these transporters may help sustain microglial functions during recovery from focal brain ischemia. Overall, our study indicates that changes in MCT expression around and also away from the ischemic area, both at the mRNA and protein levels, are a part of the metabolic adaptations taking place in the brain after ischemia.

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