scholarly journals Effect of Ischemia-Induced Cochlear Inflammation on Auditory Responses in Male Rats

2021 ◽  
Author(s):  
Hamed Fanaei ◽  
Akram Pourbakht ◽  
Sadegh Jafarzadeh
Keyword(s):  
Oxidative Stress ◽  
Ischemic Injury ◽  
Auditory Brainstem ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Stress Effect ◽  
Auditory Responses ◽  
Tnf Α ◽  
Bilateral Carotid ◽  
Brainstem Response

Background and Aim: Ischemic injury is a major cause of hearing loss and oxidative stress is an important part of ischemic injury. The goal of this study was to evaluate the cochlear oxidative stress effect on auditory responses in male rats. Methods: Cochlear oxidative stress was induced by bilateral carotid artery occlusion for 20 minutes. The rats were evaluated by biochemical inflammatory factors tumor necrosis factor-α [TNF-α] and C-reactive protein (CRP) in the day before and 1st, 4th, and 7th days following surgery. The auditory brainstem response (ABR) and electrocochleography (ECochG) were evaluated on the day before surgery and 14th, 21th and 28th days after surgery. Results: TNF-α and CRP levels concentrations increased one day after ischemia and subsequently decreased on the 7th day. The click and tone burst evoked ABR showed increased thresholds on day14th, 21th, and 28th. The highest threshold was recorded on day14th. The ECochG results also were abnormal for 55%, 70%, and 45% of cases on day 14th, 21th, and 28th, respectively. Conclusion: Cochlear oxidative stress affects hearing sensitivity. The ABR shows elevated thresholds and abnormal ECochG was found in many cases.

Osteocalcin prevents insulin resistance, hepatic inflammation and autophagy associated with high-fat diet induced fatty liver hemorrhagic syndrome in aged laying hens

2020 ◽  
Author(s):  
Xiaoling Wu ◽  
Xinyu Zou ◽  
Mi Zhang ◽  
Haiqiang Hu ◽  
Xueliang Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Inflammatory Reaction ◽  
High Fat Diet ◽  
Laying Hens ◽  
Density Lipoprotein ◽  
Inflammatory Factors ◽  
Pathological Changes ◽  
High Fat ◽  
Tnf Α

Abstract Background: Osteocalcin (OCN), as an energy-regulating hormone, involves in preventing nonalcoholic steatohepatitis. Laying hens have been used as an animal model for investigating liver function and related metabolic disordersas that the synthesis of fat in laying hens is much faster than in mammals with limited adipose tissue. The aim of this study was to investigate the effects of OCN on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Methods: Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of three treatments: normal diet (ND + vehicle , ND+V), high-fat diet (HFD + vehicle, HFD+V), and HFD + OCN (3 μg/bird, 1 time/2 days, i.m.) for 40 days. At experimental day 30, oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed. At the end of experiment, the hens were euthanized followed blood collection. The plasma aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 (IL-1), IL-6, and tumor Necrosis Factor-alpha (TNF-α) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by Real-time PCR. And oxidative stress was evaluated using Malondialdehyde (MDA) and Glutathione peroxidase (GSH-Px) assay kits. Results: The results showed HFD hens had more severe liver haemorrhage and fibrosis than ND hens. The ultra-microstructural examination showed that hepatocytes of HFD hens appeared necrotic pyknosis associated with great intracellular electron, mitochondrial swelling, shrunk nucleus and absence of autolysosomes. OCN mitigated these pathological changes by improved HFD hens’ insulin resistance via alleviating the glucose intolerence and improving insulin sensitivity; inhibited HFD-induced oxidative stress as evidenced by decreased liver concentrations of MDA but increased GSH-Px; and reduced the inflammatory reaction with reducing blood IL-6 and TNF-α concentrations and mRNA expressions. Conclusion: These results suggest a high-fat diet promotes the FLHS development in aged hens, while OCN prevents the FLHS process through inhibiting insulin resistance, inflammatory reaction, oxidative stress and fibrosis, and acting autophagy.

scholarly journals Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Ju-Bin Kang ◽  
Dong-Ju Park ◽  
Murad-Ali Shah ◽  
Myeong-Ok Kim ◽  
Phil-Ok Koh
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Calcium Binding ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Adult Mice ◽  
Tnf Α ◽  
Factor Α ◽  
And Oxidative Stress ◽  
Necrosis Factor

Abstract Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.

scholarly journals Ginseng Berry Extract Rich in Phenolic Compounds Attenuates Oxidative Stress but not Cardiac Remodeling post Myocardial Infarction

2019 ◽  
Vol 20 (4) ◽  
pp. 983 ◽  
Author(s):  
Mihir Parikh ◽  
Pema Raj ◽  
Liping Yu ◽  
Jo-Ann Stebbing ◽  
Suvira Prashar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
T Cell ◽  
Phenolic Compounds ◽  
Cytokine Production ◽  
T Cell Subsets ◽  
Male Rats ◽  
Ginseng Root ◽  
Rat Hearts ◽  
Tnf Α

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague–Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.

Lack of Trigeminal Nerve Toxicity in Rats Exposed to Trichloroethylene Vapor for 13 Weeks

2006 ◽  
Vol 25 (6) ◽  
pp. 531-540 ◽  
Author(s):  
Ralph R. Albee ◽  
Pamela J. Spencer ◽  
Keith A. Johnson ◽  
Greg J. Bradley ◽  
Brian R. Marable ◽  
...  
Keyword(s):  
Trigeminal Nerve ◽  
Auditory Brainstem ◽  
Female Rats ◽  
Male Rats ◽  
Fischer 344 ◽  
Clinical Observations ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Brainstem Response ◽  
Effect Level

Male and female Fischer-344 rats were exposed to 1,1,2-trichloroethylene (TCE) at 250, 800, or 2500 ppm for 6 h/day, 5 days/week, for 13 weeks. Weekly body weights and daily clinical observations were recorded and a functional observational battery (FOB) was performed monthly. Postexposure neurotoxicological evaluations included an electrodiagnostic evaluation of auditory function, the trigeminal nerve, and a comprehensive neuropathological examination. After 8 weeks of exposure, female, but not male, rats exposed to 2500 ppm were slightly more reactive to handling than the controls but not after 13 weeks of exposure. After 13 weeks, female rats exposed to 2500 ppm TCE were slightly more active during the 1-min observation period than the controls. There were no treatment-related differences in grip performance, landing foot splay, or on the trigeminal nerve–evoked potential at any dose. At 2500 ppm TCE, mild frequency-specific hearing deficits were observed, including elevated tone-pip auditory brainstem response thresholds. Focal loss of hair cells in the upper basal turn of the cochlea was observed in 2500 ppm–exposed rats. Except for the cochleas of 2500 ppm–exposed rats, no treatment-related lesions were noted during the neuro-histopathologic examination. The no-observable-adverse-effect level for this study was 800 ppm based on ototoxicity at 2500 ppm.

scholarly journals Klotho protects chondrocyte viability via FOXO1/3 in osteoarthritis

2021 ◽  
Vol 20 (9) ◽  
pp. 1961-1968
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Protective Effect ◽  
Collagen I ◽  
Inflammatory Factors ◽  
Ros Production ◽  
Chondrocyte Viability ◽  
Tnf Α ◽  
Collagen Ii

Purpose: To investigate the effect of Klotho and FOXO1/3 on the CH viability in OA.Methods: The survival rate of CHs, Klotho and FOXO1/3 protein expression, and ROS production were measured in the OA cartilages of different degenerative phases. H2O2 was also used to injure CHs, and the cell viability, Klotho and FOXO1/3 expressions, as well as ROS levels were investigated to clarify the effect of exogenic Klotho on the injured CHs. Additionally, in order to verify the role of FOXO1/3 in Klotho-treated CHs, SOD2, GPX1, inflammatory factors, collagen I/II, SOX9, and Runx-2 levels were analyzed by silencing FOXO1 and FOXO3 expression via siRNA transfection.Results: Klotho and FOXO1/3 expressions significantly decreased, and ROS production increased in severely human OA cartilage (p <0.05). Besides, H2O2 affected CHs viability with the suppression of Klotho and FOXO1/3 expression but ROS production was elevated. Exogenic Klotho application partly reversed the injury caused by H2O2. Furthermore, Klotho treatment of the injured CHs contributed to SOD2 and GPX1 expressions, and suppressed IL-1β, IL-6, TNF-α and MMP-13 production, resulting in  the upregulation of collagen II and SOX9 as well as downregulation of collagen I and Runx-2. However, the protective effect of Klotho was weakened by FOXO1 and FOXO3 gene silencing.Conclusion: Klotho protects CHs viability by suppressing oxidative stress and inflammation, which is associated with the mediation of FOXO1 and FOXO3. These findings provide new insights into the treatment of OA.

Cisplatin Toxicology: The Role of Pro-inflammatory Cytokines and GABA Transporters in Cochlear Spiral Ganglion

2020 ◽  
Vol 25 (45) ◽  
pp. 4820-4826 ◽  
Author(s):  
Dongmei Gao ◽  
Hong Yu ◽  
Bo Li ◽  
Li Chen ◽  
Xiaoyu Li ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Spiral Ganglion ◽  
Auditory Brainstem ◽  
Protein Levels ◽  
Gaba Transporters ◽  
Tnf Α ◽  
Neuronal Tissues ◽  
Brainstem Response ◽  
Cochlear Spiral Ganglion ◽  
Pro Inflammatory Cytokines

Background: The current study was conducted to examine the specific activation of pro-inflammatory cytokines (PICs), namely IL-1β, IL-6 and TNF-α in the cochlear spiral ganglion of rats after ototoxicity induced by cisplatin. Since γ-aminobutyric acid (GABA) and its receptors are involved in pathophysiological processes of ototoxicity, we further examined the role played by PICs in regulating expression of GABA transporter type 1 and 3 (GAT-1 and GAT-3), as two essential subtypes of GATs responsible for the regulation of extracellular GABA levels in the neuronal tissues. Methods: ELISA and western blot analysis were employed to examine the levels of PICs and GATs; and auditory brainstem response was used to assess ototoxicity induced by cisplatin. Results: IL-1β, IL-6 and TNF-α as well as their receptors were significantly increased in the spiral ganglion of ototoxic rats as compared with sham control animals (P<0.05, ototoxic rats vs. control rats). Cisplatin-ototoxicity also induced upregulation of the protein levels of GAT-1 and GAT-3 in the spiral ganglion (P<0.05 vs. controls). In addition, administration of inhibitors to IL-1β, IL-6 and TNF-α attenuated amplification of GAT-1 and GAT-3 and improved hearing impairment induced by cisplatin. Conclusion: Our data indicate that PIC signals are activated in the spiral ganglion during cisplatin-ototoxicity which thereby leads to upregulation of GABA transporters. As a result, it is likely that de-inhibition of GABA system is enhanced in the cochlear spiral ganglion. This supports a role for PICs in engagement of the signal mechanisms associated with cisplatin-ototoxicity, and has pharmacological implications to target specific PICs for GABAergic dysfunction and vulnerability related to cisplatin-ototoxicity.

Abstract 451: PNS-R1 Attenuates the Development of Atherosclerosis in ApoE-Deficient Mouse Model

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Yu Chen ◽  
Chenglin Jia ◽  
Minqi Xiong ◽  
Jingang Cui ◽  
Qinbo Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Therapeutic Agent ◽  
Pathological Condition ◽  
Atherosclerotic Lesion ◽  
Panax Notoginseng ◽  
Inflammatory Factors ◽  
Active Components ◽  
Tnf Α ◽  
First Time

Atherosclerosis is a chronic pathological condition featured by accumulation of lipids and fibrous elements in the artery. Atherosclerosis remains as the primary cause of cardiovascular diseases and agents that effectively intervenes the development of atherosclerosis are still needed. Panax notoginseng has been extensively used as therapeutic agent in Asia to treat cardiovascular disorders. Panax notoginseng saponins (PNS) is the major class of active components of Panax notoginseng. PNS has been reported to possess anti-atherosclerotic effect. However, which component of PNS is responsible for this effect remains unknown. The current study evaluated the effects of a component unique to PNS, PNS-R1, on atherosclerosis in ApoE-/- mouse model. Histological examination revealed that the extent of atherosclerotic lesion was significantly alleviated in PNS-R1-treated ApoE-/- mice compared to that from the ApoE-/- controls. Meanwhile, PNS-R1 treatment significantly reduced the level of oxidative stress in the atherosclerotic lesion, which was prominently enhanced in ApoE-/- controls. This effect on oxidative stress was corroborated by increased serum level of GSH and SOD and decreased level of MDH in PNS-treated mice. Furthermore, PNS-R1 treatment significantly decreased the levels of total cholesterol, triglycerides and increased the level of HDL without affecting the level of LDL, suggesting an effect of PNS-R1 on lipid metabolism, which could in part contribute to its action in attenuating atherosclerosis. Additionally, the levels of inflammatory factors including IL-2, IL-6, TNF-α, γ-IFN and ox-LDL were markedly reduced in PNS-R1-treated mice compared to that from the ApoE-/- controls, demonstrating a significant anti-inflammatory effect of PNS-R1 in the development of atherosclerosis. Expression of microRNAs known to be involved in the pathogenesis of atherosclerosis was further evaluated and showed that PNS-R1 treatment led to a significant reduction in the expression of miR-122, miR-132 and miR-155. Collectively, our results provided for the first time the experimental evidence supporting the anti-atherosclerotic effects of PNS-R1, which could be a promising therapeutic agent treating atherosclerosis.

scholarly journals Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease

2021 ◽  
pp. 1-10
Author(s):  
Ke Sun ◽  
Xiaojing Tang ◽  
Shuwei Song ◽  
Yuan Gao ◽  
Hongjing Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vascular Calcification ◽  
Systemic Inflammation ◽  
Inflammatory Factors ◽  
Uremic Toxin ◽  
Inflammatory Factor ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Tnf Α

<b><i>Introduction:</i></b> Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. <b><i>Methods:</i></b> A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE<sup>−/−</sup> mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe <i>Oxalobacter formigenes</i> (<i>O. formigenes</i>) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). <b><i>Results:</i></b> Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The <i>O. formigenes</i> intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the <i>O. formigenes</i> group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. <b><i>Conclusions:</i></b> Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by <i>O. formigenes</i> might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD.

p38 and ERK1/2 MAPKs mediate the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis

2007 ◽  
Vol 293 (6) ◽  
pp. H3524-H3531 ◽  
Author(s):  
Sanjiv Dhingra ◽  
Anita K. Sharma ◽  
Dinender K. Singla ◽  
Pawan K. Singal
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Cardiac Myocyte ◽  
Cell Injury ◽  
Male Rats ◽  
Tnf Α ◽  
Myocyte Apoptosis ◽  
Cardiac Myocyte Apoptosis ◽  
Induced Changes

It is known that TNF-α increases the production of ROS and decreases antioxidant enzymes, resulting in an increase in oxidative stress. IL-10 appears to modulate these effects. The present study investigated the role of p38 and ERK1/2 MAPKs in mediating the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-α ( ratio 1) for 4 h. H2O2(100 μM) as a positive control and the antioxidant Trolox (20 μmol/l) were used to confirm the involvement of oxidative stress. H2O2treatment increased oxidative stress and apoptosis; TNF-α mimicked these effects. Exposure to TNF-α significantly increased ROS production, caused cell injury, and increased the number of apoptotic cells and Bax-to-Bcl-xl ratio. This change was associated with an increase in the phospho-p38 MAPK-to-total p38 MAPK ratio and a decrease in the phospho-ERK1/2-to-total ERK1/2 ratio. IL-10 treatment by itself had no effect on these parameters, but it prevented the above-listed changes caused by TNF-α. The antioxidant Trolox modulated TNF-α-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-α-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-α-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-α and IL-10 in cardiac myocyte apoptosis.

scholarly journals Prophage Gene Rv2650c Enhances Intracellular Survival of Mycobacterium smegmatis

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Fan ◽  
Zichen Liu ◽  
Zhibin Wan ◽  
Hanlu Zou ◽  
Mengzhi Ji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Virulence Factors ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Inflammatory Factors ◽  
Bacterial Pathogenicity ◽  
Tnf Α ◽  
The World ◽  
And Control

BackgroundInduced by the pathogen Mycobacterium tuberculosis, tuberculosis remains one of the most dangerous infectious diseases in the world. As a special virus, prophage is domesticated by its host and are major contributors to virulence factors for bacterial pathogenicity. The function of prophages and their genes in M. tuberculosis is still unknown.MethodsRv2650c is a prophage gene in M. tuberculosis genome. We constructed recombinant Mycobacterium smegmatis (M. smegmatis) to observe bacteria morphology and analyze the resistance to various adverse environments. Recombinant and control strains were used to infect macrophages, respectively. Furthermore, we performed ELISA experiments of infected macrophages.ResultsRv2650c affected the spread of colonies of M. smegmatis and enhanced the resistance of M. smegmatis to macrophages and various stress agents such as acid, oxidative stress, and surfactant. ELISA experiments revealed that the Rv2650c can inhibit the expression of inflammatory factors TNF-α, IL-10, IL-1β, and IL-6.ConclusionThis study demonstrates that the prophage gene Rv2650c can inhibit the spread of colonies and the expression of inflammatory factors and promote intracellular survival of M. smegmatis. These results build the foundation for the discovery of virulence factors of M. tuberculosis, and provide novel insights into the function of the prophage in Mycobacterium.

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