scholarly journals Effects of Irbesartan Pretreatment on Pancreatic β-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Cuihong Chen ◽  
Li Li ◽  
Haijing Qin ◽  
Zhenxing Huang ◽  
Jing Xian ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Damage ◽  
Quantitative Polymerase Chain Reaction ◽  
Fasting Blood Glucose ◽  
Mitogen Activated Protein Kinase ◽  
Control Group

The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic β-cell apoptosis in a streptozotocin- (STZ-) induced acute mouse model of prediabetes. Twenty-four male BALB/C mice (18–22 g) were randomly divided into three groups: normal control group (NC, n=6), STZ group (STZ, n=8), and irbesartan + STZ group (IRB + STZ, n=10). In the IRB + STZ group, mice were administered irbesartan (300 mg/kg per day) by gavage for one week. The STZ group and IRB + STZ group received STZ (80 mg/kg by intraperitoneal (IP) injection once). The NC group received normal saline (80 mg/kg by IP injection once). Fasting blood glucose prior to STZ injection and presacrifice was analysed using samples withdrawn from the caudal vein to confirm the induction of prediabetes. Haematoxylin and eosin staining, immunohistochemical detection of insulin, and apoptosis analysis were performed. Reverse transcription-quantitative polymerase chain reaction was used to detect angiotensin II type 1 receptor (AT1R), caspase-3, and p38 mitogen-activated protein kinase (MAPK) mRNA expression. Blood glucose was significantly higher in the STZ group (9.01 ± 1.1089 vs 4.78 ± 0.7026) and IRB + STZ group (7.86 ± 1.1811 vs 4.78 ± 0.7026) compared with the NC group (P<0.05). In comparison to the STZ group, the islet cell damage was marginally improved in the IRB + STZ group, and the IRB + STZ group had a significantly lower apoptotic rate than the STZ group (22.42 ± 8.3675 vs 50.86 ± 5.3395, P<0.001). AT1R expression in the IRB + STZ group was lower than that in the STZ group (1.56 ± 1.2207 vs 3.92 ± 2.4392, P<0.05). The mRNA expression of caspase-3 in pancreatic tissue was significantly lower in the IRB + STZ group than in the STZ group (0.90 ± 0.7272 vs 1.88 ± 1.0572, P<0.05). Similarly, the IRB + STZ group also had lower p38MAPK levels than the STZ group (1.16 ± 1.0642 vs 2.55 ± 1.7925, P>0.05). In conclusion, irbesartan pretreatment improved glucose levels and insulin secretion and decreased islet β-cell apoptosis to protect islet β cells in an STZ-induced acute prediabetic mouse model.

scholarly journals Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

2018 ◽  
Vol 51 (5) ◽  
pp. 2341-2358 ◽  
Author(s):  
Xiaowei Nie ◽  
Youjin Dai ◽  
Yuan Zheng ◽  
Dan Bao ◽  
Qin Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Premature Ovarian Failure ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Oocyte Quality ◽  
Ovarian Failure ◽  
Control Group ◽  
Mrna Levels ◽  
Primordial Follicles ◽  
Ovarian Aging

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.

Effect of Sophora Japonica Total Flavonoids on Mouse Models of Hyperglycemia and Diabetes Model

2014 ◽  
Vol 664 ◽  
pp. 397-401 ◽  
Author(s):  
Ming San Miao ◽  
Bo Lin Cheng ◽  
Na Jiang
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Islet Cell ◽  
Cell Damage ◽  
Control Group ◽  
Total Flavonoids ◽  
Model Group ◽  
Sophora Japonica ◽  
Glucose Levels ◽  
Blood Glucose Levels

Objective: To investigate the effects of Sophora japonica total flavonoids hyperglycemia and diabetes in mice models. Methods: intraperitoneal injection of epinephrine, intravenous injection of freshly prepared alloxan or intravenous injection of streptozotocin, alloxan build adrenaline or hyperglycemia model streptozotocin diabetic model. Glucose values ​​were selected for each experiment> 11.1mmol / L, with a significantly more drinking, eating, and more urinary symptoms in mice 60, according to blood glucose levels were randomly divided into six groups, namely large, medium and small doses of Sophora japonica total flavonoids group, metformin group, the control group and model group. And were fed the appropriate medication, model group and the control group fed with the same volume of saline solution. Results: Sophora japonica total flavonoids can significantly reduce the adrenaline and alloxan mice with high blood sugar glucose levels, improve liver glycogen content; can significantly reduce the streptozotocin-diabetic mouse model of blood glucose levels and improve hepatic glycogen,can significantly improve the streptozotocin-induced islet cell damage. Conclusion: Sophora japonica total flavonoids mouse model of hyperglycemia and diabetes mellitus have a better hypoglycemic effect of its hypoglycemic effect and promote glycogen synthesis, reduce islet cell damage.

scholarly journals Pengaruh yoghurt dan soyghurt kayu manis (Cinnamomum burmannii) terhadap kadar glukosa darah, insulin serum, dan malondialdehyde tikus pra sindrom metabolik

2020 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Ninik Rustanti ◽  
Vifin Zakiahtin Nafsih ◽  
Rosita Nur Avisha ◽  
Dewi Marfu’ah Kurniawati ◽  
Rachma Purwanti ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Blood Glucose ◽  
Cell Damage ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Control Group ◽  
Sprague Dawley ◽  
Control Group Design ◽  
The Difference

Background: Pre metabolic syndrome is characterized by two of five risk factors: central obesity, dyslipidemia, hypertension, and increased fasting blood glucose. Cinnamon yogurt and soygurt contain antioxidants and fiber which can improve insulin sensitivity and blood glucose homeostasis and prevent cell damage in pre-metabolic syndrome conditionsObjective: This study aimed to determine the effect of cinnamon yogurt and soygurt on fasting blood glucose (FBG), serum insulin, and malondialdehyde (MDA) levels in pre-metabolic syndrome rats.Method: This study was an experimental study with a pre and post-test control group design. The subjects were 15 male Sprague Dawley rats which were divided into 5 normal control mice (K) and 10 pre metabolic syndrome mice with a diet high in fat and fructose for group P1 (yogurt) and P2 (soygurt) each of 5 mice. The yogurt and soygurt were given as much as 3.4 ml / g BW for 28 days. FBG levels were measured by the GOD-PAP method, while serum insulin and MDA levels were by the ELISA method. Different tests before and after treatment using Paired t-test or Wilcoxon. The difference tests between groups using the One-Way ANOVA test or Kruskal Wallis.Results: There were no differences in FBG and MDA levels between groups after intervention (p> 0.05). The highest percentage reduction in FBG in the P2 (-11.59%), then P1 (-4.06%). The decrease in MDA levels in group P1 = 19.17%, and P2 = 15.44% lower than K = 24.43%. After the intervention, the insulin level in group P2 (0.46 ng / ml) was significantly higher than P1 (0.318 ng/ml), but both were not different from K (0.384 ng / ml).Conclusion: There was no significant effect on the administration of cinnamon yogurt and soygurt to FBG, serum insulin, and MDA levels.

Anti-diabetic activity of diphenhydramine in diabetic rats

2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Group Iv ◽  
Diabetic Rat ◽  
Control Group ◽  
Group I

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.

Effect of Dapagliflozin on Intestinal Flora in MafA-deficient Mice

2018 ◽  
Vol 24 (27) ◽  
pp. 3223-3231 ◽  
Author(s):  
Luyao Li ◽  
Shiyao Xu ◽  
Tingting Guo ◽  
Shouliang Gong ◽  
Chuan Zhang
Keyword(s):  
Blood Glucose ◽  
High Throughput Sequencing ◽  
Fatty Acid Content ◽  
Fasting Blood Glucose ◽  
Intestinal Flora ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Short Chain ◽  
Control Group ◽  
Deficient Mice

Objective: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes. Methods: Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks. Mouse body weights and fasting blood glucose levels were measured, and intestinal short-chain fatty acids were measured by gas chromatography. A series of methods was used to analyse the number of primary harmful bacteria in the faeces, and high-throughput sequencing was used to sequence the changes in intestinal flora. Results: The weight of the mice decreased after dapagliflozin gavage, and fasting blood glucose was significantly lower than that in the control group (P < 0.001). Acetic acid and butyric acid contents in the intestinal tracts of the mice increased, and the growth of harmful microorganisms, such as Clostridium perfringens, enterococci, Enterobacteriaceae, and intestinal enterococci, was inhibited. Blautia is a species found in the experimental group and was significantly different from the control and blank groups as determined by the LDA score from highthroughput sequencing. Conclusion: Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase short-chain fatty acid content, regulate the intestinal microecological balance of the body and promote blood glucose and energy homeostasis.

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

scholarly journals Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Mouse Model ◽  
High Fat Diet ◽  
Liver Diseases ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
Herbal Formulation ◽  
Plants Extract

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

scholarly journals The effect of oat bran consumption on gestational diabetes: a randomized controlled clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zahra Barati ◽  
Mina Iravani ◽  
Majid Karandish ◽  
Mohammad Hosein Haghighizadeh ◽  
Sara Masihi
Keyword(s):  
Clinical Trial ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Fasting Blood Glucose ◽  
Intervention Group ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Standard Diet ◽  
Oat Bran ◽  
Significant Difference

Abstract Background Gestational diabetes is the most common medical complication in pregnancy, and it has many side effects for the mother and the fetus. The aim of this study was to evaluate the effect of oat bran consumption on gestational diabetes. Methods This study is a randomized clinical trial that was performed on 112 women with gestational diabetes treated with diet. Participants were randomly divided into two groups of 56. Participants in both groups were given a diet for gestational diabetes. In addition to the diet, the intervention group received 30 g of oat bran daily for 4 weeks at lunch and dinner. Tests of fasting blood glucose and two-hour postprandial (2hpp) glucose were taken from both groups: before the intervention, and 2 and 4 weeks after the start of the intervention. Data analysis was performed using SPSS statistical software (version 22) using independent t-test, as well as Chi-square and Mann-Whitney tests. P values less than 0.05 were considered statistically significant. Results There was no statistically significant difference between the two groups in terms of mean blood glucose before the intervention, while 2 and 4 weeks after the intervention, mean fasting blood glucose and two-hour postprandial (2hpp) glucose decreased significantly in the intervention group compared with the control group (P < 0.001). Conclusion Based on the results of this study, the addition of oat bran to the standard diet for pregnant women with gestational diabetes reduced fasting blood glucose and two-hour postprandial (2hpp) glucose. More detailed studies with higher sample sizes are recommended to prove the effectiveness of this valuable dietary supplement. Trial registration IRCT registration number:IRCT20191220045828N1. Registration date: 2020-04-18. Registered while recruiting.

scholarly journals Gold Nanoparticles Affect Pericyte Biology and Capillary Tube Formation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Sasikarn Looprasertkul ◽  
Amornpun Sereemaspun ◽  
Nakarin Kitkumthorn ◽  
Kanidta Sooklert ◽  
Tewarit Sarachana ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Endothelial Cell ◽  
Mrna Expression ◽  
Capillary Tube ◽  
Quantitative Polymerase Chain Reaction ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Control Group ◽  
Capillary Tubes ◽  
Cell Functions

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-β (PDGFR-β) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-β mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-β mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.

Effects of GYDENPHY caspules on streptozotocin-induced type 1 diabetic in Swiss mouse model

2021 ◽  
Vol 25 (2) ◽  
pp. 24-32
Author(s):  
Trinh Thach Thi Nguyen ◽  
Duy Tuan Nguyen ◽  
Thanh Ha Tuan Nguyen ◽  
Thi Huong Lan Do ◽  
Hoang Ngan Nguyen
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Insulin Injection ◽  
Swiss Mouse ◽  
Hypoglycemic Effect ◽  
Control Group ◽  
Water Control

Objective: Evaluation the hypoglycemic effect of Gydenphy capsules on Streptozotocin-induced type 1 diabetic in Swiss mouse model. Methods: The type 1 diabetic model was established by intraperitoneal injections of Streptozocin 150mg/kg in Swiss mouse. Then, the Gydenphy were orally administered daily at a dose of 576 mg/kg/day or 1152 mg/kg/day in 10 days. Blood glucose concentration in the Gydenphy oral groups with that of water control group and the intraperitoneal insulin injection group was compared. Results: Blood glucose concentration in the groups using Gydenphy (dose576 mg/kg/24h and dose 1152 mg/kg/24h) significal decreased compared to the distilled water group at (p <0.05 at the time of 4 hours, 8 hours; p <0.01 at the time of 3, 10 days). The hypoglycemic effect of Gydenphy at 576mg/kg/day and 1152 mg/kg/day at 4 hours, 8 hours and 3 days were inferior to insulin 0.1 UI/kg/day for glycemic control. However, the hypoglycemic effect ofGydenphy were equivalent to insulin after 10 consecutive days on treatment. Conclusion: Gydenphy capsules have hypoglycemic effects onStreptozotocin-induced type 1 diabetes in Swiss mouse model.

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