MO332THE IRRADIATION-INDUCED RENAL ISCHEMIC PRECONDITIONING IS BLUNTED BY THE ORAL ADMINISTRATION OF THE ANTI-ANGIOGENIC AGENT, SUNITINIB

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Badr Khbouz ◽  
François Lallemand ◽  
Pascal Rowart ◽  
Laurence Poma ◽  
Agnès Noel ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Real Time ◽  
Ischemic Preconditioning ◽  
Functional Enrichment ◽  
Whole Body ◽  
Control Group ◽  
Mrna Levels ◽  
Wild Type ◽  
Post Irradiation ◽  
Real Time Qpcr

Abstract Background and Aims Whole-body irradiation has been suggested to induce renal ischemic preconditioning (RIP) in rodent models, possibly via neo-angiogenesis. First, we comprehensively investigate the pathways involved in kidney-centered irradiation. Next, we assess the functional and structural impact of kidney-centered irradiation applied before ischemia/reperfusion (I/R) injury. Finally, we test whether Sunitinib-mediated inhibition of the neo-angiogenesis prevents irradiation-associated RIP. Method Experiment 1: Unilateral irradiation of the left kidney (8.56 Gy) was performed in male 10-week-old wild-type C57bl/6 mice (n=10). One month later, total kidney RNA was extracted from irradiated and control (n=5) mice for comparative high-throughput RNA-Seq (using BaseSpace Sequence Hub Illumina). Functional enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Experiment 2: Two x-ray beams (225Kv, 13mA) specifically targeted both kidneys for a total dose of 8.56Gy. The right kidneys were removed and harvested, and the left kidneys undergo 30-minute ischemia followed by 48-hour reperfusion (n=8) at Days 7-14-21-28 post irradiation. Experiment 3: Following the same protocol of renal I/R at Day14, 3 groups of male 10-week-old wild-type C57bl/6 mice were compared (n=8 per group): 1/ bilateral pre-irradiation; 2/ bilateral pre-irradiation and gavage with Sunitinib from Day2 to Day13; 3/ control group without irradiation or gavage. Results Experiment 1: Comparative transcriptomics showed a significant up-regulation of various signaling pathways, including angiogenesis (HMOX1) and stress response (HSPA1A, HSPA1B). Expressions of angiogenesis markers (CD31, TGFb1, HMOX1) showed an increase at both mRNA (real-time qPCR) and protein (immuno-staining) levels in irradiated kidneys compared to controls (p<0.01). Experiment 2: Following I/R, the blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly lower in the irradiated animals compared to controls: (BUN: 86.2±6.8 vs. 454.5±27.2mg/dl; SCr: 0.1±0.01 vs. 1.7±0.2mg/dl, p<0.01). The renal infiltration by CD11b-positive cells (187±32 vs. 477±20/mm²) and F4-80 macrophages (110±22 vs. 212±25/mm²) was significantly reduced in the irradiated group. The real-time qPCR mRNA levels of the angiogenic markers, TGFb1 and CD31, were significantly increased in the irradiated group compared to controls (p<0,01). The CD31-immunostating (quantified by FiJi) was increased in irradiated mice compared to controls (p<0.01). Experiment 3: One-way analysis of variance followed by Tukey’s test showed that, following I/R, the serum levels of BUN and SCr were lower in irradiated group compared to controls (BUN: 106.1±33.6 vs. 352.2±54.3mg/dl; SCr: 0.3±0.13 vs. 1±0.2mg/dl), and in irradiated group compared to the irradiated-exposed group to Sunitinib (BUN: 106.1±33.6 vs. 408.4±54.9mg/dl; SCr: 0.3±0.12 vs. 1.5±0.3mg/dl; p<0.01). No difference was observed between the irradiated-exposed mice to Sunitinib and the controls. Conclusion Renal irradiation induces the activation of signaling pathways involved in angiogenesis in mice. Renal pre-irradiation leads to RIP, with preserved renal function and attenuated inflammation post I/R. Exposure to the anti-angiogenic drug Sunitinib post-irradiation prevents the irradiation-induced RIP.

scholarly journals FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lexun Wang ◽  
Huijuan Wu ◽  
Yanyue Deng ◽  
Shengxi Zhang ◽  
Quxing Wei ◽  
...  
Keyword(s):  
Body Weight ◽  
Signaling Pathways ◽  
Diabetic Cardiomyopathy ◽  
Functional Enrichment ◽  
Inflammatory Factors ◽  
Interleukin 12 ◽  
Network Pharmacology ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mrna Levels

Background. The pathogenesis and clinical features of diabetic cardiomyopathy (DCM) have been well studied in the past decade; however, effective approaches to prevent and treat this disease are limited. Fufang Zhenzhu Tiaozhi (FTZ) formula, a traditional Chinese prescription, is habitually used to treat dyslipidemia and diabetes. Recently, several studies have reported the therapeutic effects of FTZ on cardiovascular diseases. However, the effects of FTZ on DCM have not yet been fully elucidated. This study investigated the effects of FTZ on DCM and determined the mechanisms underlying its efficacy. Methods. Diabetes was induced in mice by intraperitoneal injection of streptozotocin; the mice were randomly divided into a control group (Con), diabetes group (DCM), and diabetes-treated with FTZ (DCM + FTZ). Myocardial structural alterations, fibrosis biomarkers, and inflammation were observed. Besides, the potential targets and their related signaling pathways were analyzed using network pharmacology and further verified by Western blot. Results. Diabetic mice showed significant body weight loss, hyperglycemia, and excessive collagen content in the cardiac tissue, while serum and myocardial inflammatory factors significantly increased. Nerveless, treatment with FTZ for 1 month significantly improved body weight, attenuated hyperglycemia, and alleviated diabetes-associated myocardial structure and function abnormalities. Furthermore, the serum levels of interleukin 12 (IL-12) and chemokine (C–C motif) ligand 2 (CCL2) as well as the mRNA levels of cardiac IL-12, IL-6, and C–C motif chemokine receptor 2 (Ccr2) reduced after FTZ treatment. Additionally, a total of 67 active compounds and 76 potential targets related to DCM were analyzed. Pathway and functional enrichment analyses showed that FTZ mainly regulates inflammation-related pathways, including MAPK and PI3K-AKT signaling pathways. Further investigation revealed that the activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues. Conclusion. Our results suggest that FTZ exhibits therapeutic properties against DCM by ameliorating hyperglycemia-induced inflammation and fibrosis via at least partial inhibition of AKT, ERK, and STAT3 signaling pathways.

Abstract 1064: Pellino-1: A Novel Candidate In Vegf/Flk-1/MKK2 Signaling In Ischemic Preconditioning Induced Cardioprotection: A Study Using Flk +/− and MKK2 −/− Knockout Mice.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Mahesh Thirunavukkarasu ◽  
Samson Mathews Samuel ◽  
Sankar Addya ◽  
Lijun Zhan ◽  
Chi-Kuang Huang ◽  
...  
Keyword(s):  
Real Time ◽  
Ischemic Preconditioning ◽  
Knockout Mice ◽  
Real Time Pcr ◽  
Left Ventricular ◽  
List Type ◽  
Mrna Levels ◽  
Clinical Issue ◽  
Endothelial Cell Function ◽  
Vegf Signaling

VEGF modulates the complex process of angiogenesis and other various aspects of endothelial cell function through either of its two tyrosine kinase receptors, VEGFR1/Flt-1 or VEGFR2/Flk1/ KDR via its target protein MKK2. In the present study we used Flk1 +/− and MKK2 −/− knockout mice in an attempt to address an important clinical issue by identifying potential downstream candidates of VEGF signaling through Flk1 receptor that trigger cardioprotective signal during ischemic preconditioning (IP). Mouse hearts were subjected to 30 min of global ischemia and 2 hours of reperfusion (IR) in the Isolated Working Heart model. It is known that IP (4min of ischemia + 6min reperfusion, 4 cycles, before 30 min of ischemia) induces cardioprotection through the activation of the VEGF signaling cascade. The mice were randomly divided into 6 groups for both the gene knockout (KO) studies: Wild Type-Baseline (WTBL), FlkBL/ MKK2BL (KOBL), WTIR , KOIR, WTIP and KOIP. Significant reduction in left ventricular functional recovery through out reperfusion (dp/dt = 605 vs 884), diminished coronary flow (1.9 vs 2.4) and aortic flow (0.16 vs 1.2) and increased infarct size (38.4% vs. 28.41%) after reperfusion were observed in FlkIR, compared to WTIR. As expected we observed disruption in IP induced cardioprotection in FlkIP compared to WTIP. Affymetrix gene chip analysis demonstrated significant downregulation of genes (Pellino-1, MKK2, NF-ΰB) which are thought to play important roles in cardioprotection after ischemic insults in the Flk +/− mice compared to WT. These results were further validated at the mRNA expression level with Real Time PCR. Pellino-1 (Pel-1) was found to be significantly downregulated in FlkBL (0.74 vs 1), FlkIR (1.29 vs 1.35) and FlkPC (1.35 vs 1.49) as compared to their respective controls. We further validated the mRNA levels of Pel-1using Real Time PCR and RT-PCR in the MKK2 −/− mice and found that it, remained unaffected in MKK2BL as compared to its WTBL, and increased as expected in MKK2PC as compared to both MKK2BL and FlkPC (2.48 vs 1.2 and 2.48 vs 1.35, respectively). Therefore this study validated for the first time that Pel-1 is a novel downstream mediator in VEGF/FLK1 signaling and it induces IP mediated cardioprotection via MKK2 signaling.

Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPARα-dependent manner

2013 ◽  
Vol 305 (9) ◽  
pp. E1093-E1102 ◽  
Author(s):  
Andressa Bolsoni-Lopes ◽  
William T. Festuccia ◽  
Talita S. M. Farias ◽  
Patricia Chimin ◽  
Francisco L. Torres-Leal ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Palmitoleic Acid ◽  
Whole Body ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Wild Type ◽  
Acid Incorporation ◽  
Gene And Protein Expression ◽  
Fatty Acid Incorporation ◽  
Deficient Mice

We investigated whether palmitoleic acid, a fatty acid that enhances whole body glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from wild-type or PPARα-deficient mice treated with 16:1n7 (300 mg·kg−1·day−1) or oleic acid (18:1n9, 300 mg·kg−1·day−1) by gavage for 10 days were evaluated for lipolysis, TAG, and glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and pSer660-HSL. Such increase in lipolysis induced by 16:1n7, which can be prevented by pharmacological inhibition of PPARα, was associated with higher rates of PPARα binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0 increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose without affecting glyceroneogenesis and glycerokinase expression. Corroborating in vitro findings, treatment of wild-type but not PPARα-deficient mice with 16:1n7 increased primary adipocyte basal and stimulated lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7 treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose in both wild-type and PPARα-deficient mice. In conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a mechanism that requires a functional PPARα.

scholarly journals Glucagon-Like Peptide-1 (GLP-1) Reduces Mortality and Improves Lung Function in a Model of Experimental Obstructive Lung Disease in Female Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4503-4511 ◽  
Author(s):  
Niels-Erik Viby ◽  
Marie S. Isidor ◽  
Katrine B. Buggeskov ◽  
Steen S. Poulsen ◽  
Jacob B. Hansen ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Whole Body ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Female Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P < .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P < .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

MO329THE GENETIC DELETION OF THE DUAL SPECIFICITY PHOSPHATASE 3 (DUSP3) ATTENUATES KIDNEY DAMAGE FOLLOWING ISCHEMIA/REPERFUSION INJURY IN MOUSE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Badr Khbouz ◽  
Pascal Rowart ◽  
Laurence Poma ◽  
Martina Bottner ◽  
Géraldine Bolen ◽  
...  
Keyword(s):  
Real Time ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Parenchyma ◽  
Vascular Density ◽  
Mrna Levels ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Genetic Deletion ◽  
Real Time Qpcr

Abstract Background and Aims Dual Specificity Phosphatase 3 (DUSP3) is a positive regulator of the innate immune response in case of sepsis, but its role in the ischemic damage is unknown. Here, we study (i) whether and where DUSP3 is expressed in the renal parenchyma, and (ii) whether its genetic deletion in Dusp3 systemic knock-out (Dusp3-/-) mice attenuates the I/R-associated inflammation and injury. Method Experiment 1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal ischemia for 30 minutes followed by a reperfusion of 48 hours. Blood and kidneys were collected. Renal function was assessed upon I/R biomarkers, i.e. blood urea nitrogen (BUN) and creatinine (SCr). Expressions of inflammatory and immune markers were comparatively quantified at both mRNA (real-time qPCR) and protein (immuno-blotting and –staining) levels in ischemic vs. non-ischemic kidneys in Dusp3 WT vs. KO mice. Experiment 2: Ten C57BL/6 male WT and Dusp3-/- mice were anesthetized. Renal Doppler ultrasound was performed to assess the renal resistivity index (RRI). The expression of CD31 and VEGF vascular markers was quantified by the means of real-time qPCR and and immuno-staining (FiJi software). Results Experiment 1: An immuno-reactive signal for DUSP3 was detected in the glomeruli (in co-localization with nephrin) and in Meca-32-positive endothelial cells of both outer and inner medulla of mouse non-ischemic WT kidneys. No significant immunoreactivity for DUSP3 was detected in Dusp3-/- kidneys. Following renal I/R, the mRNA level of Dusp3 was increased 1.8-fold compared to baseline (p<0.001). Immunoblot quantifications showed a 77-fold increased expression of DUSP3 post renal I/R. Serum levels of I/R biomarkers were significantly lower in Dusp3-/- compared to WT mice following renal I/R (BUN: 78.4±33.7 vs. 258.9±162.9mg/dL; SCr: 0.1±0.07 vs. 0.8±0.9 mg/dL; p<0.01). At mRNA levels, Dusp3-/- ischemic kidneys showed a significantly decreased expression level of CD11b, TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-positive cells were significantly reduced in Dusp3-/- vs WT renal parenchyma post I/R. Experiment 2: The RRI non-invasively measured by ultrasound was lower in Dusp3-/- group compared to controls (0.56± 0.03 vs. 0.66±0.02; p<0.001). The Dusp3-/- non-ischemic kidneys were characterized by a 1.8-fold increased surface of CD31-positive cells compared to WT kidneys (p<0.001). At mRNA levels, the Dusp3-/- kidneys showed significantly increased basal levels of CD31 and VEGF compared to controls. Conclusion The genetic deletion of DUSP3 is associated with (i) increased renal vascular density, (ii) decreased RRI and (iii) nephroprotection against renal I/R injury.

Allogeneic Committed Hematopoietic Progenitors Are Protective Against Radiation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4871-4871
Author(s):  
Benny J. Chen ◽  
Divino Deoliveira ◽  
Nelson J. Chao
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Bone Marrow Failure ◽  
Stem Cell Marker ◽  
Whole Body ◽  
Control Group ◽  
Hematopoietic Progenitors ◽  
Post Irradiation ◽  
Histocompatibility Complex

Abstract Whole-body irradiation may lead to bone marrow failure and death. It was previously reported that congenic myeloerythroid-restricted progenitors are able to radioprotect lethally irradiated animals. However, this approach will not be practical because syngeneic/congenic donors are rarely available in humans. To solve this problem, we investigated whether allogeneic committed progenitors are also radioprotective. Hematopoietic committed progenitors were isolated by FACS based on the presence of early progenitor marker CD244 and the absence of stem cell marker CD150 (CD244+CD150−). BALB/c mice (H2d) were lethally irradiated with 8.5 Gy. Within 4 hours of irradiation, the irradiated mice were infused with 5x105 sorted hematopoietic progenitors from major histocompatibility complex mistmatched C57BL/6 donors (H2b). As shown in the Figure B, all the mice in the radiation control group died within 15 days post irradiation (median survival time: 13 days). Infusion of hematopoietic committed progenitors significantly prolonged the survival of the lethally irradiated mice (P=0.0018, median survival time: 28 days). These results are similar to the results obtained from congenic hematopoietic progenitors using 1x105 cells (Figure A, P<0.0001, median survival time: 10 days vs. 28 days). These data suggest that allogeneic hematopoietic committed progenitor cells are also able to mediate radioprotective effects. Similar to the congenic hematopoietic committed progenitors, allogeneic progenitors may also exert radioprotective effects by jumpstarting hematologic recovery post irradiation. These cells may be stockpiled and used as “off-the-shelf” products for radiation injury and other applications. Figure Figure

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism

2018 ◽  
Vol 50 (09) ◽  
pp. 696-703 ◽  
Author(s):  
Qian Xing ◽  
Zhongyan Shan ◽  
Yun Gao ◽  
Jingyuan Mao ◽  
Xiu Liu ◽  
...  
Keyword(s):  
Real Time ◽  
Fetal Brain ◽  
Mirna Expression Profile ◽  
Control Group ◽  
Mrna Levels ◽  
Neonatal Rats ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Significant Difference ◽  
Brain Tissues

AbstractTo investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3′-untranslated region (3′-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT–PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3′-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

scholarly journals D-limonene in diabetic rats

2021 ◽  
Vol 10 (3) ◽  
pp. e24-e24
Author(s):  
Shahrokh Bagheri ◽  
Mostafa Moradi Sarabi ◽  
Mohammadreza Gholami ◽  
Vahideh Assadollahi ◽  
Reza Mohammadrezaei Khorramabadi ◽  
...  
Keyword(s):  
Real Time ◽  
Kidney Tissue ◽  
Serum Levels ◽  
Diabetic Control ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Tissue Homogenate ◽  
Control Group ◽  
Mrna Levels ◽  
Male Wistar Rats

Introduction: Diabetes mellitus (DM) is a multi-factorial condition associated with oxidative stress. Limonene, as a plant-derived antioxidant, can be used for treating DM. Objectives: An investigation on antioxidant effects in diabetic rats exposed to D-limonene. Materials and Methods: Sixty male Wistar rats were categorized into six groups as follows: control (healthy rats), diabetic control (untreated diabetic rats), sham glibenclamide, diabetic glibenclamide, sham limonene, and finally diabetic limonene. Alloxan (100 mg/dL) was infused intraperitoneally to induce type 1 diabetes in rats. Rats in certain groups were given limonene (100 mg/dL) and glibenclamide (10 mg/dL) orally for 8 weeks. Subsequently, animals were killed, and their kidneys were removed. Serum levels of biochemical factors (including serum creatinine, urea, and glucose) were determined, and factors such as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) were measured in kidney tissue homogenate. The gene expression and enzymatic activity of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney were measured by real-time polymerase chain reaction (real-time PCR) and spectrophotometry, respectively. Results: Limonene treatment significantly decreased serum glucose, creatinine, and urea. Additionally, MDA, MPO, and NO significantly decreased while GSH increased after treatment with limonene. Real-time RT-PCR showed significant elevation (P<0.05) in mRNA levels of GPx, CAT, and SOD in the limonene-treated compared with the diabetic control group. Conclusion: Our results demonstrated that limonene as an herbal antioxidant had better effects on antioxidant markers compared to glibenclamide in rat models of diabetes.

scholarly journals Effect of hyperandrogenism on ovarian function

Reproduction ◽  
2015 ◽  
Vol 149 (6) ◽  
pp. 577-585 ◽  
Author(s):  
Leandro M Velez ◽  
Maria F Heber ◽  
Silvana R Ferreira ◽  
Giselle A Abruzzese ◽  
Roxana M Reynoso ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Ovarian Function ◽  
Follicular Development ◽  
Female Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Ovarian Steroidogenesis ◽  
Inflammatory Status

The objective of this work was to study the ovarian function when follicular development is induced during a hyperandrogenic condition. Female rats were injected with either equine chorionic gonadotropin (eCG group) to induce folliculogenesis or eCG together with DHEA to induce folliculogenesis in a hyperandrogenic condition (eCG+HA group). The control group was injected with vehicle. Ovarian mRNA levels of the peroxisome proliferator-activated receptor gamma (PPARγ) co-activator PGC1α, the PPARγ co-repressor NCoR, the main enzymes involved in the ovarian steroidogenesis (CYP17, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-HSD, and CYP19A), and cyclooxygenase 2 (COX2) were evaluated only by real-time PCR. COX2 was evaluated by both real-time PCR and western blot. Serum steroid hormones and both the oxidative and inflammatory statuses were also quantified. We found that eCG-induced folliculogenesis induced increased mRNA levels of PGC1α and decreased those of NCoR when compared with controls. In addition, we found an increase in serum estradiol (E2) levels and enhanced mRNA expression of CYP19A. A pro-inflammatory status and a pro-oxidant status were also established. When folliculogenesis was induced in a hyperandrogenic condition, the mRNA levels of the PPARγ co-repressor NCoR remained higher than in controls and the pro-inflammatory and pro-oxidant statuses were enhanced. In addition, the enzymes involved in ovarian steroidogenesis were altered leading to the accumulation of testosterone and an unfavorable E2/testosterone ratio. These alterations led to abnormal follicular development.

scholarly journals Co-transfection with BMP2 and FGF2 via chitosan nanoparticles potentiates osteogenesis in human adipose-derived stromal cells in vitro

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199767
Author(s):  
Ying Hu ◽  
Qing-Wei Zhao ◽  
Zheng-Cai Wang ◽  
Qing-Qing Fang ◽  
He Zhu ◽  
...  
Keyword(s):  
Real Time ◽  
Chitosan Nanoparticles ◽  
Human Adipose Tissue ◽  
Bone Morphogenetic Protein 2 ◽  
Expression Vectors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Mrna Levels ◽  
Gene And Protein Expression

Objective To investigate if co-transfection of human bone morphogenetic protein 2 (BMP-2, BMP2) and human fibroblast growth factor 2 (FGF2, FGF2) via chitosan nanoparticles promotes osteogenesis in human adipose tissue-derived stem cells (ADSCs) in vitro. Materials and Methods Recombinant BMP2 and/or FGF2 expression vectors were constructed and packaged into chitosan nanoparticles. The chitosan nanoparticles were characterized by atomic force microscopy. Gene and protein expression levels of BMP-2 and FGF2 in ADSCs in vitro were evaluated by real-time polymerase chain reaction (PCR), western blot, and enzyme-linked immunosorbent assay. Osteocalcin (OCN) and bone sialoprotein (BSP) gene expression were also evaluated by real-time PCR to assess osteogenesis. Results The prepared chitosan nanoparticles were spherical with a relatively homogenous size distribution. The BMP2 and FGF2 vectors were successfully transfected into ADSCs. BMP-2 and FGF2 mRNA and protein levels were significantly up-regulated in the co-transfection group compared with the control group. OCN and BSP mRNA levels were also significantly increased in the co-transfection group compared with cells transfected with BMP2 or FGF2 alone, suggesting that co-transfection significantly enhanced osteogenesis. Conclusions Co-transfection of human ADSCs with BMP2/FGF2 via chitosan nanoparticles efficiently promotes the osteogenic properties of ADSCs in vitro.

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