Abstract P107: Anti- Mir-510 In The Treatment Of Essential Hypertension By Using Hypertensive Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Auxzilia Preethi K ◽  
Sushmaa Chandralekha J.S ◽  
Durairaj sekar
Keyword(s):  
Gene Expression ◽  
Rat Model ◽  
Luciferase Assay ◽  
Sprague Dawley ◽  
Critical Pathways ◽  
Cardiac Tissues ◽  
In Vivo Experiments ◽  
Huvec Cells

Introduction: Hypertension (HTN) is one of the major public health complications throughout the world. Although progress has been made in HTN research, early diagnosis and treatment of HTN are yet to be flourished. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in many diseases including HTN. According to our previous report, there is direct evidence showing that miR-510 is involved in HTN. Hypothesis: We assessed the hypothesis that to decipher the critical pathways of miR-510 and PTEN in regulation of PI3K/AKT Pathways, so it can be used as a therapeutic pathway as well as biomarker. Finally, we intend to study how anti-miR-510 reduces the HTN in the hypertensive induced rat model. Methodology: Proliferation, migration, invasion and apoptosis capacity of miR-510, Anti-miR-510, PTEN and eNOS were evaluated in HUVEC Cells. The expression pattern of miR-510, anti-miR-510 and eNOS, PTEN are analyzed by qPCR and western blot The relationship between miR-510, Anti-miR-510 and PTEN are investigated by luciferase assay Deoxycorticosterone acetate (DOCA) of 70mg/kg and 1% NaCl salt induced hypertension model (Sprague Dawley rats) was used in this study. According to the dose dependent study, anti-miR-510 was administered intravenously. Histological analyses are performed to examine the hypertrophy by using cardiac tissues fixed in 1% paraformaldehyde. Results and conclusion: Our results suggested that miR-510 can directly influence the PTEN expressions in HUVEC cells. Furthermore, the in vitro experiments clearly indicated that miR-510/PI3K/AKT/PTEN axis involved in HTN. Anti-miR-510 delivery can reduce the progression of HTN in the hypertensive induced rat model. Though miR-510 is involved in HTN, but its molecular mechanism is almost unknown. So, these analyses suggested that the correlation between miR-510, PTEN, anti-miR-510 are the critical step in gene expression and regulations. Thus, all these analyses could lead in identification of therapeutic target and non-invasive biomarker for HTN. Our in vivo experiments suggesting that anti-miR-510 may act as a novel therapeutic molecule for HTN treatment.

scholarly journals Regulation of mdrlb gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro

1996 ◽  
Vol 17 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Barbara A. Hill ◽  
Paul C. Brown ◽  
Karl-Heinz Preisegger ◽  
Jeffrey A. Silverman
Keyword(s):  
Gene Expression ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Unique Effects of p53−/− Leukemic Cells On Mesenchymal Stromal Cell Gene Expression Profile in Vitro

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3468-3468
Author(s):  
Xiaoyang Ling ◽  
Ye Chen ◽  
Peter P. Ruvolo ◽  
Vivian Ruvolo ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Stromal Cell ◽  
Conflicts Of Interest ◽  
Leukemic Cells ◽  
Bone Marrow Niche ◽  
In Vivo Experiments ◽  
Cell Gene Expression

Abstract Abstract 3468 Mesenchymal stromal cells (MSC) participate in the generation of the microenvironmental bone marrow niche which protects normal and leukemic stem cells from injuries, including chemotherapy. MSC produce numerous factors that aid in this function; however, little is known about how leukemic cells affect MSC. In this study, paired murine AML cells, MLL/ENL/FIT3-ITD/p53−/− and MLL/ENL/FIT3-ITD/p53wt, originally derived from C57BL/6 mice (Zuber et al. Genes & Dev. 2009), were co-cultured with MSC from the same strain. After 48 hrs, MSC were isolated by FACS sorting using CD45−/PDGFr+ as markers. Total RNA was profiled on Illumina WG6 mouse whole-genome bead arrays by standard procedures. The significance analysis of microarrays (SAM) method identified 429 differentially-expressed genes (DEG) whose expression in MSC differed significantly (false discovery rate, 10%) in co-cultures with p53−/− (C78) vs. p53wt (C147) leukemic cells. Differences in these DEG were highly consistent in replicates (Figure 1). The results demonstrate that: 1) p53 status (p53−/− vs. p53wt) of AML cells affects GEP patterns in co-cultured MSC. Comparison of the GEP in MSC co-cultured with p53−/− (78) or p53wt (147) (Fig 1) identified the following 5 genes that showed the most significant differences (up- or down-regulated): up-regulated: WNT16, WNT5, IGFBp5, GCNT1, ATP1B1; down-regulated: NOS2, DCN, CCL7, CCL2, CAR9, CCL4. These were selected for qPCR validation, and the results confirmed the array data. In addition, immunohistochemical staining showed that WNT16 was up-regulated in MSC co-cultured with p53wt leukemic cells. In addition, CXCL5 was found up-regulated in MSC co-cultured with p53−/− leukemic cells. These results were consistent with the GEP data. 2) Leukemic cells alter MSC Signaling proteins in vitro: Western blotting showed that Stat3, Akt, PTEN, CXCL5 and HIF-1α were up- regulated in MSC co-cultured with p53−/− leukemic cells as compared to p53wt leukemic cells (48 hrs). Additional analyses showed that the downstream targets of HIF-1α, VEGFa and VEGFc, but not VEGFb, were up-regulated. Taken together, these results suggest that 1) leukemic cells with different p53 genetic background co-cultured with normal MSC have profoundly differential effects on GEP of normal MSC; 2) MSC co-cultured with p53−/− leukemic cells resulted in increased levels of onco-proteins such as Akt and HIF-1α when compared to MSC co-cultured with p53wt leukemic cells. Results suggest, for the first time, that the genetics of leukemic cells determines gene expression in co-cultured MSC. In vivo experiments are in progress to provide in vivo evidence for the existence of a novel model of leukemia-stroma interactions where the genetics of the tumor cell impacts stromal cell biology. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

4-[123I]Iodospiperone as a ligand for dopamine DA receptors: In vitro and in vivo experiments in a rat model

1992 ◽  
Vol 19 (7) ◽  
pp. 759-763
Author(s):  
J.A. Van Der Krogt ◽  
E.K.J. Pauwels ◽  
P.A.P.M. Van Doremalen ◽  
G. Wijnhoven ◽  
S. Reiffers ◽  
...  
Keyword(s):  
Rat Model ◽  
In Vivo Experiments ◽  
Da Receptors

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

2021 ◽  
pp. 036354652199455
Author(s):  
Han Xiao ◽  
Yang Chen ◽  
Muzhi Li ◽  
Qiang Shi ◽  
Yan Xu ◽  
...  
Keyword(s):  
Rat Model ◽  
Biomechanical Testing ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
The Other ◽  
Histological Evaluation ◽  
Sprague Dawley ◽  
A Cell

Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function. Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft. Study Design: Controlled laboratory study. Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing. Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups. Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model. Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.

scholarly journals Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4964
Author(s):  
Wenling Fan ◽  
Xiaotong Zhang ◽  
Wenjing Zhu ◽  
Xinyi Zhang ◽  
Liuqing Di
Keyword(s):  
Solid Dispersions ◽  
Hot Melt Extrusion ◽  
Solubility Parameters ◽  
Sprague Dawley ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Hot Melt

Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory–Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C–135 °C–140 °C–145 °C–150 °C–155 °C–160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague–Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.

scholarly journals β-Carbolines in Experiments on Laboratory Animals

2020 ◽  
Vol 21 (15) ◽  
pp. 5245
Author(s):  
Renata Zawirska-Wojtasiak ◽  
Agnieszka Fedoruk-Wyszomirska ◽  
Paulina Piechowska ◽  
Sylwia Mildner-Szkudlarz ◽  
Joanna Bajerska ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Laboratory Animals ◽  
Sprague Dawley ◽  
Behavioral Test ◽  
Second Stage ◽  
In Vivo Experiments ◽  
Sprague Dawley Rats ◽  
Coffee Substitute

Some studies have ascribed a protective effect against neurodegenerative diseases to the β-carbolines harman (H) and norharman (NH), which occur mostly in coffee and coffee substitutes. We determined the concentrations of β-carbolines and undesirable compounds (such as acrylamide) in roasted coffee substitute ingredients and found that chicory coffee was optimal. Two in vivo experiments were conducted with seventeen-month-old male Sprague Dawley rats fed a diet with the addition of pure carboline standards in the first stage, and chicory in the second. We observed an increase in the level of H and NH in blood plasma, as well as higher activity of animals in the battery behavioral test, particularly in the second stage. The results of in vitro studies—particularly the level of the expression in brain tissue of genes associated with aging processes and neurodegenerative diseases—clearly show the benefits of a diet rich in β-carbolines.

α1-Adrenoceptor subtypes in rat renal resistance vessels: in vivo and in vitro studies

2000 ◽  
Vol 278 (1) ◽  
pp. F138-F147 ◽  
Author(s):  
Max Salomonsson ◽  
Kristina Brännström ◽  
William J. Arendshorst
Keyword(s):  
Induced Response ◽  
Free Calcium ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Resistance Vessels ◽  
Free Calcium Concentration ◽  
Afferent Arterioles ◽  
High Concentrations

This study provides new information about the relative importance of different α1-adrenoceptors during norepinephrine (NE) activation in rat renal resistance vessels. In Sprague-Dawley rats, we measured renal blood flow (RBF) using electromagnetic flowmetry in vivo and the intracellular free calcium concentration ([Ca2+]i) utilizing ratiometric photometry of fura 2 fluorescence in isolated afferent arterioles. Renal arterial bolus injection of NE produced a transient 46% decrease in RBF. In microdissected afferent arterioles, NE (1 μM) elicited an immediate square-shaped increase in [Ca2+]i, from 90 to 175 nM ( P < 0.001). Chloroethylclonidine (CEC) (50 μM) had no chronic irreversible alkylating effect in vitro but exerted acute reversible blockade on norepinephrine (NE) responses both on [Ca2+]i in vitro and on RBF in vivo. The RBF response was attenuated by ∼50% by the putative α1A-adrenoceptor and α1D-adrenoceptor antagonists 5-methylurapidil (5-MU), and 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY-7378) (12.5 and 62.5 μg/h), respectively. The in vitro [Ca2+]i response to NE was blocked ∼25% and 50% by 5-MU (100 nM and 1 μM). BMY-7378 (100 nM and 1 μM) attenuated the NE-induced response by ∼40% and 100%. The degree of inhibition in vitro was similar to the in vivo experiments. In conclusion, 5-MU and BMY-7378 attenuated the NE-induced responses, although relatively high concentrations were required, suggesting involvement of both the α1A-adrenoceptor and α1D-adrenoceptor. Participation of the α1B-adrenoceptor is less likely, as we found no evidence for CEC-induced alkylation.

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