Micro-Physiological-Systems enable investigation of hypoxia induced pathological processes in human aortic valve cells and tissues

2021 ◽  
Vol 7 (2) ◽  
pp. 45-48
Author(s):  
Maximilian Winkelkotte ◽  
Florian Schmieder ◽  
Stephan Behrens ◽  
Dominic Salminger ◽  
Anett Jannasch ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Animal Experiments ◽  
Assay Condition ◽  
Hypoxic Conditions ◽  
Ldh Activity ◽  
Human Aortic Valve ◽  
Tissue Oxygen Supply ◽  
Advantageous Effect ◽  
Physiological Systems

Abstract Aortic valve (AV) stenosis is characterized by tissue fibrosis and calcification. Fibrous thickening can result in reduced tissue oxygen supply leading to pathological valvular interstitial cell (VIC) differentiation and calcification. Static 2D VIC cultures and animal models are limited in the ability to reflect human AV calcification. Culturing of VICs in micro-physiological-systems (MPS) in a pulsatile flow and the establishment of a modular AV tissue incubation chamber (TIC) are new approaches to evaluate pathophysiological processes of AV disease. Therefore, a MPS able to adjust hypoxic conditions was applied for VIC culture. A significant increase of mRNA-expression of EGLN1 and HIF1α- regulated LDHA and HIF1α nuclear localisation were proven under hypoxia. AV tissue culture was established within a TIC and viability was monitored by Resazurin-reduction in the incubation medium and visualized by LDH-activity in tissue cryosections. Viability was compared between fluid and static incubated tissues revealing an advantageous effect of the fluidic assay condition. Consecutively, the application of MPS in AV research allows i) the investigation of VIC cultures with efficient oxygen regulation and ii) the culture of porcine or human AV tissues preserving viability and specifically reflecting in vivo parameters. These methods open up new possibilities beyond static 2D culture and facilitate a reduction of animal experiments in AV research.

P6496Endovascular reconstruction from aortic valve to aortic arch by one-piece valved-fenestrated-bifurcated endografting in animal experiments

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Z P Jing ◽  
J X Feng ◽  
X H Bao ◽  
T Li ◽  
Y Zhao ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Arch ◽  
Aortic Root ◽  
Animal Experiments ◽  
Proximal Part ◽  
Minimal Invasive ◽  
Left Ventricular ◽  
Technical Success Rate

Abstract Aims The possibility of endovascular reconstruction of aortic valve, sinus of Valsalva, and ascending aorta by a minimal-invasive single endograft has not been proven in vivo. Combining our own long-term experiences from transcatheter aortic valve replacement (TAVR) and Thoracic Endovascular Repair (TEVAR) for ascending and arch dissection, we designed the special endo-graft: a novel one-piece valved-fenestrated-bifurcated endografting, and tried to endovascularly reconstruct the area from Left ventricular outflow tract to aortic arch in animal experiments. Methods and results For 20 healthy adult female pigs weighed between 62.3±2.2 kilograms, we did aortic compute tomography angiography (CTA) examinations and measured morphologic parameters of aortic root. Then we accordingly customized the valved-fenestrated-bifurcated endograft. The endograft was delivered through transapical access and endovascularly reconstructed the segment from aortic valve to proximal part of aortic arch. The overall technical success rate was 95% because of one case of delivery system failure. Instant transesophageal echography (TEE) and aortic CTA confirmed ideal position of the endograft, satisfactory function of aortic valve, and the patency of coronary arteries in all subjects. During follow-up, 12 subjects were sacrificed according to the plan and seven were followed up for 8.1±3.6 months. There was one unplanned death of cardiac infection (unplanned mortality: 5.3%). Follow-up re-examinations (aortic CTA, cardiac ultrasound, and electrocardiogram) found no adverse events. Among 12 sacrificed subjects, there was no evidence of fenestrations alignment lost and no myocardial ischemia according to the pathological analysis. Conclusion The novel one-piece valved-fenestrated-bifurcated endografting might be feasible for minimal-invasive reconstruction of aortic root in animal models, thus provided a prospect to simultaneously treat pathologies involving aortic valve and aortic root in endovascular way.

scholarly journals Feasibility of In Vivo Human Aortic Valve Modeling Using Real-Time Three-Dimensional Echocardiography

2014 ◽  
Vol 97 (4) ◽  
pp. 1255-1258 ◽  
Author(s):  
Arminder S. Jassar ◽  
Melissa M. Levack ◽  
Ricardo D. Solorzano ◽  
Alison M. Pouch ◽  
Giovanni Ferrari ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Real Time ◽  
Three Dimensional ◽  
Valve Modeling ◽  
Dimensional Echocardiography ◽  
Three Dimensional Echocardiography ◽  
Human Aortic Valve

scholarly journals In-vivo heterogeneous functional and residual strains in human aortic valve leaflets

2016 ◽  
Vol 49 (12) ◽  
pp. 2481-2490 ◽  
Author(s):  
Ankush Aggarwal ◽  
Alison M. Pouch ◽  
Eric Lai ◽  
John Lesicko ◽  
Paul A. Yushkevich ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Leaflets ◽  
Residual Strains ◽  
Human Aortic Valve

scholarly journals Degenerative aortic valve disease and diabetes: Implications for a link between proteoglycans and diabetic disorders in the aortic valve

2018 ◽  
Vol 16 (3) ◽  
pp. 254-269 ◽  
Author(s):  
Mareike Barth ◽  
Jessica I Selig ◽  
Svenja Klose ◽  
Antje Schomakers ◽  
Lena S Kiene ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aortic Valves ◽  
Potential Link ◽  
Human Aortic Valve

Degenerative aortic valve disease in combination with diabetes is an increasing burden worldwide. There is growing evidence that particularly small leucine-rich proteoglycans are involved in the development of degenerative aortic valve disease. Nevertheless, the role of these molecules in this disease in the course of diabetes has not been elucidated in detail and previous studies remain controversial. Therefore, the aim of this study is to broaden the knowledge about small leucine-rich proteoglycans in degenerative aortic valve disease and the influence of diabetes and hyperglycaemia on aortic valves and valvular interstitial cells is examined. Analyses were performed using reverse-transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, (immuno)histology and colorimetric assays. We could show that biglycan, but not decorin and lumican, is upregulated in degenerated human aortic valve cusps. Subgroup analysis reveals that upregulation of biglycan is stage-dependent. In vivo, loss of biglycan leads to stage-dependent calcification and also to migratory effects on interstitial cells within the extracellular matrix. In late stages of degenerative aortic valve disease, diabetes increases the expression of biglycan in aortic valves. In vitro, the combinations of hyperglycaemic with pro-degenerative conditions lead to an upregulation of biglycan. In conclusion, biglycan represents a potential link between degenerative aortic valve disease and diabetes.

CLINICAL FEASIBILITY OF NON-OBSTRUCTIVE AORTIC ANGIOSCOPY FOR ASSESSING ATHEROSCLEROTIC PATHOLOGY OF HUMAN AORTIC VALVE IN VIVO: A NOVEL APPROACH

2018 ◽  
Vol 71 (11) ◽  
pp. A1140
Author(s):  
Keisuke Kojima ◽  
Tadateru Takayama ◽  
Takafumi Hiro ◽  
Suguru Migita ◽  
Morikawa Tomoyuki ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Novel Approach ◽  
Human Aortic Valve

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

scholarly journals Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 315
Author(s):  
Zhenxing Wang ◽  
Zongcai Tu ◽  
Xing Xie ◽  
Hao Cui ◽  
Kin Weng Kong ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Animal Experiments ◽  
Ethyl Acetate Fraction ◽  
The Body ◽  
Total Phenolic ◽  
Antioxidant Power ◽  
Glycogen Accumulation ◽  
Inhibitory Ability

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

scholarly journals Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhibin Liao ◽  
Hongwei Zhang ◽  
Chen Su ◽  
Furong Liu ◽  
Yachong Liu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Downstream Target ◽  
Protein Levels ◽  
Elevated Expression ◽  
Rna Immunoprecipitation

Abstract Background Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. Results In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. Conclusion SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

scholarly journals In Vitro and In Vivo Biosafety Analysis of Resorbable Polyglycolic Acid-Polylactic Acid Block Copolymer Composites for Spinal Fixation

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 29
Author(s):  
Seung Kyun Yoon ◽  
Jin Ho Yang ◽  
Hyun Tae Lim ◽  
Young-Wook Chang ◽  
Muhammad Ayyoob ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Animal Experiments ◽  
Polymeric Materials ◽  
Polyglycolic Acid ◽  
Poly Lactic Acid ◽  
Skin Sensitization ◽  
Spinal Fixation ◽  
In Vivo Degradation

Herein, spinal fixation implants were constructed using degradable polymeric materials such as PGA–PLA block copolymers (poly(glycolic acid-b-lactic acid)). These materials were reinforced by blending with HA-g-PLA (hydroxyapatite-graft-poly lactic acid) and PGA fiber before being tested to confirm its biocompatibility via in vitro (MTT assay) and in vivo animal experiments (i.e., skin sensitization, intradermal intracutaneous reaction, and in vivo degradation tests). Every specimen exhibited suitable biocompatibility and biodegradability for use as resorbable spinal fixation materials.

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