scholarly journals From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

2020 ◽  
Vol 134 (8) ◽  
pp. 1001-1025 ◽  
Author(s):  
Sonya Frazier ◽  
Martin W. McBride ◽  
Helen Mulvana ◽  
Delyth Graham
Keyword(s):  
Animal Models ◽  
Cell Types ◽  
Rodent Model ◽  
Hypertensive Disorder ◽  
Model Studies ◽  
Genetic Components ◽  
Immune Mediated ◽  
Hypertensive Disorder Of Pregnancy

Abstract Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000744 ◽  
Author(s):  
Kerstin Klein
Keyword(s):  
Animal Models ◽  
Rheumatic Diseases ◽  
Transcriptional Activation ◽  
Therapeutic Strategy ◽  
Cell Types ◽  
Protein Inhibition ◽  
Different Cell Types ◽  
Novel Therapeutic

The reading of acetylation marks on histones by bromodomain (BRD) proteins is a key event in transcriptional activation. Small molecule inhibitors targeting bromodomain and extra-terminal (BET) proteins compete for binding to acetylated histones. They have strong anti-inflammatory properties and exhibit encouraging effects in different cell types in vitro and in animal models resembling rheumatic diseases in vivo. Furthermore, recent studies that focus on BRD proteins beyond BET family members are discussed.

scholarly journals The critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

2020 ◽  
Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Biological Macromolecules

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Interleukin-13 in Combination With CD40 Ligand Potently Inhibits Apoptosis in Human B Lymphocytes: Upregulation of Bcl-xL and Mcl-1

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4415-4424 ◽  
Author(s):  
Jon Lømo ◽  
Heidi Kiil Blomhoff ◽  
Sten Eirik Jacobsen ◽  
Stanislaw Krajewski ◽  
John C. Reed ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Cell Types ◽  
Cd40 Ligand ◽  
Interleukin 13

Abstract Interleukin-13 (IL-13) is a novel T-cell–derived cytokine with IL-4–like effects on many cell types. In human B lymphocytes, IL-13 induces activation, stimulates proliferation in combination with anti-IgM or anti-CD40 antibodies, and directs Ig isotype switching towards IgE and IgG4 isotypes. We show here that IL-13 also regulates human B-cell apoptosis. IL-13 reduced spontaneous apoptosis of peripheral blood B cells in vitro, as shown by measurement of DNA fragmentation using the TUNEL and Nicoletti assays. The inhibition of cell death by IL-13 alone was significant but modest, but was potently enhanced in combination with CD40 ligand (CD40L), a survival stimulus for B cells by itself. Interestingly, IL-13 increased the expression of CD40 on peripheral blood B cells, providing a possible mechanism for the observed synergy. IL-13 alone was a less potent inhibitor of apoptosis than IL-4. Moreover, there was no additive effect of combining IL-4 and IL-13 at supraoptimal concentrations, which is consistent with the notion that the IL-4 and IL-13 binding sites share a common signaling subunit. The combination of IL-13 with CD40L augmented the expression of the Bcl-2 homologues Bcl-xL and Mcl-1, suggesting this as a possible intracellular mechanism of induced survival. By contrast, levels of Bcl-2, and two other Bcl-2 family members, Bax and Bak, remained unaltered. Given the importance of the CD40-CD40L interaction in B-cell responses, these results suggest a significant role of IL-13 in the regulation of B-cell apoptosis.

scholarly journals Approaching 3R teaching in biomedical engineering

2020 ◽  
Author(s):  
Valeria Chiono
Keyword(s):  
Animal Models ◽  
Biomedical Engineering ◽  
Experimental Models ◽  
Preclinical Testing ◽  
Preclinical Trials ◽  
European Standards ◽  
Preclinical Animal Models ◽  
In Silico Models

Since its adhesion to Centro3R, Politecnico di Torino has approached 3R teaching through a new Master course, entitled “New advances in alternative preclinical trials”. This is a multidisciplinary optional course for Master students in Biomedical Engineering, with the contribution of different teachers, who are experts on different aspects of preclinical testing of biomedical devices: European Standards for preclinical experimentation; preclinical animal models; protection of animal welfare in the European legislation; the role of statistics on the application of the 3R principle; preclinical experimental models in vitro; in silico models. This contribution describes the subjects faced by the course and their importance in the context of the 3R Principle.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

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