scholarly journals S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2168
Author(s):  
Chien-Chung Huang ◽  
Tzu-Ting Tseng ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Yat-Yin Law ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
In Vivo Model ◽  
Endothelial Progenitor ◽  
Chick Chorioallantoic Membrane ◽  
Cartilage Erosion ◽  
The Impact

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment.

scholarly journals Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miguel Angel Merlos Rodrigo ◽  
Hana Michalkova ◽  
Vladislav Strmiska ◽  
Berta Casar ◽  
Piero Crespo ◽  
...  
Keyword(s):  
Cisplatin Resistance ◽  
Neuroblastoma Cells ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Chick Chorioallantoic Membrane ◽  
High Level ◽  
Cisplatin Chemoresistance ◽  
The Impact ◽  
First Time

AbstractMetallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.

Evaluation of Chemical, Antipsoriatic and Antiangiogenic Properties of Salt from Lonar Crater Lake Water

2019 ◽  
Vol 4 (3) ◽  
pp. 159-165
Author(s):  
Prakash Bansode ◽  
Indumathi Somasundaram ◽  
Apurva Birajdar ◽  
Sanjay Mishra ◽  
Dhanashree Patil ◽  
...  
Keyword(s):  
Lake Water ◽  
Crater Lake ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Chorioallantoic Membrane ◽  
Soda Lake ◽  
Antiangiogenic Activity ◽  
The Impact ◽  
Lonar Crater

Lonar Crater lake was created by the impact of a massive meteor during the Pleistocene Epoch. Being a hypersaline and hyperalkaline soda lake, rich microbial diversity is reported earlier. Lonar lake water is used by local people and tribals against skin diseases. These observations prompted us to investigate the therapeutic potential of lake water against skin diseases. In this context, we have conducted pilot study to assess the antipsoriatic and antiangiogenic activity of the salt obtained from lake water using THP1 cell line by MTT assay and antiangiogenic activity by in vivo chicken chorioallantoic membrane (CAM) assay, as there is a close relation between psoriasis and angiogenesis. The results revealed that salt possess remarkable antipsoriatic and antiangiogenic activity.

scholarly journals Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Kuo Chang ◽  
You-Han Zhong ◽  
Shan-Chi Liu ◽  
Chien-Chung Huang ◽  
Chun-Hao Tsai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Synovial Fibroblasts ◽  
Tube Formation ◽  
Endothelial Progenitor ◽  
Rheumatoid Arthritis Disease ◽  
Cartilage Erosion ◽  
And Migration ◽  
Angiopoietin 1

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA.

scholarly journals Degradation of Mitochondria and Oxidative Stress as the Main Mechanism of Toxicity of Pristine Graphene on U87 Glioblastoma Cells and Tumors and HS-5 Cells

2019 ◽  
Vol 20 (3) ◽  
pp. 650 ◽  
Author(s):  
Sławomir Jaworski ◽  
Barbara Strojny ◽  
Ewa Sawosz ◽  
Mateusz Wierzbicki ◽  
Marta Grodzik ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Pristine Graphene ◽  
Infrared Measurements ◽  
The Impact

Due to the development of nanotechnologies, graphene and graphene-based nanomaterials have attracted immense scientific interest owing to their extraordinary properties. Graphene can be used in many fields, including biomedicine. To date, little is known about the impact graphene may have on human health in the case of intentional exposure. The present study was carried out on U87 glioma cells and non-cancer HS-5 cell lines as in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane as in vivo model, on which the effects of pristine graphene platelets (GPs) were evaluated. The investigation consisted of structural analysis of GPs using transmission electron microscopy, Fourier transmission infrared measurements, zeta potential measurements, evaluation of cell morphology, assessment of cell viability, investigation of reactive oxygen species production, and investigation of mitochondrial membrane potential. The toxicity of U87 glioma tumors was evaluated by calculating the weight and volume of tumors and performing analyses of the ultrastructure, histology, and protein expression. The in vitro results indicate that GPs have dose-dependent cytotoxicity via ROS overproduction and depletion of the mitochondrial membrane potential. The mass and volume of tumors were reduced in vivo after injection of GPs. Additionally, the level of apoptotic and necrotic markers increased in GPs-treated tumors.

scholarly journals Structure and hemodynamics of vascular networks in the chorioallantoic membrane of the chicken

2016 ◽  
Vol 311 (4) ◽  
pp. H913-H926 ◽  
Author(s):  
Martin Maibier ◽  
Bettina Reglin ◽  
Bianca Nitzsche ◽  
Weiwei Xiang ◽  
Wen Wei Rong ◽  
...  
Keyword(s):  
Shear Stress ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Vascular Networks ◽  
Murray's Law ◽  
Chick Chorioallantoic Membrane ◽  
Murray’S Law ◽  
Flow Pathways ◽  
Hemodynamic Simulations

The chick chorioallantoic membrane (CAM) is extensively used as an in vivo model. Here, structure and hemodynamics of CAM vessel trees were analyzed and compared with predictions of Murray's law. CAM microvascular networks of Hamburger-Hamilton stage 40 chick embryos were scanned by videomicroscopy. Three networks with ∼3,800, 580, and 480 segments were digitally reconstructed, neglecting the capillary mesh. Vessel diameters ( D) and segment lengths were measured, and generation numbers and junctional exponents at bifurcations were derived. In selected vessels, flow velocities ( v) and hematocrit were measured. Hemodynamic simulations, incorporating the branching of capillaries from preterminal vessels, were used to estimate v, volume flow, shear stress (τ), and pressure for all segments of the largest network. For individual arteriovenous flow pathways, terminal arterial and venous generation numbers are negatively correlated, leading to low variability of total topological and morphological pathway lengths. Arteriolar velocity is proportional to diameter ( v∝ D1.03 measured, v∝ D0.93 modeling), giving nearly uniform τ levels (τ∝ D0.05). Venular trees exhibit slightly higher exponents ( v∝ D1.3, τ∝ D0.38). Junctional exponents at divergent and convergent bifurcations were 2.05 ± 1.13 and 1.97 ± 0.95 (mean ± SD) in contrast to the value 3 predicted by Murray's law. In accordance with Murray's law, τ levels are (nearly) maintained in CAM arterial (venular) trees, suggesting vascular adaptation to shear stress. Arterial and venous trees show an interdigitating arrangement providing homogeneous flow pathway properties and have preterminal capillary branches. These properties may facilitate efficient oxygen exchange in the CAM during rapid embryonic growth.

Assessment of breast cancer primary tumor material in a 3D in vivo model

2021 ◽  
pp. 1-10
Author(s):  
Cynthia Kohl ◽  
Thiha Aung ◽  
Silke Haerteis ◽  
Thomas Papathemelis
Keyword(s):  
Breast Cancer ◽  
Treatment Plan ◽  
Tumor Biology ◽  
Chorioallantoic Membrane ◽  
Tumor Model ◽  
In Vivo Model ◽  
Additional Information ◽  
Chick Chorioallantoic Membrane ◽  
The Individual

BACKGROUND: Breast cancer is the most common malignant tumor in women and highly heterogeneous with a variety of different molecular subtypes. The analysis of the individual tumor biology is necessary to develop a specific and individualized treatment plan for every patient. The chick chorioallantoic membrane (CAM) model, a 3D-in-vivo-tumor-model, could potentially provide a methodology that facilitates the gain of additional information regarding the tumor biology as well as the testing of the tumor’s individual sensitivity to different therapies. OBJECTIVE: The objective was to establish the grafting of different breast cancer primaries onto the CAM for tumor profiling and the investigation of different parameters. METHODS: Breast cancer primary tissue of different patients was grafted onto the CAM. Subsequently, 3D volume and perfusion measurements were performed during the engraftment period. Histological analyses of the tumors were carried out after the engraftment period. RESULTS: The grafting of the breast cancer primaries onto the CAM was successful. The tumors remained partially vital and displayed angiogenic development on the CAM. CONCLUSIONS: Breast cancer primary material can be grafted onto the CAM and we observed visible and measurable changes of perfusion over time.

scholarly journals N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1

2021 ◽  
Vol 9 ◽  
Author(s):  
Guo Dong ◽  
Jiangbo Yu ◽  
Gaojun Shan ◽  
Lide Su ◽  
Nannan Yu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Stat3 Pathway ◽  
Protein Levels ◽  
Chick Chorioallantoic Membrane

Atherosclerosis (AS) is a life-threatening vascular disease. RNA N6-methyladenosine (m6A) modification level is dysregulated in multiple pathophysiologic processes including AS. In this text, the roles and molecular mechanisms of m6A writer METTL3 in AS progression were explored in vitro and in vivo. In the present study, cell proliferative, migratory, and tube formation capacities were assessed through CCK-8, Transwell migration, and tube formation assays, respectively. RNA m6A level was examined through a commercial kit. RNA and protein levels of genes were measured through RT-qPCR and western blot assays, respectively. VEGF secretion level was tested through ELISA assay. JAK2 mRNA stability was detected through actinomycin D assay. The relationship of METTL3, IGF2BP1, and JAK2 was investigated through bioinformatics analysis, MeRIP, RIP, RNA pull-down, and luciferase reporter assays. An AS mouse model was established to examine the effect of METTL3 knockdown on AS development in vivo. The angiogenetic activity was examined through chick chorioallantoic membrane assay in vivo. The results showed that METTL3 was highly expressed in ox-LDL-induced dysregulated HUVECs. METTL3 knockdown inhibited cell proliferation, migration, tube formation, and VEGF expression/secretion in ox-LDL-treated HUVECs, hampered AS process in vivo, and prevented in vivo angiogenesis of developing embryos. METTL3 positively regulated JAK2 expression and JAK2/STAT3 pathway in an m6A dependent manner in HUVECs. IGF2BP1 positively regulated JAK2 expression through directly binding to an m6A site within JAK2 mRNA in HUVECs. METTL3 knockdown weakened the interaction of JAK2 and IGF2BP1. METTL3 exerted its functions through JAK2/STAT3 pathway. In conclusion, METTL3 knockdown prevented AS progression by inhibiting JAK2/STAT3 pathway via IGF2BP1.

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