scholarly journals PalaCell2D: A framework for detailed tissue morphogenesis

2021 ◽  
Author(s):  
Raphaël Conradin ◽  
Christophe Coreixas ◽  
Jonas Latt ◽  
Bastien Chopard
Keyword(s):  
Internal Pressure ◽  
Tissue Growth ◽  
Cellular Mechanisms ◽  
Simple Description ◽  
Biologically Relevant ◽  
In Vivo Experiments ◽  
Cell Shapes ◽  
And Migration ◽  
The Impact

AbstractIn silico, cell based approaches for modeling biological morphogenesis are used to test and validate our understanding of the biological and mechanical process that are at work during the growth and the organization of multi-cell tissues. As compared to in vivo experiments, computer based frameworks dedicated to tissue modeling allow us to easily test different hypotheses, and to quantify the impact of various biophysically relevant parameters.Here, we propose a formalism based on a detailed, yet simple, description of cells that accounts for intra-, inter- and extra-cellular mechanisms. More precisely, the cell growth and division is described through the space and time evolution of the membrane vertices. These vertices follow a Newtonian dynamics, meaning that their evolution is controlled by different types of forces: a membrane force (spring and bending), an adherence force (inter-cellular spring), external and internal pressure forces. Different evolution laws can be applied on the internal pressure, depending on the intra-cellular mechanism of interest. In addition to the cells dynamics, our formalism further relies on a lattice Boltzmann method, using the Palabos library, to simulate the diffusion of chemical signals. The latter aims at driving the growth and migration of a tissue by simply changing the state of the cells.All of this leads to an accurate description of the growth and division of cells, with realistic cell shapes and where membranes can have different properties. While this work is mainly of methodological nature, we also propose to validate our framework through simple, yet biologically relevant benchmark tests at both single-cell and full tissue scales. This includes free and chemically controlled cell tissue growth in an unbounded domain. The ability of our framework to simulate cell migration, cell compression and morphogenesis under external constraints is also investigated in a qualitative manner.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

scholarly journals Revision of the ARRIVE guidelines: rationale and scope

2018 ◽  
Vol 2 (1) ◽  
pp. e000002 ◽  
Author(s):  
Nathalie Percie du Sert ◽  
Viki Hurst ◽  
Amrita Ahluwalia ◽  
Sabina Alam ◽  
Douglas G Altman ◽  
...  
Keyword(s):  
System Development ◽  
Animal Research ◽  
Quality Of Reporting ◽  
Research Reporting ◽  
In Vivo Experiments ◽  
Expert Working Group ◽  
Tiered System ◽  
Initial Work ◽  
The Impact

In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy of an expert working group established to revise the guidelines and facilitate their uptake. The group’s initial work will focus on three main areas: prioritisation of the ARRIVE items into a tiered system, development of an explanation and elaboration document, and revision of specific items.

scholarly journals Combination of in vivo phage therapy data with in silico model highlights key parameters for treatment efficacy

2021 ◽  
Author(s):  
Raphaelle Delattre ◽  
Jeremy Seurat ◽  
Feyrouz Haddad ◽  
Thu-Thuy Nguyen ◽  
Baptiste Gaborieau ◽  
...  
Keyword(s):  
Phage Therapy ◽  
Biological Properties ◽  
General Strategy ◽  
In Vivo Experiments ◽  
Bacterial Dynamics ◽  
Optimal Dosing ◽  
Dosing Regimens ◽  
The Impact

The clinical (re)development of phage therapy to treat antibiotic resistant infections requires grasping specific biological properties of bacteriophages (phages) as antibacterial. However, identification of optimal dosing regimens is hampered by the poor understanding of phage-bacteria interactions in vivo. Here we developed a general strategy coupling in vitro and in vivo experiments with a mathematical model to characterize the interplay between phage and bacterial dynamics during pneumonia induced by a pathogenic strain of Escherichia coli. The model estimates some key parameters for phage therapeutic efficacy, in particular the impact of dose and route of administration on phage dynamics and the synergism of phage and the innate immune response on the bacterial clearance rate. Simulations predict a low impact of the intrinsic phage characteristics in agreement with the current semi-empirical choices of phages for compassionate treatments. Model-based approaches will foster the deployment of future phage therapy clinical trials.

scholarly journals MiR-125b-5p Inhibited The Progression of Hepatoblastoma As A Shared miRNA of The lncRNA NEAT1 and YES1

2020 ◽  
Author(s):  
Zhu Jin ◽  
Yutong Chen ◽  
Yuchen Mao ◽  
Mingjuan Gao ◽  
Zebing Zheng ◽  
...  
Keyword(s):  
Clinicopathological Characteristics ◽  
Luciferase Reporter ◽  
Tumor Growth Inhibition ◽  
Invasion And Migration ◽  
In Vivo Experiments ◽  
Reporter Assays ◽  
And Migration ◽  
Relationship Of

Abstract Background: microRNAs have been studied widely in hepatoblastoma. However, the role of miR-125b-5p and its relationship with the lncRNA sNEAT1 and YES1 in hepatoblastoma have not been reported previously. We aimed to reveal the role of NEAT1/miR-125b-5p/YES1 in the progression of hepatoblastoma.Methods: We collected tumor tissues and their adjacent tissues from 12 hepatoblastoma patients. qRT-PCR was applied to detect the expression of miR-125b-5p, and the relationship of miR-125b-5p with clinicopathological characteristics was analyzed. Dual luciferase reporter assays and RNA pull down assays were used to identify the relationships among NEAT1, miR-125b-5p and YES1. CCK8, Transwell assays and wound healing assays were used to examine cell viability, invasion and migration. In vivo experiments were also applied to detect the effect of miR-125b-5p on hepatoblastoma.Results: miR-125b-5p was significantly downregulated in hepatoblastoma tissue and cells. The higher the PRETEXT grade, the lower the miR-125b-5p level. NEAT1 could bind to miR-125b-5p and inhibit its expression. miR-125b-5p could target YES1 and inhibit its expression. Overexpression of miR-125b-5p decreased the proliferation, invasion, and migratory ability of hepatoblastoma cells. YES1 could rescue the above effects. At the same time, overexpression of miR-125b-5p resulted in decreased YES1 and tumor growth inhibition in vivo.Conclusion: miR-125b-5p acted as a shared miRNA of NEAT1 and YES1 in hepatoblastoma. Overexpression of miR-125b-5p could target YES1 and inhibit its expression, therefore inhibiting the progression of hepatoblastoma.

scholarly journals LINC00319 acts as a microRNA-335–5p sponge to accelerate tumor growth and metastasis in gastric cancer by upregulating ADCY3

2020 ◽  
Vol 318 (1) ◽  
pp. G10-G22
Author(s):  
Jun Zou ◽  
Kun Wu ◽  
Chao Lin ◽  
Zhi-Gang Jie
Keyword(s):  
Gastric Cancer ◽  
Adenylate Cyclase ◽  
Tumor Growth ◽  
Micro Rna ◽  
In Vivo Experiments ◽  
Tumorigenesis And Progression ◽  
Tumor Growth And Metastasis ◽  
And Migration

Gastric cancer (GC) is one of the most common cancers in the world and remains a heavy burden of health worldwide. Adenylate cyclase 3 ( ADCY3) is a widely expressed membrane-associated protein in human tissues and has been identified to be a new molecular target of GC. Long noncoding RNAs have a substantial influence on tumorigenesis and progression of tumors by binding to microRNAs. Therefore, this study is to clarify the mechanism by which LINC00319 sponges micro RNA-335–5p ( miR-335–5p) to influence the development of GC. Initially, microarray analysis identified GC-related differentially expressed LINC00319 and ADCY3 for this study. The interaction was confirmed that LINC00319 interacted with miR-335–5p to regulate ADCY3. Next, SGC-7901 cells presenting with the lowest LINC00319 expression and the highest miR-335–5p expression were transfected with LINC00319, miR-335–5p inhibitor, or ADCY3 vector to examine their roles in growth and metastasis of GC cells, which was further ascertained by in vivo experiments. LINC00319 was upregulated and miR-335–5p was downregulated in GC cells. LINC00319 overexpression, miR-335–5p inhibitor, or ADCY3 overexpression was shown to significantly elevate the expression of cyclin-dependent kinase 4 and metastasis associated 1, decrease that of growth arrest-specific 1, and promote tumor growth and metastasis by increasing proliferation and migration and reducing cell apoptosis. Importantly, it was found that overexpressed miR-335–5p exerted its tumor suppressive role in GC through downregulating ADCY3. Collectively, LINC00319 expedited growth and metastasis of GC by upregulating miR-335–5p-mediated ADCY3. NEW & NOTEWORTHY This study is carried out based on in vivo and in vitro studies in mice and gastric cancer (GC) cells with the aim of clarifying the role of LINC00319 on GC growth and metastasis, which associated with micro RNA-335–5p-mediated adenylate cyclase 3. Altogether, we identified LINC00319 to be a potential therapy to treat GC.

Hepatocytes are a rich source of novel aspirin-triggered 15-epi-lipoxin A4

1999 ◽  
Vol 277 (5) ◽  
pp. C870-C877 ◽  
Author(s):  
Esther Titos ◽  
Nan Chiang ◽  
Charles N. Serhan ◽  
Mario Romano ◽  
Joan Gaya ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Arachidonic Acid Metabolism ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Potent Inducer ◽  
Biologically Relevant ◽  
In Vivo Experiments ◽  
Cox 2 ◽  
Cytochrome P 450

Novel aspirin (ASA)-triggered 15-epi-lipoxins (ATL) comprise new potent bioactive eicosanoids that may contribute to the therapeutic effect of this drug. ATL biosynthesis is initiated by ASA acetylation of cyclooxygenase (COX)-2 and was originally identified during the interaction of leukocytes with either endothelial or epithelial cells. Here, we examined ATL biosynthesis in rat hepatocytes either alone or in coincubation with nonparenchymal liver cells (NPC) and in liver homogenates from ASA-treated rats. Rat hepatocytes and CC-1 cells, a rat hepatocyte cell line, displayed COX-1 but not COX-2 mRNA expression and predominantly produced thromboxane A2(TXA2) and 15-hydroxyeicosatetraenoic acid (15-HETE). In these cells, ASA shifted the arachidonic acid metabolism from TXA2 to 15-HETE in a concentration-dependent manner. In contrast, neither indomethacin, ibuprofen, valeryl salicylate, nor nimesulide was able to trigger 15-HETE biosynthesis. SKF-525A, a cytochrome P-450 inhibitor, significantly reduced the effect of ASA on 15-HETE biosynthesis. Furthermore, phenobarbital, a potent inducer of cytochrome P-450 activity, further increased ASA-induced 15-HETE production. ASA treatment of hepatocyte-NPC coincubations resulted in the generation of significant amounts of ATL. In addition, in vivo experiments demonstrated augmented hepatic levels of 15-epi-lipoxin A4 in ASA-treated rats. Taken together and considering that ASA is hydrolyzed on its first pass through the portal circulation, these data indicate that, during ASA's consumption, liver tissue generates biologically relevant amounts of ATL by COX-2-independent mechanisms.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

The role of circCNIH4 in the adipocyte's effects on metastasis of breast cancer cells.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13086-e13086
Author(s):  
Xiu Chen ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
Wound Healing ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
Non Invasive ◽  
In Vivo Experiments ◽  
And Migration ◽  
Mcf 7

e13086 Background: Obesity is associated with the risk of breast cancer(BCa) incidence and development. However, biological changes in obesity BCa individuals are still uncertain. Nowadays, circCNIH4, one of novel non-coding RNAs, was found to be a non-invasive biomarker in cancers. Methods: We verified the cancer-promoting role of obesity in BCa patients by comparing BMI indexes of 33 BCa and 44 benign tumor patients. Then we cocultured viscera adipose cells(HPA-v) and BCa cells(MCF-7/H and MDA-MB-231/H) to confirm the function of adipocytes on metastasis of BCa cells through wound healing, transwell assays. In vivo experiments were also performed. We analyzed the expression level of circCNIH4 in MCF-7/H, MDA-MB-231/H and different subtypes of BCa cells by quantitative polymerase chain reaction. Simultaneously, we identified inhibited effects of circCNIH4 on metastasis of BCa cells by wound healing, transwell assays and verified the location of circCNIH4 by FISH. Luciferase Assay was used to detect harbored miRNA. Rescue experiments were then applied. Results: We found the BMI of BCa patients(24.37±2.51) was much higher than benign patients(22.97±2.91). Metastasis of BCa cells were obviously promoted after in vitro and in vivo experiments. Then we found the expression of circCNIH4 in MCF-7/H and MDA-MB-231/H were down-regulated 0.71 and 0.52 than that in MCF-7 and MDA-MB-231. Also, circCNIH4 was positively correlated with less aggressive types of BCa cells. Overexpression of circCNIH4 in MDA-MB-231 could suppress cell invasion and migration, while silencing of it in MCF-7 promoted cell invasion and migration. The FISH assay demonstrated that circCNIH4 mainly located in the cytoplasm and might function as a “sponge” for miRNA. MiR-135b functioned as a tumor promoter gene from data of 93 BCa patients (HR = 2.27; 1.01 − 5.12), and it could be captured by circCNIH4 via luciferase and rescued assays. Conclusions: In this study, we revealed that BMI or viscera adipocytes could deteriorate prognosis of BCa and circCNIH4 could be a novel biomarker for non-invasive BCa. In details, circCNIH4 mainly suppressed the adipocyte's pro-metastasis effects on BCa by capturing miR-135b.

scholarly journals Theory of active chromatin remodeling

2019 ◽  
Author(s):  
Zhongling Jiang ◽  
Bin Zhang
Keyword(s):  
Chromatin Remodeling ◽  
Computational Models ◽  
Energy Landscape ◽  
Nucleosome Positioning ◽  
Active Chromatin ◽  
Intrinsic Signals ◽  
Biologically Relevant ◽  
The Impact ◽  
Prediction In Silico

Nucleosome positioning controls the accessible regions of chromatin and plays essential roles in DNA-templated processes. ATP driven remodeling enzymes are known to be crucial for its establishment in vivo, but their non-equilibrium nature has hindered the development of a unified theoretical framework for nucleosome positioning. Using a perturbation theory, we show that the effect of these enzymes can be well approximated by effective equilibrium models with rescaled temperatures and interactions. Numerical simulations support the accuracy of the theory in predicting both kinetic and steady-state quantities, including the effective temperature and the radial distribution function, in biologically relevant regimes. The energy landscape view emerging from our study provides an intuitive understanding for the impact of remodeling enzymes in either reinforcing or overwriting intrinsic signals for nucleosome positioning, and may help improve the accuracy of computational models for its prediction in silico.

Abstract 100: HIV Protein Tat Induces Macrophage Dysfunction and Atherosclerosis Development in LDLR-deficient Mice

2020 ◽  
Vol 40 (Suppl_1) ◽  
Author(s):  
Zhaojie Meng ◽  
Weiwei Lu ◽  
Taesik Gwag ◽  
Changcheng Zhou
Keyword(s):  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Iκb Kinase ◽  
Increased Risk ◽  
Macrophage Dysfunction ◽  
Atherosclerosis Development ◽  
And Migration ◽  
The Impact ◽  
Hiv 1

Introduction: As the average lifespan of HIV-infected patients receiving anti-retroviral therapy lengthens, morbidity and mortality from cardiovascular disease pose considerable challenges. HIV infection is consistently associated with increased risk of atherosclerosis development, but the underlying mechanisms remain elusive. HIV-1 Tat protein, a transcriptional activator of HIV virus, has been shown to activate NF-κB signaling and promote inflammation in vitro. However, the atherogenic effects of HIV-1 Tat have not been investigated in vivo. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis. We and others have previously demonstrated that NF-κB signaling functions in macrophages to regulate atherogenesis. This study aims to investigate the impact of HIV-1 Tat exposure on macrophage functions and atherogenesis. Hypothesis: HIV-1 Tat activates IκB kinase β (IKKβ), a central coordinator in inflammation through activation of NF-κB, to induce macrophage dysfunction and atherosclerosis development. Methods: To investigate the effects of HIV-1 Tat on macrophage IKKβ signaling and atherosclerosis development in vivo, myeloid-specific IKKβ-deficient LDLR-deficient (IKKβ ΔMye LDLR -/- ) mice and their control littermates (IKKβ F/F LDLR -/- ) were exposed to recombinant HIV-1 Tat for 12 weeks. The effects of HIV-1 Tat on macrophage functions including inflammatory responses, adhesion and migration properties were also studied. Results and Conclusions: HIV-1 Tat significantly increased atherosclerotic lesion size in aortic root and brachiocephalic artery of IKKβ F/F LDLR -/- but not IKKβ ΔMye LDLR -/- mice. Deficiency of myeloid IKKβ attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation in IKKβ ΔMye LDLR -/- mice. In addition, HIV-1 Tat stimulated adhesion and migration properties of control macrophages but had no effects on IKKβ-deficient macrophages. In conclusion, our findings reveal the atherogenic effects of HIV-1 Tat in vivo and demonstrate a pivot role of myeloid IKKβ in HIV-1 Tat-driven atherogenesis.

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