scholarly journals Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

2018 ◽  
Vol 19 (9) ◽  
pp. 2470 ◽  
Author(s):  
Julia Chudzian ◽  
Anna Szlachcic ◽  
Malgorzata Zakrzewska ◽  
Miroslawa Czub ◽  
Marcin Pustula ◽  
...  
Keyword(s):  
Antibody Fragment ◽  
Antibody Fragments ◽  
Signaling Cascades ◽  
Biological Processes ◽  
Cell Models ◽  
Cell Proliferation And Differentiation ◽  
Promote Tumor Growth ◽  
Proliferation And Differentiation ◽  
Tumor Types

Fibroblast growth factor 1 (FGF1) and its receptors (FGFRs) regulate crucial biological processes such as cell proliferation and differentiation. Aberrant activation of FGFRs by their ligands can promote tumor growth and angiogenesis in many tumor types, including lung or breast cancer. The development of FGF1-targeting molecules with potential implications for the therapy of FGF1-driven tumors is recently being considered a promising approach in the treatment of cancer. In this study we have used phage display selection to find scFv antibody fragments selectively binding FGF1 and preventing it from binding to its receptor. Three identified scFv clones were expressed and characterized with regard to their binding to FGF1 and ability to interfere with FGF1-induced signaling cascades activation. In the next step the scFvs were cloned to scFv-Fc format, as dimeric Fc fusions prove beneficial in prospective therapeutic application. As expected, scFvs-Fc exhibited significantly increased affinity towards FGF1. We observed strong antiproliferative activity of the scFvs and scFvs-Fc in the in vitro cell models. Presented antibody fragments serve as novel FGF1 inhibitors and can be further utilized as powerful tools to use in the studies on the selective cancer therapy.

scholarly journals Biocompatibility Characteristics of Titanium Coated with Multi Walled Carbon Nanotubes—Hydroxyapatite Nanocomposites

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 224 ◽  
Author(s):  
Jung-Eun Park ◽  
Yong-Seok Jang ◽  
Tae-Sung Bae ◽  
Min-Ho Lee
Keyword(s):  
Electron Microscopy ◽  
Carbon Nanotubes ◽  
Sol Gel ◽  
Pure Titanium ◽  
Cell Proliferation And Differentiation ◽  
Transmission Electron ◽  
Proliferation And Differentiation ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

Multi walled carbon nanotubes-hydroxyapatite (MWCNTs-HA) with various contents of MWCNTs was synthesized using the sol-gel method. MWCNTs-HA composites were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). HA particles were generated on the surface of MWCNT. Produced MWCNTs-HA nanocomposites were coated on pure titanium (PT). Characteristic of the titanium coated MWCNTs-HA was evaluated by field-emission scanning electron microscopy (FE-SEM) and XRD. The results show that the titanium surface was covered with MWCNTs-HA nanoparticles and MWCNTs help form the crystalized hydroxyapatite. Furthermore, the MWCNTs-HA coated titanium was investigated for in vitro cellular responses. Cell proliferation and differentiation were improved on the surface of MWCNT-HA coated titanium.

scholarly journals Mechanics of the cellular microenvironment as perceived by cells in vivo

2021 ◽  
Author(s):  
Alessandro Mongera ◽  
Marie Pochitaloff ◽  
Hannah J. Gustafson ◽  
Georgina A. Stooke-Vaughan ◽  
Payam Rowghanian ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Mechanical Parameters ◽  
Cellular Microenvironment ◽  
Stem Cell Maintenance ◽  
Quantitative Studies ◽  
Cell Proliferation And Differentiation ◽  
3D Microenvironment ◽  
Proliferation And Differentiation

Tissue morphogenesis and repair, as well as organ homeostasis, require cells to constantly monitor their 3D microenvironment and adapt their behaviors in response to local biochemical and mechanical cues1-6. In vitro studies have shown that substrate stiffness and stress relaxation are important mechanical parameters in the control of cell proliferation and differentiation, stem cell maintenance, cell migration 7-11, as well as tumor progression and metastasis12,13. Yet, the mechanical parameters of the microenvironment that cells perceive in vivo, within 3D tissues, remain unknown. In complex materials with strain- and time-dependent material properties, the perceived mechanical parameters depend both on the strain and timescales at which the material is mechanically probed14. Here, we quantify in vivo and in situ the mechanics of the cellular microenvironment that cells probe during vertebrate presomitic mesoderm (PSM) specification. By analyzing the magnitude and dynamics of endogenous, cell-generated strains, we show that individual cells preferentially probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. We reveal how stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. While stress relaxation timescales are spatially uniform in the tissue, most mechanical parameters, including those probed by cells, vary along the anteroposterior axis, as mesodermal progenitors commit to different lineages. Understanding the mechanical parameters that cells probe in their native 3D environment is important for quantitative studies of mechanosensation in vivo2-4,6,15 and can help design scaffolds for tissue engineering applications16-18.

Improved in-vitro biocompatibility of LZ91 Mg–Li alloy by formation of nanostructured Ti coating through surface mechanical nano-alloying treatment

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jian Sun ◽  
Xiangcun Zhu ◽  
Zhuo Chen ◽  
Yi Li ◽  
Yonghong Zhang
Keyword(s):  
Grain Size ◽  
Surface Hardness ◽  
Coated Sample ◽  
Untreated Sample ◽  
In Vitro Biocompatibility ◽  
Cell Proliferation And Differentiation ◽  
Average Grain Size ◽  
Proliferation And Differentiation ◽  
Alloy Microstructure

Abstract Surface mechanical nano-alloying treatment (SMNAT) was employed to fabricate a nanostructured Ti coating on LZ91 Mg–Li alloy. Microstructure, surface hardness and in-vitro biocompatibility of the Ti-coated sample were investigated in comparison with those of an untreated sample. Experimental results showed that a nanostructured Ti coating with a thickness of 35 to 60 μm was formed after SMNAT for 2 h. The average grain size in the top surface of the Ti coating was about 30 nm. The surface of the Ti coating is rougher than that of the untreated LZ91 sample, in which the values of Ra, Rq and Rz were 7.83, 9.57 and 14.85 μm, respectively. The hardness of the Ti coating top surface was about 483 HV. Cell proliferation and differentiation on Ti coated samples were enhanced relative to those on the untreated samples.

scholarly journals Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity

2018 ◽  
Vol 115 (26) ◽  
pp. 6786-6791 ◽  
Author(s):  
Jiaxi Wu ◽  
Huaizhu Wu ◽  
Jinping An ◽  
Christie M. Ballantyne ◽  
Jason G. Cyster
Keyword(s):  
Critical Role ◽  
T Cell Proliferation ◽  
Cell Capture ◽  
Antigen Uptake ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Missing Self

CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.

scholarly journals Effects of RAC1 on Proliferation of Hen Ovarian Prehierarchical Follicle Granulosa Cells

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1589
Author(s):  
Thobela Louis Tyasi ◽  
Xue Sun ◽  
Xuesong Shan ◽  
Simushi Liswaniso ◽  
Ignatius Musenge Chimbaka ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Biological Effects ◽  
Expression Levels ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mrna And Protein Expression ◽  
Chicken Ovary ◽  
New Evidence ◽  
Follicle Selection

RAC1 belongs to the small G protein Rho subfamily and is implicated in regulating gene expression, cell proliferation and differentiation in mammals and humans; nevertheless, the function of RAC1 in growth and development of hen ovarian follicles is still unclear. This study sought to understand the biological effects of RAC1 on granulosa cell (GC) proliferation and differentiation of hen ovarian prehierarchical follicles. Firstly, our results showed expression levels of RAC1 mRNA in the follicles with diameters of 7.0–8.0 mm, 6.0–6.9 mm and 1.0–3.9 mm were greater than other follicles (p < 0.05). The RAC1 protein was mainly expressed in oocyte and its around GCs and stromal tissues of the prehierarchical follicles by immunohistochemistry. Further investigation revealed the RAC1 gene remarkably enhanced the mRNA and protein expression levels of FSHR (a marker of follicle selection), CCND2 (a marker of cell-cycle progression and GC differentiation), PCNA (a marker of GC proliferation), StAR and CYP11A1 (markers of GC differentiation and steroidogenesis) (p < 0.05). Furthermore, our data demonstrated siRNA interference of RAC1 significantly reduced GC proliferation (p < 0.05), while RAC1 gene overexpression enhanced GC proliferation in vitro (p < 0.05). Collectively, this study provided new evidence that the biological effects of RAC1 on GC proliferation, differentiation and steroidogenesis of chicken ovary follicles.

scholarly journals Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shinichiro Hayashi ◽  
Ichiro Manabe ◽  
Yumi Suzuki ◽  
Frédéric Relaix ◽  
Yumiko Oishi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Biological Processes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Acting In Concert

Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.

scholarly journals The nerve growth factor-responsive PC12 cell line does not express the Myc dimerization partner Max.

1995 ◽  
Vol 15 (7) ◽  
pp. 3470-3478 ◽  
Author(s):  
R Hopewell ◽  
E B Ziff
Keyword(s):  
Cell Line ◽  
Pc12 Cell ◽  
Tumor Cell Line ◽  
Pc12 Cell Line ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
E Box ◽  
Associated Proteins ◽  
And Control

Heterodimerization of Max with the nuclear oncoprotein Myc and the differentiation-associated proteins Mad and Mxi1 enables these factors to bind E-box sites in DNA and control genes implicated in cell proliferation and differentiation. We show that in the PC12 pheochromocytoma tumor cell line, functional Max protein is not expressed because of the synthesis of a mutant max transcript. This transcript encodes a protein incapable of homo- or heterodimerization. Furthermore, the mutant Max protein, unlike wild-type Max, is incapable of repressing transcription from an E-box element. Synthesis of mutant max transcripts appears to be due to a homozygous chromosomal alteration within the max gene. Reintroduction of max into PC12 cells results in repression of E-box-dependent transcription and a reduction in growth rate, which may explain the loss of Max expression either during the growth of the pheochromocytoma or in subsequent passage of the PC12 cell line in vitro. Finally, the ability of these cells to divide, differentiate, and apoptose in the absence of Max demonstrates for the first time that these processes can occur via Max- and possibly Myc-independent mechanisms.

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