scholarly journals Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 757
Author(s):  
Adela Kratochvilova ◽  
Alice Ramesova ◽  
Barbora Vesela ◽  
Eva Svandova ◽  
Herve Lesot ◽  
...  
Keyword(s):  
Cell Death ◽  
Fas Ligand ◽  
Bone Cells ◽  
Expression Profiles ◽  
Negative Regulator ◽  
Bone Homeostasis ◽  
Caspase Inhibitor ◽  
The One ◽  
The Impact ◽  
Mature Bone

The Fas ligand (FasL) is known from programmed cell death, the immune system, and recently also from bone homeostasis. As such, Fas signalling is a potential target of anti-osteoporotic treatment based on the induction of osteoclastic cell death. Less attention has been paid to osteocytes, although they represent the majority of cells within the mature bone and are the key regulators. To determine the impact of FasL stimulation on osteocytes, differentiated IDG-SW3 cells were challenged by FasL, and their osteogenic expression profiles were evaluated by a pre-designed PCR array. Notably, the most downregulated gene was the one for sclerostin, which is the major marker of osteocytes and a negative regulator of bone formation. FasL stimulation also led to significant changes (over 10-fold) in the expression of other osteogenic markers: Gdf10, Gli1, Ihh, Mmp10, and Phex. To determine whether these alterations involved caspase-dependent or caspase-independent mechanisms, the IDG-SW3 cells were stimulated by FasL with and without a caspase inhibitor: Q-VD-OPh. The alterations were also detected in the samples treated by FasL along with Q-VD-OPh, pointing to the caspase-independent impact of FasL stimulation. These results contribute to an understanding of the recently emerging pleiotropic effects of Fas/FasL signalling and specify its functions in bone cells.

scholarly journals Flice-Inhibitory Protein Expression during Macrophage Differentiation Confers Resistance to FAS-Mediated Apoptosis

1999 ◽  
Vol 190 (11) ◽  
pp. 1679-1688 ◽  
Author(s):  
Harris Perlman ◽  
Lisa J. Pagliari ◽  
Constantinos Georganas ◽  
Toshiaki Mano ◽  
Kenneth Walsh ◽  
...  
Keyword(s):  
Cell Death ◽  
Fas Ligand ◽  
Negative Regulator ◽  
Death Domain ◽  
Blood Monocytes ◽  
Inhibitory Protein ◽  
Monocyte Differentiation ◽  
Host Immune Responses ◽  
Naturally Occurring ◽  
Induced Apoptosis

Macrophages differentiated from circulating peripheral blood monocytes are essential for host immune responses and have been implicated in the pathogenesis of rheumatoid arthritis and atherosclerosis. In contrast to monocytes, macrophages are resistant to Fas-induced cell death by an unknown mechanism. FLICE (Fas-associated death domain–like interleukin 1β–converting enzyme)–inhibitory protein (Flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of Fas-induced apoptosis. Here, we show that monocyte differentiation into macrophages was associated with upregulation of Flip and a decrease in Fas-mediated apoptosis. Overexpression of Flip protected monocytes from Fas-mediated apoptosis, whereas acute Flip inhibition in macrophages induced apoptosis. Addition of an antagonistic Fas ligand antibody to Flip antisense–treated macrophages rescued cultures from apoptosis, demonstrating that endogenous Flip blocked Fas-induced cell death. Thus, the expression of Flip in macrophages conferred resistance to Fas-mediated apoptosis, which may contribute to the development of inflammatory disease.

scholarly journals TRAF2 inhibits TRAIL- and CD95L-induced apoptosis and necroptosis

2014 ◽  
Vol 5 (10) ◽  
pp. e1444-e1444 ◽  
Author(s):  
I Karl ◽  
M Jossberger-Werner ◽  
N Schmidt ◽  
S Horn ◽  
M Goebeler ◽  
...  
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Protein Complexes ◽  
Combined Treatment ◽  
Death Receptor ◽  
Adaptor Protein ◽  
Negative Regulator ◽  
Interacting Protein ◽  
Induced Apoptosis ◽  
The Impact

Abstract The relevance of the adaptor protein TNF receptor-associated factor 2 (TRAF2) for signal transduction of the death receptor tumour necrosis factor receptor1 (TNFR1) is well-established. The role of TRAF2 for signalling by CD95 and the TNF-related apoptosis inducing ligand (TRAIL) DRs, however, is only poorly understood. Here, we observed that knockdown (KD) of TRAF2 sensitised keratinocytes for TRAIL- and CD95L-induced apoptosis. Interestingly, while cell death was fully blocked by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) in control cells, TRAF2-depleted keratinocytes were only partly rescued from TRAIL- and CD95L-induced cell death. In line with the idea that the only partially protective effect of zVAD-fmk on TRAIL- and CD95L-treated TRAF2-depleted keratinocytes is due to the induction of necroptosis, combined treatment with zVAD-fmk and the receptor interacting protein 1 (RIP1) inhibitor necrostatin-1 fully rescued these cells. To better understand the impact of TRAF2 levels on RIP1- and RIP3-dependent necroptosis and RIP3-independent apoptosis, we performed experiments in HeLa cells that lack endogenous RIP3 and HeLa cells stably transfected with RIP3. HeLa cells, in which necroptosis has no role, were markedly sensitised to TRAIL-induced caspase-dependent apoptosis by TRAF2 KD. In RIP3-expressing HeLa transfectants, however, KD of TRAF2 also strongly sensitised for TRAIL-induced necroptosis. Noteworthy, priming of keratinocytes with soluble TWEAK, which depletes the cytosolic pool of TRAF2-containing protein complexes, resulted in strong sensitisation for TRAIL-induced necroptosis but had only a very limited effect on TRAIL-induced apoptosis. The necroptotic TRAIL response was not dependent on endogenously produced TNF and TNFR signalling, since blocking TNF by TNFR2-Fc or anti-TNFα had no effect on necroptosis induction. Taken together, we identified TRAF2 not only as a negative regulator of DR-induced apoptosis but in particular also as an antagonist of TRAIL- and CD95L-induced necroptosis.

scholarly journals Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 404-412 ◽  
Author(s):  
Olga Dakhova ◽  
Diana O'Day ◽  
Noe Kinet ◽  
Nur Yucer ◽  
Mary Wiese ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Fas Ligand ◽  
Sperm Count ◽  
Negative Regulator ◽  
Steroidogenic Factor 1 ◽  
Adult Testis ◽  
Adult Mice ◽  
Sperm Counts ◽  
Apoptotic Activity ◽  
The One

Dickkopf-like1 (Dkkl1) encodes a glycoprotein secreted by postmeiotic male germ cells. We report here that adult Dkkl1-deficient males have elevated sperm counts caused by a decrease in postpubertal spermatocyte apoptosis and display, upon aging, increased local production of testosterone. Molecular analyses identified the Fas death ligand (FasL) as a target for Dkkl1 pro-apoptotic activity in adult mice. Accordingly, adult FasL-deficient gld mice display an increased sperm count and decreased spermatocyte apoptosis phenotype similar to the one observed in Dkkl1-deficient mice. We also show that the elevated testosterone level observed in aging Dkkl1-deficient males is secondary to increased expression in Leydig cells of CYP11A and CYP17, two genes implicated in steroidogenesis. Furthermore, treatment of Leydig cells with Dkkl1 decreases DNA binding and transcriptional activity of steroidogenic factor 1, a pivotal regulator of gene expression in testis. Thus, this study establishes Dkkl1 as a negative regulator of adult testis homeostasis and identifies a novel, Dkkl1/FasL-dependent, regulation that specifically controls the number of postpubertal spermatocytes. Dickkopf-like 1 negatively regulates adult testis biology by promoting spermatocyte apoptosis via Fas ligand activation and by limiting testosterone synthesis in Leydig cells.

Static and Dynamic Studies of Gasoline in View of its Octane Number and its Toxic Effect

2013 ◽  
Vol 12 (7) ◽  
pp. 451-459
Author(s):  
Ashraf Yehia El-Naggar ◽  
Mohamed A. Ebiad
Keyword(s):  
Toxic Effect ◽  
Aromatic Hydrocarbons ◽  
Octane Number ◽  
Liquid Fuel ◽  
Positive Impact ◽  
Hydrocarbon Composition ◽  
Different Temperatures ◽  
Different Seasons ◽  
The One ◽  
The Impact

Gasoline come primarily from petroleum cuts, it is the preferred liquid fuel in our lives. Two gasoline samples of octane numbers 91 and 95 from Saudi Arabia petrol stations were studied. This study was achieved at three different temperatures 20oC, 30oC and 50oC representing the change in temperatures of the different seasons of the year. Both the evaporated gases of light aromatic hydrocarbons (BTEX) of gasoline samples inside the tank were subjected to analyze qualitatively and quantitatively via capillary gas chromatography. The detailed hydrocarbon composition and the octane number of the studied gasoline samples were determined using detailed hydrocarbon analyzer. The idea of research is indicating the impact of light aromatic compounds in gasoline on the toxic effect of human and environment on the one hand, and on octane number of gasoline on the other hand. Although the value of octane number will be reduced but this will have a positive impact on the environment as a way to produce clean fuel.

The Development of Agritourism in the Podkarpackie Voivodeship in the Light of International and National Conditions

2017 ◽  
Vol 13 ◽  
pp. 244-261
Author(s):  
Mariola Tracz ◽  
Małgorzata Bajgier-Kowalska ◽  
Radosław Uliszak
Keyword(s):  
Development Strategy ◽  
Current State ◽  
Central Statistical ◽  
Central Statistical Office ◽  
Tourism Resources ◽  
The One ◽  
The Impact ◽  
District Offices ◽  
Socio Economic Factors

Podkarpackie Voivodeship is one of the regions of Poland in which the number of agritourism entities is very high. Therefore tourism plays a significant role in its development strategy. The aim of the paper is to identify the current state of agritourism and the changes that have occurred in the region in the years 2000–2016. Specific objectives are to determine the distribution of agritourism farms and their offer, together with a comprehensive analysis of the environmental and socio-economic factors, as well as the impact of the Slovak-Ukrainian border. The report was developed on the statistical materials from the Polish Central Statistical Office, Podkarpackie Agricultural Advisory Centre in Boguchwała and data collected from municipalities and district offices that is published on their websites, as well as through interviews with 100 owners of agritourism farms in the Podkarpackie Voivodeship. The research has shown, on the one hand, the decline in the number of farms in the region and, on the other hand, the increase in the diversity of the tourist offer of these entities. Distribution of agritourism farms is closely linked to the attractiveness of natural environment and quality of secondary tourism resources. Traditional agritourism has not yet fully used its countryside, as well as cross-border advantages of its location.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

Laughter on the Fringes

2019 ◽  
Author(s):  
Anna Peterson
Keyword(s):  
The Other ◽  
Literary Canon ◽  
Autobiographical Writing ◽  
Treasure Trove ◽  
Old Comedy ◽  
Other Hand ◽  
Aggressive Humor ◽  
The One ◽  
The Individual ◽  
The Impact

This book examines the impact that Athenian Old Comedy had on Greek writers of the Imperial era. It is generally acknowledged that Imperial-era Greeks responded to Athenian Old Comedy in one of two ways: either as a treasure trove of Atticisms, or as a genre defined by and repudiated for its aggressive humor. Worthy of further consideration, however, is how both approaches, and particularly the latter one that relegated Old Comedy to the fringes of the literary canon, led authors to engage with the ironic and self-reflexive humor of Aristophanes, Eupolis, and Cratinus. Authors ranging from serious moralizers (Plutarch and Aelius Aristides) to comic writers in their own right (Lucian, Alciphron), to other figures not often associated with Old Comedy (Libanius) adopted aspects of the genre to negotiate power struggles, facilitate literary and sophistic rivalries, and provide a model for autobiographical writing. To varying degrees, these writers wove recognizable features of the genre (e.g., the parabasis, its agonistic language, the stage biographies of the individual poets) into their writings. The image of Old Comedy that emerges from this time is that of a genre in transition. It was, on the one hand, with the exception of Aristophanes’s extant plays, on the verge of being almost completely lost; on the other hand, its reputation and several of its most characteristic elements were being renegotiated and reinvented.

Freedom of Expression versus Privacy and the Right to Reputation

2017 ◽  
Author(s):  
Dirk Voorhoof
Keyword(s):  
Public Interest ◽  
Freedom Of Expression ◽  
Media Freedom ◽  
Investigative Journalism ◽  
The Public ◽  
The Right Of Privacy ◽  
The One ◽  
Grand Chamber ◽  
The Right ◽  
The Impact

The normative perspective of this chapter is how to guarantee respect for the fundamental values of freedom of expression and journalistic reporting on matters of public interest in cases where a (public) person claims protection of his or her right to reputation. First it explains why there is an increasing number and expanding potential of conflicts between the right to freedom of expression and media freedom (Article 10 ECHR), on the one hand, and the right of privacy and the right to protection of reputation (Article 8 ECHR), on the other. In addressing and analysing the European Court’s balancing approach in this domain, the characteristics and the impact of the seminal 2012 Grand Chamber judgment in Axel Springer AG v. Germany (no. 1) are identified and explained. On the basis of the analysis of the Court’s subsequent jurisprudence in defamation cases it evaluates whether this case law preserves the public watchdog-function of media, investigative journalism and NGOs reporting on matters of public interest, but tarnishing the reputation of public figures.

Preaching and Sermons

2017 ◽  
Author(s):  
Robert H. Ellison
Keyword(s):  
Eighteenth Century ◽  
North Atlantic ◽  
Religious Revival ◽  
Early Nineteenth Century ◽  
Denominational Identity ◽  
The North ◽  
The North Atlantic ◽  
The One ◽  
The Impact

Prompted by the convulsions of the late eighteenth century and inspired by the expansion of evangelicalism across the North Atlantic world, Protestant Dissenters from the 1790s eagerly subscribed to a millennial vision of a world transformed through missionary activism and religious revival. Voluntary societies proliferated in the early nineteenth century to spread the gospel and transform society at home and overseas. In doing so, they engaged many thousands of converts who felt the call to share their experience of personal conversion with others. Though social respectability and business methods became a notable feature of Victorian Nonconformity, the religious populism of the earlier period did not disappear and religious revival remained a key component of Dissenting experience. The impact of this revitalization was mixed. On the one hand, growth was not sustained in the long term and, to some extent, involvement in interdenominational activity undermined denominational identity; on the other hand, Nonconformists gained a social and political prominence they had not enjoyed since the middle of the seventeenth century and their efforts laid the basis for the twentieth-century explosion of evangelicalism in Africa, Asia, and South America.

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